Predicting recurrent glioblastoma clinical outcome to immune checkpoint inhibition and low-dose bevacizumab with tumor in situ fluid circulating tumor DNA analysis.

OBJECTIVE: Most recurrent glioblastoma (rGBM) patients do not benefit from immune checkpoint inhibition, emphasizing the necessity for response biomarkers. This study evaluates whether tumor in situ fluid (TISF) circulating tumor DNA (ctDNA) could serve as a biomarker for response to low-dose bevacizumab (Bev) plus anti-PD-1 therapy in rGBM patients, aiming to enhance systemic responses to immunotherapy. METHODS: In this phase II trial, 32 GBM patients with first recurrence after standard therapy were enrolled and then received tislelizumab plus low-dose Bev each cycle. TISF samples were analyzed for ctDNA using a 551-gene panel before each treatment. RESULTS: The median progression-free survival (mPFS) and overall survival (mOS) were 8.2 months (95% CI, 5.2-11.1) and 14.3 months (95% CI, 6.5-22.1), respectively. The 12-month OS was 43.8%, and the objective response rate was 56.3%. Patients with more than 20% reduction in the mutant allele fraction and tumor mutational burden after treatment were significantly associated with better prognosis compared to baseline TISF-ctDNA. Among detectable gene mutations, patients with MUC16 mutation, EGFR mutation & amplification, SRSF2 amplification, and H3F3B amplification were significantly associated with worse prognosis. CONCLUSIONS: Low-dose Bev plus anti-PD-1 therapy significantly improves OS in rGBM patients, offering guiding significance for future individualized treatment strategies. TISF-ctDNA can monitor rGBM patients' response to combination therapy and guide treatment. CLINICAL TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov, NCT05540275.

Restriction Spectrum Imaging and Diffusion Kurtosis Imaging for Assessing Proliferation Status in Rectal Carcinoma.

OBJECTIVES: To investigate the application of the three-compartment restriction spectrum imaging (RSI) model, diffusion kurtosis imaging (DKI), and diffusion-weighted imaging (DWI) in predicting Ki-67 status in rectal carcinoma. METHODS: A total of 80 rectal carcinoma patients, including 47 high-proliferation (Ki-67 > 50%) cases and 33 low-proliferation (Ki-67 ≤ 50%) cases, underwent pelvic MRI were enrolled. Parameters derived from RSI (f1, f2, and f3), DKI (MD and MK), and DWI (ADC) were calculated and compared between the two groups. Logistic regression (LR) analysis was conducted to identify independent predictors and assess combined diagnosis. Area under the receiver operating characteristic curve (AUC), DeLong analysis, and calibration curve analyses were performed to evaluate diagnostic performance. RESULTS: The patients with high-proliferation rectal carcinoma exhibited significantly higher f1 and MK values and significantly lower ADC, MD, f2, and f3 values than those with low-proliferation rectal carcinoma (P < 0.05). LR analysis showed that MD, MK, and f2 were independent predictors for Ki-67 status in rectal carcinoma. Moreover, the combination of these three parameters achieved an optimal diagnostic efficacy (AUC = 0.877, sensitivity = 80.85%, specificity = 84.85%) that was significantly better than that obtained using ADC (AUC = 0.783, Z = 2.347, P = 0.019), f2 (AUC = 0.732, Z = 2.762, P = 0.006), and f3 (AUC = 0.700, Z = 3.071, P = 0.002). The combined diagnosis also showed good performance (AUC = 0.859) in the internal validation analysis based on 1000 bootstrap samples, while the calibration curve demonstrated that the combined diagnosis provided good stability. CONCLUSION: RSI, DKI, and DWI can effectively differentiate between patients with high- and low-proliferation rectal carcinoma. Furthermore, the MD, MK, and f2 imaging parameters may be a novel and promising combination biomarker for examining Ki-67 status in rectal carcinoma.

Abnormal static and dynamic brain network connectivity associated with chronic tinnitus.

