CS1 Expression Pattern in NK Cells and Correlated Factors in Plasma Cell dyscrasias: Implications for Elotuzumab Therapy and CAR-T Efficacy.

Treatment with elotuzumab alone has no discernible antitumor effect and progress in chimeric antigen receptor T cells (CAR-T) therapy targeting CS1 is relatively slow. A retrospective analysis was performed on 236 patients with multiple myeloma (MM) and 30 patients with other plasma cell dyscrasias (PCDs). CS1 expression in NK cells, lymphocytes, and monoclonal plasma cells was assessed using multiparameter flow cytometry. Furthermore, new explorations were undertaken regarding the antitumor applications of elotuzumab. Patients with MM had significantly higher CS1 expression levels in plasma cells than other patients with PCDs, with no significant differences between lymphocytes and NK cells. In both patients with MM and other PCDs, CS1 expression was significantly higher in plasma cells than in NK cells and lymphocytes. Univariate and multivariate analyses revealed a significant correlation between CS1 expression in plasma (r = 0.60; P < 0.001) and NK (r = 0.79; P < 0.001) cells. Factors such as cytogenetic abnormalities, disease progression, and survival were not associated with CS1 expression in NK cells. Moreover, this study showed that elotuzumab strongly increases the cytotoxicity of NK cells against non-plasma and plasma tumor cells independent of their CS1 expression level. This underscores the potential of elotuzumab in combination with NK cells as an effective therapeutic strategy against a broad spectrum of tumor types.

Case report: Light-chain amyloidosis responsive to selinexor in combination with daratumumab and dexamethasone (SDd) therapy.

The outcome of AL amyloidosis remains poor, particularly in patients with advanced organ involvement which takes long time to recovery. We conducted an observational study of two patients with AL amyloidosis treated with SDd regimen. Both patients successfully achieved significant hematological and organ responses without severe adverse events, and the time to organ response was remarkably shorter than previously reported. Notably, an over 15% reduction in interventricular septal thickness (IVST) was observed in patient#2 within 6 months. Up to now, SDd therapy has not been previously reported in AL amyloidosis and may be a promising option for these patients.

Radiomics-based machine learning approach for the prediction of grade and stage in upper urinary tract urothelial carcinoma-a step towards virtual biopsy.

OBJECTIVES: Upper tract urothelial carcinoma is a rare, aggressive lesion, with early detection a key to its management. This study aimed to utilise computed tomographic urogram data to develop machine learning models for predicting tumour grading and staging in upper urothelial tract carcinoma patients and to compare these predictions with histopathological diagnosis used as reference standards. METHODS: Protocol-based computed tomographic urogram data from 106 patients were obtained and visualised in 3D. Digital segmentation of the tumours was conducted by extracting textural radiomics features. They were further classified using 11 predictive models. The predicted grades and stages were compared to the histopathology of radical nephroureterectomy specimens. RESULTS: Classifier models worked well in mining the radiomics data and delivered satisfactory predictive machine learning models. The MultiLayer Panel showed 84% sensitivity and 93% specificity while predicting upper tract urothelial carcinoma grades. The Logistic Regression model showed a sensitivity of 83% and a specificity of 76% while staging. Similarly, other classifier algorithms (e.g., Support Vector classifier) provided a highly accurate prediction while grading upper tract urothelial carcinoma compared to clinical features alone or ureteroscopic biopsy histopathology. CONCLUSION: Data mining tools could handle medical imaging datasets from small (<2 cm) tumours for upper tract urothelial carcinoma. The radiomics-based machine learning algorithms provide a potential tool to model tumour grading and staging with implications for clinical practice and the upgradation of current paradigms in cancer diagnostics. CLINICAL RELEVANCE: Machine learning based on radiomics features can predict upper tract urothelial cancer grading and staging with significant improvement over ureteroscopic histopathology. The study showcased the prowess of such emerging tools in the set objectives with implications towards virtual biopsy.

A signature based on circadian rhythm-associated genes for the evaluation of prognosis and the tumour microenvironment in HNSCC.

