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1.
Sci Total Environ ; 804: 150054, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34509839

RESUMO

The deep-sea mussel Gigantidas platifrons is a representative species that relies on nutrition provided by chemoautotrophic endosymbiotic bacteria to survive in both hydrothermal vent and methane seep environments. However, vent and seep habitats have distinct geochemical features, with vents being more harsh than seeps because of abundant toxic chemical substances, particularly hydrogen sulfide (H2S). Until now, the adaptive strategies of G. platifrons in a heterogeneous environment and their sulfide detoxification mechanisms are still unclear. Herein, we conducted 16S rDNA sequencing and metatranscriptome sequencing of G. platifrons collected from a methane seep at Formosa Ridge in the South China Sea and a hydrothermal vent at Iheya North Knoll in the Mid-Okinawa Trough to provide a model for understanding environmental adaption and sulfide detoxification mechanisms, and a three-day laboratory controlled Na2S stress experiment to test the transcriptomic responses under sulfide stress. The results revealed the active detoxification of sulfide in G. platifrons gills. First, epibiotic Campylobacterota bacteria were more abundant in vent mussels and contributed to environmental adaptation by active oxidation of extracellular H2S. Notably, a key sulfide-oxidizing gene, sulfide:quinone oxidoreductase (sqr), derived from the methanotrophic endosymbiont, was significantly upregulated in vent mussels, indicating the oxidization of intracellular sulfide by the endosymbiont. In addition, transcriptomic comparison further suggested that genes involved in oxidative phosphorylation and mitochondrial sulfide oxidization pathway played important roles in the sulfide tolerance of the host mussels. Moreover, transcriptomic analysis of Na2S stressed mussels confirmed the upregulation of oxidative phosphorylation and sulfide oxidization genes in response to sulfide exposure. Overall, this study provided a systematic transcriptional analysis of both the active bacterial community members and the host mussels, suggesting that the epibionts, endosymbionts, and mussel host collaborated on sulfide detoxification from extracellular to intracellular space to adapt to harsh H2S-rich environments.

2.
Int J Med Sci ; 18(15): 3498-3505, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34522176

RESUMO

Sox transcription factors play many diverse roles during development, including regulating stem cell states, directing differentiation, and influencing the local chromatin landscape. Sox10 has been implicated in the control of stem/progenitor activity and epithelial-mesenchymal transition, yet it has not been studied in relation to the hair follicle cycle or hair follicle stem cell (HFSC) control. To elucidate the role of Sox10 in hair follicle cycle control, we performed immunohistochemical and immunofluorescence analysis of its expression during hair morphogenesis, the postnatal hair cycle, and the depilation-induced murine hair follicle cycle. During hair follicle morphogenesis, Sox10 was expressed in the hair germ and peg. In telogen, we detected nuclear Sox10 in the hair bulge and germ cell cap, where HFSCs reside, while in anagen and catagen, Sox10 was detected in the epithelial portion, such as the strands of keratinocytes, the outer root sheath (ORS) in anagen, and the regressed epithelial strand of hair follicle in catagen. These results suggest that Sox10 may be involved in early hair follicle morphogenesis and postnatal follicular cycling.

3.
Ginekol Pol ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34541650

RESUMO

OBJECTIVES: This study aimed to explore the effect of interdisciplinary and diversified health education combined with personalized nutrition intervention on FPG, 2hPG, SDS, SAS scores and pregnancy outcome of gestational diabetes mellitus (GDM). MATERIAL AND METHODS: A total of 180 GDM patients, who were admitted to our hospital between June 2019 and June 2020, were enrolled as the research subjects and randomly divided into two groups: a research group and a control group (n = 90, each). The patients in the control group received routine care while the patients in the research group received interdisciplinary and diversified health education combined with personalized nutrition intervention. The fasting blood-glucose (FPG), two-hour postprandial blood glucose (2hPBG), glycated hemoglobin (HbA1C), SDS, SAS scores, and pregnancy outcome of the two groups of pregnant women were analyzed and compared. RESULTS: The differences in the levels of FBG, 2hPBG and HbA1C between the two groups before nursing were not statistically significant. After nursing, the levels of FBG, 2hPBG, and HbA1C of the two groups of patients decreased, and the differences in each group before and after intervention were statistically significant. These indexes were lower in the research group than in the control group, the differences being statistically significant. There were no significant differences between the two groups in SAS and SDS scores before nursing, but there were statistically significant differences after nursing. The incidence of unfavorable pregnancy outcome was lower in the research group (8.89%) than in the control group (14.44%), but the difference was not statistically significant (p > 0.05). CONCLUSIONS: Interdisciplinary and diversified health education combined with personalized nutrition intervention can effectively reduce FPG, 2hPG, SDS, and SAS scores in GDM women.

