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1.
Heliyon ; 10(16): e36481, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39253111

RESUMO

Taking into account the fluctuation of the growth rate on the left and right sides of the classic QGLF, a quadratic exponential quality gain-loss function (QGLF) is created based on the asymmetric QGLF. The two scenarios of non-normal distribution (triangular distribution) and truncated normal distribution of quality characteristic values are optimized using the quadratic exponential quality gain-loss process mean. Through the case study approaches, the empirical validity and applicability of the quadratic exponential QGLF model are thoroughly assessed, confirming its effectiveness in improving quality management practices.

2.
J Magn Reson Imaging ; 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39258494

RESUMO

BACKGROUND: Middle cerebral artery (MCA) plaques are a leading cause of ischemic stroke (IS). Plaque inflammation is crucial for plaque stability and urgently needs quantitative detection. PURPOSE: To explore the utility of Controlled Aliasing in Parallel Imaging Results in Higher Acceleration (CAIPIRINHA)-Dixon-Time-resolved angiography With Interleaved Stochastic Trajectories (TWIST) (CDT) dynamic contrast-enhanced MRI (DCE-MRI) for evaluating MCA culprit plaque inflammation changes over stroke time and with diabetes mellitus (DM). STUDY TYPE: Prospective. POPULATION: Ninety-four patients (51.6 ± 12.23 years, 32 females, 23 DM) with acute IS (AIS; N = 43) and non-acute IS (non-AIS; 14 days < stroke time ≤ 3 months; N = 51). FIELD STRENGTH/SEQUENCE: 3-T, CDT DCE-MRI and three-dimensional (3D) Sampling Perfection with Application optimized Contrast using different flip angle Evolution (3D-SPACE) T1-weighted imaging (T1WI). ASSESSMENT: Stroke time (from initial IS symptoms to MRI) and DM were registered. For 94 MCA culprit plaques, Ktrans from CDT DCE-MRI and enhancement ratio (ER) from 3D-SPACE T1WI were compared between groups with and without AIS and DM. STATISTICAL TESTS: Shapiro-Wilk test, Bland-Altman analysis, Passing and Bablok test, independent t-test, Mann-Whitney U test, Chi-squared test, Fisher's exact test, receiver operating characteristics (ROC) with the area under the curve (AUC), DeLong's test, and Spearman rank correlation test with the P-value significance level of 0.05. RESULTS: Ktrans and ER of MCA culprit plaques were significantly higher in AIS than non-AIS patients (Ktrans = 0.098 s-1 vs. 0.037 s-1; ER = 0.86 vs. 0.55). Ktrans showed better AUC for distinguishing AIS from non-AIS patients (0.87 vs. 0.75) and stronger negative correlation with stroke time than ER (r = -0.60 vs. -0.34). DM patients had significantly higher Ktrans and ER than non-DM patients in IS and AIS groups. DATA CONCLUSION: Imaging by CDT DCE-MRI may allow to quantitatively evaluate MCA culprit plaques over stroke time and DM. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

3.
bioRxiv ; 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39282346

RESUMO

Besides acting as an immunological shield, the N-glycans of SARS-CoV-2 are also critical for viral life cycle. As the S2 subunit of spike is highly conserved across beta-coronaviruses, we determined the functional significance of the five 'stem N-glycans' located in S2 between N1098-N1194. Studies were performed with 31 Asn-to-Gln mutants, beta-coronavirus virus-like particles and single-cycle viral replicons. Deletions of stem N-glycans enhanced S1 shedding from trimeric spike, reduced ACE2 binding and abolished syncytia formation. When three or more N-glycans were deleted, spike expression on cell surface and incorporation into virions was both reduced. Viral entry function was progressively lost upon deleting the N1098 glycan in combination with additional glycosite modifications. In addition to SARS-CoV-2, deleting stem N-glycans in SARS-CoV and MERS-CoV spike also prevented viral entry into target cells. These data suggest multiple functional roles for the stem N-glycans, and evolutionarily conserved properties for these complex carbohydrates across human beta-coronaviruses. Author Summary: Previous work shows that the N-linked glycans of SARS-CoV-2 are essential for viral life cycle. Few natural mutations have been observed in the S2-subunit of the viral spike glycoprotein in GISAID data, and mutations are absent in the five 'stem N-glycans' located between N1098-N1194. In the post-fusion spike structure these glycans lie equidistant, ~4 nm apart, suggesting functional significance. Upon testing the hypothesis that these glycans are critical for SARS-CoV-2 function, we noted multiple roles for the complex carbohydrates including regulation of S1-subunit shedding, spike expression on cells and virions, syncytial formation/cell-cell fusion and viral entry. Besides SARS-CoV-2, these glycans were also critical for other human beta-coronaviruses. Thus, these carbohydrates represent targets for the development of countermeasures against future outbreaks.