The morbidity and mortality rates of head and neck squamous cell carcinoma (HNSCC) remain high worldwide. Therefore, there is an urgent need to identify a new prognostic biomarker to guide the personalized treatment of HNSCC patients. Increasing evidence suggests that circadian rhythm genes play an important role in the development and progression of cancer. We aimed to explore the value of circadian rhythm genes in predicting prognosis and guiding the treatment of HNSCC. We first obtained a list of circadian rhythm genes from previous research. The sequencing data were retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Finally, univariate Cox proportional hazard analysis, least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox proportional hazard analysis were performed to develop a prognostic signature (Circadian Rhythm-Related Gene Prognostic Index, CRRGPI) consisting of nine circadian rhythm genes. The signature exhibited good performance in predicting overall survival. Patients with low CRRGPI scores had lower metabolic activities and an active antitumour immunity ability. Additionally, a clinical cohort was used to further evaluate the ability of the CRRGPI to predict the efficacy of immune checkpoint inhibitors. In conclusion, the novel circadian rhythm-related gene signature can provide a precise prognostic evaluation with the potential capacity to guide individualized treatment regimens for HNSCC patients.

First-principles calculation of self-interstitial atom-impurity atom interactions in ferritic steel.

In this study, the interactions between self-interstitial atoms (SIA) and impurity atoms (Cu and P) in the body-centered cubic (bcc)-Fe matrix have been investigated using the first principles approach. The results show that Cu and P atoms are more prone to segregation on perpendicular and parallel surfaces containing dumbbell atoms, respectively. Next, by combining the charge density difference and considering the electronic structure and lattice distortion, the origin of the binding energy of complexes formed between SIA and impurity atoms was discussed. The results show that as the number of impurity atoms increases, the atomic bonds formed by the interactions between the impurity atoms decrease the binding energy between single impurity atoms and the matrix and reduce the strain field around them, resulting in an increase in the stability of the complexes. Comparison with previous experimental results revealed the reasons for the changes in atomic occupancy during the segregation of Cu and P atoms. The results provide insights into the behavior of impurity atoms in irradiated materials and provide a deeper understanding of the electron level of impurity atomization.

The role of early cerebral edema and hematoma assessment in aneurysmal subarachnoid hemorrhage (a-SAH) in predicting structural brain abnormalities in cognitive impairments-- case controlled study.

BACKGROUND: Early assessment and management of cerebral edema and hematoma following aneurysmal subarachnoid hemorrhage (a-SAH) can significantly impact clinical cognitive outcomes. However, current clinical practices lack predictive models to identify early structural brain abnormalities affecting cognition. To address this gap, we propose the development of a predictive model termed the a-SAH Early Brain Edema/Hematoma Compression Neural (Structural Brain) Networks Score System (SEBE-HCNNSS). METHODS: In this study, 202 consecutive patients with spontaneous a-SAH underwent initial computed tomography (CT) or magnetic resonance imaging (MRI) scans within 24 hours of ictus with follow-up 2 months after discharge. Using logistic regression analysis (univariate and multivariate), we evaluated the association of clinically relevant factors and various traditional scale ratings with cognitive impairment (CI). Risk factors with the highest area under the curve (AUC) values were included in the multivariate analysis and least absolute shrinkage and selection operator (LASSO) analysis or Cox regression analysis. RESULTS: A total of 177 patients were enrolled in the study, and 43 patients were classified with a high SEBE-HCNNSS grade (3 to 5). After a mean follow-up of 2 months, 121 individuals (68.36%) with a-SAH and 3 control subjects developed incident CI. The CT inter-observer reliability of the SEBE-HCNNSS scale was high, with a Kappa value of 1. Furthermore, ROC analysis identified the SEBE-HCNNSS scale (OR 3.322, 95% CI 2.312-7.237, P=0.00025) as an independent predictor of edema, CI, and unfavorable prognosis. These results were also replicated in a validation cohort. CONCLUSION: Overall, the SEBE-HCNNSS scale represents a simple assessment tool with promising predictive value for CI and clinical outcomes post-a-SAH. Our findings indicate its practical utility as a prognostic instrument for risk evaluation after a-SAH, potentially facilitating early intervention and treatment.

pH-Responsive polymer boosts cytosolic siRNA release for retinal neovascularization therapy.

