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1.
Hum Genomics ; 18(1): 55, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38822443

ABSTRACT

BACKGROUND: Although CDKN2A alteration has been explored as a favorable factor for tumorigenesis in pan-cancers, the association between CDKN2A point mutation (MUT) and intragenic deletion (DEL) and response to immune checkpoint inhibitors (ICIs) is still disputed. This study aims to determine the associations of CDKN2A MUT and DEL with overall survival (OS) and response to immune checkpoint inhibitors treatment (ICIs) among pan-cancers and the clinical features of CDKN2A-altered gastric cancer. METHODS: This study included 45,000 tumor patients that underwent tumor sequencing across 33 cancer types from four cohorts, the MSK-MetTropism, MSK-IMPACT, OrigiMed2020 and TCGA cohorts. Clinical outcomes and genomic factors associated with response to ICIs, including tumor mutational burden, copy number alteration, neoantigen load, microsatellite instability, tumor immune microenvironment and immune-related gene signatures, were collected in pan-cancer. Clinicopathologic features and outcomes were assessed in gastric cancer. Patients were grouped based on the presence of CDKN2A wild type (WT), CDKN2A MUT, CDKN2A DEL and CDKN2A other alteration (ALT). RESULTS: Our research showed that CDKN2A-MUT patients had shorter survival times than CDKN2A-WT patients in the MSK MetTropism and TCGA cohorts, but longer OS in the MSK-IMPACT cohort with ICIs treatment, particularly in patients having metastatic disease. Similar results were observed among pan-cancer patients with CDKN2A DEL and other ALT. Notably, CDKN2A ALT frequency was positively related to tumor-specific objective response rates to ICIs in MSK MetTropism and OrigiMed 2020. Additionally, individuals with esophageal carcinoma or stomach adenocarcinoma who had CDKN2A MUT had poorer OS than patients from the MSK-IMPACT group, but not those with adenocarcinoma. We also found reduced levels of activated NK cells, T cells CD8 and M2 macrophages in tumor tissue from CDKN2A-MUT or DEL pan-cancer patients compared to CDKN2A-WT patients in TCGA cohort. Gastric cancer scRNA-seq data also showed that CDKN2A-ALT cancer contained less CD8 T cells but more exhausted T cells than CDKN2A-WT cancer. A crucial finding of the pathway analysis was the inhibition of three immune-related pathways in the CDKN2A ALT gastric cancer patients, including the interferon alpha response, inflammatory response, and interferon gamma response. CONCLUSIONS: This study illustrates the CDKN2A MUT and DEL were associated with a poor outcome across cancers. CDKN2A ALT, on the other hand, have the potential to be used as a biomarker for choosing patients for ICI treatment, notably in esophageal carcinoma and stomach adenocarcinoma.


Subject(s)
Cyclin-Dependent Kinase Inhibitor p16 , Stomach Neoplasms , Tumor Microenvironment , Humans , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Stomach Neoplasms/drug therapy , Stomach Neoplasms/immunology , Cyclin-Dependent Kinase Inhibitor p16/genetics , Tumor Microenvironment/genetics , Tumor Microenvironment/immunology , Male , Female , Immune Checkpoint Inhibitors/therapeutic use , Middle Aged , Biomarkers, Tumor/genetics , Aged , Prognosis , DNA Copy Number Variations/genetics , Mutation/genetics , Microsatellite Instability
2.
Int J Biol Macromol ; : 132830, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38825264