4.
J Alzheimers Dis ; 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34542069

RESUMO

BACKGROUND: Few studies have investigated the association between cognition and brain volume associated with cerebral small vessel disease (CSVD). OBJECTIVE: We investigated the association between cognition and brain volume and neuroimaging markers of CSVD in a community-dwelling population. METHODS: Participants (n = 993, age≥35 years) from the community-based Shunyi Study were included to investigate the association between neuroimaging markers and cognition cross-sectionally. Magnetic resonance imaging markers included brain volume measurements of the total cerebrum, white matter, gray matter, and CSVD imaging markers. Cognitive performance was assessed using neuropsychological tests of the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Fuld Object Memory, digit span, Trail Making Test (TMT)-A, and TMT-B. RESULTS: For brain volume measurement, subcortical white matter fraction was positively associated with MMSE score (ß= 0.034, p = 0.0062) and MoCA score (ß= 0.034, p = 0.0174), and negatively associated with TMT-A and TMT-B completion time (ß= -2.319, p = 0.0002; ß= -2.827, p = 0.0073, respectively). For evaluation of CSVD imaging markers, the presence of lacunes was positively associated with TMT-B completion time (ß= 17.241, p = 0.0028). CONCLUSION: In community-dwelling populations, reduced white matter volumes, as a consequence of aging and vascular damage, are associated with worse global cognition and executive function. Our findings provide potential insights into the correlation between cognition and CSVD-associated subcortical white matter injury.

5.
Food Chem ; 369: 130954, 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34469839

RESUMO

This study is a contribution to explore natural protein sources as high internal phase Pickering emulsions (HIPPEs) stabilizers and to achieve full utilization of biological resources. Bamboo fungus proteins were obtained by alkaline extraction and subsequently transformed into protein gels by enzymatic cross-linking method. 1% (w/v) of bamboo protein gel particles (BGPs) were used to stabilize high HIPPEs (φ = 80%) using a one-step homogenization method. At pH 3, 9 and 11, BGPs could produce stable, gel-like oil/water HIPPEs with excellent storage stability. In contrast, at pH 5 and 7, stable HIPPEs could not be formed, which might be attributed to the variation of contact angle and electrostatic repulsion of BGPs. Structure analysis indicated that HIPPEs with gel-like structures were mainly stabilized by physical barriers and electrostatic repulsion. The present study is expected to provide new insight on comprehensive utilization of fungi sources.

6.
Microb Ecol ; 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34487211

RESUMO

Pine wood nematode, Bursaphelenchus xylophilus, as one of the greatest threats to pine trees, is spreading all over the world. Plant microorganisms play an important role in the pathogenesis of nematodes. The phyllosphere and rhizosphere bacterial and fungal communities associated with healthy Pinus koraiensis (PKa) and P. koraiensis infected by B. xylophilus at the early (PKb) and last (PKc) stages were analyzed. Our results demonstrated that pine wood nematode (PWD) could increase the phyllosphere bacterial Pielou_e, Shannon, and Simpson index; phyllosphere fungal Chao 1 index, as well as rhizosphere bacterial Pielou_e, Shannon, and Simpson index; and rhizosphere fungal Pielou_e, Shannon, and Simpson index. What's more, slight shifts of the microbial diversity were observed at the early stage of infection, and the microbial diversity increased significantly as the symptoms of infection worsened. With the infection of B. xylophilus in P. koraiensis, Bradyrhizobium (rhizosphere bacteria), Massilia (phyllosphere bacteria), and Phaeosphaeriaceae (phyllosphere fungi) were the major contributors to the differences in community compositions among different treatments. With the infection of PWD, most of the bacterial groups tended to be co-excluding rather than co-occurring. These changes would correlate with microbial ability to suppress plant pathogen, enhancing the understanding of disease development and providing guidelines to pave the way for its possible management.

