Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 559
Filtrar
1.
Thromb J ; 22(1): 57, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951855

RESUMO

OBJECTIVE: To identify recurrent venous thromboembolism (VTE) after discontinuation of anticoagulation in patients with isolated distal deep vein thrombosis based on its anatomic localization (axial or muscular veins). METHODS: Data were sourced from PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov databases in the time period up to October 2023. The study followed PRISMA guidelines using a registered protocol (CRD42023443029). Studies reporting recurrent VTE in patients with axial or muscular DVT were included in the analysis. RESULTS: Five studies with a total of 1,403 participants were evaluated. The results showed a pooled odds ratio of 1.12 (95% confidence interval 0.77-1.63) between axial and muscular DVT. Heterogeneity was low (I2 = 0%, p = 0.91) and there was no significant difference in the rate of recurrent VTE between axial and muscular DVT in each subgroup. CONCLUSIONS: Muscular and axial DVT showed comparable recurrent VTE rates after anticoagulation. However, uncertainties regarding the possibility of recurrence affecting the popliteal vein or resulting in pulmonary embolism following muscular DVT anticoagulation persisted. Randomized trials in patients with isolated distal DVT are still needed to clarify its prognosis for different anatomical thrombus locations.

2.
J Transl Med ; 22(1): 559, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38863033

RESUMO

BACKGROUND: Exploration of adaptive evolutionary changes at the genetic level in vaginal microbial communities during different stages of cervical cancer remains limited. This study aimed to elucidate the mutational profile of the vaginal microbiota throughout the progression of cervical disease and subsequently establish diagnostic models. METHODS: This study utilized a metagenomic dataset consisting of 151 subjects classified into four categories: invasive cervical cancer (CC) (n = 42), cervical intraepithelial neoplasia (CIN) (n = 43), HPV-infected (HPVi) patients without cervical lesions (n = 34), and healthy controls (n = 32). The analysis focused on changes in microbiome abundance and extracted information on genetic variation. Consequently, comprehensive multimodal microbial signatures associated with CC, encompassing taxonomic alterations, mutation signatures, and enriched metabolic functional pathways, were identified. Diagnostic models for predicting CC were established considering gene characteristics based on single nucleotide variants (SNVs). RESULTS: In this study, we screened and analyzed the abundances of 18 key microbial strains during CC progression. Additionally, 71,6358 non-redundant mutations were identified, predominantly consisting of SNVs that were further annotated into 25,773 genes. Altered abundances of SNVs and mutation types were observed across the four groups. Specifically, there were 9847 SNVs in the HPV-infected group and 14,892 in the CC group. Furthermore, two distinct mutation signatures corresponding to the benign and malignant groups were identified. The enriched metabolic pathways showed limited similarity with only two overlapping pathways among the four groups. HPVi patients exhibited active nucleotide biosynthesis, whereas patients with CC demonstrated a significantly higher abundance of signaling and cellular-associated protein families. In contrast, healthy controls showed a distinct enrichment in sugar metabolism. Moreover, biomarkers based on microbial SNV abundance displayed stronger diagnostic capability (cc.AUC = 0.87) than the species-level biomarkers (cc.AUC = 0.78). Ultimately, the integration of multimodal biomarkers demonstrated optimal performance for accurately identifying different cervical statuses (cc.AUC = 0.86), with an acceptable performance (AUC = 0.79) in the external testing set. CONCLUSIONS: The vaginal microbiome exhibits specific SNV evolution in conjunction with the progression of CC, and serves as a specific biomarker for distinguishing between different statuses of cervical disease.


Assuntos
Microbiota , Neoplasias do Colo do Útero , Vagina , Humanos , Feminino , Neoplasias do Colo do Útero/microbiologia , Neoplasias do Colo do Útero/virologia , Neoplasias do Colo do Útero/genética , Vagina/microbiologia , Microbiota/genética , Mutação/genética , Pessoa de Meia-Idade , Adulto , Polimorfismo de Nucleotídeo Único/genética , Estudos de Casos e Controles , Progressão da Doença
3.
Ecotoxicol Environ Saf ; 280: 116540, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38833982

