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BACKGROUND: Cutaneous metastases (CMs) are a manifestation of advanced cancer and can be treated with oncolytic immunotherapy. Laboratory studies suggest radiotherapy (RT) may facilitate response to immunotherapy. We hypothesized that oncolytic immunotherapy with talimogene lapherparepvec (T-VEC, an oncolytic immunotherapy that expresses granulocyte-macrophage colony stimulating factor) and RT would produce response in non-targeted metastases. METHODS: A randomized phase 2 trial of T-VEC+/-RT was conducted. Eligible patients had ≥1 CM from a solid tumor amenable to T-VEC and RT and another measurable metastasis. Tumor and overall response was assessed using modified World Health Organization (mWHO) criteria. Adverse events (AEs) and quality of life (QOL) were characterized using CTCAE v4.0 and Skindex-16, respectively. Correlative analyses of tumor genomics and the immune system were performed. RESULTS: 19 patients were randomized to receive T-VEC (n = 9) or T-VEC+RT (n = 10). One patient in each arm demonstrated complete response in the largest non-targeted metastasis. The trial was closed after the first stage of enrollment because of no overall mWHO responses, slow accrual and the COVID-19 pandemic. AEs were consistent with prior reports of T-VEC. Skin related QOL was poor before and after treatment. Median progression free survival was 1.2 and 2.5 months in the T-VEC and T-VEC+RT arms; median overall survival was 4.9 and 17.3 months in the T-VEC and T-VEC+RT arms. Analyses of peripheral blood cells and cytokines demonstrated responders exhibited several outlying lymphocyte and cytokine parameters. CONCLUSIONS: Low overall response rate, slow accrual, and the COVID-19 pandemic led to closure of this trial. Responses in non-injected and non-irradiated metastases were infrequent.
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BACKGROUND AND OBJECTIVE: Ambulatory surgery centers (ASCs) are increasingly common venues for same-day neurosurgical procedures, allowing for cost-effective, high-quality patient care. We present the first and largest series of patients undergoing diagnostic cerebral angiography at an ASC to demonstrate the effectiveness, safety, and efficiency of outpatient endovascular care. METHODS: We retrospectively reviewed data for consecutive patients who underwent diagnostic cerebral angiography at our ASC between January 1, 2024, and May 29, 2024. Data collected included vascular access approach, procedural duration, turnover time, and periprocedural complications. Using a standardized 2-week postprocedural survey, patients were asked to provide comments and rate their subjective satisfaction from a 1 to 5 scale, with "5" being completely satisfied. All cases were performed with a physician team comprising 1 attending neuroendovascular neurosurgery and 1 neuroendovascular fellow present. Fentanyl and midazolam were administered for conscious sedation in all cases. RESULTS: Among the 67 patients included in this series, the mean procedural duration was 29.4 ± 8.6 minutes. The mean turnover time was 13.7 ± 3.6 minutes. Between transradial (46 of 67 [68.7%]) and transfemoral (21 of 67 [31.3%]) access site approaches, there were no statistically significant differences in mean procedural duration (29.4 ± 8.0 vs 29.2 ± 9.9 minutes, respectively; P = .72) or turnover time (14.0 ± 3.9 vs 12.9 ± 2.8 minutes, respectively; P = .4). No complications occurred periprocedurally or within the 2-week follow-up period. A total of 48 (71.6%) of 67 patients responded to the postprocedural survey, all of whom unanimously reported a score of "5." CONCLUSION: We found that diagnostic cerebral angiography performed at our ASC was safe and effective for patient care. In addition, all survey respondents (71.6% of those provided the survey) reported highest levels of satisfaction. The integration of neuroendovascular procedures into ASCs potentially offers a cost-effective and highly efficient option in an evolving economic landscape.
