CMAN: Cascaded Multi-scale Spatial Channel Attention-guided Network for large 3D deformable registration of liver CT images.

Deformable image registration is an essential component of medical image analysis and plays an irreplaceable role in clinical practice. In recent years, deep learning-based registration methods have demonstrated significant improvements in convenience, robustness and execution time compared to traditional algorithms. However, registering images with large displacements, such as those of the liver organ, remains underexplored and challenging. In this study, we present a novel convolutional neural network (CNN)-based unsupervised learning registration method, Cascaded Multi-scale Spatial-Channel Attention-guided Network (CMAN), which addresses the challenge of large deformation fields using a double coarse-to-fine registration approach. The main contributions of CMAN include: (i) local coarse-to-fine registration in the base network, which generates the displacement field for each resolution and progressively propagates these local deformations as auxiliary information for the final deformation field; (ii) global coarse-to-fine registration, which stacks multiple base networks for sequential warping, thereby incorporating richer multi-layer contextual details into the final deformation field; (iii) integration of the spatial-channel attention module in the decoder stage, which better highlights important features and improves the quality of feature maps. The proposed network was trained using two public datasets and evaluated on another public dataset as well as a private dataset across several experimental scenarios. We compared CMAN with four state-of-the-art CNN-based registration methods and two well-known traditional algorithms. The results show that the proposed double coarse-to-fine registration strategy outperforms other methods in most registration evaluation metrics. In conclusion, CMAN can effectively handle the large-deformation registration problem and show potential for application in clinical practice. The source code is made publicly available at https://github.com/LocPham263/CMAN.git.

Characteristics and Related Factors of Bacterial Infection Among Patients With Cirrhosis.

Background: Infection causes cirrhosis to decompensate, affecting liver function and resulting in several complications, including esophageal variceal hemorrhage, hepatic encephalopathy, and hepatorenal syndrome. Objective: This study aimed to identify the prevalence, essential features, and related factors of bacterial infection among patients with cirrhosis in Vietnam. Methods: This retrospective study included 317 patients diagnosed with cirrhosis, who were divided into two groups: group 1 including 125 patients with bacterial infection and group 2 including 192 patients without bacterial infection. Infection was diagnosed on the basis of its localization. Results: Spontaneous bacterial peritonitis (SBP; 31.2%) and pneumonia (28.8%) were the most common infections identified. The procalcitonin (PCT) level had a strong diagnostic value with an area under the curve value of 0.868. The most common type of gram-negative bacteria was Escherichia coli, while the gram-positive bacteria seen were Staphylococcus, Enterococcus, and Streptococcus among the patients with infection. In the logistic regression analysis, Child-Pugh class B and C (p<0.001, OR=4.14, CI=1.90-9.03; OR=4.76, CI=2.03-11.16, respectively) and the presence of acute kidney injury (p=0.009, OR=2.57, CI=1.27-5.22) and gastrointestinal hemorrhage (p=0.035, OR=0.39, CI=0.16-0.94) significantly differed between the groups. Conclusion: The most prevalent type of bacterial infection in patients with cirrhosis is SBP, with gram-negative bacteria being the most common cause. The PCT level is useful in identifying infection in patients with cirrhosis. Decompensated cirrhosis is linked to a higher risk of infection.

The Prognostic Value of Sequential 18 F-FDG PET/CT Metabolic Parameters in Outcomes of Upper-Third Esophageal Squamous Cell Carcinoma Patients Treated with Definitive Chemoradiotherapy.

Objective The aim of this study is to determine prognostic values of sequential 18 F-FDG PET/CT metabolic parameters in locally advanced esophageal squamous cell carcinoma (ESCC) patients treated with definitive chemoradiotherapy. Materials and Methods Forty locally advanced ESCC patients treated with definitive chemoradiotherapy (dCRT) who received pre-treatment 18 F-FDG PET/CT (PET1) and 3-months post-treatment 18 F-FDG PET/CT (PET2) were enrolled in the prospective study. 18 F-FDG PET parameters of the primary tumor including maximum and mean standardized uptake values (SUVmax, SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were calculated on PET delineated primary tumor. Using Kaplan-Meier curves to estimated overall survival (OS), progression-free survival (PFS), and local-regional control (LRC). Cox regression analysis was performed to find significant prognostic factors for survival. Results With a median follow-up of 13.5 months, the 4-year OS, PFS, and LRC rates were 67.3%, 52.6%, and 53.4% respectively. Patients with MTV 2 > 5.7 had lower OS, PFS, and LRC rates than the lower MTV 2 group (p < 0.05). Univariate Cox regression analysis showed that MTV2 was a significant prognostic factor for OS, PFS, and LRC (p < 0.05). Conclusion MTV parameter of sequential 18 F-FDG PET/CT could be used as a prognostic factor for OS, PFS, and LRC in locally advanced ESCC patients treated with dCRT.