ABSTRACT

Artificial graft serves as the primary grafts used in the clinical management of sports-related injuries. Until now, optimizing its graft-host integration remains a great challenge due to the excessive inflammatory response during the inflammatory phase, coupled with an absence of tissue-inductive capacity during the regeneration phase. Here, a multi-layered regenerated silk fibroin (RSF) coating loaded with curcumin (Cur) and Zn2+ on the surface of the PET grafts (Cur@Zn2+@PET) was designed and fabricated for providing time-matched regulation specifically tailored to address issues arising at both inflammatory and regeneration phases, respectively. The release of Cur and Zn2+ from the Cur@Zn2+@PET followed a time-programmed pattern in vitro. Specifically, cellular assays revealed that Cur@Zn2+@PET initially released Cur during the inflammatory phase, thereby markedly inhibit the expression of inflammatory cytokines TNF-a and IL-1ß. Meanwhile, a significant release of Zn2+ was major part during the regeneration phase, serving to induce the osteogenic differentiation of rBMSC. Furthermore, rat model of anterior cruciate ligament reconstruction (ACLR) showed that through time-programmed drug release, Cur@Zn2+@PET could suppress the formation of fibrous interface (FI) caused by inflammatory response, combined with significant new bone (NB) formation during regeneration phase. Consequently, the implementation of the Cur@Zn2+@PET characterized by its time-programmed release patterns hold considerable promise for improving graft-host integration for sports-related injuries.

4.
mBio ; : e0119124, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38829126

ABSTRACT

Human cytomegalovirus (HCMV), a widely prevalent human beta-herpesvirus, establishes lifelong persistence in the host following primary infection. In healthy individuals, the virus is effectively controlled by HCMV-specific T cells and typically exhibits asymptomatic. The T cell immune response plays a pivotal role in combating HCMV infection, while HCMV employs various strategies to counteract it within the host. Previously, we reported that UL23, a tegument protein of HCMV, facilitates viral immune evasion from interferon-gamma (IFN-γ) responses, and it is well known that IFN-γ is mainly derived from T cells. However, the involvement of UL23 in viral immune evasion from T cell-mediated immunity remains unclear. Herein, we present compelling evidence that UL23 significantly enhances viral resistance against T cell-mediated cytotoxicity during HCMV infection from the co-culture assays of HCMV-infected cells with T cells. We found that IFN-γ plays a major role in regulating T cell cytotoxicity mediated by UL23. More interestingly, we demonstrated that UL23 not only regulates the IFN-γ downstream responses but also modulates the IFN-γ secretion by regulating T cell activities. Further experiments indicate that UL23 upregulates the expression and signaling of programmed death ligand 1 (PD-L1), which is responsible for inhibiting multiple aspects of T cell activities, including activation, apoptosis, and IFN-γ secretion, as determined through RNA-seq analysis and inhibitor-blocking experiments, ultimately facilitating viral replication and spread. Our findings highlight the potential role of UL23 as an alternative antagonist in suppressing T cell cytotoxicity and unveil a novel strategy for HCMV to evade T cell immunity. IMPORTANCE: T cell immunity is pivotal in controlling primary human cytomegalovirus (HCMV) infection, restricting periodic reactivation, and preventing HCMV-associated diseases. Despite inducing a robust T cell immune response, HCMV has developed sophisticated immune evasion mechanisms that specifically target T cell responses. Although numerous studies have been conducted on HCMV-specific T cells, the primary focus has been on the impact of HCMV on T cell recognition via major histocompatibility complex molecules. Our studies show for the first time that HCMV exploits the programmed death ligand 1 (PD-L1) inhibitory signaling pathway to evade T cell immunity by modulating the activities of T cells and thereby blocking the secretion of IFN-γ, which is directly mediated by HCMV-encoded tegument protein UL23. While PD-L1 has been extensively studied in the context of tumors and viruses, its involvement in HCMV infection and viral immune evasion is rarely reported. We observed an upregulation of PD-L1 in normal cells during HCMV infection and provided strong evidence supporting its critical role in UL23-induced inhibition of T cell-mediated cytotoxicity. The novel strategy employed by HCMV to manipulate the inhibitory signaling pathway of T cell immune activation for viral evasion through its encoded protein offers valuable insights for the understanding of HCMV-mediated T cell immunomodulation and developing innovative antiviral treatment strategies.

