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1.
Front Med (Lausanne) ; 11: 1402457, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39359921

RESUMO

This study aims to evaluate the feasibility of large language model (LLM) in answering pathology questions based on pathology reports (PRs) of colorectal cancer (CRC). Four common questions (CQs) and corresponding answers about pathology were retrieved from public webpages. These questions were input as prompts for Chat Generative Pretrained Transformer (ChatGPT) (gpt-3.5-turbo). The quality indicators (understanding, scientificity, satisfaction) of all answers were evaluated by gastroenterologists. Standard PRs from 5 CRC patients who received radical surgeries in Shanghai Changzheng Hospital were selected. Six report questions (RQs) and corresponding answers were generated by a gastroenterologist and a pathologist. We developed an interactive PRs interpretation system which allows users to upload standard PRs as JPG images. Then the ChatGPT's responses to the RQs were generated. The quality indicators of all answers were evaluated by gastroenterologists and out-patients. As for CQs, gastroenterologists rated AI answers similarly to non-AI answers in understanding, scientificity, and satisfaction. As for RQ1-3, gastroenterologists and patients rated the AI mean scores higher than non-AI scores among the quality indicators. However, as for RQ4-6, gastroenterologists rated the AI mean scores lower than non-AI scores in understanding and satisfaction. In RQ4, gastroenterologists rated the AI scores lower than non-AI scores in scientificity (P = 0.011); patients rated the AI scores lower than non-AI scores in understanding (P = 0.004) and satisfaction (P = 0.011). In conclusion, LLM could generate credible answers to common pathology questions and conceptual questions on the PRs. It holds great potential in improving doctor-patient communication.

2.
Biol Trace Elem Res ; 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39361121

RESUMO

We aimed to evaluate the relationship of dietary magnesium intake with all-cause and cause-specific mortality among patients with gout and hyperuricemia (HUA). We analyzed data of 1171 gout patients and 6707 HUA patients from the National Health and Nutrition Examination Survey (NHANES) 2007-2018 and 2001-2018, respectively. Dietary intake data were obtained from 24-h dietary recall interviews. Mortality status was determined using the NHANES public-use linked mortality fill. We used Cox regression model and restricted cubic spline analysis to probe the association of dietary magnesium intake and mortality among gout and HUA patients. During 7081 person-years of follow-up, 257 deaths were documented in gout patients, among which 74 died from cardiovascular disease (CVD) and 48 died from cancer. For HUA patients followed up for 58,216 person-years, 1315 all-cause deaths occurred, including 411 CVD deaths and 224 cancer deaths. After multifactorial adjustments, higher dietary magnesium intake was associated with lower risk of all-cause mortality. Nonlinear negative associations were found between dietary magnesium intake and CVD mortality among gout and HUA patients, with inflection points of 152.5 mg/day and 303 mg/day, respectively, and cancer mortality among HUA patients, with the inflection point of 232 mg/day. The results were robust in subgroup and sensitivity analyses. High dietary magnesium intake is linearly related to all-cause mortality, and nonlinearly associated with cause-specific mortality among gout and HUA patients.