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BACKGROUND: T2*BOLD is based on myocardial deoxyhemoglobin content to reflect the state of myocardial oxygenation. Quantitative flow ratio is a tool for assessing coronary blood flow based on invasive coronary angiography. PURPOSE: This study aimed to evaluate the correlation between T2*BOLD and QFR in the diagnosis of stenotic coronary arteries in patients with multi-vessel coronary artery disease. METHODS: Fifty patients with MVCAD with at least 1 significant coronary artery stenosis (diameter stenosis > 50%) and 21 healthy control subjects underwent coronary angiography combined with QFR measurements and cardiovascular magnetic resonance (CMR). QFR ≤ 0.80 was considered to indicate the presence of hemodynamic obstruction. RESULTS: Totally 60 (54%) obstructive vessels had hemodynamic change. Between stenotic coronary arteries (QFR ≤ 0.8) and normal vessels, T2*BOLD showed AUCs of 0.97, 0.69, and 0.91 for left anterior descending (LAD), left circumflex (LCX) and right coronary (RCA) arteries and PI displayed AUCs of 0.89, 0.77 and 0.90 (all p > 0.05, except for LAD). The AUCs of T2*BOLD between stenotic coronary arteries (QFR > 0.8) and normal vessels were 0.86, 0.72, and 0.85 for LAD, LCX and RCA; while, PI showed AUCs of 0.93, 0.86, and 0.88, respectively (p > 0.05). Moreover, T2*BOLD displayed AUCs of 0.96, 0.74, and 0.91 for coronary arteries as before between coronary arteries with stenosis (QFR ≤ 0.8 and > 0.8), but the mean PI of LAD, LCX and RCA showed no significant differences between them. CONCLUSION: T2* BOLD and QFR have good correlation in diagnosing stenotic coronary arteries with hemodynamic changes in patients with stable multi-vessel CAD. T2* BOLD is superior to semi-quantitative perfusion imaging in analyzing myocardial ischemia without stress.
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Angiografia Coronária , Estenose Coronária , Humanos , Masculino , Feminino , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/fisiopatologia , Pessoa de Meia-Idade , Angiografia Coronária/métodos , Idoso , Estudos de Casos e Controles , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/fisiopatologia , Circulação Coronária , Imageamento por Ressonância Magnética/métodosRESUMO
Mycorrhizal associations are key mutualisms that shape the structure of forest communities and multiple ecosystem functions. However, we lack a framework for predicting the varying dominance of distinct mycorrhizal associations in an integrated proxy of multifunctionality across ecosystems. Here, we used the datasets containing diversity of mycorrhizal associations and 18 ecosystem processes related to supporting, provisioning, and regulating services to examine how the dominance of ectomycorrhiza (EcM) associations affects ecosystem multifunctionality in subtropical mountain forests in Southwest China. Meanwhile, we synthesized the prevalence of EcM-dominant effects on ecosystem functioning in forest biomes. Our results demonstrated that elevation significantly modified the distributions of EcM trees and fungal dominance, which in turn influenced multiple functions simultaneously. Multifunctionality increased with increasing proportion of EcM associations, supporting the ectomycorrhizal-dominance hypothesis. Meanwhile, we observed that the impacts of EcM dominance on individual ecosystem functions exhibited different relationships among forest biomes. Our findings highlight the importance of ectomycorrhizal dominance in regulating multifunctionality in subtropical forests. However, this ectomycorrhizal feedback in shaping ecosystem functions cannot necessarily be generalized across forests. Therefore, we argue that the predictions for ecosystem multifunctionality in response to the shifts of mycorrhizal composition could vary across space and time.