6.
Plant Physiol ; 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38829837

ABSTRACT

Soybean (Glycine max [L.] Merr.) is a valuable oil crop but is also highly susceptible to environmental stress. Thus, developing approaches to enhance soybean stress resistance is vital to soybean yield improvement. In previous studies, transcription factor Alfin has been shown to serve as an epigenetic regulator of plant growth and development. However, no studies on Alfin have yet been reported in soybean. In this study, the endoplasmic reticulum (ER) stress- and reactive oxygen species (ROS)-related GmAlfin09 was identified. Screening of genes co-expressed with GmAlfin09 unexpectedly led to the identification of soybean peroxidase 6 (GmPRDX6). Further analyses revealed that both GmAlfin09 and GmPRDX6 were responsive to ER stress, with GmPRDX6 localizing to the ER under stress. Promoter binding experiments confirmed the ability of GmAlfin09 to bind to the GmPRDX6 promoter directly. When GmAlfin09 and GmPRDX6 were overexpressed in soybean, enhanced ER stress resistance and decreased ROS levels were observed. Together, these findings suggest that GmAlfin09 promotes the upregulation of GmPRDX6, and GmPRDX6 subsequently localizes to the ER, reduces ROS levels, promotes ER homeostasis, and ensures the normal growth of soybean even under ER stress. This study highlights a vital target gene for future molecular breeding of stress-resistant soybean lines.

7.
Cell Death Dis ; 15(6): 390, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38830885

ABSTRACT

Glioma is the most common and aggressive type of primary malignant brain tumor. The N6-methyladenosine (m6A) modification widely exists in eukaryotic cells and plays an important role in the occurrence and development of human tumors. However, the function and mechanism of heterogeneous nuclear ribonucleoprotein C (HNRNPC), an RNA-binding protein and m6A reader in gliomas remains to be comprehensively and extensively explored. Herein, we found that HNRNPC mRNA and protein overexpression were associated with a poor prognosis for patients with gliomas, based on the data from TCGA, the CGGA, and the TMAs. Biologically, HNRNPC knockdown markedly repressed malignant phenotypes of glioma in vitro and in vivo, whereas ectopic HNRNPC expression had the opposite effect. Integrative RNA sequencing and MeRIP sequencing analyses identified interleukin-1 receptor-associated kinase 1 (IRAK1) as a downstream target of HNRNPC. The glioma public datasets and tissue microarrays (TMAs) data indicated that IRAK1 overexpression was associated with poor prognosis, and IRAK1 knockdown significantly repressed malignant biological behavior in vitro. Mechanistically, HNRNPC maintains the mRNA stability of IRAK1 in an m6A-dependent manner, resulting in activation of the mitogen-activated protein kinase (MAPK) signaling pathway, which was necessary for the malignant behavior of glioma. Our findings demonstrate the HNRNPC-IRAK1-MAPK axis as a crucial carcinogenic factor for glioma and the novel underlying mechanism of IRAK1 upregulation, which provides a rationale for therapeutically targeting epitranscriptomic modulators in glioma.


Subject(s)
Disease Progression , Glioma , Heterogeneous-Nuclear Ribonucleoprotein Group C , Interleukin-1 Receptor-Associated Kinases , MAP Kinase Signaling System , RNA, Messenger , Humans , Glioma/genetics , Glioma/pathology , Glioma/metabolism , Interleukin-1 Receptor-Associated Kinases/metabolism , Interleukin-1 Receptor-Associated Kinases/genetics , RNA, Messenger/metabolism , RNA, Messenger/genetics , Heterogeneous-Nuclear Ribonucleoprotein Group C/metabolism , Heterogeneous-Nuclear Ribonucleoprotein Group C/genetics , Cell Line, Tumor , MAP Kinase Signaling System/genetics , Mice , RNA Stability/genetics , Mice, Nude , Animals , Gene Expression Regulation, Neoplastic , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Brain Neoplasms/metabolism , Female , Male , Adenosine/analogs & derivatives , Adenosine/metabolism , Prognosis
8.
J Tissue Eng ; 15: 20417314241254508, 2024.
Article in English | MEDLINE | ID: mdl-38826796

