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1.
Cell ; 178(3): 699-713.e19, 2019 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-31280963

RESUMO

Accurate prediction of long-term outcomes remains a challenge in the care of cancer patients. Due to the difficulty of serial tumor sampling, previous prediction tools have focused on pretreatment factors. However, emerging non-invasive diagnostics have increased opportunities for serial tumor assessments. We describe the Continuous Individualized Risk Index (CIRI), a method to dynamically determine outcome probabilities for individual patients utilizing risk predictors acquired over time. Similar to "win probability" models in other fields, CIRI provides a real-time probability by integrating risk assessments throughout a patient's course. Applying CIRI to patients with diffuse large B cell lymphoma, we demonstrate improved outcome prediction compared to conventional risk models. We demonstrate CIRI's broader utility in analogous models of chronic lymphocytic leukemia and breast adenocarcinoma and perform a proof-of-concept analysis demonstrating how CIRI could be used to develop predictive biomarkers for therapy selection. We envision that dynamic risk assessment will facilitate personalized medicine and enable innovative therapeutic paradigms.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Linfoma Difuso de Grandes Células B/patologia , Medicina de Precisão , Algoritmos , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/sangue , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , DNA Tumoral Circulante/sangue , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Terapia Neoadjuvante , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Medição de Risco , Resultado do Tratamento
2.
Cell ; 170(3): 564-576.e16, 2017 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-28753430

RESUMO

Most human epithelial tumors harbor numerous alterations, making it difficult to predict which genes are required for tumor survival. To systematically identify cancer dependencies, we analyzed 501 genome-scale loss-of-function screens performed in diverse human cancer cell lines. We developed DEMETER, an analytical framework that segregates on- from off-target effects of RNAi. 769 genes were differentially required in subsets of these cell lines at a threshold of six SDs from the mean. We found predictive models for 426 dependencies (55%) by nonlinear regression modeling considering 66,646 molecular features. Many dependencies fall into a limited number of classes, and unexpectedly, in 82% of models, the top biomarkers were expression based. We demonstrated the basis behind one such predictive model linking hypermethylation of the UBB ubiquitin gene to a dependency on UBC. Together, these observations provide a foundation for a cancer dependency map that facilitates the prioritization of therapeutic targets.


Assuntos
Neoplasias/genética , Neoplasias/patologia , Linhagem Celular Tumoral , Humanos , Interferência de RNA , Software , Ubiquitina/genética
3.
Proc Natl Acad Sci U S A ; 121(25): e2310433121, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38857402

RESUMO

Pleasure and pain are two fundamental, intertwined aspects of human emotions. Pleasurable sensations can reduce subjective feelings of pain and vice versa, and we often perceive the termination of pain as pleasant and the absence of pleasure as unpleasant. This implies the existence of brain systems that integrate them into modality-general representations of affective experiences. Here, we examined representations of affective valence and intensity in an functional MRI (fMRI) study (n = 58) of sustained pleasure and pain. We found that the distinct subpopulations of voxels within the ventromedial and lateral prefrontal cortices, the orbitofrontal cortex, the anterior insula, and the amygdala were involved in decoding affective valence versus intensity. Affective valence and intensity predictive models showed significant decoding performance in an independent test dataset (n = 62). These models were differentially connected to distinct large-scale brain networks-the intensity model to the ventral attention network and the valence model to the limbic and default mode networks. Overall, this study identified the brain representations of affective valence and intensity across pleasure and pain, promoting a systems-level understanding of human affective experiences.


Assuntos
Encéfalo , Imageamento por Ressonância Magnética , Dor , Prazer , Humanos , Prazer/fisiologia , Masculino , Feminino , Dor/fisiopatologia , Dor/psicologia , Adulto , Encéfalo/fisiologia , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Adulto Jovem , Tonsila do Cerebelo/fisiologia , Tonsila do Cerebelo/diagnóstico por imagem , Emoções/fisiologia , Córtex Pré-Frontal/fisiologia , Córtex Pré-Frontal/diagnóstico por imagem , Afeto/fisiologia
4.
Proc Natl Acad Sci U S A ; 121(13): e2309969121, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38498708