8.
Neurochem Res ; 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34498160

RESUMO

The effects of general anesthetics on the developing brain have aroused much attention in recent years. Sevoflurane, a commonly used inhalation anesthetic especially in pediatric anesthesia, can induce developmental neurotoxicity. In this study, the differentially expressed mRNAs in the hippocampus of newborn rats exposed to 3% sevoflurane for 6 h were detected by RNA-Sequencing. Those data indicated that the mRNA of Klotho was increased after exposure to sevoflurane. Moreover, the protein expression of Klotho was assayed by Western Blot. Besides over-expression and under-expression of Klotho protein, we also detected changes of cell proliferation, ROS, JC-1, and Bcl-2/Bax ratio in PC12 cells exposed to sevoflurane. After exposure to 3% sevoflurane, the expression of Klotho protein increased in the hippocampus of neonatal rats. In PC12 cells, exposure to sevoflurane could increase cellular ROS level, reduce mitochondrial membrane potential and Bcl-2/Bax ratio. While overexpression of Klotho alleviated the above changes, knockdown of Klotho aggravated the injury of sevoflurane. Klotho protein could reduce oxidative stress and mitochondrial injury induced by sevoflurane in the neuron.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34469908

RESUMO

OBJECTIVE: To compare image quality and radiation dose of split-filter TwinBeam dual-energy (SF-TBDE) with those of single-energy images (SECT) in the contrast-enhanced chest computed tomography (CT). METHODS: Two hundred patients who underwent SF-TBDE (n = 100) and SECT (n = 100) contrast-enhanced chest scanning were retrospectively analyzed. The contrast-to-noise ratio (CNR) and figure of merit (FOM)-CNR of 5 structures (lung, aorta, pulmonary artery, thyroid, and erector spinae) were calculated and subjectively evaluated by 2 independent radiologists. Radiation dose was compared using volume CT dose index and size-specific dose estimate. RESULTS: The CNR and FOM-CNR of lung and erector spinae in SF-TBDE were higher than those of SECT (P < 0.001). The differences in the subjective image quality between the 2 groups were not significant (P = 0.244). Volume CT dose index and size-specific dose estimate of SF-TBDE were lower than those of SECT (6.60 ± 1.56 vs 7.81 ± 3.02 mGy, P = 0.001; 9.25 ± 1.60 vs. 10.55 ± 3.54; P = 0.001). CONCLUSIONS: The SF-TBDE CT can provide similar image quality at a lower radiation dose compared with SECT.

10.
Signal Transduct Target Ther ; 6(1): 337, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34489403

RESUMO

SARS-CoV-2 has been reported to show a capacity for invading the brains of humans and model animals. However, it remains unclear whether and how SARS-CoV-2 crosses the blood-brain barrier (BBB). Herein, SARS-CoV-2 RNA was occasionally detected in the vascular wall and perivascular space, as well as in brain microvascular endothelial cells (BMECs) in the infected K18-hACE2 transgenic mice. Moreover, the permeability of the infected vessel was increased. Furthermore, disintegrity of BBB was discovered in the infected hamsters by administration of Evans blue. Interestingly, the expression of claudin5, ZO-1, occludin and the ultrastructure of tight junctions (TJs) showed unchanged, whereas, the basement membrane was disrupted in the infected animals. Using an in vitro BBB model that comprises primary BMECs with astrocytes, SARS-CoV-2 was found to infect and cross through the BMECs. Consistent with in vivo experiments, the expression of MMP9 was increased and collagen IV was decreased while the markers for TJs were not altered in the SARS-CoV-2-infected BMECs. Besides, inflammatory responses including vasculitis, glial activation, and upregulated inflammatory factors occurred after SARS-CoV-2 infection. Overall, our results provide evidence supporting that SARS-CoV-2 can cross the BBB in a transcellular pathway accompanied with basement membrane disrupted without obvious alteration of TJs.