ABSTRACT

Vascularized composite allotransplantation (VCA), which can effectively improve quality of life, is a promising therapy for repair and reconstruction after face or body trauma. However, intractable issues are associated with VCA, such as the inevitable multiple immunogenicities of different tissues that cause severe rejection, the limited protocols available for clinical application, and the shortage of donor sources. The existing regimens used to extend the survival of patients receiving VCAs and suppress rejection are generally the lifelong application of immunosuppressive drugs, which have side effects. Consequently, studies aiming at tissue engineering methods for VCA have become a topic. In this review, we summarize the emerging therapeutic strategies for tissue engineering aimed to prolong the survival time of VCA grafts, delay the rejection and promote prevascularization and tissue regeneration to provide new ideas for future research on VCA treatment.

9.
J Hypertens ; 42(6): 1066-1074, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38690905

ABSTRACT

OBJECTIVE: The evidence regarding the associations of circulating metabolic biomarkers with hypertension risk is scarce. We aimed to examine the associations between circulating metabolites and risk of hypertension. METHODS: We included 49 422 individuals free of hypertension at baseline with a mean (SD) age of 53.5 (8.0) years from the UK Biobank. Nuclear magnetic resonance spectroscopy was used to quantify 143 individual metabolites. Multivariable-adjusted Cox regression models were used to estimate hazard ratios and 95% confidence intervals (CIs). RESULTS: During a mean (SD) follow-up of 11.2 (1.8) years, 2686 incident hypertension cases occurred. Out of 143 metabolites, 76 were associated with incident hypertension, among which phenylalanine (hazard ratio: 1.40; 95% CI: 1.24-1.58) and apolipoprotein A1 (hazard ratio: 0.76; 95% CI: 0.66-0.87) had the strongest association when comparing the highest to the lowest quintile. In general, very-low-density lipoprotein (VLDL) particles were positively, whereas high-density lipoprotein (HDL) particles were inversely associated with risk of hypertension. Similar patterns of cholesterol, phospholipids, and total lipids within VLDL and HDL particles were observed. Triglycerides within all lipoproteins were positively associated with hypertension risk. Other metabolites showed significant associations with risk of hypertension included amino acids, fatty acids, ketone bodies, fluid balance and inflammation markers. Adding 10 selected metabolic biomarkers to the traditional hypertension risk model modestly improved discrimination (C-statistic from 0.745 to 0.752, P < 0.001) for prediction of 10-year hypertension incidence. CONCLUSION: Among UK adults, disturbances in metabolic biomarkers are associated with incident hypertension. Comprehensive metabolomic profiling may provide potential novel biomarkers to identify high-risk individuals.


Subject(s)
Biological Specimen Banks , Biomarkers , Hypertension , Humans , Hypertension/blood , Hypertension/epidemiology , United Kingdom/epidemiology , Middle Aged , Biomarkers/blood , Male , Female , Adult , Risk Factors , Aged , UK Biobank
10.
Front Psychiatry ; 15: 1406826, 2024.
Article in English | MEDLINE | ID: mdl-38694001
11.
J Infect Dis ; 2024 May 09.
Article in English | MEDLINE | ID: mdl-38723186

ABSTRACT

Targeted therapy is an attractive approach for treating infectious diseases. Affibody molecules have similar capability to antibodies that facilitate molecular recognition in both diagnostic and therapeutic applications. Targeting major outer membrane protein (MOMP) for treating infection of Chlamydia trachomatis, one of the most common sexually transmitted pathogens, is a promising therapeutic approach. Previously, we have reported a MOMP-specific affibody (ZMOMP:461) from phage display library. Here, we first fused it with modified Pseudomonas Exotoxin (PE38KDEL) and a cell-penetrating peptide (CPP) to develop an affitoxin, Z461X-CPP. We then verified the addition of both toxin and CPPs that did not affect the affinitive capability of ZMOMP:461 to MOMP. Upon uptake by C.trachomatis-infected cells, Z461X-CPP induced cell apoptosis in vitro. In animal model, Z461X significantly shortened the duration of C. trachomatis infection and prevented pathological damage in mouse reproductive system. These findings provide compelling evidence that the MOMP-specific affitoxin has great potential for targeting therapy of C. trachomatis infection.