3.
Transl Pediatr ; 13(8): 1336-1358, 2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39263297

RESUMO

Background: Diarrhea is the leading contributory factor of sickness and mortality among children under five and an economic burden for families. This study aimed to investigate the effects of mixed probiotics supplementation at different times (consecutive and alternate-hour) on intestinal microecology in Sprague-Dawley (SD) rats with acute diarrhea. Methods: A total of 40 SD rats were randomly assigned to four groups, including the control group, model group, probiotic group A, and probiotic group B. An acute diarrhea model was induced by administration of 5% dextran sulfate sodium. Rats in probiotic group A and probiotic group B were fed with Clostridium butyricum (C. butyricum), Bifidobacterium infantis (B. infantis), and Saccharomyces boulardii (S. boulardii) for a total of 7 days. Probiotic group A was fed with all probiotics simultaneously. Probiotic group B was fed with C. butyricum and B. infantis simultaneously, and then after a 2-hour interval, with S. boulardii. Metagenomic next-generation sequencing was used to analyze the fecal samples from every rat. The metagenomic sequencing used in this experiment was used to evaluate the effect of probiotics on the composition as well as function of the gut microbiota in order to gain a deeper comprehension of probiotic-host interactions on health and disease. Results: The structure of the gut microbiota in probiotic group A showed significant changes. Compared to the model group, the abundance of some beneficial bacteria had increased, including Actinobacteria (P=0.048), Lactobacillus (P=0.050), and Lactobacillus johnsonii (P=0.042), and many opportunistic pathogenic bacteria has decreased, such as Ruminococcus (P=0.001). Compared to the control group, the abundance of some beneficial bacteria had increased, including Fusobacteria (P=0.02) and Phascolarium (P=0.002), and there was a reduction in the abundance of many opportunistic pathogenic bacteria such as Roseburia (P=0.03), Lachnoclosterium (P=0.009), and Oscillibacter_sp_1-3 (P=0.002). In addition, metagenomic analysis showed that as well as an up-regulation of glycoside hydrolase expression, amino acid and inorganic ion transport, and metabolism-related pathways, there was a down-regulation of cell motility. Conclusions: Simultaneous administration of probiotics may have more positive implications in improving the gut microbiota of acute diarrhea rats.

4.
Mar Pollut Bull ; 208: 116933, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39260142

RESUMO

Coastal areas are regions of active interaction between the sea and land and are highly sensitive to changes in heavy metal contamination caused by natural and anthropogenic activities. The contents of heavy metals in 80 surface sediments in the Qizhou Island sea area in the northeast of Hainan Island were determined to assess the contamination status, spatial distribution, sources, and ecological risks. The results indicate that the main factors influencing the distribution patterns and contents of heavy metals are hydrodynamic conditions and sources of materials. The accumulation of Cd and Pb in the sediments is attributed to the combined effects of natural sources and anthropogenic input. In addition to widespread anthropogenic influence, the enrichment of Cd in the southeastern outer shelf area of the study region may be controlled by biogenic carbonate rocks or enhanced input of near-source materials during the late Pleistocene low sea level period.

6.
Sensors (Basel) ; 24(17)2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39275549

RESUMO

In the field of industrial inspection, accurate detection of thread quality is crucial for ensuring mechanical performance. Existing machine-vision-based methods for internal thread defect detection often face challenges in efficient detection and sufficient model training samples due to the influence of mechanical geometric features. This paper introduces a novel image acquisition structure, proposes a data augmentation algorithm based on Generative Adversarial Networks (GANs) to effectively construct high-quality training sets, and employs a YOLO algorithm to achieve internal thread defect detection. Through multi-metric evaluation and comparison with external threads, high-similarity internal thread image generation is achieved. The detection accuracy for internal and external threads reached 94.27% and 93.92%, respectively, effectively detecting internal thread defects.

7.
Molecules ; 29(18)2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39339396

RESUMO

The prevalence of antimicrobial resistance reduces the effectiveness of antimicrobial drugs in the prevention and treatment of infectious diseases caused by pathogens such as bacteria, fungi, and viruses. Microbial secondary metabolites have been recognized as important sources for new drug discovery and development, yielding a wide range of structurally novel and functionally diverse antimicrobial drugs for the treatment of a variety of diseases that are considered good producers of novel antimicrobial drugs. Bacteria produce a wide variety of antimicrobial compounds, and thus, antibiotics derived from natural products still dominate over purely synthetic antibiotics among the antimicrobial drugs developed and introduced over the last four decades. Among them, Pseudomonas aeruginosa secondary metabolites constitute a richly diverse source of antimicrobial substances with good antimicrobial activity. Therefore, they are regarded as an outstanding resource for finding novel bioactive compounds. The exploration of antimicrobial compounds among Pseudomonas aeruginosa metabolites plays an important role in drug development and biomedical research. Reports on the secondary metabolites of Pseudomonas aeruginosa, many of which are of pharmacological importance, hold great promise for the development of effective antimicrobial drugs against microbial infections by drug-resistant pathogens. In this review, we attempt to summarize published articles from the last twenty-five years (2000-2024) on antimicrobial secondary metabolites from Pseudomonas aeruginosa.