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Florestas , Micorrizas , Micorrizas/fisiologia , Clima Tropical , China , Ecossistema , Modelos Biológicos , Árvores/microbiologia , Árvores/fisiologia , Biodiversidade , AltitudeRESUMO
OBJECTIVES: Endocardial trabeculae undergo varicose changes and hyperplasia in response to hemodynamic influences and are a variable phenotype reflecting changes in disease. Fractal analysis has been used to analyze the complexity of endocardial trabeculae in a variety of cardiomyopathies. The aim of this paper was to quantify the myocardial trabecular complexity through fractal analysis and to investigate its predictive value for the diagnosis of heart failure with preserved ejection fraction (HFpEF) in patients with multivessel coronary artery disease (CAD). METHODS: The retrospective study population consisted of 97 patients with multivessel CAD, 39 of them were diagnosed with HFpEF, while 46 healthy volunteers were recruited as controls. Fractal dimension (FD) was obtained through fractal analysis of endocardial trabeculae on LV short-axis cine images. Logistic regression analyses were used to confirm the predictors and compare different prediction models. RESULTS: Mean basal FD was significantly higher in patients with HFpEF than in patients without HFpEF or in the healthy group (median: 1.289; IQR: 0.078; p < 0.05). Mean basal FD was also a significant independent predictor in univariate and multivariate logistic regression (OR: 1.107 and 1.043, p < 0.05). Furthermore, adding FD to the prediction model improved the calibration and accuracy of the model (c-index: 0.806). CONCLUSION: The left ventricular FD obtained with fractal analysis can reflect the complexity of myocardial trabeculae and has an independent predictive value for the diagnosis of HFpEF in patients with multivessel CAD. Including FD into the diagnostic model can help improve the diagnosis. CRITICAL RELEVANCE STATEMENT: Differences show in the complexity of endocardial trabeculae in multivessel coronary artery disease patients, and obtaining fractal dimensions (FD) by fractal analysis can help identify heart failure with preserved ejection fraction (HFpEF) patients. KEY POINTS: The complexity of myocardial trabeculae differs among patients with multivessel coronary artery disease. Left ventricular fractal dimensions can reflect the complexity of the myocardial trabecular. Fractal dimensions have predictive value for the diagnosis of heart failure with preserved ejection fraction.
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BACKGROUND: Coronary artery wall contrast enhancement (CE) has been applied to non-invasive visualization of changes to the coronary artery wall in systemic lupus erythematosus (SLE). This study investigated the feasibility of quantifying CE to detect coronary involvement in IgG4-related disease (IgG4-RD), as well as the influence on disease activity assessment. METHODS: A total of 93 subjects (31 IgG4-RD; 29 SLE; 33 controls) were recruited in the study. Coronary artery wall imaging was performed in a 3.0 T MRI scanner. Serological markers and IgG4-RD Responder Index (IgG4-RD-RI) scores were collected for correlation analysis. RESULTS: Coronary wall CE was observed in 29 (94 %) IgG4-RD patients and 22 (76 %) SLE patients. Contrast-to-noise ratio (CNR) and total CE area were significantly higher in patient groups compared to controls (CNR: 6.1 ± 2.7 [IgG4-RD] v. 4.2 ± 2.3 [SLE] v. 1.9 ± 1.5 [control], P < 0.001; Total CE area: 3.0 [3.0-6.6] v. 1.7 [1.5-2.6] v. 0.3 [0.3-0.9], P < 0.001). In the IgG4-RD group, CNR and total CE area were correlated with the RI (CNR: r = 0.55, P = 0.002; total CE area: r = 0.39, P = 0.031). RI´ scored considering coronary involvement by CE, differed significantly from RI scored without consideration of CE (RI v. RI´: 15 ± 6 v. 16 ± 6, P < 0.001). CONCLUSIONS: Visualization and quantification of CMR coronary CE by CNR and total CE area could be utilized to detect subclinical and clinical coronary wall involvement, which is prevalent in IgG4-RD. The potential inclusion of small and medium-sized vessel involvements in the assessment of disease activity in IgG4-RD is worthy of further investigation.
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Chinese Assam tea (Camellia sinensis var. assamica) is an important tea crop with a long history of cultivation in Yunnan, China. Despite its potential value as a genetic resource, its genetic diversity and domestication/breeding history remain unclear. To address this issue, we genotyped 469 ancient tea plant trees representing 26 C. sinensis var. assamica populations, plus two of its wild relatives (six and three populations of C. taliensis and C. crassicolumna, respectively) using 16 nuclear microsatellite loci. Results showed that Chinese Assam tea has a relatively high, but comparatively lower gene diversity (HS = 0.638) than the wild relative C. crassicolumna (HS = 0.658). Clustering in STRUCTURE indicated that Chinese Assam tea and its two wild relatives formed distinct genetic groups, with considerable interspecific introgression. The Chinese Assam tea accessions clustered into three gene pools, corresponding well with their geographic distribution. However, NewHybrids analysis indicated that 68.48% of ancient Chinese Assam tea plants from Xishuangbanna were genetic intermediates between the Puer and Lincang gene pools. In addition, 10% of the ancient Chinese Assam tea individuals were found to be hybrids between Chinese Assam tea and C. taliensis. Our results suggest that Chinese Assam tea was domesticated separately in three gene pools (Puer, Lincang and Xishuangbanna) in the Mekong River valley and that the hybrids were subsequently selected during the domestication process. Although the domestication history of Chinese Assam tea in southwestern Yunnan remains complex, our results will help to identify valuable genetic resources that may be useful in future tea breeding programs.