4.
Artigo em Inglês | MEDLINE | ID: mdl-39220211

RESUMO

Diffusion MRI (dMRI) streamline tractography, the gold-standard for in vivo estimation of white matter (WM) pathways in the brain, has long been considered as a product of WM microstructure. However, recent advances in tractography demonstrated that convolutional recurrent neural networks (CoRNN) trained with a teacher-student framework have the ability to learn to propagate streamlines directly from T1 and anatomical context. Training for this network has previously relied on high resolution dMRI. In this paper, we generalize the training mechanism to traditional clinical resolution data, which allows generalizability across sensitive and susceptible study populations. We train CoRNN on a small subset of the Baltimore Longitudinal Study of Aging (BLSA), which better resembles clinical scans. We define a metric, termed the epsilon ball seeding method, to compare T1 tractography and traditional diffusion tractography at the streamline level. We show that under this metric T1 tractography generated by CoRNN reproduces diffusion tractography with approximately three millimeters of error.

5.
Artigo em Inglês | MEDLINE | ID: mdl-39220623

RESUMO

Whole brain segmentation with magnetic resonance imaging (MRI) enables the non-invasive measurement of brain regions, including total intracranial volume (TICV) and posterior fossa volume (PFV). Enhancing the existing whole brain segmentation methodology to incorporate intracranial measurements offers a heightened level of comprehensiveness in the analysis of brain structures. Despite its potential, the task of generalizing deep learning techniques for intracranial measurements faces data availability constraints due to limited manually annotated atlases encompassing whole brain and TICV/PFV labels. In this paper, we enhancing the hierarchical transformer UNesT for whole brain segmentation to achieve segmenting whole brain with 133 classes and TICV/PFV simultaneously. To address the problem of data scarcity, the model is first pretrained on 4859 T1-weighted (T1w) 3D volumes sourced from 8 different sites. These volumes are processed through a multi-atlas segmentation pipeline for label generation, while TICV/PFV labels are unavailable. Subsequently, the model is finetuned with 45 T1w 3D volumes from Open Access Series Imaging Studies (OASIS) where both 133 whole brain classes and TICV/PFV labels are available. We evaluate our method with Dice similarity coefficients(DSC). We show that our model is able to conduct precise TICV/PFV estimation while maintaining the 132 brain regions performance at a comparable level. Code and trained model are available at: https://github.com/MASILab/UNesT/wholebrainSeg.

