Deep Learning Nomogram for the Identification of Deep Stromal Invasion in Patients With Early-Stage Cervical Adenocarcinoma and Adenosquamous Carcinoma: A Multicenter Study.

BACKGROUND: Deep stromal invasion (DSI) is one of the predominant risk factors that determined the types of radical hysterectomy (RH). Thus, the accurate assessment of DSI in cervical adenocarcinoma (AC)/adenosquamous carcinoma (ASC) can facilitate optimal therapy decision. PURPOSE: To develop a nomogram to identify DSI in cervical AC/ASC. STUDY TYPE: Retrospective. POPULATION: Six hundred and fifty patients (mean age of 48.2 years) were collected from center 1 (primary cohort, 536), centers 2 and 3 (external validation cohorts 1 and 2, 62 and 52). FIELD STRENGTH/SEQUENCE: 5-T, T2-weighted imaging (T2WI, SE/FSE), diffusion-weighted imaging (DWI, EPI), and contrast-enhanced T1-weighted imaging (CE-T1WI, VIBE/LAVA). ASSESSMENT: The DSI was defined as the outer 1/3 stromal invasion on pathology. The region of interest (ROI) contained the tumor and 3 mm peritumoral area. The ROIs of T2WI, DWI, and CE-T1WI were separately imported into Resnet18 to calculate the DL scores (TDS, DDS, and CDS). The clinical characteristics were retrieved from medical records or MRI data assessment. The clinical model and nomogram were constructed by integrating clinical independent risk factors only and further combining DL scores based on primary cohort and were validated in two external validation cohorts. STATISTICAL TESTS: Student's t-test, Mann-Whitney U test, or Chi-squared test were used to compare differences in continuous or categorical variables between DSI-positive and DSI-negative groups. DeLong test was used to compare AU-ROC values of DL scores, clinical model, and nomogram. RESULTS: The nomogram integrating menopause, disruption of cervical stromal ring (DCSRMR), DDS, and TDS achieved AU-ROCs of 0.933, 0.807, and 0.817 in evaluating DSI in primary and external validation cohorts. The nomogram had superior diagnostic ability to clinical model and DL scores in primary cohort (all P < 0.0125 [0.05/4]) and CDS (P = 0.009) in external validation cohort 2. DATA CONCLUSION: The nomogram achieved good performance for evaluating DSI in cervical AC/ASC. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Intratumoral and peritumoral MRI radiomics nomogram for predicting parametrial invasion in patients with early-stage cervical adenocarcinoma and adenosquamous carcinoma.

OBJECTIVE: To develop a comprehensive nomogram based on MRI intra- and peritumoral radiomics signatures and independent risk factors for predicting parametrial invasion (PMI) in patients with early-stage cervical adenocarcinoma (AC) and adenosquamous carcinoma (ASC). METHODS: A total of 460 patients with IB to IIB cervical AC and ASC who underwent preoperative MRI examination and radical trachelectomy/hysterectomy were retrospectively enrolled and divided into primary, internal validation, and external validation cohorts. The original (Ori) and wavelet (Wav)-transform features were extracted from the volumetric region of interest of the tumour (ROI-T) and 3mm- and 5mm-peritumoral rings (ROI-3 and ROI-5), respectively. Then the Ori and Ori-Wav feature-based radiomics signatures from the tumour (RST) and 3 mm- and 5 mm-peritumoral regions (RS3 and RS5) were independently built and their diagnostic performances were compared to select the optimal ones. Finally, the nomogram was developed by integrating optimal intra- and peritumoral signatures and clinical independent risk factors based on multivariable logistic regression analysis. RESULTS: FIGO stage, disruption of the cervical stromal ring on MRI (DCSRMR), parametrial invasion on MRI (PMIMR), and serum CA-125 were identified as independent risk factors. The nomogram constructed by integrating independent risk factors, Ori-Wav feature-based RST, and RS5 yielded AUCs of 0.874 (0.810-0.922), 0.885 (0.834-0.924), and 0.966 (0.887-0.995) for predicting PMI in the primary, internal and external validation cohorts, respectively. Furthermore, the nomogram was superior to radiomics signatures and clinical model for predicting PMI in three cohorts. CONCLUSION: The nomogram can preoperatively, accurately, and noninvasively predict PMI in patients with early-stage cervical AC and ASC. CLINICAL RELEVANCE STATEMENT: The nomogram can preoperatively, accurately, and noninvasively predict PMI and facilitate precise treatment decisions regarding chemoradiotherapy or radical hysterectomy in patients with early-stage cervical AC and ASC. KEY POINTS: The accurate preoperative prediction of PMI in early-stage cervical AC and ASC can facilitate precise treatment decisions regarding chemoradiotherapy or radical hysterectomy. The nomogram integrating independent risk factors, Ori-Wav feature-based RST, and RS5 can preoperatively, accurately, and noninvasively predict PMI in early-stage cervical AC and ASC. The nomogram was superior to radiomics signatures and clinical model for predicting PMI in early-stage cervical AC and ASC.