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The different electrolyte conditions, e.g., pH value, for driving efficient HER and OER are one of the major issues hindering the aim for electrocatalytic water splitting in a high efficiency. In this regard, seeking durable and active HER electrocatalysts to align the alkaline conditions of the OER is a promising solution. However, the success in this strategy will depend on a fundamental understanding about the HER mechanism at the atomic scale. In this work, we have provided thorough understanding for the electrochemical HER mechanisms in KOH over Ni- and Co-based hollow pyrite microspheres by in operando X-ray spectroscopies and DFT calculations, including NiS2, CoS2, and Ni0.5Co0.5S2. We discovered that the Ni sites in hollow NiS2 microspheres were very stable and inert, while the Co sites in hollow CoS2 microspheres underwent reduction and generated Co metallic crystal domains under HER. The generation of Co metallic sites would further deactivate H2 evolution due to the large hydrogen desorption free energy (-1.73 eV). In contrast, the neighboring Ni and Co sites in hollow Ni0.5Co0.5S2 microspheres exhibited the electronic interaction to elevate the reactivity of Ni and facilitate the stability of Co without structure or surface degradation. The energy barrier in H2O adsorption/dissociation was only 0.73 eV, followed by 0.06 eV for hydrogen desorption over the Ni0.5Co0.5S2 surface, revealing Ni0.5Co0.5S2 as a HER electrocatalyst with higher durability and activity than NiS2 and CoS2 in the alkaline medium due to the synergy of neighboring Ni and Co sites. We believe that the findings in our work offer a guidance toward future catalyst design.
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Niche convergence or conservatism have been proposed as essential mechanisms underlying elevational plant community assembly in tropical mountain ecosystems. Subtropical mountains, compared to tropical mountains, are likely to be shaped by a mixing of different geographic affinities of species and remain somehow unclear. Here, we used 31 0.1-ha permanent plots distributed in subtropical forests on the eastern and western aspects of the Gaoligong Mountains, southwest China between 1498 m and 3204 m a.sl. to evaluate how niche-based and biogeographic processes shape tree community assembly along elevational gradients. We analyzed the elevational patterns of taxonomic, phylogenetic and functional diversity, as well as of individual traits, and assessed the relative importance of environmental effects on these diversity measures. We then classified tree species as being either tropical affiliated or temperate affiliated and estimated their contribution to the composition of biogeographic affinities. Species richness decreased with elevation, and species composition showed apparent turnover across the aspects and elevations. Most traits exhibited convergent patterns across the entire elevational gradient. Phylogenetic and functional diversity showed opposing patterns, with phylogenetic diversity increasing and functional diversity decreasing with elevation. Soil nutrients, especially phosphorus and nitrogen, appeared to be the main abiotic variables driving the elevational diversity patterns. Communities at lower elevations were occupied by tropical genera, while highlands contained species of tropical and temperate biogeographic affinities. Moreover, the high phylogenetic diversity at high elevations were likely due to differences in evolutionary history between temperate and tropical species. Our results highlight the importance of niche convergence of tropical species and the legacy of biogeographic history on the composition and structure of subtropical mountain forests. Furthermore, limited soil phosphorus caused traits divergence and the partitioning for different forms of phosphorus may explain the high biodiversity found in phosphorus-limited subtropical forests.