Small interfering RNA (siRNA) has a promising future in the treatment of ocular diseases due to its high efficiency, specificity, and low toxicity in inhibiting the expression of target genes and proteins. However, due to the unique anatomical structure of the eye and various barriers, delivering nucleic acids to the retina remains a significant challenge. In this study, we rationally design PACD, an A-B-C type non-viral vector copolymer composed of a hydrophilic PEG block (A), a siRNA binding block (B) and a pH-responsive block (C). PACDs can self-assemble into nanosized polymeric micelles that compact siRNAs into polyplexes through simple mixing. By evaluating its pH-responsive activity, gene silencing efficiency in retinal cells, intraocular distribution, and anti-angiogenesis therapy in a mouse model of hypoxia-induced angiogenesis, we demonstrate the efficiency and safety of PACD in delivering siRNA in the retina. We are surprised to discover that, the PACD/siRNA polyplexes exhibit remarkable intracellular endosomal escape efficiency, excellent gene silencing, and inhibit retinal angiogenesis. Our study provides design guidance for developing efficient nonviral ocular nucleic acid delivery systems.

Effects of different phosphorus fertilizers on cadmium absorption and accumulation in rice under low-phosphorus and rich-cadmium soil.

Rice is the main food crops with the higher capacity for cadmium (Cd) uptake, necessitating the urgent need for remediation measures to address Cd in paddy soil. Reasonable agronomic methods are convenient and favorable for fixing the issue. In this study, a pot experiment was employed to evaluate the effects of two foliar (NaH2PO4, SDP; KH2PO4, PDP) and two solid phosphate fertilizers (double-superphosphate, DSP; calcium-magnesium phosphate, CMP) on uptake and remobilization of Cd in rice plants under the low-P and rich-Cd soil. The results revealed that these four phosphorus fertilizer significantly down-regulated the relative expression of OsNRAMP5 involved in Cd absorption, while up-regulated OsPCS1 expression and increased distribution of Cd into the cell wall in roots. Furthermore, phosphorus fertilizer resulted in a significant decrease in the relative expression of OsLCT1 in stems and OsLCD in leaves, decreased the transfer factor of Cd from shoots to grains, and ulterior reduced the Cd accumulation in three protein components of globulin, albumin, and glutelin, making the average Cd concentration of brown rice decreased by 82.96%. These results comprehensively indicate that in situations with similar soil backgrounds, the recommended application of solid CMP and foliar PDP can alleviate the toxicity of Cd by reducing its absorption and remobilization.

κ-Opioid receptor activation attenuates osteoarthritis synovitis by regulating macrophage polarization through the NF-κB pathway.

Osteoarthritis (OA) is a prevalent and chronic joint disease that affects the aging population, causing pain and disability. Macrophages in synovium are important mediators of synovial inflammatory activity and pathological joint pain. Previous studies have demonstrated the significant involvement of κ-opioid receptor (KOR) in the regulation of pain and inflammation. Our study reveals a significant reduction in synovial KOR expression among patients and mice with OA. Here, we find that KOR activation effectively inhibits the expressions of the LPS-induced-inflammatory cytokines TNF-α and IL-6 by inhibiting macrophage M1 phenotype. Mechanistically, KOR activation effectively suppresses the proinflammatory factor secretion of macrophages by inhibiting the translocation of NF-κB into the nucleus. Our animal experiments reveal that activation of KOR effectively alleviates knee pain and prevents synovitis progression in OA mice. Consistently, KOR administration suppresses the expressions of M1 macrophage markers and the NF-κB pathway in the synovium of the knee. Collectively, our study suggests that targeting KOR may be a viable strategy for treating OA by inhibiting synovitis and improving joint pain in affected patients.

Characteristics of Klebsiella pneumoniae pyogenic liver abscess from 2010-2021 in a tertiary teaching hospital of South China.