Prognostic Role of Diastolic Left Ventricular Mechanical Dyssynchrony by Gated Single Photon Emission Computed Tomography Myocardial Perfusion Imaging in Post-Myocardial Infarction.

Objective This study is aimed to assess the prognostic value of diastolic left ventricular mechanical dyssynchrony (LVMD) measured by gated-single photon emission computed tomography (GSPECT) myocardial perfusion imaging (MPI) in post-myocardial infarction (MI). Subjects and Methods The study was conducted on 106 post-MI from January 2015 to January 2019. First, the indices of diastolic LVMD phase standard deviation (PSD) and histogram bandwidth (HBW) of post-MI were measured using the Cardiac Emory Toolbox. Subsequently, the post-MI patients were followed up, and the primary endpoint was major adverse cardiac events (MACEs). Finally, the prognostic value of dyssynchrony parameters for MACE was analyzed by the receiver-operating characteristics curve and survival analyses. Results With the cut-off values of 55.5 degrees of PSD, the sensitivity and specificity in prediction of MACE were 75% and 80.8%, with the cut-off values of 174.5 degrees of HBW, the sensitivity and specificity were 75% and 83.3% respectively. There was a significant difference of time to MACE between groups of PSD less than 55.5 degrees and more than 55.5 degrees. PSD, HBW, and left ventricle ejection fraction (LVEF) assessed on GSPECT were significant factors in the prediction of MACE. Conclusion Diastolic LVMD parameters of PSD and HBW derived from GSPECT are significant prognostic factors in predicting MACE in post-MI patients.

Quantification of liver-Lung shunt fraction on 3D SPECT/CT images for selective internal radiation therapy of liver cancer using CNN-based segmentations and non-rigid registration.

PURPOSE: Selective internal radiation therapy (SIRT) has been proven to be an effective treatment for hepatocellular carcinoma (HCC) patients. In clinical practice, the treatment planning for SIRT using 90Y microspheres requires estimation of the liver-lung shunt fraction (LSF) to avoid radiation pneumonitis. Currently, the manual segmentation method to draw a region of interest (ROI) of the liver and lung in 2D planar imaging of 99mTc-MAA and 3D SPECT/CT images is inconvenient, time-consuming and observer-dependent. In this study, we propose and evaluate a nearly automatic method for LSF quantification using 3D SPECT/CT images, offering improved performance compared with the current manual segmentation method. METHODS: We retrospectively acquired 3D SPECT with non-contrast-enhanced CT images (nCECT) of 60 HCC patients from a SPECT/CT scanning machine, along with the corresponding diagnostic contrast-enhanced CT images (CECT). Our approach for LSF quantification is to use CNN-based methods for liver and lung segmentations in the nCECT image. We first apply 3D ResUnet to coarsely segment the liver. If the liver segmentation contains a large error, we dilate the coarse liver segmentation into the liver mask as a ROI in the nCECT image. Subsequently, non-rigid registration is applied to deform the liver in the CECT image to fit that obtained in the nCECT image. The final liver segmentation is obtained by segmenting the liver in the deformed CECT image using nnU-Net. In addition, the lung segmentations are obtained using 2D ResUnet. Finally, LSF quantitation is performed based on the number of counts in the SPECT image inside the segmentations. Evaluations and Results: To evaluate the liver segmentation accuracy, we used Dice similarity coefficient (DSC), asymmetric surface distance (ASSD), and max surface distance (MSD) and compared the proposed method to five well-known CNN-based methods for liver segmentation. Furthermore, the LSF error obtained by the proposed method was compared to a state-of-the-art method, modified Deepmedic, and the LSF quantifications obtained by manual segmentation. The results show that the proposed method achieved a DSC score for the liver segmentation that is comparable to other state-of-the-art methods, with an average of 0.93, and the highest consistency in segmentation accuracy, yielding a standard deviation of the DSC score of 0.01. The proposed method also obtains the lowest ASSD and MSD scores on average (2.6 mm and 31.5 mm, respectively). Moreover, for the proposed method, a median LSF error of 0.14% is obtained, which is a statically significant improvement to the state-of-the-art-method (p=0.004), and is much smaller than the median error in LSF manual determination by the medical experts using 2D planar image (1.74% and p<0.001). CONCLUSIONS: A method for LSF quantification using 3D SPECT/CT images based on CNNs and non-rigid registration was proposed, evaluated and compared to state-of-the-art techniques. The proposed method can quantitatively determine the LSF with high accuracy and has the potential to be applied in clinical practice.