Assuntos
Membrana Basal/metabolismo , Barreira Hematoencefálica/metabolismo , COVID-19/metabolismo , SARS-CoV-2/metabolismo , Junções Íntimas/metabolismo , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , Membrana Basal/patologia , Membrana Basal/virologia , Barreira Hematoencefálica/patologia , Barreira Hematoencefálica/virologia , COVID-19/genética , COVID-19/patologia , Chlorocebus aethiops , Modelos Animais de Doenças , Humanos , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Transgênicos , SARS-CoV-2/genética , Junções Íntimas/genética , Junções Íntimas/patologia , Junções Íntimas/virologia , Células Vero
11.
PLoS Genet ; 17(9): e1009760, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34491994

RESUMO

Unisexual taxa are commonly considered short-lived as the absence of meiotic recombination is supposed to accumulate deleterious mutations and hinder the creation of genetic diversity. However, the gynogenetic gibel carp (Carassius gibelio) with high genetic diversity and wide ecological distribution has outlived its predicted extinction time of a strict unisexual reproduction population. Unlike other unisexual vertebrates, males associated with supernumerary microchromosomes have been observed in gibel carp, which provides a unique system to explore the rationales underlying male occurrence in unisexual lineage and evolution of unisexual reproduction. Here, we identified a massively expanded satellite DNA cluster on microchromosomes of hexaploid gibel carp via comparing with the ancestral tetraploid crucian carp (Carassius auratus). Based on the satellite cluster, we developed a method for single chromosomal fluorescence microdissection and isolated three male-specific microchromosomes in a male metaphase cell. Genomic anatomy revealed that these male-specific microchromosomes contained homologous sequences of autosomes and abundant repetitive elements. Significantly, several potential male-specific genes with transcriptional activity were identified, among which four and five genes displayed male-specific and male-biased expression in gonads, respectively, during the developmental period of sex determination. Therefore, the male-specific microchromosomes resembling common features of sex chromosomes may be the main driving force for male occurrence in gynogenetic gibel carp, which sheds new light on the evolution of unisexual reproduction.

12.
Front Endocrinol (Lausanne) ; 12: 738138, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34531829

RESUMO

Objective: Our goal was to investigate the correlation between papillary thyroid carcinoma (PTC) characteristics on ultrasonography and metastases of lymph nodes posterior to the right recurrent laryngeal nerve (LN-prRLN). There is still no good method for clinicians to judge whether a patient needs LN-prRLN resection before surgery, and we also wanted to establish a new scoring system to determine whether patients with papillary thyroid carcinoma require LN-prRLN resection before surgery. Patients and Methods: There were 482 patients with right or bilateral PTC who underwent thyroid gland resection from December 2015 to December 2017 recruited as study subjects. The relationship between the PTC characteristics on ultrasonography and the metastases of LN-prRLN was analyzed by univariate and logistic regression analyses. Based on the risk factors identified in univariate and logistic regression analysis, a nomogram-based LN-prRLN prediction model was established. Result: LN-prRLN were removed from all patients, of which 79 had LN-prRLN metastasis, with a metastasis rate of 16.39%. Multivariate logistic regression analysis revealed that LN-prRLN metastasis was closely related to sex, age, blood supply, larger tumors (> 1 cm) and capsular invasion. A risk prediction model has been established and fully verified. The calibration curve used to evaluate the nomogram shows that the consistency index was 0.75 ± 0.065. Conclusion: Preoperative clinical data, such as sex, age, abundant blood supply, larger tumor (> 1 cm) and capsular invasion, are positively correlated with LN-prRLN metastasis. Our scoring system can help surgeons non-invasively determine which patients should undergo LN-prRLN resection before surgery. We recommend that LN-prRLN resection should be performed when the score is above 103.1.