OBJECTIVES: Pyogenic liver abscess (PLA) is a severe and potentially fatal infectious disease. Klebsiella pneumoniae (K. pneumoniae) is the predominant pathogen responsible for PLA. This study aims to investigate the clinical characteristics and prognostic factors of K. pneumoniae-induced pyogenic liver abscess (KP-PLA), particularly those caused by carbapenem-resistant K. pneumoniae (CRKP). METHODS: Analyses were performed on PLA patients from January 2010 to December 2021, to investigate the differences of K. pneumoniae from other etiologically infected PLA patients. Univariate and multivariate logistic regression analyses were used to compare prognostic factors between patients with carbapenem-resistant K. pneumoniae PLA (CRKP-PLA) and patients with carbapenem-sensitive K. pneumoniae PLA. RESULTS: Univariate analysis demonstrated a significant association between KP-PLA and factors including diabetes mellitus (P < 0.001), cholecystitis and cholelithiasis (P = 0.032), single abscess (P = 0.016), and abscesses with a diameter over 50 mm (P = 0.004). The CRKP group exhibited a higher prevalence of therapeutic interventions before K. pneumoniae infection, including abdominal surgery, mechanical ventilation, sputum suction, tracheal cannula, routine drainage of the abdominal cavity, and peripherally inserted central venous catheters (P < 0.05). Multivariate logistic regression analysis revealed that admission to the intensive care unit was an independent risk factor associated with CRKP-PLA (odds ratio 36; 95% confidence interval 1.77-731.56; P = 0.020). CONCLUSION: The KP-PLA patients were significantly associated with diabetes and were more likely to have single abscesses larger than 50 mm. PLA patients with a history of admission to intensive care unit or invasive therapeutic procedures should be given special consideration if combined with CRKP infection.

Factors influencing the diagnostic and prognostic values of circulating tumor cells in breast cancer: a meta-analysis of 8,935 patients.

Background: Circulating tumor cells (CTCs) could serve as a predictive biomarker in breast cancer (BC). Due to its high heterogeneity, the diagnostic and prognostic values of CTC are challenging. Methods: We searched published studies from the databases of PubMed, Cochrane Library, Embase, and MEDLINE. The detection capability and hazard ratios (HRs) of CTCs were extracted as the clinical diagnosis and prognosis evaluation. Subgroup analyses were divided according to the detection methods, continents, treatment periods, therapeutic plans, and cancer stages. Results: In this study, 35 publications had been retrieved with 8,935 patients enrolled. The diagnostic efficacy of CTC detection has 74% sensitivity and 98% specificity. The positive CTC detection (CTC+) would predict worse OS and PFS/DFS in both mid-therapy and post-therapy (HROS, 3.09; 95% CI, 2.17-4.39; HRPFS/DFS, 2.06; 95% CI, 1.72-2.47). Moreover, CTC+ indicated poor survival irrespective of the treatment phases and sampling times (HROS, 2.43; 95% CI, 1.85-3.19; HRPFS/DFS, 1.82; 95% CI, 1.66-1.99). The CTC+ was associated with poor survival regardless of the continents of patients (HROS = 2.43; 95% CI, 1.85-3.19). Conclusion: Our study suggested that CTC+ was associated with a worse OS and PFS/DFS in the Asian population. The detection method, the threshold level of CTC+, therapeutic approaches, and sampling times would not affect its diagnostic and prognostic values.

A novel two-step administration of XPO-1 inhibitor may enhance the effect of anti-BCMA CAR-T in relapsed/refractory extramedullary multiple myeloma.

BACKGROUND: Extramedullary disease usually implies a dismal outcome in relapsed/refractory multiple myeloma patients, and requires novel treatment approaches. We designed a trial using Selinexor, a nuclear export protein 1 inhibitor, together with anti-B cell maturation antigen (BCMA) chimeric antigen receptor (CAR)-T cell product CT103A to treat these patients, and describe the first two cases in this report. METHODS: Selinexor was administered with a novel two-step schedule in bridging therapy and in maintenance. The clinical responses and adverse events were recorded after CAR-T infusion and Selinexor administration. In vitro analysis of the influence of Selinexor on CAR-T cell function was performed using myeloma cell lines. RESULTS: After infusion, both patients achieved stringent complete remission (sCR), and were maintained in sCR at data-cutoff, with survival over 13 and 10 months, respectively. Neither immune effector cell-associated neurotoxicity syndrome nor over grade 2 cytokine release syndrome was observed. Meanwhile, the patients showed good tolerance to the combination. In addition, we demonstrated that low dose of Selinexor could upregulate the expression of BCMA on plasma cell lines and subsequently enhance the function of CAR-T cell in vitro. CONCLUSIONS: The combination of Selinexor and CT103A exerts preliminary synergistic effect, and can be developed as a promising strategy for relapsed/refractory extramedullary myeloma.