In order to comprehensively understand the changes of brain networks in patients with chronic tinnitus, this study combined static and dynamic analysis methods to explore the abnormalities of brain networks. Thirty-two patients with chronic tinnitus and 30 age-, sex- and education-matched healthy controls (HC) were recruited. Independent component analysis was used to identify resting-state networks (RSNs). Static and dynamic functional network connectivity (FNC) were performed. The temporal properties of brain network including mean dwell time (MDT), fraction time (FT) and numbers of transitions (NT) were calculated. Two-sample t test and Spearman's correlation were used for group compares and correlation analysis. Four RSNs showed abnormal FNC including auditory network (AUN), default mode network (DMN), attention network (AN) and sensorimotor network (SMN). For static analysis, tinnitus patients showed significantly decreased FNC in AUN-DMN, AUN-AN, DMN-AN, and DMN-SMN than HC [p < 0.05, false discovery rate (FDR) corrected]. For dynamic analysis, tinnitus patients showed significantly decreased FNC in DMN-AN in state 3 (p < 0.05, FDR corrected). MDT in state 3 was significantly decreased in tinnitus patients (t = 2.039, P = 0.046). In the tinnitus group, the score of tinnitus functional index (TFI) was negatively correlated with MDT and FT in state 4, and the duration of tinnitus was positively correlated with FT in state 1 and NT. Chronic tinnitus causes abnormal brain network connectivity. These abnormal brain networks help to clarify the mechanism of tinnitus generation and chronicity, and provide a potential basis for the treatment of tinnitus.

Dynamic evolution of COVID-19 vaccine hesitancy over 2021-2023 among Chinese population: Repeated nationwide cross-sectional study.

Globally, the rollout of COVID-19 vaccine had been faced with a significant barrier in the form of vaccine hesitancy. This study adopts a multi-stage perspective to explore the prevalence and determinants of COVID-19 vaccine hesitancy, focusing on their dynamic evolutionary features. Guided by the integrated framework of the 3Cs model (complacency, confidence, and convenience) and the EAH model (environmental, agent, and host), this study conducted three repeated national cross-sectional surveys. These surveys carried out from July 2021 to February 2023 across mainland China, targeted individuals aged 18 and older. They were strategically timed to coincide with three critical vaccination phases: universal coverage (stage 1), partial coverage (stage 2), and key population coverage (stage 3). From 2021 to 2023, the surveys examined sample sizes of 29 925, 6659, and 5407, respectively. The COVID-19 vaccine hesitation rates increased from 8.39% in 2021 to 29.72% in 2023. Urban residency, chronic condition, and low trust in vaccine developer contributed to significant COVID-19 vaccine hesitancy across the pandemic. Negative correlations between the intensity of vaccination policies and vaccine hesitancy, and positive correlations between vaccine hesitancy and long COVID, were confirmed. This study provides insights for designing future effective vaccination programs for emerging vaccine-preventable infectious X diseases.

Evaluating Large Language Models for Automated Reporting and Data Systems Categorization: Cross-Sectional Study.

BACKGROUND: Large language models show promise for improving radiology workflows, but their performance on structured radiological tasks such as Reporting and Data Systems (RADS) categorization remains unexplored. OBJECTIVE: This study aims to evaluate 3 large language model chatbots-Claude-2, GPT-3.5, and GPT-4-on assigning RADS categories to radiology reports and assess the impact of different prompting strategies. METHODS: This cross-sectional study compared 3 chatbots using 30 radiology reports (10 per RADS criteria), using a 3-level prompting strategy: zero-shot, few-shot, and guideline PDF-informed prompts. The cases were grounded in Liver Imaging Reporting & Data System (LI-RADS) version 2018, Lung CT (computed tomography) Screening Reporting & Data System (Lung-RADS) version 2022, and Ovarian-Adnexal Reporting & Data System (O-RADS) magnetic resonance imaging, meticulously prepared by board-certified radiologists. Each report underwent 6 assessments. Two blinded reviewers assessed the chatbots' response at patient-level RADS categorization and overall ratings. The agreement across repetitions was assessed using Fleiss κ. RESULTS: Claude-2 achieved the highest accuracy in overall ratings with few-shot prompts and guideline PDFs (prompt-2), attaining 57% (17/30) average accuracy over 6 runs and 50% (15/30) accuracy with k-pass voting. Without prompt engineering, all chatbots performed poorly. The introduction of a structured exemplar prompt (prompt-1) increased the accuracy of overall ratings for all chatbots. Providing prompt-2 further improved Claude-2's performance, an enhancement not replicated by GPT-4. The interrun agreement was substantial for Claude-2 (k=0.66 for overall rating and k=0.69 for RADS categorization), fair for GPT-4 (k=0.39 for both), and fair for GPT-3.5 (k=0.21 for overall rating and k=0.39 for RADS categorization). All chatbots showed significantly higher accuracy with LI-RADS version 2018 than with Lung-RADS version 2022 and O-RADS (P<.05); with prompt-2, Claude-2 achieved the highest overall rating accuracy of 75% (45/60) in LI-RADS version 2018. CONCLUSIONS: When equipped with structured prompts and guideline PDFs, Claude-2 demonstrated potential in assigning RADS categories to radiology cases according to established criteria such as LI-RADS version 2018. However, the current generation of chatbots lags in accurately categorizing cases based on more recent RADS criteria.

