ATR-mediated phosphorylation of FANCI regulates dormant origin firing in response to replication stress.

Excess dormant origins bound by the minichromosome maintenance (MCM) replicative helicase complex play a critical role in preventing replication stress, chromosome instability, and tumorigenesis. In response to DNA damage, replicating cells must coordinate DNA repair and dormant origin firing to ensure complete and timely replication of the genome; how cells regulate this process remains elusive. Herein, we identify a member of the Fanconi anemia (FA) DNA repair pathway, FANCI, as a key effector of dormant origin firing in response to replication stress. Cells lacking FANCI have reduced number of origins, increased inter-origin distances, and slowed proliferation rates. Intriguingly, ATR-mediated FANCI phosphorylation inhibits dormant origin firing while promoting replication fork restart/DNA repair. Using super-resolution microscopy, we show that FANCI co-localizes with MCM-bound chromatin in response to replication stress. These data reveal a unique role for FANCI as a modulator of dormant origin firing and link timely genome replication to DNA repair.

Impact of respiratory motion on 18 F-FDG PET radiomics stability: Clinical evaluation with a digital PET scanner.

PURPOSE: 18 F-FDG PET quantitative features are susceptible to respiratory motion. However, studies using clinical patient data to explore the impact of respiratory motion on 18 F-FDG PET radiomic features are limited. In this study, we investigated the impact of respiratory motion on radiomics stability with clinical 18 F-FDG PET images using a data-driven gating (DDG) algorithm on the digital PET scanner. MATERIALS AND METHODS: A total of 101 patients who underwent oncological 18 F-FDG PET scans were retrospectively included. A DDG algorithm combined with a motion compensation technique was used to extract the PET images with respiratory motion correction. 18 F-FDG-avid lesions from the thorax to the upper abdomen were analyzed on the non-DDG and DDG PET images. The lesions were segmented with a 40% threshold of the maximum standardized uptake. A total of 725 radiomic features were computed from the segmented lesions, including first-order, shape, texture, and wavelet features. The intraclass correlation coefficient (ICC) and coefficient of variation (COV) were calculated to evaluate feature stability. An ICC above 0.9 and a COV below 5% were considered high stability. RESULTS: In total, 168 lesions with and without respiratory motion correction were analyzed. Our results indicated that most 18 F-FDG PET radiomic features are sensitive to respiratory motion. Overall, only 27 out of 725 (3.72%) radiomic features were identified as highly stable, including one from the first-order features (entropy), one from the shape features (sphericity), four from the gray-level co-occurrence matrix features (normalized and unnormalized inverse difference moment, joint entropy, and sum entropy), one from the gray-level run-length matrix features (run entropy), and 20 from the wavelet filter-based features. CONCLUSION: Respiratory motion has a significant impact on 18 F-FDG PET radiomics stability. The highly stable features identified in our study may serve as potential candidates for further applications, such as machine learning modeling.

Selective modulation of the functions of a conserved DNA motor by a histone fold complex.

Budding yeast Mph1 helicase and its orthologs drive multiple DNA transactions. Elucidating the mechanisms that regulate these motor proteins is central to understanding genome maintenance processes. Here, we show that the conserved histone fold MHF complex promotes Mph1-mediated repair of damaged replication forks but does not influence the outcome of DNA double-strand break repair. Mechanistically, scMHF relieves the inhibition imposed by the structural maintenance of chromosome protein Smc5 on Mph1 activities relevant to replication-associated repair through binding to Mph1 but not DNA. Thus, scMHF is a function-specific enhancer of Mph1 that enables flexible response to different genome repair situations.

Genomic and Glycolytic Entropy Are Reliable Radiogenomic Heterogeneity Biomarkers for Non-Small Cell Lung Cancer.