Assuntos
Produtos Biológicos , Pseudomonas aeruginosa , Pseudomonas aeruginosa/efeitos dos fármacos , Produtos Biológicos/farmacologia , Produtos Biológicos/química , Antibacterianos/farmacologia , Antibacterianos/química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Humanos , Testes de Sensibilidade Microbiana
8.
Small ; : e2405092, 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39324256

RESUMO

In acute lung injury, destruction of the lung endothelial glycocalyx leads to vessel permeabilization and contributes to pulmonary edema and inflammation. Heparan sulfate, which accounts for >70% of glycosaminoglycans in the endothelial glycocalyx, plays a crucial physiological anti-inflammatory role. To treat acute lung injury, it is explored whether a two-step in vivo bioorthogonal chemistry strategy can covalently link intravenously administered heparan sulfate to the lung vascular endothelium and the damaged glycocalyx. First, fusogenic liposomes (EBP-Tz-FLs) carrying the reactive group tetrazine (Tz), and an E-selectin-binding peptide (EBP) to target the lung inflammatory endothelium are administered intravenously. This step aimed to anchor the tetrazine group to the membrane of inflammatory endothelial cells. Second, heparan sulfate (HS-TCO) conjugated to the trans-cyclooctene (TCO) group, which spontaneously reacts with Tz, is injected intravenously, leading to covalent heparan sulfate addition to the vascular endothelium. In a mouse model of acute lung injury, this approach substantially reduced vascular permeability and attenuated lung tissue infiltration. The EBP-Tz-FLs and HS-TCO showed favorable biocompatibility and safety both in vitro and in vivo. The proposed strategy shows good promise in acute lung injury therapy and covalently anchoring functional molecules onto the membrane of target cells.

9.
Clin Exp Rheumatol ; 2024 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-39263792

RESUMO

OBJECTIVES: To explore whether the balance of CD226 and TIGIT is disturbed in CD3+CD56-TCRαß+CD4-CD8- (DN) T cells and have a better understanding of the potential role of DN T cells in the pathogenesis of primary Sjögren's syndrome (pSS). METHODS: The percentage of DN T cells as well as the expression of CD226 and TIGIT was identified by flowmetry. After in vitro stimulation, we further detected the expression of activation and cytotoxic marker, as well as intracellular cytokines secreted by DN T cells. RESULTS: DN T cells were found to expand in the peripheral blood of pSS patients (1.77±0.66%) and correlate with IgG (r=0.451, p<0.05), C3 (r=-0.438, p<0.05) and C4 (r=-0.470, p<0.05). Imbalanced CD226/TIGIT was observed on peripheral DN T cells of pSS patients, especially the overexpression of inhibitory immunoreceptor TIGIT. The expression ratio of TIGIT and CD226 on DN T cells was elevated in pSS patients and correlated with ESSDAI scores≥5 (r=0.743, p<0.05). Besides, these DN T cells were found to be activated and show strong cytotoxicity. CONCLUSIONS: The balance between CD226 and TIGIT on DN T cells was disturbed and correlated with the disease activity in pSS patients, which may be implicated in the pathogenesis of pSS.