RESUMO

In this study, we model and predict rice yields by integrating molecular marker variation, varietal productivity, and climate, focusing on the Southern U.S. rice-growing region. This region spans the states of Arkansas, Louisiana, Texas, Mississippi, and Missouri and accounts for 85% of total U.S. rice production. By digitizing and combining four decades of county-level variety acreage data (1970 to 2015) with varietal information from genotyping-by-sequencing data, we estimate annual historical county-level allele frequencies. These allele frequencies are used together with county-level weather and yield data to develop ten machine learning models for yield prediction. A two-layer meta-learner ensemble model that combines all ten methods is externally evaluated against observations from historical Uniform Regional Rice Nursery trials (1980 to 2018) conducted in the same states. Finally, the ensemble model is used with forecasted weather from the Coupled Model Intercomparison Project across the 110 rice-growing counties to predict production in the coming decades for Composite Variety Groups assembled based on year of release, breeding program, and several breeding trends. Results indicate positive effects over time of public breeding on rice resilience to future climates, and potential reasons are discussed.


Assuntos
Oryza , Oryza/genética , Mudança Climática , Melhoramento Vegetal , Clima , Tempo (Meteorologia)
5.
Brief Bioinform ; 25(3)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38742520

RESUMO

The dynamic evolution of the severe acute respiratory syndrome coronavirus 2 virus is primarily driven by mutations in its genetic sequence, culminating in the emergence of variants with increased capability to evade host immune responses. Accurate prediction of such mutations is fundamental in mitigating pandemic spread and developing effective control measures. This study introduces a robust and interpretable deep-learning approach called PRIEST. This innovative model leverages time-series viral sequences to foresee potential viral mutations. Our comprehensive experimental evaluations underscore PRIEST's proficiency in accurately predicting immune-evading mutations. Our work represents a substantial step in utilizing deep-learning methodologies for anticipatory viral mutation analysis and pandemic response.


Assuntos
COVID-19 , Evasão da Resposta Imune , Mutação , SARS-CoV-2 , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Humanos , COVID-19/virologia , COVID-19/imunologia , COVID-19/genética , Evasão da Resposta Imune/genética , Aprendizado Profundo , Evolução Molecular , Pandemias
6.
Proc Natl Acad Sci U S A ; 120(10): e2216894120, 2023 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-36848555

RESUMO

Drought tolerance is a highly complex trait controlled by numerous interconnected pathways with substantial variation within and across plant species. This complexity makes it difficult to distill individual genetic loci underlying tolerance, and to identify core or conserved drought-responsive pathways. Here, we collected drought physiology and gene expression datasets across diverse genotypes of the C4 cereals sorghum and maize and searched for signatures defining water-deficit responses. Differential gene expression identified few overlapping drought-associated genes across sorghum genotypes, but using a predictive modeling approach, we found a shared core drought response across development, genotype, and stress severity. Our model had similar robustness when applied to datasets in maize, reflecting a conserved drought response between sorghum and maize. The top predictors are enriched in functions associated with various abiotic stress-responsive pathways as well as core cellular functions. These conserved drought response genes were less likely to contain deleterious mutations than other gene sets, suggesting that core drought-responsive genes are under evolutionary and functional constraints. Our findings support a broad evolutionary conservation of drought responses in C4 grasses regardless of innate stress tolerance, which could have important implications for developing climate resilient cereals.


Assuntos
Sorghum , Zea mays , Zea mays/genética , Sorghum/genética , Secas , Grão Comestível/genética , Poaceae
7.
J Neurosci ; 44(18)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38508713

RESUMO

Economic choice theories usually assume that humans maximize utility in their choices. However, studies have shown that humans make inconsistent choices, leading to suboptimal behavior, even without context-dependent manipulations. Previous studies showed that activation in value and motor networks are associated with inconsistent choices at the moment of choice. Here, we investigated if the neural predispositions, measured before a choice task, can predict choice inconsistency in a later risky choice task. Using functional connectivity (FC) measures from resting-state functional magnetic resonance imaging (rsfMRI), derived before any choice was made, we aimed to predict subjects' inconsistency levels in a later-performed choice task. We hypothesized that rsfMRI FC measures extracted from value and motor brain areas would predict inconsistency. Forty subjects (21 females) completed a rsfMRI scan before performing a risky choice task. We compared models that were trained on FC that included only hypothesized value and motor regions with models trained on whole-brain FC. We found that both model types significantly predicted inconsistency levels. Moreover, even the whole-brain models relied mostly on FC between value and motor areas. For external validation, we used a neural network pretrained on FC matrices of 37,000 subjects and fine-tuned it on our data and again showed significant predictions. Together, this shows that the tendency for choice inconsistency is predicted by predispositions of the nervous system and that synchrony between the motor and value networks plays a crucial role in this tendency.