U-shaped fusion convolutional transformer based workflow for fast optical coherence tomography angiography generation in lips.

Oral disorders, including oral cancer, pose substantial diagnostic challenges due to late-stage diagnosis, invasive biopsy procedures, and the limitations of existing non-invasive imaging techniques. Optical coherence tomography angiography (OCTA) shows potential in delivering non-invasive, real-time, high-resolution vasculature images. However, the quality of OCTA images are often compromised due to motion artifacts and noise, necessitating more robust and reliable image reconstruction approaches. To address these issues, we propose a novel model, a U-shaped fusion convolutional transformer (UFCT), for the reconstruction of high-quality, low-noise OCTA images from two-repeated OCT scans. UFCT integrates the strengths of convolutional neural networks (CNNs) and transformers, proficiently capturing both local and global image features. According to the qualitative and quantitative analysis in normal and pathological conditions, the performance of the proposed pipeline outperforms that of the traditional OCTA generation methods when only two repeated B-scans are performed. We further provide a comparative study with various CNN and transformer models and conduct ablation studies to validate the effectiveness of our proposed strategies. Based on the results, the UFCT model holds the potential to significantly enhance clinical workflow in oral medicine by facilitating early detection, reducing the need for invasive procedures, and improving overall patient outcomes.

Identification of miRNAs Involved in Intracranial Aneurysm Rupture in Cigarette-Smoking Patients.

INTRODUCTION: Smoking is an independent risk factor for the formation and rupture of intracranial aneurysms (IA). However, the underlying mechanism remains unclear. METHODS: In this study, we performed miRNA sequencing on plasma from 10 smoking patients with IA, 10 non-smoking patients with IA, and 10 healthy controls. The differentially expressed miRNAs (DE miRNAs) between smoking and non-smoking patients with IA were identified. Functional and pathway enrichment analysis is employed to investigate the potential functions of those DE miRNA target genes. The correlations with the clinical parameters were assessed using receiver operating characteristic curve (ROC) analysis. RESULTS: In total, we identified 428 DE miRNAs. Functional enrichment analysis showed the target genes were significantly enriched in biological aspects related to cell characteristics, such as cell cycle, cell differentiation, and cell migration. Pathway analysis showed DE miRNAs mainly enriched in the PI3K-Akt signaling pathway, Focal adhesion, and JAK-STAT signaling pathway. The expressions of miR-574-5p, miR-151a-3p, and miR-652-3p correlated well with aneurysm parameters. The AUC of miR-574-5p, miR-151a-3p, and miR-652-3p were 97%, 92%, and 99%, respectively. CONCLUSION: Our study indicated that smoking significantly altered the plasma miRNA profile in patients with IA. The expression of miR-574-5p, miR-151a-3p, and miR-652-3p correlated with aneurysm parameters, which may play a significant role in the formation and rupture of IA.

Development of an intraoral handheld optical coherence tomography-based angiography probe for multi-site oral imaging.

Oral cancer, primarily oral squamous cell carcinomas (OSCC), is a major health concern worldwide. The current gold standard for the diagnosis of OSCC is biopsy and histopathological analysis, which is invasive and can place a huge financial burden on the healthcare system. Optical coherence tomography-based angiography (OCTA) is a non-invasive imaging technique that shows promise as an imaging modality to aid the diagnosis of OSCC. This Letter outlines the development of a handheld intraoral OCT probe applied to a swept-source OCT system with an angiography function for oral applications. The probe has a thin body with a diameter of 17.8 mm and a two-lens system with a working distance that is adjustable from 20.92 mm to 24.08 mm, a field of view 9 mm in diameter, an imaging depth of ∼1.7 mm, and resolutions of 39.38 µm (laterally) and 33.37 µm (axially). This probe was used to scan 14 oral sites to evaluate its ability to scan various sites in the oral cavity. This system has the potential to reduce invasive procedures and aid early OSCC diagnosis.