10.
J Natl Cancer Cent ; 4(3): 280-287, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39281716

RESUMO

Background: The homologous recombination deficiency (HRD) score serves as a promising biomarker to identify patients who are eligible for treatment with PARP inhibitors (PARPi). Previous studies have suggested a 3-biomarker Genomic Instability Score (GIS) threshold of ≥ 42 as a valid biomarker to predict response to PARPi in patients with ovarian cancer and breast cancer. However, the GIS threshold for prostate cancer (PCa) is still lacking. Here, we conducted an exploratory analysis to investigate an appropriate HRD score threshold and to evaluate its ability to predict response to PARPi in PCa patients. Methods: A total of 181 patients with metastatic castration-resistant PCa were included in this study. Tumor tissue specimens were collected for targeted next-generation sequencing for homologous recombination repair (HRR) genes and copy number variation (CNV) analysis. The HRD score was calculated based on over 50,000 single-nucleotide polymorphisms (SNP) distributed across the human genome, incorporating three SNP-based assays: loss of heterozygosity, telomeric allelic imbalance, and large-scale state transition. The HRD score threshold was set at the last 5th percentile of the HRD scores in our cohort of known HRR-deficient tumors. The relationship between the HRD score and the efficacy in 16 patients of our cohort who received PARPi treatment were retrospectively analyzed. Results: Genomic testing was succeeded in 162 patients. In our cohort, 61 patients (37.7%) had HRR mutations (HRRm). BRCA mutations occurred in 15 patients (9.3%). The median HRD score was 4 (ranged from 0 to 57) in the total cohort, which is much lower than that in breast and ovarian cancers. Patients who harbored HRRm and BRCA or TP53 mutations had higher HRD scores. CNV occured more frequently in patients with HRRm. The last 5th percentile of HRD scores was 43 in the HRR-mutant cohort and consequently HRD high was defined as HRD scores ≥ 43. In the 16 patients who received PARPi in our cohort, 4 patients with a high HRD score achieved an objective response rate (ORR) of 100% while 12 patients with a low HRD score achieved an ORR of 8.3%. Progression-free survival (PFS) in HRD high patients was longer compared to HRD low patients, regardless of HRRm. Conclusions: A HRD score threshold of 43 was established and preliminarily validated to predict the efficacy of PARPi in this study. Future studies are needed to further verify this threshold.

11.
Food Chem ; 463(Pt 2): 141231, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39298845

RESUMO

Wheat bran (WB) was solid-state fermented by either Lacticaseibacillus rhamnosus (LGG), Levilactobacillus brevis (LB) or Lactiplantibacillus plantarum (LP), respectively, and then their corresponding physicochemical and metabolic characteristics were investigated. Current study revealed fermentation of either Lacticaseibacillus rhamnosus or Lactiplantibacillus plantarum quickly generated lactic acid, but not for Levilactobacillus brevis. Importantly, all LAB fermentation promoted total phenolic acids contents, fermentation of LB-WB led to the greatest total phenolic content, followed by LGG-WB, with the least for LP-WB. Moreover, LGG fermentation significantly increased levels of oleic acid, stearic acid and phosphoenolpyruvic acid on carbon metabolism and fatty acid biosynthesis, while LB fermentation mainly increased levels of L-phenylalanine, cholecalciferol, D-gluconic acid and D-glucarate with the influence on the entire metabolic pathway. In contrast, LP fermentation significantly decreased levels of alpha-ketoglutaric acid, cis-aconitic acid on the citrate cycle (TCA cycle). This study revealed their corresponding metabolic characteristics, which might highlight potentially individual nutritional aspects.

13.
ACS Omega ; 9(34): 36434-36444, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39220479

RESUMO

The microstructures and thermochemical behavior of the energetic composites composed of core-shell structured µAl@NiO microparticles were characterized. These core-shell microparticles were synthesized using a wet-chemistry-based one-pot process, where the assembly was proposed to be driven by the electrostatic force between negatively charged Al and positively charged Ni-NH3 ions. Electron microscopic images demonstrated the formation of NiO nanoparticles adhering to the surface of microsized Al particles with different equivalence ratios. Thermal analysis revealed two consecutive exothermic peaks resulting from the initial thermite reaction between 890 and 960 °C and subsequently the intermetallic/alloy formation reactions between 1000 and 1040 °C. The latter was further confirmed by the endothermic peaks of Al-Ni alloy melting at higher temperatures. The formation of alloy was substantiated by the melting of AlNi3, AlNi, and Al3Ni. The onset temperature of the first exothermic peak decreased with increasing nominal equivalence ratio of the core-shell. Compared to the physically mixed (PM) composite, the core-shell structures decreased the activation energy of the thermite reaction by a mere 9.24 kJ/mol; however, it increased the combustibility by the manifold. The PM composite was not able to be ignited at all by a 5 W laser, while the core-shell counterpart ignited at 2.55 ms and was completely combusted within 6.50 ms accompanying a violent impulse.