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Altitude , Biodiversidade , Florestas , Árvores , China , Filogenia , Ecossistema , Clima TropicalRESUMO
The cool temperate origin of gymnosperm Taxus species in East Asia is specifically diverse and widespread. Certain lineages have managed to extend their distribution further south to subtropical and tropical islands such as Taiwan and the Philippines. To address questions including whether these insular lineages, recently identified as T. phytonii, have become genetically distinct from each other and from their continental relatives, and when and how they colonized their residing islands, we sampled over 11 populations, covering 179 Taxus individuals from Taiwan and the Philippines. Using four cpDNA and one nuclear marker, we showed in population genetic and genealogical analyses that the two insular lineages were genetically distinct from each other and also from other continental Taxus and that they represented each other's closest relative. Estimated with the coalescent-based multi-type tree (MTT) analyses, we inferred an origin of Taiwanese T. phytonii more ancient than 2.49 Mya and that of Philippine T. phytonii more ancient than 1.08 Mya. In addition, the divergence demographic history revealed by both MTT and isolation with migration (IM) analyses indicated the presence of recent post-split migrations from a continental taxon, T. mairei, to Taiwanese T. phytonii, as well as from Taiwanese T. phytonii to Philippine T. phytonii. Overall, this study suggests Taiwan as a stepping stone through which the temperate-origin yew trees can extend their distributions to tropical regions such as the Philippines.
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In situ cyclized polyacrylonitrile (CPAN) is developed to replace n-type metal oxide semiconductors (TiO2 or SnO2) as an electron selective layer (ESL) for highly efficient and stable n-i-p perovskite solar cells (PSCs). The CPAN layer is fabricated via facile in situ cyclization reaction of polyacrylonitrile (PAN) coated on a conducting glass substrate. The CPAN layer is robust and insoluble in common solvents, and possesses n-type semiconductor properties with a high electron mobility of 4.13×10-3â cm2 V-1 s-1. With the CPAN as an ESL, the PSC affords a power conversion efficiency (PCE) of 23.12 %, which is the highest for the n-i-p PSCs with organic ESLs. Moreover, the device with the CPAN layer holds superior operational stability, maintaining over 90 % of their initial efficiency after 500â h continuous light soaking. These results confirm that the CPAN layer would be a desirable low-cost and efficient ESL for n-i-p PSCs and other photoelectronic devices with high performance and stability.
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PURPOSE: Locally advanced, unresectable basal cell carcinoma (LA BCC) can be treated with radiation therapy (RT), but locoregional control (LRC) rates are unsatisfactory. Vismodegib is a hedgehog pathway inhibitor (HPI) active in BCC that may radiosensitize BCC. We evaluated the combination of vismodegib and RT for patients with LA BCC. METHODS: In this multicenter, single-arm, phase II study, patients with unresectable LA BCC received 12 weeks of induction vismodegib, followed by 7 weeks of concurrent vismodegib and RT. The primary end point was LRC rate at 1 year after the end of treatment. Secondary end points included objective response, progression-free survival (PFS), overall survival (OS), safety, and patient-reported quality of life (PRQOL). RESULTS: Twenty-four patients received vismodegib; five were unable to complete 12 weeks of induction therapy. LRC was achieved in 91% (95% CI, 68 to 98) of patients at 1 year. The response rate was 63% (95% CI, 38 to 84) after induction vismodegib and 83% (95% CI, 59 to 96) after concurrent vismodegib and RT. With a median follow-up of 5.7 years, 1-year PFS and OS rates were 100% and 96%, and at 5 years PFS and OS rates were 78% and 83%, respectively. Distant metastasis or BCC-related death has not been observed. The most frequent treatment-related adverse events (AEs) were dysgeusia, fatigue, and myalgias occurring in 83%, 75%, and 75% of patients. No grade 4 to 5 treatment-related AEs occurred. PRQOL demonstrated clinically meaningful improvements in all subscales, with emotions and functioning improvements persisting for a year after the end of treatment. CONCLUSION: In patients with unresectable LA BCC, the combination of vismodegib and RT yielded high rates of LRC and PFS and durable improvements in PRQOL.