6.
BMC Infect Dis ; 24(1): 1015, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39304817

RESUMO

BACKGROUND: Serum (1,3)-ß-D-glucan (BDG) detection for diagnosis of Pneumocystis jirovecii pneumonia (PJP) in non-human immunodeficiency virus (HIV) immunocompromised patients lacks intensive care unit (ICU)-specific data. We aimed to assess its performance and determine the optimal cutoff for PJP in ICU population. METHODS: This retrospective study included critically ill non-HIV immunocompromised patients admitted to a medical ICU with suspected pneumonia, undergoing simultaneous microbiological testing for P. jirovecii on lower respiratory tract specimens and serum BDG. Confounders affecting BDG positivity were explored by multivariable logistic regression. Optimal cut-offs were derived from Youden's index for the entire cohort and subgroups stratified by confounders. Diagnostic performance of serum BDG was estimated at different cutoffs. RESULTS: Of 400 patients included, 42% were diagnosed with PJP and 58.3% had positive serum BDG. Serum BDG's area under the receiver operating characteristic curve was 0.90 (0.87-0.93). At manufacturer's 150 pg/ml cut-off, serum BDG had high sensitivity and negative predictive value (94%), but low specificity and positive predictive value (67%). Confounders associated with a positive serum BDG in PJP diagnosis included IVIG infusion within 3 days (odds ratio [OR] 9.24; 95% confidence interval [CI] 4.09-20.88, p < 0.001), other invasive fungal infections (OR 4.46; 95% CI 2.10-9.49, p < 0.001) and gram-negative bacteremia (OR 29.02; 95% CI 9.03-93.23, p < 0.001). The application of optimal BDG cut-off values determined by Youden's index (252 pg/ml, 390 pg/ml, and 202 pg/ml) specific for all patients and subgroups with or without confounders improved the specificity (79%, 74%, and 88%) and corresponding PPV (75%, 65%, and 85%), while maintaining reasonable sensitivity and NPV. CONCLUSIONS: Tailoring serum BDG cutoff specific to PJP and incorporating consideration of confounders could enhance serum BDG's diagnostic performance in the ICU settings.


Assuntos
Unidades de Terapia Intensiva , Pneumocystis carinii , Pneumonia por Pneumocystis , beta-Glucanas , Humanos , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/sangue , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , beta-Glucanas/sangue , Pneumocystis carinii/isolamento & purificação , Idoso , Hospedeiro Imunocomprometido , Proteoglicanas , Curva ROC , Sensibilidade e Especificidade , Estado Terminal , Adulto
8.
Genet Sel Evol ; 56(1): 60, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39227836

RESUMO

BACKGROUND: Accurate breed identification is essential for the conservation and sustainable use of indigenous farm animal genetic resources. In this study, we evaluated the phylogenetic relationships and genomic breed compositions of 13 sheep breeds using SNP and InDel data from whole genome sequencing. The breeds included 11 Chinese indigenous and 2 foreign commercial breeds. We compared different strategies for breed identification with respect to different marker types, i.e. SNPs, InDels, and a combination of SNPs and InDels (named SIs), different breed-informative marker detection methods, and different machine learning classification methods. RESULTS: Using WGS-based SNPs and InDels, we revealed the phylogenetic relationships between 11 Chinese indigenous and two foreign sheep breeds and quantified their purities through estimated genomic breed compositions. We found that the optimal strategy for identifying these breeds was the combination of DFI_union for breed-informative marker detection, which integrated the methods of Delta, Pairwise Wright's FST, and Informativeness for Assignment (namely DFI) by merging the breed-informative markers derived from the three methods, and KSR for breed assignment, which integrated the methods of K-Nearest Neighbor, Support Vector Machine, and Random Forest (namely KSR) by intersecting their results. Using SI markers improved the identification accuracy compared to using SNPs or InDels alone. We achieved accuracies over 97.5% when using at least the 1000 most breed-informative (MBI) SI markers and even 100% when using 5000 SI markers. CONCLUSIONS: Our results provide not only an important foundation for conservation of these Chinese local sheep breeds, but also general approaches for breed identification of indigenous farm animal breeds.


Assuntos
Cruzamento , Mutação INDEL , Polimorfismo de Nucleotídeo Único , Ovinos , Animais , Cruzamento/métodos , China , Genética Populacional/métodos , Filogenia , Ovinos/genética , Sequenciamento Completo do Genoma/métodos , Sequenciamento Completo do Genoma/veterinária
9.
Nat Commun ; 15(1): 7783, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39237589

RESUMO

The artificial photocatalytic synthesis based on graphitic carbon nitride (g-C3N4) for H2O2 production is evolving rapidly. However, the simultaneous production of high-value products at electron and hole sites remains a great challenge. Here, we use transformable potassium iodide to obtain semi-crystalline g-C3N4 integrated with the I-/I3- redox shuttle mediators for efficient generation of H2O2 and benzaldehyde. The system demonstrates a prominent catalytic efficiency, with a benzaldehyde yield of 0.78 mol g-1 h-1 and an H2O2 yield of 62.52 mmol g-1 h-1. Such a constructed system can achieve an impressive 96.25% catalytic selectivity for 2e- oxygen reduction, surpassing previously reported systems. The mechanism study reveals that the strong crystal electric field from iodized salt enhances photo-generated charge carrier separation. The I-/I3- redox mediators significantly boost charge migration and continuous electron and proton supply for dual-channel catalytic synthesis. This groundbreaking work in photocatalytic co-production opens neoteric avenues for high-value synthesis.