14.
Angew Chem Int Ed Engl ; : e202412754, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39219249

RESUMO

Acidic CO2 electrolysis offers a promising strategy to achieve high carbon utilization and high energy efficiency. However, challenges remain in suppressing the competitive hydrogen evolution reaction (HER) and improving product selectivity. High concentrations of potassium ions (K+) can suppress HER and accelerate CO2 reduction, but they still inevitably suffer from salt precipitation problems. In this study, we demonstrate that the sulfonate-based polyelectrolyte, polystyrene sulfonate (PSS), enables to reconstruct the electrode-electrolyte interface to significantly enhance the acidic CO2 electrolysis. Mechanistic studies reveal that PSS induces high local K+ concentrations through electrostatic interaction between PSS anions and K+. In situ spectroscopy reveals that PSS reshapes the interfacial hydrogen-bond (H-bond) network, which is attributed to the H-bonds between PSS anions and hydrated proton as well as the steric hindrance of the additive molecules. This greatly weakens proton transfer kinetics and leads to the suppression of undesirable HER. As a result, a Faradaic efficiency of 93.9% for CO can be achieved at 250 mA cm-2, simultaneous with a high single-pass carbon efficiency of 72.2% on commercial Ag catalysts in acid. This study highlights the important role of the electrode-electrolyte interface induced by polyelectrolyte additives in promoting electrocatalytic reactions.

15.
Food Sci Nutr ; 12(8): 5426-5441, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39139945

RESUMO

Golden buckwheat, also called Fagopyrum dibotrys (D. Don) H. Hara, is a plant of the genus Buckwheat in the buckwheat family. The aim of this study was to screen the bioactive ingredients of golden buckwheat extract and investigate the protective effect on acute lung injury (ALI). The ethyl acetate extract (EAE) was identified as the active fraction in LPS-induced RAW264.7 cells, with gallic acid, proanthocyanidin B2, and epicatechin at 0.0563%, 0.3707%, and 0.3868%, respectively. At the same time, 20 compounds (mainly flavonoids and organic acids) were identified by UPLC-Q-Exactive Orbitrap-HRMS in EAE. Furthermore, the EAE reduced lung histopathology scores in mice with ALI, decreased the dry-to-wet weight ratio of lung tissue, and significantly inhibited the concentrations of IL-1ß, TNFα, and IL-6 in bronchoalveolar lavage fluid (BALF). It also reduced the number of leukocytes, decreased the activity of MPO in lung tissue, and inhibited the levels of TLR4/NLRP3 pathway mRNA and protein in lung tissue. Our study indicated that golden buckwheat as a source of functional food prevents or treats associated lung diseases by modulating the activation of the TLR4/NLRP3 signaling pathway.

16.
Food Funct ; 15(17): 8956, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39129536

RESUMO

Correction for 'Attenuation of metabolic syndrome in the ob/ob mouse model by resistant starch intervention is dose dependent' by Anqi Wang et al., Food Funct., 2019, 10, 7940-7951, https://doi.org/10.1039/C9FO01771B.

17.
Sci Data ; 11(1): 910, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39174585

RESUMO

Culter alburnus is extensively distributed in various rivers and lakes across China. As a widely adaptive fish species, it has significant economic values and special ecological roles. To meet research demands and provide better genomic resources, in this research, a chromosome-level genome assembly was constructed using HiFi long-reads and Hi-C sequencing data. Compared with the published versions, our genome assembly is of higher quality with only 31 gaps and closer to its true structure and sequence. The genome size was 1.052 Gb, with a contig N50 of 32.92 Mb and a scaffold N50 of 43.09 Mb. 55 contigs were anchored to 24 chromosomes on the basis of Hi-C data. A total of 598.23 Mb of repetitive sequences were annotated and 28,228 protein-coding genes were predicted. Additionally, BUSCO assessment indicated assembly and annotation scores of 98.3% and 99.2%, respectively. This high-quality genome will provide scientific support for excavating the species characteristics of C. alburnus and exploring its molecular mechanisms in response to environmental changes and stress.