RESUMO

The widespread utilization of polyethylene terephthalate (PET) has caused a variety of environmental and health problems. Compared with traditional thermomechanical or chemical PET cycling, the biodegradation of PET may offer a more feasible solution. Though the PETase from Ideonalla sakaiensis (IsPETase) displays interesting PET degrading performance under mild conditions; the relatively low thermal stability of IsPETase limits its practical application. In this study, enzyme-catalysed PET degradation was investigated with the promising IsPETase mutant HotPETase (HP). On this basis, a carbohydrate-binding module from Bacillus anthracis (BaCBM) was fused to the C-terminus of HP to construct the PETase mutant (HLCB) for increased PET degradation. Furthermore, to effectively improve PET accessibility and PET-degrading activity, the truncated outer membrane hybrid protein (FadL) was used to expose PETase and BaCBM on the surface of E. coli (BL21with) to develop regenerable whole-cell biocatalysts (D-HLCB). Results showed that, among the tested small-molecular weight ester compounds (p-nitrophenyl phosphate (pNPP), p-Nitrophenyl acetate (pNPA), 4-Nitrophenyl butyrate (pNPB)), PETase displayed the highest hydrolysing activity against pNPP. HP displayed the highest catalytic activity (1.94 µM(p-NP)/min) at 50 °C and increased longevity at 40 °C. The fused BaCBM could clearly improve the catalytic performance of PETase by increasing the optimal reaction temperature and improving the thermostability. When HLCB was used for PET degradation, the yield of monomeric products (255.7 µM) was ∼25.5 % greater than that obtained after 50 h of HP-catalysed PET degradation. Moreover, the highest yield of monomeric products from the D-HLCB-mediated system reached 1.03 mM. The whole-cell catalyst D-HLCB displayed good reusability and stability and could maintain more than 54.6 % of its initial activity for nine cycles. Finally, molecular docking simulations were utilized to investigate the binding mechanism and the reaction mechanism of HLCB, which may provide theoretical evidence to further increase the PET-degrading activities of PETases through rational design. The proposed strategy and developed variants show potential for achieving complete biodegradation of PET under mild conditions.


Assuntos
Biodegradação Ambiental , Burkholderiales , Escherichia coli , Polietilenotereftalatos , Polietilenotereftalatos/química , Polietilenotereftalatos/metabolismo , Burkholderiales/enzimologia , Escherichia coli/genética , Bacillus anthracis/enzimologia , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/química , Engenharia de Proteínas
4.
PLoS Genet ; 20(6): e1011314, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38857306

RESUMO

INTRODUCTION: Glioblastoma (GBM) invasion studies have focused on coding genes, while few studies evaluate long non-coding RNAs (lncRNAs), transcripts without protein-coding potential, for role in GBM invasion. We leveraged CRISPR-interference (CRISPRi) to evaluate invasive function of GBM-associated lncRNAs in an unbiased functional screen, characterizing and exploring the mechanism of identified candidates. METHODS: We implemented a CRISPRi lncRNA loss-of-function screen evaluating association of lncRNA knockdown (KD) with invasion capacity in Matrigel. Top screen candidates were validated using CRISPRi and oligonucleotide(ASO)-mediated knockdown in three tumor lines. Clinical relevance of candidates was assessed via The Cancer Genome Atlas(TCGA) and Genotype-Tissue Expression(GTEx) survival analysis. Mediators of lncRNA effect were identified via differential expression analysis following lncRNA KD and assessed for tumor invasion using knockdown and rescue experiments. RESULTS: Forty-eight lncRNAs were significantly associated with 33-83% decrease in invasion (p<0.01) upon knockdown. The top candidate, LINC03045, identified from effect size and p-value, demonstrated 82.7% decrease in tumor cell invasion upon knockdown, while LINC03045 expression was significantly associated with patient survival and tumor grade(p<0.0001). RNAseq analysis of LINC03045 knockdown revealed that WASF3, previously implicated in tumor invasion studies, was highly correlated with lncRNA expression, while WASF3 KD was associated with significant decrease in invasion. Finally, WASF3 overexpression demonstrated rescue of invasive function lost with LINC03045 KD. CONCLUSION: CRISPRi screening identified LINC03045, a previously unannotated lncRNA, as critical to GBM invasion. Gene expression is significantly associated with tumor grade and survival. RNA-seq and mechanistic studies suggest that this novel lncRNA may regulate invasion via WASF3.