Radiogenomic heterogeneity features in 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) have become popular in non-small cell lung cancer (NSCLC) research. However, the reliabilities of genomic heterogeneity features and of PET-based glycolytic features in different image matrix sizes have yet to be thoroughly tested. We conducted a prospective study with 46 NSCLC patients to assess the intra-class correlation coefficient (ICC) of different genomic heterogeneity features. We also tested the ICC of PET-based heterogeneity features from different image matrix sizes. The association of radiogenomic features with clinical data was also examined. The entropy-based genomic heterogeneity feature (ICC = 0.736) is more reliable than the median-based feature (ICC = -0.416). The PET-based glycolytic entropy was insensitive to image matrix size change (ICC = 0.958) and remained reliable in tumors with a metabolic volume of <10 mL (ICC = 0.894). The glycolytic entropy is also significantly associated with advanced cancer stages (p = 0.011). We conclude that the entropy-based radiogenomic features are reliable and may serve as ideal biomarkers for research and further clinical use for NSCLC.

Co-opting the Fanconi anemia genomic stability pathway enables herpesvirus DNA synthesis and productive growth.

DNA damage associated with viral DNA synthesis can result in double-strand breaks that threaten genome integrity and must be repaired. Here, we establish that the cellular Fanconi anemia (FA) genomic stability pathway is exploited by herpes simplex virus 1 (HSV-1) to promote viral DNA synthesis and enable its productive growth. Potent FA pathway activation in HSV-1-infected cells resulted in monoubiquitination of FA effector proteins FANCI and FANCD2 (FANCI-D2) and required the viral DNA polymerase. FANCD2 relocalized to viral replication compartments, and FANCI-D2 interacted with a multisubunit complex containing the virus-encoded single-stranded DNA-binding protein ICP8. Significantly, whereas HSV-1 productive growth was impaired in monoubiquitination-defective FA cells, this restriction was partially surmounted by antagonizing the DNA-dependent protein kinase (DNA-PK), a critical enzyme required for nonhomologous end-joining (NHEJ). This identifies the FA-pathway as a cellular factor required for herpesvirus productive growth and suggests that FA-mediated suppression of NHEJ is a fundamental step in the viral life cycle.

Clinical Efficacy and Safety of Reduced-Dose Prasugrel versus Clopidogrel in Patients Undergoing Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objectives: This systematic review and meta-analysis of randomized controlled trials (RCTs) compared the clinical efficacy and safety of reduced-dose prasugrel (loading dose: 20 mg; daily maintenance dose: 3.75 mg) and clopidogrel in patients undergoing percutaneous coronary intervention (PCI). Methods: PubMed, Embase, and the Cochrane Library database were searched for relevant articles from inception to March 8, 2021. Only RCTs that compared the clinical efficacy and safety of reduced-dose prasugrel and clopidogrel treatment in adult patients undergoing PCI were included. The primary outcome was the risk of major cardiovascular events (MACEs). Results: Four RCTs involving 2464 patients were included. The overall risk of MACEs was 8.3% (102/1235) in the study group (reduced-dose prasugrel) and 9.8% (121/1229) in the control group (clopidogrel). No significant difference was observed in the risk of MACEs between the study and control groups (risk ratio: 0.84, 95% confidence interval: 0.65-1.08, I 2 = 0%). In addition, cardiovascular-related death, all-cause death, nonfatal myocardial infarction, nonfatal stroke, revascularization, and stent thrombosis did not differ significantly between the two groups. Apart from a higher risk of minor bleeding in the study group, reduced-dose prasugrel had a similar bleeding risk to clopidogrel. Conclusions: The clinical efficacy of reduced-dose prasugrel is comparable to that of clopidogrel; however, the risk of minor bleeding should be considered when prescribing this regimen for patients undergoing PCI.

Value of early evaluation of treatment response using 18F-FDG PET/CT parameters and the Epstein-Barr virus DNA load for prediction of outcome in patients with primary nasopharyngeal carcinoma.