10.
Environ Pollut ; : 124963, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39278555

RESUMO

Groundwater pollution from valley type landfills is concerning, and natural attenuation by contaminants is increasingly relied upon. However, the reliability of natural attenuation in such complex sites has been called into question due to incomplete understanding of their attenuation mechanisms. Therefore, we conducted field investigations, monitoring analyses, mathematical statistics, and machine learning techniques to elucidate the natural attenuation mechanisms of pollutants within bedrock fissures at a prototypical valley type landfill located in the east Yanshan Mountains, China. Our results indicate that 50% of the monitored indicators showed extreme pollution in bedrock fissure aquifers, due to seepage from the valley type landfill site. Ammonia nitrogen, arsenic, cadmium, lead, iron, manganese, and mercury were among the contaminants that could pose serious risks to human health. Pollutant concentrations in bedrock fissure aquifers were lower during the rainy season compared to the dry season as the aquifer was rapidly recharged by strong rainfall runoff. The initial concentration of bedrock fissure water generally increased during the flow through the landfill. However, significant natural attenuation of total dissolved solids, oxygen consumption, ammonia, cadmium, and lead occurred after passing through the landfill (p<0.05), with attenuation coefficients of 0.0041 m-1, 2.56×E-5m-2, 4.18×E-5m-2、0.0015 m-0.99, and 6.83×E-33m-12.49, respectively. The driving mechanisms for natural attenuation include physical migration, leaching, microbiological degradation, and adsorption, primarily occurring within 600-650 m downstream of the landfill boundary. This study makes fundamental contribution to the understanding of the migration and natural attenuation process of leachate pollutants in bedrock fissure aquifer, which will provide a scientific basis for implementation of natural attenuation strategies in complex site remediation. Future research should examine more precise evidence of natural attenuation feasibility in complex sites in conjunction with monitoring networks.

11.
BMC Infect Dis ; 24(1): 967, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39271977

RESUMO

BACKGROUND: There are multiple antibiotic regimens for the treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) in clinical practice. We conducted this meta-analysis to compare the efficacy and safety of cefiderocol-based regimens and colistin-based regimens in the treatment of CRAB infections. METHODS: Two authors independently searched the PubMed, Web of Science, Embase, and Cochrane databases from their establishment to April 15, 2024, to search for randomized controlled trials (RCTs) or cohort studies, and compared the clinical efficacy and safety of cefiderocol-based regimens and colistin-based regimens in the treatment of CRAB infections. The Newcastle Ottawa Scale (NOS) checklist was used to evaluate the quality of the included studies. The primary outcome was all-cause mortality, and subgroup analysis was conducted on the basis of the site of infection and the risk of bias in the studies. Trial sequential analysis (TSA) was then conducted. RESULTS: Six observational studies were included, with 251 cases in the cefiderocol-based group and 372 cases in the colistin-based group. Compared to the colistin-based group, the cefiderocol-based group had lower all-cause mortality (RR = 0.71, 95% CI: 0.54-0.92, P = 0.01) and 30-day mortality (RR = 0.64, 95% CI: 0.43-0.95, P = 0.03). However, for the 14-day and 28-day mortality rates, there was no statistically significant difference between two groups. According to the subgroup analysis, among patients with bloodstream infection (BSI), the cefiderocol-based group had lower all-cause mortality, but it did not reduce the mortality of ventilator-associated pneumonia (VAP) patients. The result of TSA showed that our conclusions are reliable. There was no significant statistical difference in the microbiological cure rate, clinical cure rate, or duration of hospitalization. In addition, the cefiderocol-based group did not have an increased incidence of acute kidney injury (AKI). CONCLUSIONS: Compared with the colistin-based regimens, the cefiderocol-based regimens were significantly associated with a lower risk of mortality in CRAB-infected patients, especially for patients with BSI. However, they did not show any advantages in terms of the clinical cure rate or microbiological cure rate, nor did they reduce the incidence of AKI. PROSPERO REGISTRATION NUMBER: CRD42023487213.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Antibacterianos , Carbapenêmicos , Cefiderocol , Colistina , Colistina/uso terapêutico , Colistina/farmacologia , Acinetobacter baumannii/efeitos dos fármacos , Humanos , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/mortalidade , Infecções por Acinetobacter/microbiologia , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Carbapenêmicos/uso terapêutico , Carbapenêmicos/farmacologia , Cefalosporinas/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Resultado do Tratamento
12.
J Am Chem Soc ; 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39276081