Comparative Assessment of Different Ultrasound Technologies in the Detection of Prostate Cancer: A Systematic Review and Meta-Analysis.

The present study aimed to assess the diagnostic test accuracy of different ultrasound scanning technologies in the detection of prostate cancer. A systematic search was conducted using the Cochrane Guidelines for Screening and Diagnostic Tests. We performed a systematic search in the international databases PubMed, Medline, Ovid, Embase and Cochrane Library. Searches were designed to find all studies that evaluated Micro-US, mpUS, SWE and CEUS as the main detection modalities for prostate cancer. This study was registered with Research Registry of systematic review and meta-analysis. The QUADAS-2 tool was utilized to perform quality assessment and bias analysis. The literature search generated 1376 studies. Of these, 320 studies were screened for eligibility, with 1056 studies being excluded. Overall, 26 studies with a total of 6370 patients met the inclusion criteria. The pooled sensitivity for grayscale, CEUS, SWE, Micro-US and mpUS modalities were 0.66 (95% CI 0.54-0.73) 0.73 (95% CI 0.58-0.88), 0.82 (95% CI 0.75-0.90), 0.85 (95% CI 0.76-0.94) and 0.87 (95% CI 0.71-1.03), respectively. Moreover, the pooled specificity for grayscale, CEUS, SWE, Micro-US and mpUS modalities were 0.56 (95% CI 0.21-0.90), 0.78 (95% CI 0.67-0.88), 0.76 (95% CI 0.65-0.88), 0.43 (95% CI 0.28-0.59) and 0.68 (95% CI 0.54-0.81), respectively. In terms of sensitivity, substantial heterogeneity between studies was detected (I2 = 72%, p = 0.000 < 0.05). In relation to specificity, extreme heterogeneity was detected (I2 = 93%, p = 0.000 < 0.05). Some studies proved that advanced ultrasound modalities such as mpUS, Micro-US, shear-wave elastography, contrast enhanced and micro-ultrasound are promising methods for the detection of prostate cancer.

Source and migration patterns of heavy metals and human health risk assessment of heavy metals in soil-corn straw-flue gas system.

The process of rapid urbanization in Northeast China has resulted in severe heavy metal pollution in the environment. In this study, we investigated the characteristics of heavy metal pollution in soil-corn straw and its combustion flue gas system, and the health risks of heavy metal pollution. The results showed that Cu and Zn in soil were more easily absorbed by corn straw roots. Heavy metals in soil, corn straw and flue gas from corn straw burning all pose some health risk to humans, and are more harmful to children than adults. The concentrations of heavy metals in both soil and flue gas from corn straw burning have reached extremely high ecological risk. The main sources of heavy metal elements in soils are, in order, industrial production, agricultural production activities and metallurgical production. This study highlights the key issues of heavy metal contamination in soil-corn straw and its combustion flue gas system, provides an auxiliary guide for the next step in analyzing the transfer mechanisms, and suggests a rational approach to mitigate heavy metal contamination.

Radionecrosis mimicking pseudo­progression in a patient with lung cancer and brain metastasis following the combination of anti­PD­1 therapy and stereotactic radiosurgery: A case report.

Brain metastases (BMs) usually develop in patients with non-small cell lung cancer. In addition to systemic therapy, radiation therapy and surgery, anti-programmed cell death-ligand 1 (PD-L1) therapy is another promising clinical anticancer treatment modality. However, the optimal timing and drug-drug interactions of anti-PD-L1 therapy with other combined treatments remain to be elucidated. Treatment with anti-PD-L1 therapy is associated with an increased risk of radionecrosis (RN) regardless of tumor histology. The present study described a case of RN in a patient with lung adenocarcinoma and with BM who received anti-PD-L1 therapy. Before anti-PD-L1 treatment, the patient received whole brain radiotherapy. During durvalumab treatment, the intracranial metastases regressed. The progression of intracranial lesions 9 months later prompted a second-line of therapy with PD-L1 inhibitor durvalumab and stereotactic radiotherapy (SRT). Despite stereotactic irradiation, the lesions progressed further, leading to surgical resection. On examination, RN was detected, but there was no evidence of metastatic lung cancer. The aim of the present study was to present the longitudinal change in magnetic resonance imaging in RN following STR and anti-PD-L1 combined therapy. The atypical image of RN is conditionally important for making an accurate preoperative diagnosis.