PURPOSE: To determine the value of early evaluation of response to concurrent chemoradiotherapy (CCRT) using 18F-FDG PET-derived parameters and the Epstein-Barr virus (EBV) DNA titre in outcome prediction in patients with primary nasopharyngeal carcinoma (NPC). METHODS: Sixty patients with primary NPC were prospectively enrolled. All patients underwent 18F-FDG PET/CT before and during CCRT. The plasma EBV DNA titre was measured along with the PET/CT-derived parameters. Changes in EBV DNA titre and PET/CT-derived parameters during CCRT were analysed in relation to response to treatment, recurrence-free survival (RFS) and overall survival (OS). RESULTS: A total lesion glycolysis (TLG) reduction ratio of ≤0.6 and a detectable EBV DNA titre during CCRT were predictors of an unfavourable response to treatment, RFS and OS. In multivariate analysis, a TLG reduction ratio of ≤0.6 predicted incomplete remission (p = 0.002) and decreased RFS (p = 0.003). The proportion of patients with a TLG reduction ratio of >0.6 who achieved a complete response was more than twice that of patients with a TLG reduction ratio of ≤0.6. A detectable EBV DNA titre, a TLG reduction ratio of ≤0.6 and older age were independently associated with a poorer OS (p = 0.037, 0.009 and 0.016, respectively). A scoring system was developed based on these independent predictors of OS. Patients with a score of 1 and 2/3 had poorer survival outcomes than those with a score of 0 (hazard ratio 4.756, p = 0.074, and hazard ratio 18.973, p = 0.001, respectively). This scoring system appeared to be superior to the traditional TNM staging system (p < 0.001 versus p = 0.175). CONCLUSION: Early evaluation of response to CCRT using 18F-FDG PET-derived parameters and the EBV DNA titre can predict outcome in patients with primary NPC. A combination of interim PET parameters and the EBV DNA titre enables better stratification of patients into subgroups with different survival rates.

The aquatic animals' transcriptome resource for comparative functional analysis.

BACKGROUND: Aquatic animals have great economic and ecological importance. Among them, non-model organisms have been studied regarding eco-toxicity, stress biology, and environmental adaptation. Due to recent advances in next-generation sequencing techniques, large amounts of RNA-seq data for aquatic animals are publicly available. However, currently there is no comprehensive resource exist for the analysis, unification, and integration of these datasets. This study utilizes computational approaches to build a new resource of transcriptomic maps for aquatic animals. This aquatic animal transcriptome map database dbATM provides de novo assembly of transcriptome, gene annotation and comparative analysis of more than twenty aquatic organisms without draft genome. RESULTS: To improve the assembly quality, three computational tools (Trinity, Oases and SOAPdenovo-Trans) were employed to enhance individual transcriptome assembly, and CAP3 and CD-HIT-EST software were then used to merge these three assembled transcriptomes. In addition, functional annotation analysis provides valuable clues to gene characteristics, including full-length transcript coding regions, conserved domains, gene ontology and KEGG pathways. Furthermore, all aquatic animal genes are essential for comparative genomics tasks such as constructing homologous gene groups and blast databases and phylogenetic analysis. CONCLUSION: In conclusion, we establish a resource for non model organism aquatic animals, which is great economic and ecological importance and provide transcriptomic information including functional annotation and comparative transcriptome analysis. The database is now publically accessible through the URL http://dbATM.mbc.nctu.edu.tw/ .

Transcriptome sequencing based annotation and homologous evidence based scaffolding of Anguilla japonica draft genome.

BACKGROUND: Anguilla japonica (Japanese eel) is currently one of the most important research subjects in eastern Asia aquaculture. Enigmatic life cycle of the organism makes study of artificial reproduction extremely limited. Henceforth genomic and transcriptomic resources of eels are urgently needed to help solving the problems surrounding this organism across multiple fields. We hereby provide a reconstructed transcriptome from deep sequencing of juvenile (glass eels) whole body samples. The provided expressed sequence tags were used to annotate the currently available draft genome sequence. Homologous information derived from the annotation result was applied to improve the group of scaffolds into available linkage groups. RESULTS: With the transcriptome sequence data combined with publicly available expressed sequence tags evidences, 18,121 genes were structurally and functionally annotated on the draft genome. Among them, 3,921 genes were located in the 19 linkage groups. 137 scaffolds covering 13 million bases were grouped into the linkage groups in additional to the original partial linkage groups, increasing the linkage group coverage from 13 to 14%. CONCLUSIONS: This annotation provide information of the coding regions of the genes supported by transcriptome based evidence. The derived homologous evidences pave the way for phylogenetic analysis of important genetic traits and the improvement of the genome assembly.