Assuntos
Regulação Neoplásica da Expressão Gênica , Glioblastoma , Invasividade Neoplásica , RNA Longo não Codificante , RNA Longo não Codificante/genética , Humanos , Glioblastoma/genética , Glioblastoma/patologia , Invasividade Neoplásica/genética , Linhagem Celular Tumoral , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Sistemas CRISPR-Cas , Técnicas de Silenciamento de Genes , Movimento Celular/genética , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética
5.
Parasit Vectors ; 17(1): 277, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38943202

RESUMO

BACKGROUND: Chicken coccidiosis is a protozoan disease that leads to considerable economic losses in the poultry industry. Live oocyst vaccination is currently the most effective measure for the prevention of coccidiosis. However, it provides limited protection with several drawbacks, such as poor immunological protection and potential reversion to virulence. Therefore, the development of effective and safe vaccines against chicken coccidiosis is still urgently needed. METHODS: In this study, a novel oral vaccine against Eimeria tenella was developed by constructing a recombinant Lactobacillus plantarum (NC8) strain expressing the E. tenella RON2 protein. We administered recombinant L. plantarum orally at 3, 4 and 5 days of age and again at 17, 18 and 19 days of age. Meanwhile, each chick in the commercial vaccine group was immunized with 3 × 102 live oocysts of coccidia. A total of 5 × 104 sporulated oocysts of E. tenella were inoculated in each chicken at 30 days. Then, the immunoprotection effect was evaluated after E. tenella infection. RESULTS: The results showed that the proportion of CD4+ and CD8+ T cells, the proliferative ability of spleen lymphocytes, inflammatory cytokine levels and specific antibody titers of chicks immunized with recombinant L. plantarum were significantly increased (P < 0.05). The relative body weight gains were increased and the number of oocysts per gram (OPG) was decreased after E. tenella challenge. Moreover, the lesion scores and histopathological cecum sections showed that recombinant L. plantarum can significantly relieve pathological damage in the cecum. The ACI was 170.89 in the recombinant L. plantarum group, which was higher than the 150.14 in the commercial vaccine group. CONCLUSIONS: These above results indicate that L. plantarum expressing RON2 improved humoral and cellular immunity and enhanced immunoprotection against E. tenella. The protective efficacy was superior to that of vaccination with the commercial live oocyst vaccine. This study suggests that recombinant L. plantarum expressing the RON2 protein provides a promising strategy for vaccine development against coccidiosis.


Assuntos
Galinhas , Coccidiose , Eimeria tenella , Lactobacillus plantarum , Doenças das Aves Domésticas , Proteínas de Protozoários , Vacinas Protozoárias , Vacinação , Animais , Eimeria tenella/imunologia , Eimeria tenella/genética , Coccidiose/prevenção & controle , Coccidiose/veterinária , Coccidiose/imunologia , Doenças das Aves Domésticas/prevenção & controle , Doenças das Aves Domésticas/parasitologia , Vacinas Protozoárias/imunologia , Vacinas Protozoárias/genética , Vacinas Protozoárias/administração & dosagem , Lactobacillus plantarum/genética , Lactobacillus plantarum/imunologia , Administração Oral , Proteínas de Protozoários/imunologia , Proteínas de Protozoários/genética , Vacinação/veterinária , Anticorpos Antiprotozoários/sangue , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética
6.
Fundam Res ; 4(3): 678-689, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38933195

RESUMO

Triple-negative breast cancer (TNBC) is the most challenging breast cancer subtype. Molecular stratification and target therapy bring clinical benefit for TNBC patients, but it is difficult to implement comprehensive molecular testing in clinical practice. Here, using our multi-omics TNBC cohort (N = 425), a deep learning-based framework was devised and validated for comprehensive predictions of molecular features, subtypes and prognosis from pathological whole slide images. The framework first incorporated a neural network to decompose the tissue on WSIs, followed by a second one which was trained based on certain tissue types for predicting different targets. Multi-omics molecular features were analyzed including somatic mutations, copy number alterations, germline mutations, biological pathway activities, metabolomics features and immunotherapy biomarkers. It was shown that the molecular features with therapeutic implications can be predicted including the somatic PIK3CA mutation, germline BRCA2 mutation and PD-L1 protein expression (area under the curve [AUC]: 0.78, 0.79 and 0.74 respectively). The molecular subtypes of TNBC can be identified (AUC: 0.84, 0.85, 0.93 and 0.73 for the basal-like immune-suppressed, immunomodulatory, luminal androgen receptor, and mesenchymal-like subtypes respectively) and their distinctive morphological patterns were revealed, which provided novel insights into the heterogeneity of TNBC. A neural network integrating image features and clinical covariates stratified patients into groups with different survival outcomes (log-rank P < 0.001). Our prediction framework and neural network models were externally validated on the TNBC cases from TCGA (N = 143) and appeared robust to the changes in patient population. For potential clinical translation, we built a novel online platform, where we modularized and deployed our framework along with the validated models. It can realize real-time one-stop prediction for new cases. In summary, using only pathological WSIs, our proposed framework can enable comprehensive stratifications of TNBC patients and provide valuable information for therapeutic decision-making. It had the potential to be clinically implemented and promote the personalized management of TNBC.