13.
Front Immunol ; 12: 702971, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34531856

RESUMO

Polyploidy and subsequent diploidization provide genomic opportunities for evolutionary innovations and adaptation. The researches on duplicated gene evolutionary fates in recurrent polyploids have seriously lagged behind that in paleopolyploids with diploidized genomes. Moreover, the antiviral mechanisms of Viperin remain largely unclear in fish. Here, we elaborate the distinct antiviral mechanisms of two viperin homeologs (Cgviperin-A and Cgviperin-B) in auto-allo-hexaploid gibel carp (Carassius gibelio). First, Cgviperin-A and Cgviperin-B showed differential and biased expression patterns in gibel carp adult tissues. Subsequently, using co-immunoprecipitation (Co-IP) screening analysis, both CgViperin-A and CgViperin-B were found to interact with crucian carp (C. auratus) herpesvirus (CaHV) open reading frame 46 right (ORF46R) protein, a negative herpesvirus regulator of host interferon (IFN) production, and to promote the proteasomal degradation of ORF46R via decreasing K63-linked ubiquitination. Additionally, CgViperin-B also mediated ORF46R degradation through autophagosome pathway, which was absent in CgViperin-A. Moreover, we found that the N-terminal α-helix domain was necessary for the localization of CgViperin-A and CgViperin-B at the endoplasmic reticulum (ER), and the C-terminal domain of CgViperin-A and CgViperin-B was indispensable for the interaction with degradation of ORF46R. Therefore, the current findings clarify the divergent antiviral mechanisms of the duplicated viperin homeologs in a recurrent polyploid fish, which will shed light on the evolution of teleost duplicated genes.

16.
Nanoscale ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34519753

RESUMO

To date, outstanding linear and nonlinear optical properties of tellurene, caused by multiple two-dimensional (2D) phases and optical anisotropy, have attracted considerable interest for potential nanophotonics applications. In this work, the ultrafast nonlinear optical (NLO) properties of α-tellurene have been studied via Z-scan and pump-probe techniques at a broadband spectral region. Typical saturable absorption and band filling effects are observed in tellurene due to the Pauli exclusion principle. Analysis using density functional theory (DFT) computation shows the enhancements in NLO response within the ultraviolet-visible absorption spectral region are owing to the increased optical intraband transition in tellurene. Moreover, the effects of varying the photon energy of the probe pulse were explored. Our results indicated that probe pulses with higher photon energies can make smaller differential transmission signal, this effect is found to be negatively correlated with calculated joint density of states (JDOS). These results offer insights into the intrinsic photophysics of 2D tellurene, driving its applications in photonic and optoelectronic fields.

17.
Phys Med ; 90: 1-5, 2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34521015

RESUMO

PURPOSE: Electronic portal imaging detector (EPID)-based patient positioning verification is an important component of safe radiotherapy treatment delivery. In computer simulation studies, learning-based approaches have proven to be superior to conventional gamma analysis in the detection of positioning errors. To approximate a clinical scenario, the detectability of positioning errors via EPID measurements was assessed using radiomics analysis for patients with thyroid-associated ophthalmopathy. METHODS: Treatment plans of 40 patients with thyroid-associated ophthalmopathy were delivered to a solid anthropomorphic head phantom. To simulate positioning errors, combinations of 0-, 2-, and 4-mm translation errors in the left-right (LR), superior-inferior (SI), and anterior-posterior (AP) directions were introduced to the phantom. The positioning errors-induced dose differences between measured portal dose images were used to predict the magnitude and direction of positioning errors. The detectability of positioning errors was assessed via radiomics analysis of the dose differences. Three classification models-support vector machine (SVM), k-nearest neighbors (KNN), and XGBoost-were used for the detection of positioning errors (positioning errors larger or smaller than 3 mm in an arbitrary direction) and direction classification (positioning errors larger or smaller than 3 mm in a specific direction). The receiver operating characteristic curve and the area under the ROC curve (AUC) were used to evaluate the performance of classification models. RESULTS: For the detection of positioning errors, the AUC values of SVM, KNN, and XGBoost models were all above 0.90. For LR, SI, and AP direction classification, the highest AUC values were 0.76, 0.91, and 0.80, respectively. CONCLUSIONS: Combined radiomics and machine learning approaches are capable of detecting the magnitude and direction of positioning errors from EPID measurements. This study is a further step toward machine learning-based positioning error detection during treatment delivery with EPID measurements.