Effect of mechanical ventilation under intubation on respiratory tract change of bacterial count and alteration of bacterial flora.

Background: The most common 'second strike' in mechanically ventilated patients is a pulmonary infection caused by the ease with which bacteria can invade and colonize the lungs due to mechanical ventilation. At the same time, metastasis of lower airway microbiota may have significant implications in developing intubation mechanical ventilation lung inflammation. Thus, we establish a rat model of tracheal intubation with mechanical ventilation and explore the effects of mechanical ventilation on lung injury and microbiological changes in rats. To provide a reference for preventing and treating bacterial flora imbalance and pulmonary infection injury caused by mechanical ventilation of tracheal intubation. Methods: Sprague-Dawley rats were randomly divided into Control, Mechanical ventilation under intubation (1, 3, 6 h) groups, and Spontaneously breathing under intubation (1, 3, 6 h). Lung histopathological injury scores were evaluated. 16SrDNA sequencing was performed to explore respiratory microbiota changes, especially, changes of bacterial count and alteration of bacterial flora. Results: Compared to groups C and SV, critical pathological changes in pulmonary lesions occurred in the MV group after 6 h (p < 0.05). The Alpha diversity and Beta diversity of lower respiratory tract microbiota in MV6, SV6, and C groups were statistically significant (p < 0.05). The main dominant bacterial phyla in the respiratory tract of rats were Proteobacteria, Firmicutes, Bacteroidetes, and Cyanobacteria. Acinetobacter radioresistens in group C was significant, Megaonas in group MV6 was significantly increased, and Parvibacter in group SV6 was significantly increased. Anaerobic, biofilm formation, and Gram-negative bacteria-related functional genes were altered during mechanical ventilation with endotracheal intubation. Conclusion: Mechanical ventilation under intubation may cause dysregulation of lower respiratory microbiota in rats.

The diagnostic performance of ADC value for tumor grade, deep myometrial invasion and lymphovascular space invasion in endometrial cancer: a meta-analysis.

BACKGROUND: Disputes exist regarding whether the apparent diffusion coefficient (ADC) can differentiate the tumor grade, deep myometrial invasion and lymphovascular space invasion (LVSI) in endometrial cancer. The aim of this review was to assess the diagnostic performance of the ADC value in endometrial cancer. MATERIAL AND METHODS: The PubMed, Web of Science, Embase and Cochrane Library databases were searched for studies that used the ADC value to assess tumor grade, deep myometrial invasion and LVSI in endometrial cancer. We used forest plots to analyze the heterogeneity and generate the pooled sensitivity (SEN) and specificity (SPE). We used summary receiver operating characteristic (SROC) curves to work out the area under the SROC curve (AUC). Likelihood ratios (LRs) were also obtained. RESULTS: Of the 460 identified studies, 11 studies met our inclusion criteria and were included. Overall, nine studies (491 patients) aimed at differentiating high tumor grade had a pooled SEN, SPE and AUC of 77%, 73% and 81%, respectively; three studies (181 patients) for differentiating deep myometrial invasion had a pooled SEN, SPE and AUC of 71%, 67% and 77%, respectively; and two studies (106 patients) for differentiating LVSI had a pooled SEN and SPE of 66% and 74%, respectively. The positive and negative LRs were 2.77 and 0.35 for the tumor grade, 2.08 and 0.45 for deep myometrial invasion, and 2.48 and 0.45 for LVSI. CONCLUSION: This meta-analysis showed that the ADC value had a moderate diagnostic performance for the tumor grade, deep myometrial invasion and LVSI in endometrial cancer.