Quantitative Expression of Latent Disease Factors in Individuals Associated with Psychopathology Dimensions and Treatment Response.

Psychiatric comorbidity is common in symptom-based diagnoses like autism spectrum disorder (ASD), attention/deficit hyper-activity disorder (ADHD), and obsessive-compulsive disorder (OCD). However, these co-occurring symptoms mediated by shared and/or distinct neural mechanisms are difficult to profile at the individual level. Capitalizing on unsupervised machine learning with a hierarchical Bayesian framework, we derived latent disease factors from resting-state functional connectivity data in a hybrid cohort of ASD and ADHD and delineated individual associations with dimensional symptoms based on canonical correlation analysis. Models based on the same factors generalized to previously unseen individuals in a subclinical cohort and one local OCD database with a subset of patients undergoing neurosurgical intervention. Four factors, identified as variably co-expressed in each patient, were significantly correlated with distinct symptom domains (r = -0.26-0.53, P < 0.05): behavioral regulation (Factor-1), communication (Factor-2), anxiety (Factor-3), adaptive behaviors (Factor-4). Moreover, we demonstrated Factor-1 expressed in patients with OCD and Factor-3 expressed in participants with anxiety, at the degree to which factor expression was significantly predictive of individual symptom scores (r = 0.18-0.5, P < 0.01). Importantly, peri-intervention changes in Factor-1 of OCD were associated with variable treatment outcomes (r = 0.39, P < 0.05). Our results indicate that these data-derived latent disease factors quantify individual factor expression to inform dimensional symptom and treatment outcomes across cohorts, which may promote quantitative psychiatric diagnosis and personalized intervention.

Tri-Compartmental Restriction Spectrum Imaging Based on 18F-FDG PET/MR for Identification of Primary Benign and Malignant Lung Lesions.

BACKGROUND: Restriction spectrum imaging (RSI), as an advanced quantitative diffusion-weighted magnetic resonance imaging technique, has the potential to distinguish primary benign and malignant lung lesions. OBJECTIVE: To explore how well the tri-compartmental RSI performs in distinguishing primary benign from malignant lung lesions compared with diffusion-weighted imaging (DWI), and to further explore whether positron emission tomography/magnetic resonance imaging (PET/MRI) can improve diagnostic efficacy. STUDY TYPE: Prospective. POPULATION: 137 patients, including 108 malignant and 29 benign lesions (85 males, 52 females; average age = 60.0 ± 10.0 years). FIELD STRENGTH/SEQUENCE: T2WI, T1WI, multi-b value DWI, MR-based attenuation correction, and PET imaging on a 3.0 T whole-body PET/MR system. ASSESSMENT: The apparent diffusion coefficient (ADC), RSI-derived parameters (restricted diffusion f 1 $$ {f}_1 $$ , hindered diffusion f 2 $$ {f}_2 $$ , and free diffusion f 3 $$ {f}_3 $$ ) and the maximum standardized uptake value (SUVmax) were calculated and analyzed for diagnostic efficacy individually or in combination. STATISTICAL TESTS: Student's t-test, Mann-Whitney U test, receiver operating characteristic (ROC) curves, Delong test, Spearman's correlation analysis. P < 0.05 was considered statistically significant. RESULTS: The f 1 $$ {f}_1 $$ , SUVmax were significantly higher, and f 3 $$ {f}_3 $$ , ADC were significantly lower in the malignant group [0.717 ± 0.131, 9.125 (5.753, 13.058), 0.194 ± 0.099, 1.240 (0.972, 1.407)] compared to the benign group [0.504 ± 0.236, 3.390 (1.673, 6.030), 0.398 ± 0.195, 1.485 ± 0.382]. The area under the ROC curve (AUC) values ranked from highest to lowest as follows: AUC (SUVmax) > AUC ( f 3 $$ {f}_3 $$ ) > AUC ( f 1 $$ {f}_1 $$ ) > AUC (ADC) > AUC ( f 2 $$ {f}_2 $$ ) (AUC = 0.819, 0.811, 0.770, 0.745, 0549). The AUC (AUC = 0.900) of the combined model of RSI with PET was significantly higher than that of either single-modality imaging. CONCLUSION: RSI-derived parameters ( f 1 $$ {f}_1 $$ , f 3 $$ {f}_3 $$ ) might help to distinguish primary benign and malignant lung lesions and the discriminatory utility of f 2 $$ {f}_2 $$ was not observed. The RSI exhibits comparable or potentially enhanced performance compared with DWI, and the combined RSI and PET model might improve diagnostic efficacy. TECHNICAL EFFICACY: Stage 2.