Prognostic value of combining clinical factors, 18F-FDG PET-based intensity, volumetric features, and deep learning predictor in patients with EGFR-mutated lung adenocarcinoma undergoing targeted therapies: a cross-scanner and temporal validation study.

OBJECTIVE: To investigate the prognostic value of 18F-FDG PET-based intensity, volumetric features, and deep learning (DL) across different generations of PET scanners in patients with epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma receiving tyrosine kinase inhibitor (TKI) treatment. METHODS: We retrospectively analyzed the pre-treatment 18F-FDG PET of 217 patients with advanced-stage lung adenocarcinoma and actionable EGFR mutations who received TKI as first-line treatment. Patients were separated into analog (n = 166) and digital (n = 51) PET cohorts. 18F-FDG PET-derived intensity, volumetric features, ResNet-50 DL of the primary tumor, and clinical variables were used to predict progression-free survival (PFS). Independent prognosticators were used to develop prediction model. Model was developed and validated in the analog and digital PET cohorts, respectively. RESULTS: In the analog PET cohort, female sex, stage IVB status, exon 19 deletion, SUVmax, metabolic tumor volume, and positive DL prediction independently predicted PFS. The model devised from these six prognosticators significantly predicted PFS in the analog (HR = 1.319, p < 0.001) and digital PET cohorts (HR = 1.284, p = 0.001). Our model provided incremental prognostic value to staging status (c-indices = 0.738 vs. 0.558 and 0.662 vs. 0.598 in the analog and digital PET cohorts, respectively). Our model also demonstrated a significant prognostic value for overall survival (HR = 1.198, p < 0.001, c-index = 0.708 and HR = 1.256, p = 0.021, c-index = 0.664 in the analog and digital PET cohorts, respectively). CONCLUSIONS: Combining 18F-FDG PET-based intensity, volumetric features, and DL with clinical variables may improve the survival stratification in patients with advanced EGFR-mutated lung adenocarcinoma receiving TKI treatment. Implementing the prediction model across different generations of PET scanners may be feasible and facilitate tailored therapeutic strategies for these patients.

Augmenting dermal collagen synthesis through hyaluronic acid-based microneedle-mediated delivery of poly(l-lactic acid) microspheres.

Poly(L-lactic acid) (PLLA) can stimulate collagen synthesis through a foreign body response. However, inappropriate injection techniques and localized PLLA clustering can lead to complications and adverse events. This study developed a composite microneedle (MN) device comprising an array of PLLA microsphere (PLLA MP)-loaded hyaluronic acid needle tips with a supporting patch (PLLA MP-MN). This device was designed to deliver PLLA MPs precisely and uniformly to the dermis and to provide dual stimulation through MN puncture and MP implantation, thereby enabling the rapid and long-lasting regeneration of dermal collagen. When applied to rat skin, the MN array evenly distributed the PLLA MPs throughout the penetrated regions, which prevented local PLLA overdosing and elicited a milder inflammatory response compared with that induced by intradermal PLLA MP injections. An in vivo efficacy study revealed that MN-mediated delivery of PLLA MPs not only promptly initiated collagen production through microwound-triggered wound-healing cascades in the early treatment stage but also enabled the long-term stimulation of collagen deposition through MP-induced foreign body reactions, thereby significantly enhancing neocollagenesis. This innovative PLLA MP-MN system can augment the benefits and minimize the adverse effects associated with traditional PLLA fillers, providing a safe and reliable anti-aging therapeutic option.

Topical Antibiotic Prophylaxis for Preventing Surgical Site Infections of Clean Wounds: A Systematic Review and Meta-Analysis.