12.
iScience ; 27(4): 109297, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38715943

ABSTRACT

The One Health (OH) approach is used to control/prevent zoonotic events. However, there is a lack of tools for systematically assessing OH practices. Here, we applied the Global OH Index (GOHI) to evaluate the global OH performance for zoonoses (GOHI-Zoonoses). The fuzzy analytic hierarchy process algorithm and fuzzy comparison matrix were used to calculate the weights and scores of five key indicators, 16 subindicators, and 31 datasets for 160 countries and territories worldwide. The distribution of GOHI-Zoonoses scores varies significantly across countries and regions, reflecting the strengths and weaknesses in controlling or responding to zoonotic threats. Correlation analyses revealed that the GOHI-Zoonoses score was associated with economic, sociodemographic, environmental, climatic, and zoological factors. Additionally, the Human Development Index had a positive effect on the score. This study provides an evidence-based reference and guidance for global, regional, and country-level efforts to optimize the health of people, animals, and the environment.

13.
Chem Commun (Camb) ; 60(42): 5554-5557, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38712366

ABSTRACT

Zirconia as a polycrystalline catalyst can be effectively tuned by doping low-valence elements and meanwhile form abundant oxygen vacancies. Herein, the crystalline structures of zirconia are modulated by scandium doping and proposed as a robust catalyst for nitrate reduction to ammonia. The tetragonal zirconia achieves a maximum ammonia yield of 16.03 mg h-1 mgcat.-1, superior to the other crystal forms. DEMS tests unveil the reaction pathway and theoretical calculations reveal the low free energy of -0.22 eV for nitrate adsorption at the tetragonal zirconia.

14.
Heliyon ; 10(9): e30214, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38707310

ABSTRACT

Background: Accumulating small unruptured intracranial aneurysms are detected due to the improved quality and higher frequency of cranial imaging, but treatment remains controversial. While surgery or endovascular treatment is effective for small aneurysms with a high risk of rupture, such interventions are unnecessary for aneurysms with a low risk of rupture. Consequently, it is imperative to accurately identify small aneurysms with a low risk of rupture. The purpose of this study was to develop a clinically practical model to predict small aneurysm ruptures based on a radiomics signature and clinical risk factors. Methods: A total of 293 patients having an aneurysm with a diameter of less than 5 mm, including 199 patients (67.9 %) with a ruptured aneurysm and 94 patients (32.1 %) without a ruptured aneurysm, were included in this study. Digital subtraction angiography or surgical treatment was required in all cases. Data on the clinical risk factors and the features on computed tomography angiography images associated with the aneurysm rupture status were collected simultaneously. We developed a clinical-radiomics model to predict aneurysm rupture status using multivariate logistic regression analysis. The combined clinical-radiomics model was constructed by nomogram analysis. The diagnostic performance, clinical utility, and model calibration were evaluated by operating characteristic curve analysis, decision curve analysis, and calibration analysis. Results: A combined clinical-radiomics model (Area Under Curve [AUC], 0.85; 95 % confidence interval [CI], 0.757-0.947) showed effective performance in the operating characteristic curve analysis. In the validation cohort, the performance of the combined model was better than that of the radiomics model (AUC, 0.75; 95 % CI, 0.645-0.865; Delong's test p-value = 0.01) and the clinical model (AUC, 0.74; 95 % CI, 0.625-0.851; Delong's test p-value <0.01) alone. The results of the decision curve, nomogram, and calibration analyses demonstrated the clinical utility and good fitness of the combined model. Conclusion: Our study demonstrated the effectiveness of a clinical-radiomics model for predicting rupture status in small aneurysms.