State-specific Regulation of Electrical Stimulation in the Intralaminar Thalamus of Macaque Monkeys: Network and Transcriptional Insights into Arousal.

Long-range thalamocortical communication is central to anesthesia-induced loss of consciousness and its reversal. However, isolating the specific neural networks connecting thalamic nuclei with various cortical regions for state-specific anesthesia regulation is challenging, with the biological underpinnings still largely unknown. Here, simultaneous electroencephalogram-fuctional magnetic resonance imaging (EEG-fMRI) and deep brain stimulation are applied to the intralaminar thalamus in macaques under finely-tuned propofol anesthesia. This approach led to the identification of an intralaminar-driven network responsible for rapid arousal during slow-wave oscillations. A network-based RNA-sequencing analysis is conducted of region-, layer-, and cell-specific gene expression data from independent transcriptomic atlases and identifies 2489 genes preferentially expressed within this arousal network, notably enriched in potassium channels and excitatory, parvalbumin-expressing neurons, and oligodendrocytes. Comparison with human RNA-sequencing data highlights conserved molecular and cellular architectures that enable the matching of homologous genes, protein interactions, and cell types across primates, providing novel insight into network-focused transcriptional signatures of arousal.

Radiomics analysis for prediction of lymph node metastasis after neoadjuvant chemotherapy based on pretreatment MRI in patients with locally advanced cervical cancer.

Background: This study aims to develop and validate a pretreatment MRI-based radiomics model to predict lymph node metastasis (LNM) following neoadjuvant chemotherapy (NACT) in patients with locally advanced cervical cancer (LACC). Methods: Patients with LACC who underwent NACT from two centers between 2013 and 2022 were enrolled retrospectively. Based on the lymph node (LN) status determined in the pathology reports after radical hysterectomy, patients were categorized as LN positive or negative. The patients from center 1 were assigned as the training set while those from center 2 formed the validation set. Radiomics features were extracted from pretreatment sagittal T2-weighted imaging (Sag-T2WI), axial diffusion-weighted imaging (Ax-DWI), and the delayed phase of dynamic contrast-enhanced sagittal T1-weighted imaging (Sag-T1C) for each patient. The K-best and least absolute shrinkage and selection operator (LASSO) methods were employed to reduce dimensionality, and the radiomics features strongly associated with LNM were selected and used to construct three single-sequence models. Furthermore, clinical variables were incorporated through multivariate regression analysis and fused with the selected radiomics features to construct the clinical-radiomics combined model. The diagnostic performance of the models was assessed using receiver operating characteristic (ROC) curve analysis. The clinical utility of the models was evaluated by the area under the ROC curve (AUC) and decision curve analysis (DCA). Results: A total of 282 patients were included, comprising 171 patients in the training set, and 111 patients in the validation set. Compared to the Sag-T2WI model (AUC, 95%CI, training set, 0.797, 0.722-0.782; validation set, 0.648, 0.521-0.776) and the Sag-T1C model (AUC, 95%CI, training set, 0.802, 0.723-0.882; validation set, 0.630, 0.505-0.756), the Ax-DWI model exhibited the highest diagnostic performance with AUCs of 0.855 (95%CI, 0.791-0.919) in training set, and 0.753 (95%CI, 0.638-0.867) in validation set, respectively. The combined model, integrating selected features from three sequences and FIGO stage, surpassed predictive ability compared to the single-sequence models, with AUC of 0.889 (95%CI, 0.833-0.945) and 0.859 (95%CI, 0.781-0.936) in the training and validation sets, respectively. Conclusions: The pretreatment MRI-based radiomics model, integrating radiomics features from three sequences and clinical variables, exhibited superior performance in predicting LNM following NACT in patients with LACC.

Clinical Implementation of Total-Body PET in China.