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Anilidas , Carcinoma Basocelular , Piridinas , Neoplasias Cutâneas , Humanos , Anilidas/uso terapêutico , Anilidas/efeitos adversos , Anilidas/administração & dosagem , Piridinas/uso terapêutico , Piridinas/efeitos adversos , Piridinas/administração & dosagem , Carcinoma Basocelular/patologia , Carcinoma Basocelular/tratamento farmacológico , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/radioterapia , Neoplasias Cutâneas/mortalidade , Idoso de 80 Anos ou mais , Qualidade de Vida , Adulto , Quimiorradioterapia/efeitos adversos , Intervalo Livre de ProgressãoRESUMO
BACKGROUND: The safety and efficacy of neoadjuvant immunochemotherapy (nICT) for locally advanced gastric cancer (LAGC) remain controversial. METHODS: Patients with LAGC who received either nICT or neoadjuvant chemotherapy (nCT) at 3 tertiary referral teaching hospitals in China between January 2016 and October 2022 were analyzed. After propensity-score matching (PSM), comparing the radiological response, pathological response rate, perioperative outcomes, and early recurrence between the two groups. RESULTS: After PSM, 585 patients were included, with 195 and 390 patients comprising the nICT and nCT groups, respectively. The nICT group exhibited a higher objective response rate (79.5% vs. 59.0%; P <0.001), pathological complete response rate (14.36% vs. 6.41%; P =0.002) and major pathological response rate (39.49% vs. 26.15%; P =0.001) compared with the nCT group. The incidence of surgical complications (17.44% vs. 16.15%, P =0.694) and the proportion of perioperative textbook outcomes (80.0% vs. 81.0%; P =0.767) were similar in both groups. The nICT group had a significantly lower proportion of early recurrence than the nCT group (29.7% vs. 40.8%; P =0.047). Furthermore, the multivariable logistic analysis revealed that immunotherapy was an independent protective factor against early recurrence [odds ratio 0.62 (95% CI 0.41-0.92); P =0.018]. No significant difference was found in neoadjuvant therapy drug toxicity between the two groups (51.79% vs. 45.38%; P =0.143). CONCLUSIONS: Compared with nCT, nICT is safe and effective, which significantly enhanced objective and pathological response rates and reduced the risk for early recurrence among patients with LAGC. TRIAL REGISTRATION: Clinical Trials.gov.
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Gastrectomia , Laparoscopia , Terapia Neoadjuvante , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/terapia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Gastrectomia/efeitos adversos , Idoso , Laparoscopia/efeitos adversos , Resultado do Tratamento , China , Estudos Retrospectivos , Imunoterapia/métodos , Imunoterapia/efeitos adversos , Pontuação de Propensão , AdultoRESUMO
BACKGROUND: Obesity has become a serious public health issue, significantly elevating the risk of various complications. It is a well-established contributor to Heart failure with preserved ejection fraction (HFpEF). Evaluating HFpEF in obesity is crucial. Epicardial adipose tissue (EAT) has emerged as a valuable tool for validating prognostic biomarkers and guiding treatment targets. Hence, assessing EAT is of paramount importance. Cardiovascular magnetic resonance (CMR) imaging is acknowledged as the gold standard for analyzing cardiac function and morphology. We hope to use CMR to assess EAT as a bioimaging marker to evaluate HFpEF in obese patients. AIM: To assess the diagnostic utility of CMR for evaluating heart failure with preserved ejection fraction [HFpEF; left ventricular (LV) ejection fraction ≥ 50%] by measuring the epicardial adipose tissue (EAT) volumes and EAT mass in obese patients. METHODS: Sixty-two obese patients were divided into two groups for a case-control study based on whether or not they had heart failure with HFpEF. The two groups were defined as HFpEF+ and HFpEF-. LV geometry, global systolic function, EAT volumes and EAT mass of all subjects were obtained using cine magnetic resonance sequences. RESULTS: Forty-five patients of HFpEF- group and seventeen patients of HFpEF+ group were included. LV mass index (g/m2) of HFpEF+ group was higher than HFpEF- group (P < 0.05). In HFpEF+ group, EAT volumes, EAT volume index, EAT mass, EAT mass index and the ratio of EAT/[left atrial (LA) left-right (LR) diameter] were higher compared to HFpEF- group (P < 0.05). In multivariate analysis, Higher EAT/LA LR diameter ratio was associated with higher odds ratio of HFpEF. CONCLUSION: EAT/LA LR diameter ratio is highly associated with HFpEF in obese patients. It is plausible that there may be utility in CMR for assessing obese patients for HFpEF using EAT/LA LR diameter ratio as a diagnostic biomarker. Further prospective studies, are needed to validate these proof-of-concept findings.