RESUMO

Creating nanomachines capable of precisely capturing, organizing, and regulating the activity of target biomolecules holds profound significance for advancing nanotechnology and therapeutics. Here, we develop a multistage reconfigurable DNA nanocage that can enclose and modulate proteins through multivalent interactions, activated by specific molecular signals. By strategically designing and manipulating the strut architecture of the DNA nanocages, we can achieve precise control over their reconfiguration among pyramid, square, and linear branch shapes. Additionally, we demonstrated its ability to capture thrombin and effectively inhibit its coagulation activity by incorporating two thrombin-targeting aptamers into the designed arms of the DNA nanocage. The activity of thrombin can be recovered by rearranging the conformation of the DNA nanocage and exposing the protein, thereby activating the coagulation process. This approach enriches the design toolbox for dynamic nanomachines and inspires a new strategy for protein encapsulation and regulation with potential future therapeutic applications.

13.
Materials (Basel) ; 17(17)2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39274775

RESUMO

For materials with high stacking fault energy (SFE), such as aluminum alloys, dynamic recovery (DRV) and dynamic recrystallization (DRX) are essential softening mechanisms during plastic deformation, which lead to the continuous generation and refinement of newborn subgrains (2° ˂ misorientation angle ˂ 15°). The present work investigates the influence of compression parameters on the evolution of the substructures for a 1050 aluminum alloy at elevated temperatures. The alloy microstructure was investigated under deformation temperatures ranging from 300 °C to 500 °C and strain rates from 0.01 to 0.1 s-1, respectively. A well-defined substructure and subsequent subgrain refinement provided indication of the evolution laws of the substructure under high-temperature compression. Corresponding experimental data on the average subgrain size under various compression conditions were obtained. Two different independent average subgrain size evolution models (empirical and substructure-based) were used and applied with several internal state variables. The substructure model employed physical variables to simulate subgrain refinement and thermal coarsening during deformation, incorporating a corresponding dislocation density evolution model. The correlation coefficient (R) and root mean square error (RMSE) of the substructure-based model were calculated to be 0.98 and 5.7%, respectively. These models can provide good estimates of the average subgrain size, with both predictions and experiments reproducing the expected subgrain size evolution using physically meaningful variables during continuous deformation.

14.
Neurosci Lett ; 842: 137958, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39218292

RESUMO

BACKGROUND: 40 Hz light flickering has shown promise as a non-invasive therapeutic approach for alleviating both pathological features and cognitive impairments in Alzheimer's disease (AD) model mice and AD patients. Additionally, vision may influence olfactory function through cross-modal sensory interactions. OBJECTIVE: To investigate the impact of 40 Hz light flickering on olfactory behavior in AD model mice and to explore the underlying mechanisms of this intervention. METHODS: We used immunofluorescence techniques to observe the activation of the olfactory bulb (OB) in C57BL/6J mice under 40 Hz light flickering. A buried food test was conducted to evaluate olfactory behavior in AD mice. Additionally, RNA sequencing technology was employed to detect transcriptional alterations in the OBs of AD mice following light stimulation. RESULTS: 40 Hz light flickering was found to effectively activate the OB. This stimulation led to enhanced olfactory behavior and did not alter P-tau protein mRNA levels within the OBs of AD mice. RNA sequencing revealed significant transcriptional changes in the OBs under flickering, particularly related to immune responses. CONCLUSION: Vision can influence olfactory function through cross-modal sensory interactions in rodent models. 40 Hz light stimulation improved olfactory performance in AD mice. However, the improvement in olfaction in AD mice is not related to changes in P-tau mRNA levels. Instead, it may be associated with an altered immune response, providing a scientific basis for the clinical treatment of olfactory disorders in Alzheimer's disease.