Total-body (TB) PET/CT is a groundbreaking tool that has brought about a revolution in both clinical application and scientific research. The transformative impact of TB PET/CT in the realms of clinical practice and scientific exploration has been steadily unfolding since its introduction in 2018, with implications for its implementation within the health care landscape of China. TB PET/CT's exceptional sensitivity enables the acquisition of high-quality images in significantly reduced time frames. Clinical applications have underscored its effectiveness across various scenarios, emphasizing the capacity to personalize dosage, scan duration, and image quality to optimize patient outcomes. TB PET/CT's ability to perform dynamic scans with high temporal and spatial resolution and to perform parametric imaging facilitates the exploration of radiotracer biodistribution and kinetic parameters throughout the body. The comprehensive TB coverage offers opportunities to study interconnections among organs, enhancing our understanding of human physiology and pathology. These insights have the potential to benefit applications requiring holistic TB assessments. The standard topics outlined in The Journal of Nuclear Medicine were used to categorized the reviewed articles into 3 sections: current clinical applications, scan protocol design, and advanced topics. This article delves into the bottleneck that impedes the full use of TB PET in China, accompanied by suggested solutions.

Cross-ancestry genome-wide association studies of brain imaging phenotypes.

Genome-wide association studies of brain imaging phenotypes are mainly performed in European populations, but other populations are severely under-represented. Here, we conducted Chinese-alone and cross-ancestry genome-wide association studies of 3,414 brain imaging phenotypes in 7,058 Chinese Han and 33,224 white British participants. We identified 38 new associations in Chinese-alone analyses and 486 additional new associations in cross-ancestry meta-analyses at P < 1.46 × 10-11 for discovery and P < 0.05 for replication. We pooled significant autosomal associations identified by single- or cross-ancestry analyses into 6,443 independent associations, which showed uneven distribution in the genome and the phenotype subgroups. We further divided them into 44 associations with different effect sizes and 3,557 associations with similar effect sizes between ancestries. Loci of these associations were shared with 15 brain-related non-imaging traits including cognition and neuropsychiatric disorders. Our results provide a valuable catalog of genetic associations for brain imaging phenotypes in more diverse populations.

Accurate Whole-Brain Image Enhancement for Low-Dose Integrated PET/MR Imaging Through Spatial Brain Transformation.

Positron emission tomography/magnetic resonance imaging (PET/MRI) systems can provide precise anatomical and functional information with exceptional sensitivity and accuracy for neurological disorder detection. Nevertheless, the radiation exposure risks and economic costs of radiopharmaceuticals may pose significant burdens on patients. To mitigate image quality degradation during low-dose PET imaging, we proposed a novel 3D network equipped with a spatial brain transform (SBF) module for low-dose whole-brain PET and MR images to synthesize high-quality PET images. The FreeSurfer toolkit was applied to derive the spatial brain anatomical alignment information, which was then fused with low-dose PET and MR features through the SBF module. Moreover, several deep learning methods were employed as comparison measures to evaluate the model performance, with the peak signal-to-noise ratio (PSNR), structural similarity (SSIM) and Pearson correlation coefficient (PCC) serving as quantitative metrics. Both the visual results and quantitative results illustrated the effectiveness of our approach. The obtained PSNR and SSIM were 41.96 ±4.91 dB (p<0.01) and 0.9654 ±0.0215 (p<0.01), which achieved a 19% and 20% improvement, respectively, compared to the original low-dose brain PET images. The volume of interest (VOI) analysis of brain regions such as the left thalamus (PCC = 0.959) also showed that the proposed method could achieve a more accurate standardized uptake value (SUV) distribution while preserving the details of brain structures. In future works, we hope to apply our method to other multimodal systems, such as PET/CT, to assist clinical brain disease diagnosis and treatment.

Clinical study on the prediction of ALN metastasis based on intratumoral and peritumoral DCE-MRI radiomics and clinico-radiological characteristics in breast cancer.