Multi-center study on predicting breast cancer lymph node status from core needle biopsy specimens using multi-modal and multi-instance deep learning.

The objective of our study is to develop a deep learning model based on clinicopathological data and digital pathological image of core needle biopsy specimens for predicting breast cancer lymph node metastasis. We collected 3701 patients from the Fourth Hospital of Hebei Medical University and 190 patients from four medical centers in Hebei Province. Integrating clinicopathological data and image features build multi-modal and multi-instance (MMMI) deep learning model to obtain the final prediction. For predicting with or without lymph node metastasis, the AUC was 0.770, 0.709, 0.809 based on the clinicopathological features, WSI and MMMI, respectively. For predicting four classification of lymph node status (no metastasis, isolated tumor cells (ITCs), micrometastasis, and macrometastasis), the prediction based on clinicopathological features, WSI and MMMI were compared. The AUC for no metastasis was 0.770, 0.709, 0.809, respectively; ITCs were 0.619, 0.531, 0.634, respectively; micrometastasis were 0.636, 0.617, 0.691, respectively; and macrometastasis were 0.748, 0.691, 0.758, respectively. The MMMI model achieved the highest prediction accuracy. For prediction of different molecular types of breast cancer, MMMI demonstrated a better prediction accuracy for any type of lymph node status, especially in the molecular type of triple negative breast cancer (TNBC). In the external validation sets, MMMI also showed better prediction accuracy in the four classification, with AUC of 0.725, 0.757, 0.525, and 0.708, respectively. Finally, we developed a breast cancer lymph node metastasis prediction model based on a MMMI model. Through all cases tests, the results showed that the overall prediction ability was high.

Preoperative imaging accuracy in size determination of prostate cancer in men undergoing radical prostatectomy for clinically localised disease.

OBJECTIVES: To compare the accuracy of pre-surgical prostate size measurements using mpMRI and USWE with imaging-based 3D-printed patient-specific whole-mount moulds facilitated histopathology, and to assess whether size assessment varies between clinically significant and non-significant cancerous lesions including their locations in different zones of the prostate. METHODS: The study population included 202 men with clinically localised prostate cancer opting for radical surgery derived from two prospective studies. Protocol-based imaging data was used for measurement of size of prostate cancer in clinically localised disease using MRI (N = 106; USWE (N = 96). Forty-eight men overlapped between two studies and formed the validation cohort. The primary outcome of this study was to assess the accuracy of pre-surgical prostate cancerous size measurements using mpMRI and USWE with imaging-based 3D-printed patient-specific whole-mount moulds facilitated histopathology as a reference standard. Independent-samples T-tests were used for the continuous variables and a nonparametric Mann-Whitney U test for independent samples was applied to examine the distribution and median differences between mpMRI and USWE groups. RESULTS: A significant number of men had underestimation of prostate cancer using both mpMRI (82.1%; 87/106) and USWE (64.6%; 62/96). On average, tumour size was underestimated by a median size of 7 mm in mpMRI, and 1 mm in USWE. There were 327 cancerous lesions (153 with mpMRI and 174 for USWE). mpMRI and USWE underestimated the majority of cancerous lesions (108/153; 70.6%) and (88/174; 50.6%), respectively. Validation cohort data confirmed these findings MRI had a nearly 20% higher underestimation rate than USWE (χ2 (1, N = 327) = 13.580, p = 0.001); especially in the mid and apical level of the gland. Clinically non-significant cancers were underestimated in significantly higher numbers in comparison to clinically significant cancers. CONCLUSIONS: Size measurement of prostate cancers on preoperative imaging utilising maximum linear extent technique, underestimated the extent of cancer. Further research is needed to confirm our observations using different sequences, methods and approaches for cancer size measurement.