Comparison of MRI features among squamous cell carcinoma, adenocarcinoma and adenosquamous carcinoma, usual-type endocervical adenocarcinoma and gastric adenocarcinoma of cervix.

OBJECTIVE: To compare and explore the characteristics of squamous cell carcinoma (SCC), adenocarcinoma (AC) and adenosquamous carcinoma (ASC), usual-type endocervical adenocarcinoma (UEA) and gastric adenocarcinoma (GAC) of cervix. MATERIALS AND METHODS: A total of 728 cervical cancers (254 cases of AC, 252 cases of ASC, and 222 cases of SCC) confirmed by histopathology were retrospectively reviewed. Among AC, 119 UEA and 47 GAC were included. Clinical baseline data and tumor morphological features on MRI (including tumor location, shape, diameter and volume, margin, growth pattern, presence of fluid component or cyst, heterogenous and peritumoral enhancement) of all cases were collected and analyzed. The signal intensity (SI) of tumor and gluteus maximus muscle were measured and their ratios (SIR) were calculated based on T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) and contrast-enhanced T1WI at arterial and delay phases (A/DCE-T1WI). These clinical and MRI features were compared between SCC, AC and ASC, UEA and GAC, and the specific ones of each subtype were identified. RESULTS: There was a significant difference in SCC-Ag, CA-199, CEA, ADC value, SIR-DWI, presence of intratumor cyst and peritumoral enhancement between AC and ASC; in patient age, menopausal status, International Federation of Gynecology and Obstetrics (FIGO) stage, SCC-Ag, CA-125, CA-199, CEA, tumor shape, growth pattern, margin, presence of intratumor fluid component and cyst, tumor diameter and volume, ADC value, SIR-T1WI, SIR-T2WI, and SIR-DWI between SCC and AC, as well as SCC and ASC. Also, there was a significant difference in deep stromal invasion (DSI), peritumoral and heterogenous enhancement between SCC and AC, and in SIR-ACE-T1WI between SCC and ASC. There was a significant difference in reproductive history, menopausal status, FIGO stage, CA-199, DSI, lymph node metastasis (LNM), parametrial invasion (PMI), tumor location, shape, margin, growth pattern, presence of fluid component and cyst, tumor diameter and volume, SIR-T1WI, SIR-DWI, and heterogenous enhancement between GAC and UEA. CONCLUSION: The clinical and MRI features with significant differences among SCC, AC and ASC, and between UEA and GAC, can help to identify each subtype of cervical cancer.

Two New Mitogenomes of Bibionidae and Their Comparison within the Infraorder Bibionomorpha (Diptera).

Despite the worldwide distribution and rich diversity of the infraorder Bibionomorpha in Diptera, the characteristics of mitochondrial genomes (mitogenomes) are still little-known, and the phylogenetics and evolution of the infraorder remains controversial. In the present study, we report complete and annotated mitogenome sequences of Penthetria simplioipes and Plecia hardyi representing Bibionidae. This is the first report of the complete mitogenomes for the superfamily Bibionoidea. There are 37 genes in each of the complete mitogenomes of all 20 studied species from eight families of four superfamilies within infraorder Bibionomorpha. The Ka/Ks analysis suggests that all 13 PCGs have undergone purifying selection. The gene rearrangement events exist in some families (Keroplatidae, Sciaridae, and Cecidomyiidae) but not in Mycetophilidae in Sciaroidea and also in Scatopsoidea, Anisopodoidea, and Bibionoidea, which suggests that these rearrangement events are derived in the late period in the evolution of the Bibionomorpha. The phylogenetic analysis suggests the phylogenetic relationships of Scatopsoidea + (Anisopodoidea + (Bibionoidea + Sciaroidea)) in Bibionomorpha. The divergence time analysis suggests that Bibionomorpha originated in the Triassic, Scatopsoidea and Anisopodoidea in the late Triassic, Bibionoidea in the Jurassic, and Sciaroidea in the Jurassic to the Cretaceous. The work lays a base for the study of mitogenomes in Bibionomorpha but further work and broader taxon sampling are necessary for a better understanding of the phylogenetics and evolution of the infraorder.