Objective: To investigate the value of predicting axillary lymph node (ALN) metastasis based on intratumoral and peritumoral dynamic contrast-enhanced MRI (DCE-MRI) radiomics and clinico-radiological characteristics in breast cancer. Methods: A total of 473 breast cancer patients who underwent preoperative DCE-MRI from Jan 2017 to Dec 2020 were enrolled. These patients were randomly divided into training (n=378) and testing sets (n=95) at 8:2 ratio. Intratumoral regions (ITRs) of interest were manually delineated, and peritumoral regions of 3 mm (3 mmPTRs) were automatically obtained by morphologically dilating the ITR. Radiomics features were extracted, and ALN metastasis-related radiomics features were selected by the Mann-Whitney U test, Z score normalization, variance thresholding, K-best algorithm and least absolute shrinkage and selection operator (LASSO) algorithm. Clinico-radiological risk factors were selected by logistic regression and were also used to construct predictive models combined with radiomics features. Then, 5 models were constructed, including ITR, 3 mmPTR, ITR+3 mmPTR, clinico-radiological and combined (ITR+3 mmPTR+ clinico-radiological) models. The performance of models was assessed by sensitivity, specificity, accuracy, F1 score and area under the curve (AUC) of receiver operating characteristic (ROC), calibration curves and decision curve analysis (DCA). Results: A total of 2264 radiomics features were extracted from each region of interest (ROI), 3 and 10 radiomics features were selected for the ITR and 3 mmPTR, respectively. 5 clinico-radiological risk factors were selected, including lesion size, human epidermal growth factor receptor 2 (HER2) expression, vascular cancer thrombus status, MR-reported ALN status, and time-signal intensity curve (TIC) type. In the testing set, the combined model showed the highest AUC (0.839), specificity (74.2%), accuracy (75.8%) and F1 Score (69.3%) among the 5 models. DCA showed that it had the greatest net clinical benefit compared to the other models. Conclusion: The intra- and peritumoral radiomics models based on DCE-MRI could be used to predict ALN metastasis in breast cancer, especially for the combined model with clinico-radiological characteristics showing promising clinical application value.

BcABF1 Plays a Role in the Feedback Regulation of Abscisic Acid Signaling via the Direct Activation of BcPYL4 Expression in Pakchoi.

Abscisic acid-responsive element-binding factor 1 (ABF1), a key transcription factor in the ABA signal transduction process, regulates the expression of downstream ABA-responsive genes and is involved in modulating plant responses to abiotic stress and developmental processes. However, there is currently limited research on the feedback regulation of ABF1 in ABA signaling. This study delves into the function of BcABF1 in Pakchoi. We observed a marked increase in BcABF1 expression in leaves upon ABA induction. The overexpression of BcABF1 not only spurred Arabidopsis growth but also augmented the levels of endogenous IAA. Furthermore, BcABF1 overexpression in Arabidopsis significantly decreased leaf water loss and enhanced the expression of genes associated with drought tolerance in the ABA pathway. Intriguingly, we found that BcABF1 can directly activate BcPYL4 expression, a critical receptor in the ABA pathway. Similar to BcABF1, the overexpression of BcPYL4 in Arabidopsis also reduces leaf water loss and promotes the expression of drought and other ABA-responsive genes. Finally, our findings suggested a novel feedback regulation mechanism within the ABA signaling pathway, wherein BcABF1 positively amplifies the ABA signal by directly binding to and activating the BcPYL4 promoter.

Assessment of Lung Nodule Detection and Lung CT Screening Reporting and Data System Classification Using Zero Echo Time Pulmonary MRI.

BACKGROUND: The detection rate of lung nodules has increased considerably with CT as the primary method of examination, and the repeated CT examinations at 3 months, 6 months or annually, based on nodule characteristics, have increased the radiation exposure of patients. So, it is urgent to explore a radiation-free MRI examination method that can effectively address the challenges posed by low proton density and magnetic field inhomogeneities. PURPOSE: To evaluate the potential of zero echo time (ZTE) MRI in lung nodule detection and lung CT screening reporting and data system (lung-RADS) classification, and to explore the value of ZTE-MRI in the assessment of lung nodules. STUDY TYPE: Prospective. POPULATION: 54 patients, including 21 men and 33 women. FIELD STRENGTH/SEQUENCE: Chest CT using a 16-slice scanner and ZTE-MRI at 3.0T based on fast gradient echo. ASSESSMENT: Nodule type (ground-glass nodules, part-solid nodules, and solid nodules), lung-RADS classification, and nodule diameter (manual measurement) on CT and ZTE-MRI images were recorded. STATISTICAL TESTS: The percent of concordant cases, Kappa value, intraclass correlation coefficient (ICC), Wilcoxon signed-rank test, Spearman's correlation, and Bland-Altman. The p-value <0.05 is considered significant. RESULTS: A total of 54 patients (age, 54.8 ± 11.9 years; 21 men) with 63 nodules were enrolled. Compared with CT, the total nodule detection rate of ZTE-MRI was 85.7%. The intermodality agreement of ZTE-MRI and CT lung nodules type evaluation was substantial (Kappa = 0.761), and the intermodality agreement of ZTE-MRI and CT lung-RADS classification was moderate (Kappa = 0.592). The diameter measurements between ZTE-MRI and CT showed no significant difference and demonstrated a high degree of interobserver (ICC = 0.997-0.999) and intermodality (ICC = 0.956-0.985) agreements. DATA CONCLUSION: The measurement of nodule diameter by pulmonary ZTE-MRI is similar to that by CT, but the ability of lung-RADS to classify nodes from MRI images still requires further research. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Radiomics analysis of intratumoral and different peritumoral regions from multiparametric MRI for evaluating HER2 status of breast cancer: A comparative study.