Assuntos
Cromossomos , Cyprinidae , Genoma , Animais , Cyprinidae/genética , Anotação de Sequência Molecular , China , Tamanho do Genoma
18.
Se Pu ; 42(8): 758-765, 2024 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-39086244

RESUMO

Milk is an important consumer product with high nutritional value. The presence of veterinary drug residues in milk owing to the indiscriminate use of veterinary drugs may affect consumer health. In the mass spectrometric analysis of trace compounds, chromatographic co-eluting components easily interfere with the mass spectral signals obtained, affecting the accuracy of qualitative and quantitative analyses. Matrix purification is a promising method to reduce the matrix effect. Chitosan is a natural biopolymer with numerous active functional groups such as amino, acetyl, and hydroxyl groups; these groups can adsorb lipids through hydrophobic and electrostatic interactions. Chitosan also has the advantages of low production cost, stable chemical properties, and convenient modification. Novel chitosan-based materials are promising candidates for lipid purification. In this study, a chitosan membrane was modified with trimethoxyoctadecylsilane (C18-CSM). C18-CSM was prepared through one-step hydrolysis and used as a dispersive solid phase extraction (DSPE) adsorbent to purify the matrix during milk pretreatment. We combined C18-CSM with ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap mass spectrometry (UHPLC-Q/Exactive Orbitrap MS) to develop an effective method for the extraction and determination of ofloxacin, enrofloxacin, ciprofloxacin, diazepam, and metronidazole in milk. C18-CSM was characterized using scanning electron microscopy, Fourier transform infrared spectroscopy, and water contact angle testing. The results indicated that the material has a rough surface and uniformly dense cross-section. The water contact angle of C18-CSM was 104°, indicating its good hydrophobicity. The pretreatment conditions (extraction solvent, dosage of NaCl, extraction frequency, and dosage of C18-CSM) that influenced the recoveries of the five veterinary drugs were investigated in detail. The optimal conditions were established as follows: 5% formic acid in acetonitrile, 1 g NaCl, extraction 1 time, 20 mg C18-CSM. Separation was performed on a Hypersil GOLD VANQUISH column (100 mm×2.1 mm, 1.9 µm). The mobile phase consisted of 0.1% formic acid aqueous solution and 0.1% formic acid in acetonitrile, and was flowed at a rate of 0.3 mL/min. The sample injection volume was 1 µL, and the column temperature was maintained at 25 ℃. Mass spectrometric analysis was performed in positive electrospray ionization mode. To verify the necessity of the purification material, the matrix effect was investigated using the matrix-matched standard curve method. The use of C18-CSM reduced the matrix effects of the five necessity drugs from the range of -22%-8.8% to the range of -13%-3.6%, indicating that C18-CSM is a highly efficient DSPE material. Under optimal conditions, the developed method showed good linearities within the range of 0.5-100 µg/L, with correlation coefficients (r2)≥0.9970. The limits of detection(LODs) and quantification (LOQs) were 0.2 µg/L and 0.5 µg/L, respectively. To assess the accuracy and precision of the method, we prepared milk samples with three spiked levels (low, medium, and high). The recoveries of the five veterinary drugs were ranged from 79.5% to 115%, and the intra-day and inter-day relative standard deviations were 7.0%-13% (n=6) and 1.3%-11% (n=3), respectively. This study provides a simple, accurate, and reliable method for the rapid and simultaneous determination of the five veterinary drug residues in milk.