15.
Nat Ecol Evol ; 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39284921

RESUMO

The onset of sedentism on the Tibetan Plateau is often presumed to be associated with the dispersal of agriculture or farmers from archaeological sites located in the low elevation margins of the plateau. Previous studies of the plateau assumed that all foragers were probably mobile, but few systematic excavations at forager sites have been conducted to inform us about their settlement patterns. Here we report the world's highest elevation sedentary way of living exhibited by the Mabu Co site at 4,446 metres above sea level, deep in the interior of the Tibetan Plateau 4,400-4,000 years ago. Our interdisciplinary study indicates that the site was occupied by Indigenous inhabitants of the plateau, representing the earliest known DNA evidence of foragers who predominantly harbour the southern plateau ancestry. The evidence shows that they had a sedentary lifestyle primarily supported by fishing at nearby lakes, supplemented by mammal and bird hunting, as well as small-scale exchanges of millet and rice crops.

16.
Sci Rep ; 14(1): 21497, 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39277691

RESUMO

The miniaturization of antennas is crucial as it improves the integration of wireless communication system. In order to achieve miniaturization of antennas, a performance-constrained multi-objective optimization method (PCMOM) considering the size and return loss is proposed. In the PCMOM method, an optimization strategy based on a multi-port network model is introduced, enabling the formation of antennas with various structures. Furthermore, we integrate the constraint of return loss performance into the non-dominated sorting genetic algorithm II (NSGA-II), eliminating solutions that do not meet performance requirements. Three pixel antennas are designed using the PCMOM method and two of them are fabricated. Experimental results demonstrate that the proposed PCMOM method can effectively address the complex trade-off issues in antenna miniaturization design.

17.
Bioresour Technol ; 413: 131464, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39278364

RESUMO

The explosive and biorefractory nature of nitrocellulose (NC) poses major risks to both humans and the environment. Expanding the range of microorganisms capable of degrading NC is essential, though the most effective known microorganisms, Desulfovibrio genera and Fusarium solani, achieve degradation rates of 5%-25%. Here, a novel strain, Rhodococcus pyridinivorans LZ1 was isolated, demonstrating the ability to degrade NC, with its growth potentially enhanced by the presence of NC. The degradation process was monitored by assessing changes in nitrate, nitrite, and ammonium. Notably, the -OH strength of NC increased over time, whereas the energetic functional groups (-NO2 and O-NO2) diminished. Furthermore, the presence of NC enhanced nitrate esterase activity 1-2-fold, indicating that ammonification was the primary pathway for NC biodegradation. By converting the nitrate ester of NC into hydroxyl, R. pyridinivorans LZ1 mitigates the harmful effects of NC, offering a promising approach for the treatment of NC waste and wastewater.

18.
Mol Med ; 30(1): 152, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39289602

RESUMO

VEXAS syndrome, an uncommon yet severe autoimmune disorder stemming from a mutation in the UBA1 gene, is the focus of this paper. The overview encompasses its discovery, epidemiological traits, genetic underpinnings, and clinical presentations. Delving into whether distinct genotypes yield varied clinical phenotypes in VEXAS patients, and the consequent adjustment of treatment strategies based on genotypic and clinical profiles necessitates thorough exploration within the clinical realm. Additionally, the current therapeutic landscape and future outlook are examined, with particular attention to the potential therapeutic roles of IL-6 inhibitors and JAK inhibitors, alongside an elucidation of prevailing limitations and avenues for further research. This study contributes essential theoretical groundwork and clinical insights for both diagnosing and managing VEXAS syndrome.