18.
Food Chem ; 370: 131056, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34530346

RESUMO

A novel multi-residue method, magnetic solid-phase extraction combined with LC-MS/MS, was proposed for simultaneous enantiomeric determination of eight chiral pesticides in water and fruit juices. Fe3O4@C@UiO-66 was firstly used to extract and enrich pesticides, showing excellent adsorption capacity, which was proved by adsorption kinetic and thermodynamic experiments. Multiple extraction parameters were optimized by Plackett-Burman and Box-Behnken design. Under optimized conditions, good linearity (1.0-200 ng L-1, R2 ≥ 0.9953) for all analytes, detection limits (0.10 to 0.35 ng L-1), quantitation limits (0.35 to 1.00 ng L-1), recoveries (83.68-95.99%), and precision (intra-day RSD ≤ 7.06%, inter-day RSD ≤ 9.40%) were obtained, meeting the requirements of pesticides residues analysis. It is worth mentioning that eight chiral pesticides can be separated quickly within 19 min. The above results indicate that the proposed method with satisfactory sensitivity and accuracy has the potential for routine analysis of chiral pesticide residues in aqueous samples.

19.
J Hazard Mater ; 423(Pt B): 127139, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34537653

RESUMO

Accurate determination of antibiotic resistance genes (ARGs) in environmental DNA molecules (eDNA) is challenging owing to its low abundance in the aquatic environment. Here we report a facile and cost-efficient approach to extract trace amount of eDNAs in the aquatic environment using LnPO4 nanomaterials. Among the nanomaterials, less crystalline TbPO4 nanoneedles was identified as the most prominent candidate for long stranded DNA and short stranded DNA with adsorption efficiency above 97%. The adsorbed DNA was washed off from TbPO4 nanoneedles by optimized eluant (85% PBS, 15% EtOH, 4 g/L glycine, pH 10.0) with an optimal DNA recovery of 78.83%. Our approach showed a comparable or better eDNA extraction efficiency than a commercial extraction method for different environmental samples, but 89% less cost. The high purity of the extracted eDNA was demonstrated by a high A260/280 ratio. Using qPCR experiment, the occurrence of six common ARGs in the eDNA were detected with abundance ranging from 4.06 × 103 to 3.51 × 109 copies/L in river samples. This specific DNA capturer is valuable for the evaluation of spatial and temporal dynamic of ARGs pollution to provide insight into the potential risk with regard to the human health.

20.
JAMA Netw Open ; 4(9): e2126337, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34550383

RESUMO

Importance: Although tumor-infiltrating lymphocytes (TILs) are an important histopathologic characteristic reflecting host immune response in patients with melanoma, their prognostic value remains controversial. Because manual review of medical records is labor intensive, a survival analysis using a large patient cohort with comprehensive clinical and histopathologic characteristics is lacking. Objective: To assess the prognostic significance of TILs among patients with cutaneous melanoma using a large cohort established through natural language processing (NLP) algorithms. Design, Setting, and Participants: This retrospective cohort study analyzed the medical records of 14 436 patients with cutaneous melanoma at Brigham and Women's Hospital between June 1, 2004, and December 31, 2019. Patients were followed up to death or censored at their last clinical visit. Main Outcome and Measures: The primary outcome was overall survival (OS). Survival analysis was conducted using Kaplan-Meier curves, the log-rank test, and Cox proportional hazards regression analysis. Results: A total of 14 436 patients with cutaneous melanoma were identified in the institution's pathology information system. Using NLP, we established a study cohort of 2624 patients (1462 men [55.7%]; median age, 61 years [interquartile range, 50-72 years]) who had vertical growth phase melanoma with TIL status scored. Absent TILs were identified in 434 patients (16.5%), nonbrisk TILs in 1916 patients (73.0%), and brisk TILs in 274 patients (10.4%). The 5-year survival rate was 71.0% (95% CI, 65.5%-76.9%) among patients with an absence of TILs, 73.8% (95% CI, 71.1%-76.5%) among patients with nonbrisk TILs, and 85.2% (95% CI, 80.0%-90.7%) among patients with brisk TILs. Brisk TILs were significantly associated with improved OS (adjusted hazard ratio, 0.63; 95% CI, 0.42-0.95; P = .03; 14.2% OS advantage at 5 years), and nonbrisk TILs were not associated with improved OS (adjusted hazard ratio, 0.87; 95% CI, 0.68-1.11; P = .25), compared with the absence of TILs. Conclusions and Relevance: This study provides evidence based on a large patient cohort from a single institution that suggests that brisk TILs represent an independent prognostic factor for OS among patients with primary cutaneous melanoma. The study also suggests that NLP is a highly efficient tool to facilitate large-scale analyses that involve free-text clinical data.

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