7.
Am J Surg Pathol ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38934254

RESUMO

The World Health Organization (WHO) diagnostic criteria for malignant phyllodes tumor (MPT) may miss a significant number of MPTs with metastatic potential. New refined diagnostic criteria (Refined Criteria) for MPT were recently proposed. The aim of this study is to validate the Refined Criteria. This validation study included 136 borderline (borderline phyllodes tumor [BoPT]) and MPT cases that were not included in the initial study. We evaluated tumor classifications based on both the Refined Criteria and the WHO criteria. The Refined Criteria defines MPT when these criteria are met (1) stromal overgrowth with ≥ 1 feature(s) of marked stromal cellularity, marked stromal cytologic atypia, or ≥10 mitoses per 10 high-power fields (10 mitoses/10 HPFs) or (2) marked stromal cellularity with ≥1 feature(s) of marked stromal cytologic atypia, ≥10 mitoses/10 HPFs or permeative border. The WHO criteria require all 5 morphologic features (stromal overgrowth, permeative border, marked stromal cellularity, marked stromal cytologic atypia, and ≥10 mitoses/10 HPFs) for an MPT diagnosis. Using the Refined Criteria, none of the 61 BoPTs developed metastasis and 40.0% of the 75 MPTs developed metastases; local recurrence was seen in 11.5% BoPTs and 25.3% MPTs. Using the WHO criteria, 9.6% of the 94 BoPTs developed metastases and 50.0% of the 42 MPTs developed metastases; 14.9% of the BoPTs had local recurrence and 28.6% of the MPTs had local recurrence. Nine (30.0%) of the 30 tumors that developed distant metastases were diagnosed as BoPTs by the WHO criteria. When we combined the 75 MPTs from this validation cohort with the 65 MPT cases from the published data using the Refined Criteria, 50 (35.7%) of the 140 MPTs developed metastases, whereas 8 cases with metastases were <5 cm. In the univariate analysis with log-rank test, stromal overgrowth, marked stromal cellularity, marked stromal cytologic atypia, ≥10 mitoses/10 HPFs, presence of heterologous components other than liposarcomatous component, and presence of stromal necrosis were significantly associated with the risk of metastasis (all with P < 0.05). In multivariate analysis with Cox proportional hazard regression, stromal overgrowth and marked stromal cellularity were significantly associated with metastasis (both with P < 0.001). The Refined Criteria are superior to the WHO criteria in predicting the clinical outcomes of BoPTs and MPTs. Using the Refined Criteria, 35.7% of 140 patients with MPT developed metastases, whereas none (0%) of the patients with BoPT developed metastases. Patients with MPT have a high metastatic rate; these patients may benefit from systemic chemotherapy or targeted therapies. In contrast, patients with BoPT may be managed with complete local excision alone without chemotherapy.