MRI Texture Analysis for Preoperative Prediction of Lymph Node Metastasis in Patients with Nonsquamous Cell Cervical Carcinoma.

RATIONALE AND OBJECTIVES: To preoperatively predict lymph node metastasis (LNM) in patients with cervical nonsquamous cell carcinoma (non-SCC) based on magnetic resonance imaging (MRI) texture analysis. MATERIALS AND METHODS: This retrospective study included 104 consecutive patients (mean age of 47.2 ± 11.3 years) with stage IB-IIA cervical non-SCC. According to the ratio of 7:3, 72, and 32 patients were randomly divided into the training and testing cohorts. A total of 272 original features were extracted. In the process of feature selection, features with intraclass correlation coefficients (ICCs) less than 0.8 were eliminated. The Pearson correlation coefficient (PCC) and analysis of variance (ANOVA) were applied to reduce redundancy, overfitting, and selection biases. Further, a support vector machine (SVM) with linear kernel function was applied to select the optimal feature set with a high discrimination power. RESULTS: The T2WI + DWI-based, T2WI + DWI + CE-T1WI-based and T2WI + DWI + LNS-MRI (LN status on MRI)-based SVM models yielded an AUC and accuracy of 0.78 and 0.79; 0.79 and 0.69; 0.79 and 0.81 for predicting LNM in the training cohort, and 0.82 and 0.78; 0.82 and 0.69; 0.79 and 0.72 in the testing cohort. The T2WI + DWI-based, T2WI + DWI + CE-T1WI-based and T2WI + DWI + LNS-MRI-based SVM models performed better than morphologic criteria of LNS-MRI and yield similar discrimination abilities in predicting LNM in the training and testing cohorts (all p-value > 0.05). In addition, the T2WI + DWI-based and T2WI + DWI + LNS-MRI-based SVM models showed robust performance in the AC and ASC subgroups (all p-value > 0.05). CONCLUSION: The T2WI + DWI-based, T2WI + DWI + CE-T1WI-based and T2WI+DWI+LNS-MRI-based SVM models showed similar good discrimination ability and performed better than the morphologic criteria of LNS-MRI in predicting LNM in patients with cervical non-SCC. The inclusion of the CE-T1WI sequence and morphologic criteria of LNS-MRI did not significantly improve the performance of the T2WI + DWI-based model. The T2WI + DWI-based and T2WI + DWI + LNS-MRI-based SVM models showed robust performance in the subgroup analysis.

Analysis of hydrochloride 4-methyl-piperazine-1-carbodithioc acid 3-cyano-3,3-diphenyl-propyl ester and its metabolites in rats by HPLC-ESI/ITMSn / 药学学报

<p><b>AIM</b>To identify the main metabolites of hydrochloride 4-methyl-piperazine-1-carbodithioc acid 3-cyano-3,3-diphenyl-propyl ester (TM208) in rats.</p><p><b>METHODS</b>Rat feces, urine and plasma samples were collected after ig 500 mg x kg(-1) TM208, then the samples were extracted and concentrated using ethyl acetate. The treated samples were analyzed by HPLC-ESI/ITMSn. The structures of metabolites were elucidated according to the rules of drug metabolism and disposition in vivo and the characteristic fragmentation behaviors of TM208 in ESI-ITMSn.</p><p><b>RESULTS</b>Eight phase I metabolites were identified existing in rat feces, five of them were also found in rat urine and plasma, but no phase II metabolite was found.</p><p><b>CONCLUSION</b>The HPLC-ESI/ITMSn method is rapid, highly sensitive and specific and it is suitable for the identification of TM208 and its metabolites in rats.</p>