Assuntos
Comportamento de Escolha , Imageamento por Ressonância Magnética , Humanos , Feminino , Masculino , Comportamento de Escolha/fisiologia , Imageamento por Ressonância Magnética/métodos , Adulto , Adulto Jovem , Encéfalo/fisiologia , Encéfalo/diagnóstico por imagem , Rede Nervosa/fisiologia , Rede Nervosa/diagnóstico por imagem , Conectoma/métodos , Mapeamento Encefálico/métodos , Vias Neurais/fisiologia , Vias Neurais/diagnóstico por imagem , Assunção de Riscos
8.
Cereb Cortex ; 34(5)2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38715408

RESUMO

Speech comprehension in noise depends on complex interactions between peripheral sensory and central cognitive systems. Despite having normal peripheral hearing, older adults show difficulties in speech comprehension. It remains unclear whether the brain's neural responses could indicate aging. The current study examined whether individual brain activation during speech perception in different listening environments could predict age. We applied functional near-infrared spectroscopy to 93 normal-hearing human adults (20 to 70 years old) during a sentence listening task, which contained a quiet condition and 4 different signal-to-noise ratios (SNR = 10, 5, 0, -5 dB) noisy conditions. A data-driven approach, the region-based brain-age predictive modeling was adopted. We observed a significant behavioral decrease with age under the 4 noisy conditions, but not under the quiet condition. Brain activations in SNR = 10 dB listening condition could successfully predict individual's age. Moreover, we found that the bilateral visual sensory cortex, left dorsal speech pathway, left cerebellum, right temporal-parietal junction area, right homolog Wernicke's area, and right middle temporal gyrus contributed most to prediction performance. These results demonstrate that the activations of regions about sensory-motor mapping of sound, especially in noisy conditions, could be sensitive measures for age prediction than external behavior measures.


Assuntos
Envelhecimento , Encéfalo , Compreensão , Ruído , Espectroscopia de Luz Próxima ao Infravermelho , Percepção da Fala , Humanos , Adulto , Percepção da Fala/fisiologia , Masculino , Feminino , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Pessoa de Meia-Idade , Adulto Jovem , Idoso , Compreensão/fisiologia , Encéfalo/fisiologia , Encéfalo/diagnóstico por imagem , Envelhecimento/fisiologia , Mapeamento Encefálico/métodos , Estimulação Acústica/métodos
9.
Cereb Cortex ; 34(2)2024 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-38186011

RESUMO

Researches have reported the close association between fingers and arithmetic. However, it remains unclear whether and how finger training can benefit arithmetic. To address this issue, we used the abacus-based mental calculation (AMC), which combines finger training and mental arithmetic learning, to explore the neural correlates underlying finger-related arithmetic training. A total of 147 Chinese children (75 M/72 F, mean age, 6.89 ± 0.46) were recruited and randomly assigned into AMC and control groups at primary school entry. The AMC group received 5 years of AMC training, and arithmetic abilities and resting-state functional magnetic resonance images data were collected from both groups at year 1/3/5. The connectome-based predictive modeling was used to find the arithmetic-related networks of each group. Compared to controls, the AMC's positively arithmetic-related network was less located in the control module, and the inter-module connections between somatomotor-default and somatomotor-control modules shifted to somatomotor-visual and somatomotor-dorsal attention modules. Furthermore, the positive network of the AMC group exhibited a segregated connectivity pattern, with more intra-module connections than the control group. Overall, our results suggested that finger motor representation with motor module involvement facilitated arithmetic-related network segregation, reflecting increased autonomy of AMC, thus reducing the dependency of arithmetic on higher-order cognitive functions.