15.
Small ; : e2400997, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38712477

ABSTRACT

Dielectric capacitors are widely used in advanced electrical and electronic systems due to the rapid charge/discharge rates and high power density. High comprehensive energy storage properties are the ultimate ambition in the field of application achievements. Here, the high-entropy strategy is proposed to design and fabricate single-phase homogeneous (Bi0.5Ba0.1Sr0.1Ca0.2Na0.1)(Fe0.5Ti0.3Zr0.1Nb0.1)O3 ceramic, the hierarchical heterostructure including rhombohedral-tetragonal multiphase nanoclusters and locally disordered oxygen octahedral tilt can lead to the increased dielectric relaxation, diffused phase transition, diverse local polarization configurations, grain refinement, ultrasmall polar nanoregions, large random field, delayed polarization saturation and improved breakdown field. Accordingly, a giant Wrec ≈13.3 J cm-3 and a high η ≈78% at 66.4 kV mm-1 can be simultaneously achieved in the lead-free high-entropy BiFeO3-based ceramic, showing an obvious advantage in overall energy-storage properties over BiFeO3-based lead-free ceramics. Moreover, an ultrafast discharge rate (t0.9 = 18 ns) can be achieved at room temperature, concomitant with favorable temperature stability in the range of 20-160 °C, due to the enhanced diffuse phase transition and fast polarization response. This work provides a feasible pathway to design and generate dielectric materials exhibiting high comprehensive energy-storage performance.

16.
Front Pharmacol ; 15: 1379338, 2024.
Article in English | MEDLINE | ID: mdl-38738180

ABSTRACT

Background: Chinese patent medicine is commonly used in China as an important treatment mechanism to thwart the progression of chronic kidney disease (CKD) stages 3-5, among which Niaoduqing granules are a representative Chinese patent medicine; however, its long-term efficacy on CKD prognosis remains unclear. Methods: Patients were grouped according to Niaoduqing granule prescription duration (non-Niaoduqing granule (non-NDQ) group vs Niaoduqing granule (NDQ) group). Serum creatinine (SCr) variation was compared using a generalized linear mixed model (GLMM). Multivariate Cox regression models were constructed, adjusting for confounding factors, to explore the risk of composite outcomes (receiving renal replacement therapy (RRT) or having an estimated glomerular filtration rate (eGFR)<5 mL/min/1.73 m2, ≥50% decline in the eGFR from the baseline, and doubling of SCr) in individuals consuming Niaoduqing granules. Results: A total of 1,271 patients were included, with a median follow-up duration of 29.71 (12.10, 56.07) months. The mean SCr Z-scores for the non-NDQ group and NDQ group were -0.175 and 0.153, respectively, at baseline (p = 0.015). The coefficients of the NDQ group from visit 1 to visit 5 were -0.207 (95% CI: -0.346, -0.068, p = 0.004), -0.214 (95% CI: 0.389, -0.039, p = 0.017), -0.324 (95% CI: 0.538, -0.109, p = 0.003), -0.502 (95% CI: 0.761, -0.243, p = 0.000), and -0.252 (95% CI: 0.569, 0.065, p = 0.119), respectively. The survival probability was significantly higher in the NDQ group (p = 0.0039). Taking Niaoduqing granules was a significant protective factor for thwarting disease progression (model 1: HR 0.654 (95% CI 0.489-0.875, p = 0.004); model 2: HR 0.646 (95% CI 0.476, 0.877, p = 0.005); and model 3: HR 0.602 (95% CI 0.442, 0.820, p = 0.001)). Conclusion: The long-term use of Niaoduqing granules improved SCr variation and lowered the risk of CKD progression by 39.8%.