Background: Topical antibiotic agents are not generally indicated for preventing of surgical site infections (SSIs) in clean incisions, and the drug concentrations that should be delivered to local incision sites remain uncertain. The aim of this study was to critically assess the efficacy of topical antibiotic agents in comparison with non-antibiotic agents for preventing SSIs in clean incisions by performing a systematic review and meta-analysis. Methods: We conducted a search of literature in PubMed, Embase, and Cochrane Databases and included randomized controlled trials (RCTs) on topical antibiotic use for patients with clean post-surgical incisions. The primary outcome was the incidence of SSI, presented as the event rate. Eleven RCTs were included. Results: Using random-effects modeling, the pooled risk ratio (RR) of developing a post-surgical incisions infection was 0.83 (95% confidence interval [CI], 0.61-1.16; I2, 0%). In subgroup analyses, no reductions in SSI were observed when topical antibiotic agents were used to treat incisions due to spinal (RR, 0.75; 95% CI, 0.40-1.38; I2, 0%), orthopedic (RR, 0.69; 95% CI, 0.37-1.29; I2, 0%), dermatologic (RR, 0.77; 95% CI, 0.39-1.55; I2, 65%), or cardiothoracic surgeries (RR, 1.31; 95% CI, 0.83-2.06; I2: 0%). The incidence of SSI across different operative phases did not differ for the application of topical antibiotic agents compared with non-antibiotic agents (RR, 0.80; 95% CI, 0.56-1.14; I2, 0%). Conclusions: The results of this meta-analysis show that topical antibiotic agents provide no clinical benefit for preventing SSI in clean incisions.

TGF-ß1 conjugated to gold nanoparticles results in protein conformational changes and attenuates the biological function.

Gold nanoparticles (AuNPs) are widely used as carriers or therapeutic agents due to their great biocompatibility and unique physical properties. Transforming growth factor-beta 1 (TGF-ß1), a member of the cysteine-knot structural superfamily, plays a pivotal role in many diseases and is known as an immunosuppressive agent that attenuates immune response resulting in tumor growth. The results reported herein reflect strong interactions between TGF-ß1 and the surface of AuNPs when incubated with serum-containing medium, and demonstrate a time- and dose-dependent pattern. Compared with other serum proteins that can also bind to the AuNP surface, AuNP-TGFß1 conjugate is a thermodynamically favored compound. Epithelial cells undergo epithelial-mesenchymal transition (EMT) upon treatment with TGF-ß1; however, treatment with AuNPs reverses this effect, as detected by cell morphology and expression levels of EMT markers. TGF-ß1 is found to bind to AuNPs through S-Au bonds by X-ray photoelectron spectroscopy. Fourier transform infrared spectroscopy is employed to analyze the conformational changes of TGF-ß1 on the surface of AuNPs. The results indicate that TGF-ß1 undergoes significant conformational changes at both secondary and tertiary structural levels after conjugation to the AuNP surface, which results in the deactivation of TGF-ß1 protein. An in vivo experiment also shows that addition of AuNPs attenuates the growth of TGF-ß1-secreting murine bladder tumor 2 cells in syngeneic C3H/HeN mice, but not in immunocompromised NOD-SCID mice, and this is associated with an increase in the number of tumor-infiltrating CD4⁺ and CD8⁺ T lymphocytes and a decrease in the number of intrasplenic Foxp3(+) lymphocytes. The findings demonstrate that AuNPs may be a promising agent for modulating tumor immunity through inhibiting immunosuppressive TGF-ß1 signaling.

Current progress in dengue vaccines.

Dengue is one of the most important emerging vector-borne viral diseases. There are four serotypes of dengue viruses (DENV), each of which is capable of causing self-limited dengue fever (DF) or even life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). The major clinical manifestations of severe DENV disease are vascular leakage, thrombocytopenia, and hemorrhage, yet the detailed mechanisms are not fully resolved. Besides the direct effects of the virus, immunopathological aspects are also involved in the development of dengue symptoms. Although no licensed dengue vaccine is yet available, several vaccine candidates are under development, including live attenuated virus vaccines, live chimeric virus vaccines, inactivated virus vaccines, and live recombinant, DNA and subunit vaccines. The live attenuated virus vaccines and live chimeric virus vaccines are undergoing clinical evaluation. The other vaccine candidates have been evaluated in preclinical animal models or are being prepared for clinical trials. For the safety and efficacy of dengue vaccines, the immunopathogenic complications such as antibody-mediated enhancement and autoimmunity of dengue disease need to be considered.