8.
Thromb J ; 22(1): 47, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38840142

RESUMO

OBJECTIVE: To compare the predictive efficacy of the PADUA and Caprini models for pulmonary embolism (PE) in gynecological inpatients, analyze the risk factors for PE, and validate whether both models can effectively predict mortality rates. METHODS: A total of 355 gynecological inpatients who underwent computed tomography pulmonary angiography (CTPA) were included in the retrospective analysis. The comparative assessment of the predictive capabilities for PE between the PADUA and Caprini was carried out using receiver operating characteristic (ROC) curves. Logistic regression analysis was used to identify risk factors associated with PE. Additionally, Kaplan-Meier survival analysis plots were generated to validate the predictive efficacy for mortality rates. RESULTS: Among 355 patients, the PADUA and Caprini demonstrated the area under the curve (AUC) values of 0.757 and 0.756, respectively. There was no statistically significant difference in the AUC between the two models (P = 0.9542). Multivariate logistic analysis revealed immobility (P < 0.001), history of venous thromboembolism (VTE) (P = 0.002), thrombophilia (P < 0.001), hormonal treatment (P = 0.022), and obesity (P = 0.019) as independent risk factors for PE. Kaplan-Meier survival analysis demonstrated the reliable predictive efficacy of both the Caprini (P = 0.00051) and PADUA (P = 0.00031) for mortality. ROC for the three- and six-month follow-ups suggested that the Caprini model exhibited superior predictive efficacy for mortality. CONCLUSIONS: The PADUA model can serve as a simple and effective tool for stratifying high-risk gynecological inpatients before undergoing CTPA. The Caprini model demonstrated superior predictive efficacy for mortality rates.

9.
Food Chem Toxicol ; 189: 114750, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38777166

RESUMO

This study aims to investigate the associations of bisphenols with sex and thyroid hormones in cord blood among newborns. Four bisphenols, three hormones related to gonadal function, and four parameters related to thyroid function were measured in umbilical cord blood in 378 mother-newborn pairs. Multivariable linear regression, quantile-based g-computation (QGC), and Bayesian kernel machine regression were used. In the multivariable linear regression, bisphenol A (BPA) was associated with increased testosterone (TT) (regression coefficient, ß = 0.049, 95% confidence interval, CI: 0.013,0.085; p = 0.007) and free tri-iodothyronine (FT3) levels (ß = 0.019, 95% CI: 0.003, 0.035; p = 0.023), and decreased thyroid peroxidase antibody (TPOAb) (ß = -0.053, 95% CI: 0.098, -0.008; p = 0.021). Consistently associations were observed in males, except TT, which was observed in females, and bisphenol AF (BPAF) was associated with decreased follicle-stimulating hormone (FSH) in females. These associations were also observed in a mixture of bisphenols. Moreover, we observed maternal prepregnancy body mass index (BMI) and delivery mode disparity in the relationship between bisphenols and sex and thyroid hormones. This study suggests that bisphenols may exert effects on sex and thyroid hormones in newborns, the effect may vary with sex differences, maternal prepregnancy BMI, and delivery mode.


Assuntos
Compostos Benzidrílicos , Sangue Fetal , Fenóis , Hormônios Tireóideos , Humanos , Fenóis/sangue , Sangue Fetal/química , Feminino , Masculino , Recém-Nascido , Compostos Benzidrílicos/sangue , Hormônios Tireóideos/sangue , Adulto , Gravidez , Testosterona/sangue , Disruptores Endócrinos/sangue , Tri-Iodotironina/sangue
10.
Cell ; 187(12): 3024-3038.e14, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38781969

RESUMO

Plants frequently encounter wounding and have evolved an extraordinary regenerative capacity to heal the wounds. However, the wound signal that triggers regenerative responses has not been identified. Here, through characterization of a tomato mutant defective in both wound-induced defense and regeneration, we demonstrate that in tomato, a plant elicitor peptide (Pep), REGENERATION FACTOR1 (REF1), acts as a systemin-independent local wound signal that primarily regulates local defense responses and regenerative responses in response to wounding. We further identified PEPR1/2 ORTHOLOG RECEPTOR-LIKE KINASE1 (PORK1) as the receptor perceiving REF1 signal for plant regeneration. REF1-PORK1-mediated signaling promotes regeneration via activating WOUND-INDUCED DEDIFFERENTIATION 1 (WIND1), a master regulator of wound-induced cellular reprogramming in plants. Thus, REF1-PORK1 signaling represents a conserved phytocytokine pathway to initiate, amplify, and stabilize a signaling cascade that orchestrates wound-triggered organ regeneration. Application of REF1 provides a simple method to boost the regeneration and transformation efficiency of recalcitrant crops.