Purpose: To investigate the potential of radiomics signatures (RSs) from intratumoral and peritumoral regions on multiparametric magnetic resonance imaging (MRI) to noninvasively evaluate HER2 status in breast cancer. Method: In this retrospective study, 992 patients with pathologically confirmed breast cancers who underwent preoperative MRI were enrolled. The breast cancer lesions were segmented manually, and the intratumor region of interest (ROIIntra) was dilated by 2, 4, 6 and 8 mm (ROIPeri2mm, ROIPeri4mm, ROIPeri6mm, and ROIPeri8mm, respectively). Quantitative radiomics features were extracted from dynamic contrast-enhanced T1-weighted imaging (DCE-T1), fat-saturated T2-weighted imaging (T2) and diffusion-weighted imaging (DWI). A three-step procedure was performed for feature selection, and RSs were constructed using a support vector machine (SVM) to predict HER2 status. Result: The best single-area RSs for predicting HER2 status were DCE_Peri4mm-RS, T2_Peri4mm-RS, and DWI_Peri4mm-RS, yielding areas under the curve (AUCs) of 0.716 (95% confidence interval (CI), 0.648-0.778), 0.706 (95% CI, 0.637-0.768), and 0.719 (95% CI, 0.651-0.780), respectively, in the test set. The optimal RSs combining intratumoral and peritumoral regions for evaluating HER2 status were DCE-T1_Intra + DCE_Peri4mm-RS, T2_Intra + T2_Peri6mm-RS and DWI_Intra + DWI_Peri4mm-RS, with AUCs of 0.752 (95% CI, 0.686-0.810), 0.754 (95% CI, 0.688-0.812) and 0.725 (95% CI, 0.657-0.786), respectively, in the test set. Combining three sequences in the ROIIntra, ROIPeri2mm, ROIPeri4mm, ROIPeri6mm and ROIPeri8mm areas, the optimal RS was DCE-T1_Peri4mm + T2_Peri4mm + DWI_Peri4mm-RS, achieving an AUC of 0.795 (95% CI, 0.733-0.849) in the test set. Conclusion: This study systematically explored the influence of the intratumoral region, different peritumoral sizes and their combination in radiomics analysis for predicting HER2 status in breast cancer based on multiparametric MRI and found the optimal RS.

Prediction of tumor origin in cancers of unknown primary origin with cytology-based deep learning.

Cancer of unknown primary (CUP) site poses diagnostic challenges due to its elusive nature. Many cases of CUP manifest as pleural and peritoneal serous effusions. Leveraging cytological images from 57,220 cases at four tertiary hospitals, we developed a deep-learning method for tumor origin differentiation using cytological histology (TORCH) that can identify malignancy and predict tumor origin in both hydrothorax and ascites. We examined its performance on three internal (n = 12,799) and two external (n = 14,538) testing sets. In both internal and external testing sets, TORCH achieved area under the receiver operating curve values ranging from 0.953 to 0.991 for cancer diagnosis and 0.953 to 0.979 for tumor origin localization. TORCH accurately predicted primary tumor origins, with a top-1 accuracy of 82.6% and top-3 accuracy of 98.9%. Compared with results derived from pathologists, TORCH showed better prediction efficacy (1.677 versus 1.265, P < 0.001), enhancing junior pathologists' diagnostic scores significantly (1.326 versus 1.101, P < 0.001). Patients with CUP whose initial treatment protocol was concordant with TORCH-predicted origins had better overall survival than those who were administrated discordant treatment (27 versus 17 months, P = 0.006). Our study underscores the potential of TORCH as a valuable ancillary tool in clinical practice, although further validation in randomized trials is warranted.

Laser capture microdissection transcriptome (LCM RNA-seq) reveals BcDFR is a key gene in anthocyanin synthesis of non-heading Chinese cabbage.