Assuntos
Mapeamento Encefálico , Aprendizagem , Criança , Humanos , Imageamento por Ressonância Magnética , Neuroimagem , Encéfalo
10.
Am J Respir Crit Care Med ; 209(3): 288-298, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37812796

RESUMO

Rationale: The global burden of sepsis is greatest in low-resource settings. Melioidosis, infection with the gram-negative bacterium Burkholderia pseudomallei, is a frequent cause of fatal sepsis in endemic tropical regions such as Southeast Asia. Objectives: To investigate whether plasma metabolomics would identify biological pathways specific to melioidosis and yield clinically meaningful biomarkers. Methods: Using a comprehensive approach, differential enrichment of plasma metabolites and pathways was systematically evaluated in individuals selected from a prospective cohort of patients hospitalized in rural Thailand with infection. Statistical and bioinformatics methods were used to distinguish metabolomic features and processes specific to patients with melioidosis and between fatal and nonfatal cases. Measurements and Main Results: Metabolomic profiling and pathway enrichment analysis of plasma samples from patients with melioidosis (n = 175) and nonmelioidosis infections (n = 75) revealed a distinct immuno-metabolic state among patients with melioidosis, as suggested by excessive tryptophan catabolism in the kynurenine pathway and significantly increased levels of sphingomyelins and ceramide species. We derived a 12-metabolite classifier to distinguish melioidosis from other infections, yielding an area under the receiver operating characteristic curve of 0.87 in a second validation set of patients. Melioidosis nonsurvivors (n = 94) had a significantly disturbed metabolome compared with survivors (n = 81), with increased leucine, isoleucine, and valine metabolism, and elevated circulating free fatty acids and acylcarnitines. A limited eight-metabolite panel showed promise as an early prognosticator of mortality in melioidosis. Conclusions: Melioidosis induces a distinct metabolomic state that can be examined to distinguish underlying pathophysiological mechanisms associated with death. A 12-metabolite signature accurately differentiates melioidosis from other infections and may have diagnostic applications.


Assuntos
Burkholderia pseudomallei , Melioidose , Sepse , Humanos , Melioidose/diagnóstico , Melioidose/microbiologia , Estudos Prospectivos , Metabolômica
11.
Proc Natl Acad Sci U S A ; 119(14): e2103400119, 2022 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-35344422

RESUMO

SignificanceOnly an estimated 1 to 10% of Earth's species have been formally described. This discrepancy between the number of species with a formal taxonomic description and actual number of species (i.e., the Linnean shortfall) hampers research across the biological sciences. To explore whether the Linnean shortfall results from poor taxonomic practice or not enough taxonomic effort, we applied machine-learning techniques to build a predictive model to identify named species that are likely to contain hidden diversity. Results indicate that small-bodied species with large, climatically variable ranges are most likely to contain hidden species. These attributes generally match those identified in the taxonomic literature, indicating that the Linnean shortfall is caused by societal underinvestment in taxonomy rather than poor taxonomic practice.


Assuntos
Biodiversidade , Mamíferos , Animais , Filogenia
12.
Nano Lett ; 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39120132

RESUMO

Modern nanotechnology has generated numerous datasets from in vitro and in vivo studies on nanomaterials, with some available on nanoinformatics portals. However, these existing databases lack the digital data and tools suitable for machine learning studies. Here, we report a nanoinformatics platform that accurately annotates nanostructures into machine-readable data files and provides modeling toolkits. This platform, accessible to the public at https://vinas-toolbox.com/, has annotated nanostructures of 14 material types. The associated nanodescriptor data and assay test results are appropriate for modeling purposes. The modeling toolkits enable data standardization, data visualization, and machine learning model development to predict properties and bioactivities of new nanomaterials. Moreover, a library of virtual nanostructures with their predicted properties and bioactivities is available, directing the synthesis of new nanomaterials. This platform provides a data-driven computational modeling platform for the nanoscience community, significantly aiding in the development of safe and effective nanomaterials.

13.
BMC Bioinformatics ; 25(1): 167, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38671342

RESUMO

BACKGROUND: Numerous transcriptomic-based models have been developed to predict or understand the fundamental mechanisms driving biological phenotypes. However, few models have successfully transitioned into clinical practice due to challenges associated with generalizability and interpretability. To address these issues, researchers have turned to dimensionality reduction methods and have begun implementing transfer learning approaches. METHODS: In this study, we aimed to determine the optimal combination of dimensionality reduction and regularization methods for predictive modeling. We applied seven dimensionality reduction methods to various datasets, including two supervised methods (linear optimal low-rank projection and low-rank canonical correlation analysis), two unsupervised methods [principal component analysis and consensus independent component analysis (c-ICA)], and three methods [autoencoder (AE), adversarial variational autoencoder, and c-ICA] within a transfer learning framework, trained on > 140,000 transcriptomic profiles. To assess the performance of the different combinations, we used a cross-validation setup encapsulated within a permutation testing framework, analyzing 30 different transcriptomic datasets with binary phenotypes. Furthermore, we included datasets with small sample sizes and phenotypes of varying degrees of predictability, and we employed independent datasets for validation. RESULTS: Our findings revealed that regularized models without dimensionality reduction achieved the highest predictive performance, challenging the necessity of dimensionality reduction when the primary goal is to achieve optimal predictive performance. However, models using AE and c-ICA with transfer learning for dimensionality reduction showed comparable performance, with enhanced interpretability and robustness of predictors, compared to models using non-dimensionality-reduced data. CONCLUSION: These findings offer valuable insights into the optimal combination of strategies for enhancing the predictive performance, interpretability, and generalizability of transcriptomic-based models.