17.
Chem Rev ; 2024 May 16.
Article in English | MEDLINE | ID: mdl-38754042

ABSTRACT

Ferroelectrics have become indispensable components in various application fields, including information processing, energy harvesting, and electromechanical conversion, owing to their unique ability to exhibit electrically or mechanically switchable polarization. The distinct polar noncentrosymmetric lattices of ferroelectrics make them highly responsive to specific crystal structures. Even slight changes in the lattice can alter the polarization configuration and response to external fields. In this regard, strain engineering has emerged as a prevalent regulation approach that not only offers a versatile platform for structural and performance optimization within ferroelectrics but also unlocks boundless potential in various functional materials. In this review, we systematically summarize the breakthroughs in ferroelectric-based functional materials achieved through strain engineering and progress in method development. We cover research activities ranging from fundamental attributes to wide-ranging applications and novel functionalities ranging from electromechanical transformation in sensors and actuators to tunable dielectric materials and information technologies, such as transistors and nonvolatile memories. Building upon these achievements, we also explore the endeavors to uncover the unprecedented properties through strain engineering in related chemical functionalities, such as ferromagnetism, multiferroicity, and photoelectricity. Finally, through discussions on the prospects and challenges associated with strain engineering in the materials, this review aims to stimulate the development of new methods for strain regulation and performance boosting in functional materials, transcending the boundaries of ferroelectrics.

18.
Schizophr Bull ; 2024 May 16.
Article in English | MEDLINE | ID: mdl-38754993

ABSTRACT

BACKGROUND AND HYPOTHESIS: Schizophrenia (SZ) is a prevalent mental disorder that imposes significant health burdens. Diagnostic accuracy remains challenging due to clinical subjectivity. To address this issue, we explore magnetic resonance imaging (MRI) as a tool to enhance SZ diagnosis and provide objective references and biomarkers. Using deep learning with graph convolution, we represent MRI data as graphs, aligning with brain structure, and improving feature extraction, and classification. Integration of multiple modalities is expected to enhance classification. STUDY DESIGN: Our study enrolled 683 SZ patients and 606 healthy controls from 7 hospitals, collecting structural MRI and functional MRI data. Both data types were represented as graphs, processed by 2 graph attention networks, and fused for classification. Grad-CAM with graph convolution ensured interpretability, and partial least squares analyzed gene expression in brain regions. STUDY RESULTS: Our method excelled in the classification task, achieving 83.32% accuracy, 83.41% sensitivity, and 83.20% specificity in 10-fold cross-validation, surpassing traditional methods. And our multimodal approach outperformed unimodal methods. Grad-CAM identified potential brain biomarkers consistent with gene analysis and prior research. CONCLUSIONS: Our study demonstrates the effectiveness of deep learning with graph attention networks, surpassing previous SZ diagnostic methods. Multimodal MRI's superiority over unimodal MRI confirms our initial hypothesis. Identifying potential brain biomarkers alongside gene biomarkers holds promise for advancing objective SZ diagnosis and research in SZ.

20.
Soc Sci Med ; 351: 116958, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38759384

ABSTRACT

While empirical studies have observed that homeownership is associated with improved mental health conditions, research indicates that this relationship might vary by race. Moreover, such a White-Black disparity in the impacts of homeownership on mental health could be complexed by poverty status, as maintaining one's homeownership could be a financial burden for people living in poverty status, defined by the US official poverty threshold. We add to the existing literature by analyzing the impacts of homeownership on psychological distress, simultaneously disaggregating by race and poverty status using survey data from the Panel Study on Income Dynamics from the 2017 and 2019 waves (N = 7059). Propensity score weighting and doubly robust estimation are applied to estimate causal inference for the impact of 2017 homeownership on 2019 psychological distress using negative binomial models. First, we found the impacts of homeownership on reducing psychological distress are significant for White Americans, not for Black Americans. Second, we found such a White-Black disparity is only observable for populations not living in poverty. On the other hand, for populations living in poverty, homeownership no longer lowers psychological distress for either race. Findings suggest that financial support and mental health support are needy to address inequality in the impacts of homeownership on mental health, which could simultaneously vary by poverty status and race. Implications are discussed.

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