Assuntos
Proteínas de Plantas , Regeneração , Transdução de Sinais , Solanum lycopersicum , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Solanum lycopersicum/metabolismo , Regulação da Expressão Gênica de Plantas , Peptídeos/metabolismo
12.
Genome Res ; 34(5): 740-756, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38744529

RESUMO

Although DNA N 6-adenine methylation (6mA) is best known in prokaryotes, its presence in eukaryotes has recently generated great interest. Biochemical and genetic evidence supports that AMT1, an MT-A70 family methyltransferase (MTase), is crucial for 6mA deposition in unicellular eukaryotes. Nonetheless, the 6mA transmission mechanism remains to be elucidated. Taking advantage of single-molecule real-time circular consensus sequencing (SMRT CCS), here we provide definitive evidence for semiconservative transmission of 6mA in Tetrahymena thermophila In wild-type (WT) cells, 6mA occurs at the self-complementary ApT dinucleotide, mostly in full methylation (full-6mApT); after DNA replication, hemi-methylation (hemi-6mApT) is transiently present on the parental strand, opposite to the daughter strand readily labeled by 5-bromo-2'-deoxyuridine (BrdU). In ΔAMT1 cells, 6mA predominantly occurs as hemi-6mApT. Hemi-to-full conversion in WT cells is fast, robust, and processive, whereas de novo methylation in ΔAMT1 cells is slow and sporadic. In Tetrahymena, regularly spaced 6mA clusters coincide with the linker DNA of nucleosomes arrayed in the gene body. Importantly, in vitro methylation of human chromatin by the reconstituted AMT1 complex recapitulates preferential targeting of hemi-6mApT sites in linker DNA, supporting AMT1's intrinsic and autonomous role in maintenance methylation. We conclude that 6mA is transmitted by a semiconservative mechanism: full-6mApT is split by DNA replication into hemi-6mApT, which is restored to full-6mApT by AMT1-dependent maintenance methylation. Our study dissects AMT1-dependent maintenance methylation and AMT1-independent de novo methylation, reveals a 6mA transmission pathway with a striking similarity to 5-methylcytosine (5mC) transmission at the CpG dinucleotide, and establishes 6mA as a bona fide eukaryotic epigenetic mark.


Assuntos
Adenina , Metilação de DNA , Tetrahymena thermophila , Tetrahymena thermophila/genética , Tetrahymena thermophila/metabolismo , Adenina/metabolismo , Adenina/análogos & derivados , Replicação do DNA , DNA de Protozoário/genética , DNA de Protozoário/metabolismo
13.
Nat Rev Cancer ; 24(6): 382-398, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38698126

RESUMO

In the past two decades, technological advances have brought unprecedented insights into the paediatric cancer genome revealing characteristics distinct from those of adult cancer. Originating from developing tissues, paediatric cancers generally have low mutation burden and are driven by variants that disrupt the transcriptional activity, chromatin state, non-coding cis-regulatory regions and other biological functions. Within each tumour, there are multiple populations of cells with varying states, and the lineages of some can be tracked to their fetal origins. Genome-wide genetic screening has identified vulnerabilities associated with both the cell of origin and transcription deregulation in paediatric cancer, which have become a valuable resource for designing new therapeutic approaches including those for small molecules, immunotherapy and targeted protein degradation. In this Review, we present recent findings on these facets of paediatric cancer from a pan-cancer perspective and provide an outlook on future investigations.


Assuntos
Neoplasias , Humanos , Neoplasias/genética , Neoplasias/patologia , Criança , Mutação , Genoma Humano , Regulação Neoplásica da Expressão Gênica
14.
Histopathology ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38719547

RESUMO

BACKGROUND AND OBJECTIVES: Current national or regional guidelines for the pathology reporting on invasive breast cancer differ in certain aspects, resulting in divergent reporting practice and a lack of comparability of data. Here we report on a new international dataset for the pathology reporting of resection specimens with invasive cancer of the breast. The dataset was produced under the auspices of the International Collaboration on Cancer Reporting (ICCR), a global alliance of major (inter-)national pathology and cancer organizations. METHODS AND RESULTS: The established ICCR process for dataset development was followed. An international expert panel consisting of breast pathologists, a surgeon, and an oncologist prepared a draft set of core and noncore data items based on a critical review and discussion of current evidence. Commentary was provided for each data item to explain the rationale for selecting it as a core or noncore element, its clinical relevance, and to highlight potential areas of disagreement or lack of evidence, in which case a consensus position was formulated. Following international public consultation, the document was finalized and ratified, and the dataset, which includes a synoptic reporting guide, was published on the ICCR website. CONCLUSIONS: This first international dataset for invasive cancer of the breast is intended to promote high-quality, standardized pathology reporting. Its widespread adoption will improve consistency of reporting, facilitate multidisciplinary communication, and enhance comparability of data, all of which will help to improve the management of invasive breast cancer patients.