Assuntos
Interleucina-6 , Inibidores de Janus Quinases , Enzimas Ativadoras de Ubiquitina , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Inibidores de Janus Quinases/uso terapêutico , Enzimas Ativadoras de Ubiquitina/genética , Enzimas Ativadoras de Ubiquitina/antagonistas & inibidores , Mutação , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/genética , Doenças Autoimunes/diagnóstico
19.
Theranostics ; 14(13): 5123-5140, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39267775

RESUMO

Background: Vasculogenic mimicry (VM) induced by Epstein-Barr virus (EBV) infection plays an important role in resistance to anti-vascular endothelial growth factor (VEGF) therapy in EBV-associated epithelial cancers; however, the interaction between VM and the immune microenvironment has not been systematically investigated. Methods: IHC and multiplex IHC analysis the relationships among tumour-associated macrophage (TAM), VM and EBV infection in EBV-associated epithelial cancer biopsies. In vitro and in vivo evidence using CRISPR-Cas9 system engineered EBV-infected epithelial cancer cells and mouse models support functional role and mechanism for M2c-like macrophages in the VM formation. The prediction of VM in the effectiveness of anti-angiogenic agent was analysed using clinical datasets. Results: EBV-associated epithelial cancer biopsies revealed that infiltration of the TAM surrounding the VM is closely associated with EBV infection. AKT/mTOR/HIF-1α pathway in EBV-infected epithelial cancer cells control the secretion of CCL5 and CSF-1, enabling the recruitment of monocytes and their differentiation into M2c macrophages which promote VM formation by MMP9. Combination of anti-angiogenesis agents and HIF-1α inhibitor caused marked decreases in CD31-positive micro-vessels, VM, and M2c-like macrophages. VM scores can be used as biomarkers to predict the efficacy of anti-angiogenic agent therapy in EBV-associated epithelial cancers. Conclusions: Our findings define a secretory cross-talk between tumour cells and the immune microenvironment in EBV-associated epithelial cancer, revealing an unexpected role of EBV in epithelial cancer cells, controlling VM formation via M2c-like macrophages.


Assuntos
Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Neovascularização Patológica , Microambiente Tumoral , Macrófagos Associados a Tumor , Humanos , Microambiente Tumoral/imunologia , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/metabolismo , Animais , Neovascularização Patológica/metabolismo , Neovascularização Patológica/virologia , Camundongos , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/imunologia , Linhagem Celular Tumoral , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Quimiocina CCL5/metabolismo , Inibidores da Angiogênese/farmacologia , Metaloproteinase 9 da Matriz/metabolismo , Feminino
20.
J Med Imaging (Bellingham) ; 11(5): 054003, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39234425

RESUMO

Purpose: Segmentation is essential for tissue quantification and characterization in studies of aging and age-related and metabolic diseases and the development of imaging biomarkers. We propose a multi-method and multi-atlas methodology for automated segmentation of functional muscle groups in three-dimensional (3D) thigh magnetic resonance images. These groups lie anatomically adjacent to each other, rendering their manual delineation a challenging and time-consuming task. Approach: We introduce a framework for automated segmentation of the four main functional muscle groups of the thigh, gracilis, hamstring, quadriceps femoris, and sartorius, using chemical shift encoded water-fat magnetic resonance imaging (CSE-MRI). We propose fusing anatomical mappings from multiple deformable models with 3D deep learning model-based segmentation. This approach leverages the generalizability of multi-atlas segmentation (MAS) and accuracy of deep networks, hence enabling accurate assessment of volume and fat content of muscle groups. Results: For segmentation performance evaluation, we calculated the Dice similarity coefficient (DSC) and Hausdorff distance 95th percentile (HD-95). We evaluated the proposed framework, its variants, and baseline methods on 15 healthy subjects by threefold cross-validation and tested on four patients. Fusion of multiple atlases, deformable registration models, and deep learning segmentation produced the top performance with an average DSC of 0.859 and HD-95 of 8.34 over all muscles. Conclusions: Fusion of multiple anatomical mappings from multiple MAS techniques enriches the template set and improves the segmentation accuracy. Additional fusion with deep network decisions applied to the subject space offers complementary information. The proposed approach can produce accurate segmentation of individual muscle groups in 3D thigh MRI scans.

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