Assuntos
Quitosana , Resíduos de Drogas , Contaminação de Alimentos , Espectrometria de Massas , Leite , Drogas Veterinárias , Animais , Leite/química , Resíduos de Drogas/análise , Cromatografia Líquida de Alta Pressão , Quitosana/química , Drogas Veterinárias/análise , Contaminação de Alimentos/análise
19.
Bioinformatics ; 40(8)2024 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-39189955

RESUMO

MOTIVATION: Transcriptome-wide association study (TWAS) aims to identify trait-associated genes regulated by significant variants to explore the underlying biological mechanisms at a tissue-specific level. Despite the advancement of current TWAS methods to cover diverse traits, traditional approaches still face two main challenges: (i) the lack of methods that can guarantee finite-sample false discovery rate (FDR) control in identifying trait-associated genes; and (ii) the requirement for individual-level data, which is often inaccessible. RESULTS: To address this challenge, we propose a powerful knockoff inference method termed TWAS-GKF to identify candidate trait-associated genes with a guaranteed finite-sample FDR control. TWAS-GKF introduces the main idea of Ghostknockoff inference to generate knockoff variables using only summary statistics instead of individual-level data. In extensive studies, we demonstrate that TWAS-GKF successfully controls the finite-sample FDR under a pre-specified FDR level across all settings. We further apply TWAS-GKF to identify genes in brain cerebellum tissue from the Genotype-Tissue Expression (GTEx) v8 project associated with schizophrenia (SCZ) from the Psychiatric Genomics Consortium (PGC), and genes in liver tissue related to low-density lipoprotein cholesterol (LDL-C) from the UK Biobank, respectively. The results reveal that the majority of the identified genes are validated by Open Targets Validation Platform. AVAILABILITY AND IMPLEMENTATION: The R package TWAS.GKF is publicly available at https://github.com/AnqiWang2021/TWAS.GKF.


Assuntos
Estudo de Associação Genômica Ampla , Transcriptoma , Transcriptoma/genética , Humanos , Estudo de Associação Genômica Ampla/métodos , Esquizofrenia/genética , Perfilação da Expressão Gênica/métodos , Algoritmos , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas
20.
Nutr J ; 23(1): 89, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39123196

RESUMO

BACKGROUND: We aimed to probe the association of serum 25-hydroxyvitamin D [25(OH)D] concentrations with all-cause and cause-specific mortality among patients with gout and hyperuricemia (HUA). METHODS: The study included 1169 gout patients and 7029 HUA patients from the National Health and Nutrition Examination Survey (NHANES) 2007-2018 and 2001-2018, respectively. The association between serum 25(OH)D and mortality was evaluated by Cox proportional hazard and restricted cubic spline models. RESULTS: Among participants with gout and HUA, the weighted mean concentrations of serum 25(OH)D were 71.49 ± 30.09 nmol/L and 64.81 ± 26.92 nmol/L, respectively. Vitamin D deficiency occurred in 29.68% of gout patients and 37.83% of HUA patients. During 6783 person-years of follow-up among gout patients, 248 all-cause deaths occurred, among which 76 died from cardiovascular disease (CVD) and 49 died from cancer. 1375 HUA patients were recorded for all-cause mortality during 59,859 person-years of follow-up, including 427 CVD deaths and 232 cancer deaths. After multifactorial adjustment, per one-unit increment in natural log-transformed 25(OH)D was associated with lower risk of 55% all-cause mortality and 61% CVD mortality among gout patients, and a 45% reduced risk of cancer mortality among HUA patients. Restricted cubic splines showed a U-shaped relationship with all-cause and CVD mortality among HUA patients, with inflection points of 72.7 nmol/L and 38.0 nmol/L, respectively. The results were robust in subgroup and sensitivity analyses. CONCLUSIONS: Serum 25(OH)D was negatively linearly correlated with mortality among gout patients, whereas U-shaped correlated with mortality in HUA patients. These results indicate that adequate vitamin D status could prevent premature death.


Assuntos
Causas de Morte , Gota , Hiperuricemia , Inquéritos Nutricionais , Vitamina D , Humanos , Gota/sangue , Gota/mortalidade , Gota/complicações , Hiperuricemia/sangue , Hiperuricemia/mortalidade , Hiperuricemia/complicações , Vitamina D/análogos & derivados , Vitamina D/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Inquéritos Nutricionais/estatística & dados numéricos , Adulto , Idoso , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/sangue , Neoplasias/mortalidade , Neoplasias/sangue , Neoplasias/complicações , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/mortalidade , Modelos de Riscos Proporcionais
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