Assuntos
Fenótipo , Transcriptoma , Transcriptoma/genética , Humanos , Perfilação da Expressão Gênica/métodos , Aprendizado de Máquina , Biologia Computacional/métodos , Algoritmos , Análise de Componente Principal
14.
Neuroimage ; 290: 120558, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38437909

RESUMO

The prolonged duration of chronic low back pain (cLBP) inevitably leads to changes in the cognitive, attentional, sensory and emotional processing brain regions. Currently, it remains unclear how these alterations are manifested in the interplay between brain functional and structural networks. This study aimed to predict the Oswestry Disability Index (ODI) in cLBP patients using multimodal brain magnetic resonance imaging (MRI) data and identified the most significant features within the multimodal networks to aid in distinguishing patients from healthy controls (HCs). We constructed dynamic functional connectivity (dFC) and structural connectivity (SC) networks for all participants (n = 112) and employed the Connectome-based Predictive Modeling (CPM) approach to predict ODI scores, utilizing various feature selection thresholds to identify the most significant network change features in dFC and SC outcomes. Subsequently, we utilized these significant features for optimal classifier selection and the integration of multimodal features. The results revealed enhanced connectivity among the frontoparietal network (FPN), somatomotor network (SMN) and thalamus in cLBP patients compared to HCs. The thalamus transmits pain-related sensations and emotions to the cortical areas through the dorsolateral prefrontal cortex (dlPFC) and primary somatosensory cortex (SI), leading to alterations in whole-brain network functionality and structure. Regarding the model selection for the classifier, we found that Support Vector Machine (SVM) best fit these significant network features. The combined model based on dFC and SC features significantly improved classification performance between cLBP patients and HCs (AUC=0.9772). Finally, the results from an external validation set support our hypotheses and provide insights into the potential applicability of the model in real-world scenarios. Our discovery of enhanced connectivity between the thalamus and both the dlPFC (FPN) and SI (SMN) provides a valuable supplement to prior research on cLBP.


Assuntos
Conectoma , Dor Lombar , Humanos , Dor Lombar/diagnóstico por imagem , Encéfalo , Tálamo , Imageamento por Ressonância Magnética/métodos
15.
Am J Epidemiol ; 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38775285

RESUMO

Polysocial risk scores were recently proposed as a strategy to improve clinical relevance of knowledge about social determinants of health. The objective of this paper was to assess if the polysocial risk score model improves prediction of cognition and all-cause mortality in middle-aged and older adults beyond simpler models including a smaller set of key social determinants of health. We used a sample of 13,773 individuals aged 50+ at baseline from the 2006 to 2018 waves of the Health and Retirement Study, a US population-based longitudinal cohort. Four linear mixed models were compared: two simple models including a priori selected covariates and two polysocial risk score models which used LASSO regularization to select covariates among 9 or 21 candidate social predictors. All models included age. Predictive accuracy was assessed via R-squared and root mean-squared prediction error (RMSPE) using training/test split and cross-validation. For predicting cognition, the simple model including age, race, gender, and education had an R-squared of 0.31 and an RMSPE of 0.880. Compared with this, the most complex polysocial risk score selected 12 predictors (R-squared=0.35 and RMSPE=0.858; 2.2% improvement). For all-cause mortality, the simple model including age, race, gender, and education had an AUROC of 0.747, while the most complex polysocial risk score did not demonstrate improved performance (AUROC = 0.745). Models built on a smaller set of key social determinants performed comparably to models built on a more complex set of social "risk factors".