15.
World J Clin Cases ; 12(14): 2370-2381, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38765751

RESUMO

BACKGROUND: In observational studies, dietary intakes are associated with gastroesophageal reflux disease (GERD). AIM: To conduct a two-sample mendelian randomization (MR) analysis to determine whether those associations are causal. METHODS: To explore the relationship between dietary intake and the risk of GERD, we extracted appropriate single nucleotide polymorphisms from genome-wide association study data on 24 dietary intakes. Three methods were adopted for data analysis: Inverse variance weighting, weighted median methods, and MR-Egger's method. The odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the causal association between dietary intake and GERD. RESULTS: Our univariate Mendelian randomization (UVMR) results showed significant evidence that pork intake (OR, 2.83; 95%CI: 1.76-4.55; P = 1.84 × 10-5), beer intake (OR, 2.70, 95%CI: 2.00-3.64; P = 6.54 × 10-11), non-oily fish intake (OR, 2.41; 95%CI: 1.49-3.91; P = 3.59 × 10-4) have a protective effect on GERD. In addition, dried fruit intake (OR, 0.37; 95%CI: 0.27-0.50; 6.27 × 10-11), red wine intake (OR, 0.34; 95%CI: 0.25-0.47; P = 1.90 × 10-11), cheese intake (OR, 0.46; 95%CI: 0.39-0.55; P =3.73 × 10-19), bread intake (OR, 0.72; 95%CI: 0.56-0.92; P = 0.0009) and cereal intake (OR, 0.45; 95%CI: 0.36-0.57; P = 2.07 × 10-11) were negatively associated with the risk of GERD. There was a suggestive association for genetically predicted coffee intake (OR per one SD increase, 1.22, 95%CI: 1.03-1.44; P = 0.019). Multivariate Mendelian randomization further confirmed that dried fruit intake, red wine intake, cheese intake, and cereal intake directly affected GERD. In contrast, the impact of pork intake, beer intake, non-oily fish intake, and bread intake on GERD was partly driven by the common risk factors for GERD. However, after adjusting for all four elements, there was no longer a suggestive association between coffee intake and GERD. CONCLUSION: This study provides MR evidence to support the causal relationship between a broad range of dietary intake and GERD, providing new insights for the treatment and prevention of GERD.

16.
Microbes Infect ; : 105350, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38723999

RESUMO

The widespread transmission of SARS-CoV-2 in humans poses a serious threat to public health security, and a growing number of studies have discovered that SARS-CoV-2 infection in wildlife and mutate over time. This article mainly reports the first systematic review and meta-analysis of the prevalence of SARS-CoV-2 in wildlife. The pooled prevalence of the 29 included articles was calculated by us using a random effects model (22.9%) with a high heterogeneity (I2 = 98.7%, p = 0.00). Subgroup analysis and univariate regression analysis found potential risk factors contributing to heterogeneity were country, wildlife species, sample type, longitude, and precipitation. In addition, the prevalence of SARS-CoV-2 in wildlife increased gradually over time. Consequently, it is necessary to comprehensively analyze the risk factors of SARS-CoV-2 infection in wildlife and develop effective control policies, as well as to monitor the mutation of SARS-CoV-2 in wildlife at all times to reduce the risk of SARS-CoV-2 transmission among different species.