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Accurate myocardial segmentation is crucial in the diagnosis and treatment of myocardial infarction (MI), especially in Late Gadolinium Enhancement (LGE) cardiac magnetic resonance (CMR) images, where the infarcted myocardium exhibits a greater brightness. However, segmentation annotations for LGE images are usually not available. Although knowledge gained from CMR images of other modalities with ample annotations, such as balanced-Steady State Free Precession (bSSFP), can be transferred to the LGE images, the difference in image distribution between the two modalities (i.e., domain shift) usually results in a significant degradation in model performance. To alleviate this, an end-to-end Variational autoencoder based feature Alignment Module Combining Explicit and Implicit features (VAMCEI) is proposed. We first re-derive the Kullback-Leibler (KL) divergence between the posterior distributions of the two domains as a measure of the global distribution distance. Second, we calculate the prototype contrastive loss between the two domains, bringing closer the prototypes of the same category across domains and pushing away the prototypes of different categories within or across domains. Finally, a domain discriminator is added to the output space, which indirectly aligns the feature distribution and forces the extracted features to be more favorable for segmentation. In addition, by combining CycleGAN and VAMCEI, we propose a more refined multi-stage unsupervised domain adaptation (UDA) framework for myocardial structure segmentation. We conduct extensive experiments on the MSCMRSeg 2019, MyoPS 2020 and MM-WHS 2017 datasets. The experimental results demonstrate that our framework achieves superior performances than state-of-the-art methods.
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Algoritmos , Coração , Imageamento por Ressonância Magnética , Humanos , Coração/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Infarto do Miocárdio/diagnóstico por imagem , Aprendizado de Máquina não Supervisionado , Processamento de Imagem Assistida por Computador/métodos , Bases de Dados Factuais , Interpretação de Imagem Assistida por Computador/métodosRESUMO
Purpureocillium lavendulum is an important biocontrol agent against plant-parasitic nematodes, primarily infecting them with conidia. However, research on the regulatory genes and pathways involved in its conidiation is still limited. In this study, we employed Agrobacterium tumefaciens-mediated genetic transformation to generate 4,870 random T-DNA insertion mutants of P. lavendulum. Among these mutants, 131 strains exhibited abnormal conidiation, and further in-depth investigations were conducted on two strains (designated as #5-197 and #5-119) that showed significantly reduced conidiation. Through whole-genome re-sequencing and genome walking, we identified the T-DNA insertion sites in these strains and determined the corresponding genes affected by the insertions, namely Plhffp and Plpif1. Both genes were knocked out through homologous recombination, and phenotypic analysis revealed a significant difference in conidiation between the knockout strains and the wild-type strain (ku80). Upon complementation of the ΔPlpif1 strain with the corresponding wildtype allele, conidiation was restored to a level comparable to ku80, providing further evidence of the involvement of this gene in conidiation regulation in P. lavendulum. The knockout of Plhffp or Plpif1 reduced the antioxidant capacity of P. lavendulum, and the absence of Plhffp also resulted in decreased resistance to SDS, suggesting that this gene may be involved in the integrity of the cell wall. RT-qPCR showed that knockout of Plhffp or Plpif1 altered expression levels of several known genes associated with conidiation. Additionally, the analysis of nematode infection assays with Caenorhabditis elegans indicated that the knockout of Plhffp and Plpif1 indirectly reduced the pathogenicity of P. lavendulum towards the nematodes. The results demonstrate that Agrobacterium tumefaciens - mediated T-DNA insertion mutagenesis, gene knockout, and complementation can be highly effective for identifying functionally important genes in P. lavendulum.