BACKGROUND: Purple non-heading Chinese cabbage [Brassica campestris (syn. Brassica rapa) ssp. chinensis] has become popular because of its richness in anthocyanin. However, anthocyanin only accumulates in the upper epidermis of leaves. Further studies are needed to investigate the molecular mechanisms underlying the specific accumulation of it. RESULTS: In this study, we used the laser capture frozen section method (LCM) to divide purple (ZBC) and green (LBC) non-heading Chinese cabbage leaves into upper and lower epidermis parts (Pup represents the purple upper epidermis, Plow represents the purple lower epidermis, Gup represents the green upper epidermis, Glow represents the green lower epidermis). Through transcriptome sequencing, we found that the DIHYDROFLAVONOL 4-REDUCTASE-encoding gene BcDFR, is strongly expressed in Pup but hardly in others (Plow, Gup, Glow). Further, a deletion and insertion in the promoter of BcDFR in LBC were found, which may interfere with BcDFR expression. Subsequent analysis of gene structure and conserved structural domains showed that BcDFR is highly conserved in Brassica species. The predicted protein-protein interaction network of BcDFR suggests that it interacts with almost all functional proteins in the anthocyanin biosynthesis pathway. Finally, the results of the tobacco transient expression also demonstrated that BcDFR promotes the synthesis and accumulation of anthocyanin. CONCLUSIONS: BcDFR is specifically highly expressed on the upper epidermis of purple non-heading Chinese cabbage leaves and regulates anthocyanin biosynthesis and accumulation. Our study provides new insights into the functional analysis and transcriptional regulatory network of anthocyanin-related genes in purple non-heading Chinese cabbage.

Amide proton transfer-weighted imaging and stretch-exponential model DWI based 18F-FDG PET/MRI for differentiation of benign and malignant solitary pulmonary lesions.

OBJECTIVES: To differentiate benign and malignant solitary pulmonary lesions (SPLs) by amide proton transfer-weighted imaging (APTWI), mono-exponential model DWI (MEM-DWI), stretched exponential model DWI (SEM-DWI), and 18F-FDG PET-derived parameters. METHODS: A total of 120 SPLs patients underwent chest 18F-FDG PET/MRI were enrolled, including 84 in the training set (28 benign and 56 malignant) and 36 in the test set (13 benign and 23 malignant). MTRasym(3.5 ppm), ADC, DDC, α, SUVmax, MTV, and TLG were compared. The area under receiver-operator characteristic curve (AUC) was used to assess diagnostic efficacy. The Logistic regression analysis was used to identify independent predictors and establish prediction model. RESULTS: SUVmax, MTV, TLG, α, and MTRasym(3.5 ppm) values were significantly lower and ADC, DDC values were significantly higher in benign SPLs than malignant SPLs (all P < 0.01). SUVmax, ADC, and MTRasym(3.5 ppm) were independent predictors. Within the training set, the prediction model based on these independent predictors demonstrated optimal diagnostic efficacy (AUC, 0.976; sensitivity, 94.64%; specificity, 92.86%), surpassing any single parameter with statistical significance. Similarly, within the test set, the prediction model exhibited optimal diagnostic efficacy. The calibration curves and DCA revealed that the prediction model not only had good consistency but was also able to provide a significant benefit to the related patients, both in the training and test sets. CONCLUSION: The SUVmax, ADC, and MTRasym(3.5 ppm) were independent predictors for differentiation of benign and malignant SPLs, and the prediction model based on them had an optimal diagnostic efficacy.

Individualized functional connectivity markers associated with motor and mood symptoms of Parkinson's disease.

Parkinson's disease (PD) is a complex neurological disorder characterized by many motor and non-motor symptoms. While most studies focus on the motor symptoms of the disease, it is important to identify markers that underlie different facets of the disease. In this case-control study, we sought to discover reliable, individualized functional connectivity markers associated with both motor and mood symptoms of PD. Using functional MRI, we extensively sampled 166 patients with PD (64 women, 102 men; mean age=61.8 years, SD=7.81) and 51 healthy control participants (32 women, 19 men; mean age=55.68 years, SD=7.62). We found that a model consisting of 44 functional connections predicted both motor (UPDRS-III: Pearson r=0.21, FDR-adjusted p=0.006) and mood symptoms (HAMD: Pearson r=0.23, FDR-adjusted p=0.006; HAMA: Pearson r=0.21, FDR-adjusted p=0.006). Two sets of connections contributed differentially to these predictions. Between-network connections, mainly connecting the sensorimotor and visual large-scale functional networks, substantially contributed to the prediction of motor measures, while within-network connections in the insula and sensorimotor network contributed more so to mood prediction. The middle to posterior insula region played a particularly important role in predicting depression and anxiety scores. We successfully replicated and generalized our findings in two independent PD datasets. Taken together, our findings indicate that sensorimotor and visual network markers are indicative of PD brain pathology, and that distinct subsets of markers are associated with motor and mood symptoms of PD.