Single photon emission computed tomography/computed tomography for malignant otitis externa: lesion not shown on planar image.

Malignant otitis externa is a severe and rare infection of the external acoustic meatus. Triphasic bone and (67)Ga scintigraphies are used to initial detect and follow-up the response of therapy. With single photon emission computed tomography/computed tomography images, the diagnostic sensitivity is higher. We presented a case with malignant otitis externa with initial negative planar scintigraphic finding. The lesion was detected by photon emission computed tomography/computed tomography images. We concluded that the photon emission computed tomography/computed tomography should be performed routinely for patients with suspected malignant otitis externa, even without evidence of lesion on planar images.

The Fast Growth and Quick Spread of Synchronous Tumors.

A 47-year-old man was diagnosed with left buccal squamous cell carcinoma using FDG PET/CT, by which focal lesions in the left buccal and left neck lymph node were found. Three months after the operation, CT images revealed a left lower lung lesion. Pathology indicated a left lower lung adenocarcinoma. Second FDG PET/CT was performed more than 11 days later, and lesions with intense FDG uptake were found in the left lower lung, metastatic to the lymph nodes, lungs, bones, and liver. The prior FDG PET/CT scan showed negative findings in the lungs. However, lung cancer with multiple metastases appeared 4 months later.

Influence of the methodological aspects of the dichotomization of total metabolic tumor volume measured through baseline fluorine-18 fluorodeoxyglucose PET on survival prediction in lymphoma.

OBJECTIVE: The total metabolic tumor volume (TMTV) measured from fluorine-18 fluorodeoxyglucose (18F-FDG) PET can be useful for determining the prognosis of patients with lymphoma. Stratifying patients into high- and low-TMTV risk groups requires a cutoff point, which is determined through the dichotomization method. This study investigated whether different TMTV dichotomization methods influenced survival prediction in patients with lymphoma. METHODS: We retrospectively enrolled 129 patients with lymphoma who had undergone baseline 18F-FDG PET. TMTV was calculated using a fixed standardized uptake value threshold of 4.0. A total of six methods were employed to determine the optimal TMTV cutoff point using receiver-operating characteristic curve analyses, X-Tile bioinformatics software, and the Cutoff Finder web application. The prognostic performance of each method in survival prediction was examined. RESULTS: The median (interquartile range) TMTV was 123 cm3 (21-335 cm3). The optimal TMTV cutoff values for predicting progression-free survival (PFS) and overall survival (OS) were in the range of 144-748 cm3. The cutoff points were used to dichotomize patients into two groups with distinct prognoses. All TMTV dichotomizations were significantly predictive of PFS and OS. The survival curves showed significant differences between the high- and low-TMTV groups. The C-indices of the survival models did not significantly differ in any of the dichotomizations. CONCLUSION: The prognostic significance of TMTV was maintained regardless of the methodological aspects of dichotomization. However, the optimal TMTV cutoff point varied according to the chosen dichotomization method. Care should be taken when establishing an optimal TMTV cutoff point for clinical use.

The combined tumor-nodal glycolytic entropy improves survival stratification in nonsmall cell lung cancer with locoregional disease.

OBJECTIVE: To investigate whether combining primary tumor and metastatic nodal glycolytic heterogeneity on 18 F-fluorodeoxyglucose PET ( 18 F-FDG PET) improves prognostic prediction in nonsmall cell lung cancer (NSCLC) with locoregional disease. METHODS: We retrospectively analyzed 18 F-FDG PET-derived features from 94 patients who had undergone curative treatments for regional nodal metastatic NSCLC. Overall survival (OS) and progression-free survival (PFS) were analyzed using univariate and multivariate Cox regression models. We used the independent prognosticators to construct models to predict survival. RESULTS: Combined entropy (entropy derived from the combination of the primary tumor and metastatic nodes) and age independently predicted OS (both P = 0.008) and PFS ( P = 0.007 and 0.050, respectively). At the same time, the Eastern Cooperative Oncology Group status was another independent risk factor for unfavorable OS ( P = 0.026). Our combined entropy-based models outperformed the traditional staging system (c-index = 0.725 vs. 0.540, P < 0.001 for OS; c-index = 0.638 vs. 0.511, P = 0.003 for PFS) and still showed prognostic value in subgroups according to sex, histopathology, and different initial curative treatment strategies. CONCLUSION: Combined primary tumor-nodal glycolytic heterogeneity independently predicted survival outcomes. In combination with clinical risk factors, our models provide better survival predictions and may enable tailored treatment strategies for NSCLC with locoregional disease.