16.
Am J Transplant ; 24(3): 458-467, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37468109

RESUMO

Primary graft dysfunction (PGD) is the leading cause of morbidity and mortality in the first 30 days after lung transplantation. Risk factors for the development of PGD include donor and recipient characteristics, but how multiple variables interact to impact the development of PGD and how clinicians should consider these in making decisions about donor acceptance remain unclear. This was a single-center retrospective cohort study to develop and evaluate machine learning pipelines to predict the development of PGD grade 3 within the first 72 hours of transplantation using donor and recipient variables that are known at the time of donor offer acceptance. Among 576 bilateral lung recipients, 173 (30%) developed PGD grade 3. The cohort underwent a 75% to 25% train-test split, and lasso regression was used to identify 11 variables for model development. A K-nearest neighbor's model showing the best calibration and performance with relatively small confidence intervals was selected as the final predictive model with an area under the receiver operating characteristics curve of 0.65. Machine learning models can predict the risk for development of PGD grade 3 based on data available at the time of donor offer acceptance. This may improve donor-recipient matching and donor utilization in the future.


Assuntos
Transplante de Pulmão , Disfunção Primária do Enxerto , Humanos , Estudos Retrospectivos , Disfunção Primária do Enxerto/diagnóstico , Disfunção Primária do Enxerto/etiologia , Transplante de Pulmão/efeitos adversos , Fatores de Risco , Pulmão
17.
Clin Immunol ; 265: 110296, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38914361

RESUMO

Proliferative lupus nephritis (PLN) is a serious organ-threatening manifestation of systemic lupus erythematosus (SLE) that is associated with high mortality and renal failure. Here, we analyzed data from 1287 SLE patients with renal manifestations, including 780 of which were confirmed as proliferative or non-proliferative LN patients by renal biopsy, divided into a training cohort (547 patients) and a validation cohort (233 patients). By applying a least absolute shrinkage and selection operator (LASSO) regression approach combined with multivariate logistic regression analysis to build a nomogram for prediction of PLN that was then assessed by receiver operating characteristic (ROC) curves, calibration curves, and clinical decision curves (DCA) in both the training and validation cohorts. The area under the ROC curve (AUC) of the model in the training cohort was 0.921 (95% confidence interval (CI): 0.895-0.946), the AUC of internal validation in the training cohort was 0.909 and the AUC of external validation was 0.848 (95% CI: 0.796-0.900). The nomogram showed good performance as evaluated using calibration and DCA curves. Taken together, our results indicate that our nomogram that comprises 12 significantly relevant variables could be clinically valuable to prognosticate on the risk of PLN in SLE, so as to improve patient prognoses.


Assuntos
Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Nomogramas , Humanos , Feminino , Masculino , Adulto , Lúpus Eritematoso Sistêmico/complicações , Rim/patologia , Curva ROC , Pessoa de Meia-Idade , Prognóstico , Adulto Jovem , Estudos de Coortes , Fatores de Risco
18.
Gastroenterology ; 164(6): 966-977.e17, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36758837

RESUMO

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) can progress to cirrhosis and hepatic decompensation, but whether genetic variants influence the rate of progression to cirrhosis or are useful in risk stratification among patients with NAFLD is uncertain. METHODS: We included participants from 2 independent cohorts, they Michigan Genomics Initiative (MGI) and UK Biobank (UKBB), who had NAFLD defined by elevated alanine aminotransferase (ALT) levels in the absence of alternative chronic liver disease. The primary predictors were genetic variants and metabolic comorbidities associated with cirrhosis. We conducted time-to-event analyses using Fine-Gray competing risk models. RESULTS: We included 7893 and 46,880 participants from MGI and UKBB, respectively. In univariable analysis, PNPLA3-rs738409-GG genotype, diabetes, obesity, and ALT of ≥2× upper limit of normal were associated with higher incidence rate of cirrhosis in both MGI and UKBB. PNPLA3-rs738409-GG had additive effects with clinical risk factors including diabetes, obesity, and ALT elevations. Among patients with indeterminate fibrosis-4 (FIB4) scores (1.3-2.67), those with diabetes and PNPLA3-rs738409-GG genotype had an incidence rate of cirrhosis comparable to that of patients with high-risk FIB4 scores (>2.67) and 2.9-4.8 times that of patients with diabetes but CC/CG genotypes. In contrast, FIB4 <1.3 was associated with an incidence rate of cirrhosis significantly lower than that of FIB4 of >2.67, even in the presence of clinical risk factors and high-risk PNPLA3 genotype. CONCLUSIONS: PNPLA3-rs738409 genotype and diabetes identified patients with NAFLD currently considered indeterminate risk (FIB4 1.3-2.67) who had a similar risk of cirrhosis as those considered high-risk (FIB4 >2.67). PNPLA3 genotyping may improve prognostication and allow for prioritization of intensive intervention.