18.
Heliyon ; 10(8): e29331, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38644848

RESUMO

Rationale and objectives: Radiomic models based on normal-resolution (NR) computed tomography angiography (CTA) images can fail to distinguish between symptomatic and asymptomatic carotid atherosclerotic plaques. This study aimed to explore the effectiveness of a deep learning-based three-dimensional super-resolution (SR) CTA radiomic model for improved identification of symptomatic carotid atherosclerotic plaques. Materials and methods: A total of 193 patients with carotid atherosclerotic plaques were retrospectively enrolled and allocated into either a symptomatic (n = 123) or an asymptomatic (n = 70) groups. SR CTA images were derived from NR CTA images using deep learning-based three-dimensional SR technology. Handcrafted radiomic features were extracted from both the SR and NR CTA images and three risk models were developed based on manually measured quantitative CTA characteristics and NR and SR radiomic features. Model performances were assessed via receiver operating characteristic, calibration, and decision curve analyses. Results: The SR model exhibited the optimal performance (area under the curve [AUC] 0.820, accuracy 0.802, sensitivity 0.854, F1 score 0.847) in the testing cohort, outperforming the other two models. The calibration curve analyses and Hosmer-Lemeshow test demonstrated that the SR model exhibited the best goodness of fit, and decision curve analysis revealed that SR model had the highest clinical value and potential patient benefits. Conclusions: Deep learning-based three-dimensional SR technology could improve the CTA-based radiomic models in identifying symptomatic carotid plaques, potentially providing more accurate and valuable information to guide clinical decision-making to reduce the risk of ischemic stroke.

19.
Sensors (Basel) ; 24(8)2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38676075

RESUMO

Geological hazards in Xinxian County, Xinyang City, Henan Province, are characterized by their small scale, wide distribution, and significant influence from regional tectonics. This study focuses on collapses and landslide hazards within the area, selecting twelve evaluation factors: aspect, slope shape, normalized difference vegetation index (NDVI), topographic relief, distance from geological structure, slope, distance from roads, land use cover type, area of land change (2012-2022), average annual rainfall (2012-2022), and river network density. Utilizing data from historical disaster sites across the region, the information quantity method and hierarchical analysis method are employed to ascertain the information quantity and weight of each factor. Subsequently, a random forest model is applied to perform susceptibility zoning of geological hazards in Xinxian County and to examine the characteristics of these geological disasters. The results show that in the study area, the primary factors influencing the development of geohazards are the distance from roads, rock groups, and distance from geological structure areas. A comparison of the susceptibility results obtained through two methods, the analytic hierarchy process information quantity method and the random forests model, reveals that the former exhibits a higher accuracy. This model categorizes the geohazard susceptibility in the study area into four levels: low, medium, high, and very high. Notably, the areas of very high and high susceptibility together cover 559.17 km2, constituting 35.99% of the study area's total area, and encompass 57 disaster sites, which represent 72.15% of all disaster sites. Geological hazards in Xinxian County frequently manifest on steep canyon inclines, along the curved and concave banks of mountain rivers, within watershed regions, on gully inclines, atop steep cliffs, and on artificially created slopes, among other sites. Areas with very high and high vulnerability to these hazards are mainly concentrated near the county's geological formations. The gneiss formations are widely exposed in Xinxian County, and the gneisses' strength is significantly changed under weathering, which makes the properties of the different degrees of weathering of the rock and soil bodies play a decisive role in the stability of the slopes. This paper provides a basis for evaluating and preventing geologic hazards in the Dabie mountainous area of the South Henan Province, and the spatial planning of the national territory.

20.
ACS Biomater Sci Eng ; 10(4): 2385-2397, 2024 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-38538611

RESUMO

Bone is a complex organic-inorganic composite tissue composed of ∼30% organics and ∼70% hydroxyapatite (HAp). Inspired by this, we used 30% collagen and 70% HAp extracted from natural bone using the calcination method to generate a biomimetic bone composite hydrogel scaffold (BBCHS). In one respect, BBCHS, with a fixed proportion of inorganic and organic components similar to natural bone, exhibits good physical properties. In another respect, the highly biologically active and biocompatible HAp from natural bone effectively promotes osteogenic differentiation, and type I collagen facilitates cell adhesion and spreading. Additionally, the well-structured porosity of the BBCHS provides sufficient growth space for bone marrow mesenchymal stem cells (BMSCs) while promoting substance exchange. Compared to the control group, the new bone surface of the defective location in the B-HA70+Col group is increased by 3.4-fold after 8 weeks of in vivo experiments. This strategy enables the BBCHS to closely imitate the chemical makeup and physical structure of natural bone. With its robust biocompatibility and osteogenic activity, the BBCHS can be easily adapted for a wide range of bone repair applications and offers promising potential for future research and development.


Assuntos
Durapatita , Osteogênese , Durapatita/farmacologia , Durapatita/química , Alicerces Teciduais/química , Biomimética , Hidrogéis/farmacologia , Colágeno/farmacologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...