A comparison of 18 F-FDG PET-based radiomics and deep learning in predicting regional lymph node metastasis in patients with resectable lung adenocarcinoma: a cross-scanner and temporal validation study.

OBJECTIVE: The performance of 18 F-FDG PET-based radiomics and deep learning in detecting pathological regional nodal metastasis (pN+) in resectable lung adenocarcinoma varies, and their use across different generations of PET machines has not been thoroughly investigated. We compared handcrafted radiomics and deep learning using different PET scanners to predict pN+ in resectable lung adenocarcinoma. METHODS: We retrospectively analyzed pretreatment 18 F-FDG PET from 148 lung adenocarcinoma patients who underwent curative surgery. Patients were separated into analog (n = 131) and digital (n = 17) PET cohorts. Handcrafted radiomics and a ResNet-50 deep-learning model of the primary tumor were used to predict pN+ status. Models were trained in the analog PET cohort, and the digital PET cohort was used for cross-scanner validation. RESULTS: In the analog PET cohort, entropy, a handcrafted radiomics, independently predicted pN+. However, the areas under the receiver-operating-characteristic curves (AUCs) and accuracy for entropy were only 0.676 and 62.6%, respectively. The ResNet-50 model demonstrated a better AUC and accuracy of 0.929 and 94.7%, respectively. In the digital PET validation cohort, the ResNet-50 model also demonstrated better AUC (0.871 versus 0.697) and accuracy (88.2% versus 64.7%) than entropy. The ResNet-50 model achieved comparable specificity to visual interpretation but with superior sensitivity (83.3% versus 66.7%) in the digital PET cohort. CONCLUSION: Applying deep learning across different generations of PET scanners may be feasible and better predict pN+ than handcrafted radiomics. Deep learning may complement visual interpretation and facilitate tailored therapeutic strategies for resectable lung adenocarcinoma.

Glucose metabolic heterogeneity correlates with pathological features and improves survival stratification of resectable lung adenocarcinoma.

OBJECTIVE: We investigated whether glycolytic heterogeneity correlated with histopathology, and further stratified the survival outcomes pertaining to resectable lung adenocarcinoma. METHODS: We retrospectively analyzed the 18F-fluorodeoxyglucose positron emission tomography-derived entropy and histopathology from 128 patients who had undergone curative surgery for lung adenocarcinoma. Disease-free survival (DFS) and overall survival (OS) were analyzed using univariate and multivariate Cox regression models. Independent predictors were used to construct survival prediction models. RESULTS: Entropy significantly correlated with histopathology, including tumor grades, lympho-vascular invasion, and visceral pleural invasion. Furthermore, entropy was an independent predictor of unfavorable DFS (p = 0.031) and OS (p = 0.004), while pathological nodal metastasis independently predicted DFS (p = 0.009). Our entropy-based models outperformed the traditional staging system (c-index = 0.694 versus 0.636, p = 0.010 for DFS; c-index = 0.704 versus 0.630, p = 0.233 for OS). The models provided further survival stratification in subgroups comprising different tumor grades (DFS: HR = 2.065, 1.315, and 1.408 for grade 1-3, p = 0.004, 0.001, and 0.039, respectively; OS: HR = 25.557, 6.484, and 2.570, for grade 1-3, p = 0.006, < 0.001, and = 0.224, respectively). CONCLUSION: The glycolytic heterogeneity portrayed by entropy is associated with aggressive histopathological characteristics. The proposed entropy-based models may provide more sophisticated survival stratification in addition to histopathology and may enable personalized treatment strategies for resectable lung cancer.