Assuntos
Diabetes Mellitus , Hepatopatia Gordurosa não Alcoólica , Humanos , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/genética , Predisposição Genética para Doença , Genótipo , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Cirrose Hepática/genética , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/genética , Obesidade/complicações , Polimorfismo de Nucleotídeo Único
19.
Hum Brain Mapp ; 45(5): e26654, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38520361

RESUMO

Obesity represents a significant public health concern and is linked to various comorbidities and cognitive impairments. Previous research indicates that elevated body mass index (BMI) is associated with structural changes in white matter (WM). However, a deeper characterization of body composition is required, especially considering the links between abdominal obesity and metabolic dysfunction. This study aims to enhance our understanding of the relationship between obesity and WM connectivity by directly assessing the amount and distribution of fat tissue. Whole-body magnetic resonance imaging (MRI) was employed to evaluate total adipose tissue (TAT), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT), while MR liver spectroscopy measured liver fat content in 63 normal-weight, overweight, and obese males. WM connectivity was quantified using microstructure-informed tractography. Connectome-based predictive modeling was used to predict body composition metrics based on WM connectomes. Our analysis revealed a positive dependency between BMI, TAT, SAT, and WM connectivity in brain regions involved in reward processing and appetite regulation, such as the insula, nucleus accumbens, and orbitofrontal cortex. Increased connectivity was also observed in cognitive control and inhibition networks, including the middle frontal gyrus and anterior cingulate cortex. No significant associations were found between WM connectivity and VAT or liver fat. Our findings suggest that altered neural communication between these brain regions may affect cognitive processes, emotional regulation, and reward perception in individuals with obesity, potentially contributing to weight gain. While our study did not identify a link between WM connectivity and VAT or liver fat, further investigation of the role of various fat depots and metabolic factors in brain networks is required to advance obesity prevention and treatment approaches.


Assuntos
Imageamento por Ressonância Magnética , Substância Branca , Masculino , Humanos , Substância Branca/patologia , Distribuição Tecidual , Imagem Corporal Total , Obesidade/diagnóstico por imagem , Obesidade/complicações , Tecido Adiposo/diagnóstico por imagem , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia
20.
BMC Plant Biol ; 24(1): 494, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831264

RESUMO

BACKGROUND ACMELLA RADICANS: (Jacquin) R.K. Jansen is a new invasive species record for Yunnan Province, China. Native to Central America, it has also been recently recorded invading other parts of Asia. To prevent this weed from becoming a serious issue, an assessment of its ecological impacts and potential distribution is needed. We predicted the potential distribution of A. radicans in China using the MaxEnt model and its ecological impacts on local plant communities and soil nutrients were explored. RESULTS: Simulated training using model parameters produced an area under curve value of 0.974, providing a high degree of confidence in model predictions. Environmental variables with the greatest predictive power were precipitation of wettest month, isothermality, topsoil TEB (total exchangeable bases), and precipitation seasonality, with a cumulative contribution of more than 72.70% and a cumulative permutation importance of more than 69.20%. The predicted potential suitable area of A. radicans in China is concentrated in the southern region. Projected areas of A. radicans ranked as high and moderately suitable comprised 5425 and 26,338 km2, accounting for 0.06 and 0.27% of the Chinese mainland area, respectively. Over the 5 years of monitoring, the population density of A. radicans increased while at the same time the population density and importance values of most other plant species declined markedly. Community species richness, diversity, and evenness values significantly declined. Soil organic matter, total N, total P, available N, and available P concentrations decreased significantly with increasing plant cover of A. radicans, whereas pH, total K and available K increased. CONCLUSION: Our study was the first to show that A. radicans is predicted to expand its range in China and may profoundly affect plant communities, species diversity, and the soil environment. Early warning and monitoring of A. radicans must be pursued with greater vigilance in southern China to prevent its further spread.


Assuntos
Espécies Introduzidas , China , Solo/química , Ecossistema
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