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Background and aims: The cachexia index (CXI) is a novel biomarker for estimating cancer cachexia. The cachexia index based on hand-grip strength (H-CXI) has been recently developed as a simple proxy for CXI. The present study aims to compare both the H-CXI and CXI for the prediction of cancer cachexia and postoperative outcomes in patients who underwent radical colectomy for colorectal cancer. Methods: Patients who underwent radical operations for colorectal cancer were included in this study. Cancer cachexia was diagnosed according to the international consensus outlined by Fearon et al. The cachexia index (CXI) was calculated as [skeletal muscle index (SMI) × serum albumin/neutrophil-to-lymphocyte ratio (NLR)]. The H-CXI was calculated as [hand-grip strength (HGS)/height2 × serum albumin/NLR]. The SMI was measured based on the preoperative CT images at the third lumbar vertebra (L3) level. HGS was measured before surgery. Results: From July 2014 to May 2021, a total of 1,411 patients were included in the present study, of whom 361 (25.6%) were identified as having cancer cachexia. Patients with cachexia had a lower CXI (p < 0.001) and lower H-CXI (p < 0.001) than those without cachexia. A low CXI but not low H-CXI independently predicted cancer cachexia in the multivariate analysis (OR 1.448, p = 0.024). Both a low CXI (HR 1.476, p < 0.001 for OS; HR 1.611, p < 0.001 for DFS) and low H-CXI (HR 1.369, p = 0.007 for OS; HR 1.642, p < 0.001 for DFS) were independent predictors for overall survival (OS) and disease-free survival (DFS) after adjusting for the same covariates. A low H-CXI but not low CXI was an independent risk factor for postoperative complications (OR 1.337, p = 0.044). No significant association was found between cancer cachexia and postoperative complications. Conclusion: The CXI and H-CXI exhibited better prognostic value than cancer cachexia for the prediction of postoperative outcomes in patients who underwent radical colectomy for colorectal cancer. The H-CXI was a superior index over the CXI in predicting short-term clinical outcomes, whereas the CXI demonstrated a closer correlation with Fearon's criteria for cancer cachexia. Ideal tools for the assessment of cancer cachexia should incorporate not only weight loss but also muscle mass, physical function, and inflammatory state.
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PURPOSE: The temporal evolution of ventricular trabecular complexity and its correlation with major adverse cardiovascular events (MACE) remain indeterminate in patients presenting with acute ST elevation myocardial infarction (STEMI). METHODS: This retrospective analysis enrolled patients undergoing primary percutaneous coronary intervention (pPCI) for acute STEMI, possessing cardiac magnetic resonance (CMR) data in the acute (within 7 days), subacute (1 month after pPCI), and chronic phases (6 months after pPCI) from January 2015 to January 2020 at the three participating sites. Fractal dimensions (FD) were measured for the global, infarct, and remote regions of left ventricular trabeculae during each phase. The potential association of FD with MACE was analyzed using multivariate Cox regression. RESULTS: Among the 200 analyzed patients (182 men; median age, 61 years; age range, 50-66 years), 37 (18.5%) encountered MACE during a median follow-up of 31.2 months. FD exhibited a gradual decrement (global FD at acute, subacute, and chronic phases: 1.253 ± 0.049, 1.239 ± 0.046, 1.230 ± 0.045, p < 0.0001), with a more pronounced decrease observed in patients subsequently experiencing MACE (p < 0.001). The global FD at the subacute phase correlated with MACE (hazard ratio 0.89 (0.82, 0.97), p = 0.01), and a global FD value below 1.26 was associated with a heightened risk. CONCLUSION: In patients post-STEMI, the global FD, serving as an indicator of left ventricular trabeculae complexity, independently demonstrated an association with subsequent major adverse cardiovascular events, beyond factors encompassing left ventricular ejection fraction, indexed left ventricular end-diastolic volume, infarct size, heart rate, NYHA class, and post-pPCI TIMI flow. CRITICAL RELEVANCE STATEMENT: In patients who have had an ST-segment elevation myocardial infarction, global fractal dimension, as a measure of left ventricular trabeculae complexity, provided independent association with subsequent major adverse cardiovascular event. KEY POINTS: ⢠Global and regional FD decreased after STEMI, and more so in patients with subsequent MACE. ⢠Lower global FD at the subacute phase and Δglobal FD from acute to subacute phase were associated with subsequent MACE besides clinical and CMR factors. ⢠Global FD at the subacute phase independently correlated with MACE and global FD value below 1.26 was associated with higher risk.