The First Lanthipeptide from Lactobacillus iners, Inecin L, Exerts High Antimicrobial Activity against Human Vaginal Pathogens.

Vaginal infections continue to be a serious public health issue, and developing new approaches to address antibiotic-resistant pathogens is an urgent task. The dominant vaginal Lactobacillus species and their active metabolites (e.g., bacteriocins) have the potential to defeat pathogens and help individuals recover from disorders. Here, we describe for the first time a novel lanthipeptide, inecin L, a bacteriocin from Lactobacillus iners with posttranslational modifications. The biosynthetic genes of inecin L were actively transcribed in the vaginal environment. Inecin L was active against the prevailing vaginal pathogens, such as Gardnerella vaginalis and Streptococcus agalactiae, at nanomolar concentrations. We demonstrated that the antibacterial activity of inecin L was closely related to the N terminus and the positively charged His13 residue. In addition, inecin L was a bactericidal lanthipeptide that showed little effect on the cytoplasmic membrane but inhibited the cell wall biosynthesis. Thus, the present work characterizes a new antimicrobial lanthipeptide from a predominant species of the human vaginal microbiota. IMPORTANCE The human vaginal microbiota plays essential roles in preventing pathogenic bacteria, fungi, and viruses from invading. The dominant vaginal Lactobacillus species show great potential to be developed as probiotics. However, the molecular mechanisms (such as bioactive molecules and their modes of action) involved in the probiotic properties remain to be determined. Our work describes the first lanthipeptide molecule from the dominant Lactobacillus iners. Additionally, inecin L is the only lanthipeptide found among the vaginal lactobacilli thus far. Inecin L shows strong antimicrobial activity toward the prevalent vaginal pathogens and antibiotic-resistant strains, suggesting that inecin L is a potent antibacterial molecule for drug development. In addition, our results show that inecin L exhibits specific antibacterial activity related to the residues in the N-terminal region and ring A, which will contribute to structure-activity relationship studies in lacticin 481-like lanthipeptides.

Novel third-generation tyrosine kinase inhibitor for newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia: a case study.

Although Philadelphia chromosome-positive acute leukemia (Ph + -ALL) has been revolutionized with tyrosine kinase inhibitors (TKIs), resistance and mutation are universal events during treatment with first-generation and second-generation TKIs. The present third-generation TKI has a dose-dependent, increased risk of serious cardiovascular events and the sensitivity is poor for patients with ≥2 mutations accompanied by the T315I mutation. Thus, novel and well-tolerated TKIs should be explored. This study analyzes the efficacy and advert effects of olverembatinib, a novel third TKI, in the treatment of newly diagnosed adult Ph + -ALL in induction therapy. Four adult patients with newly diagnosed Ph + -ALL were treated with olverembatinib as the first-line treatment. For induction therapy, these patients received 40 mg of oral olverembatinib quaque omni die for 28 days, 1 mg/kg/d of prednisone for 14 days, then tapered and stopped at 28 days and vindesine 4 mg/d at days 1, 8 and 15. After induction therapy, these patients received median or high-dose of cytarabine and methotrexate combined with oral olverembatinib as consolidation therapy. Then the allogeneic hematopoietic stem cell transplantation (allo-HSCT) was performed. All patients reached complete remission with a complete cytogenetic response after induction therapy. Two patients reached major molecular remission and one with complete molecular remission. Before allo-HSCT, all the patients achieved complete molecular remission. All the patients have survived disease-free for 3-6 months. No severe advert effects were observed. It is well-tolerated and effective for olverembatinib in the treatment of newly diagnosed adult patients with Ph + -ALL. A prospective study should be performed to further testify the role.

Screening and treatment of brain metastasis from papillary thyroid carcinoma: a case series.

BACKGROUND: The brain metastasis from differentiated thyroid carcinoma (DTC) is a rare condition and its prognosis is poor. The standard protocol for screening and treatment of patients with brain metastases from papillary thyroid cancer (PTC) remains controversial. This report aims to share the experience of a single center in the management of brain metastases from DTC. MATERIAL AND METHODS: Five patients with brain metastases were identified from 5000 patients with DTC attending the department of nuclear medicine, Hospital 108 between 2016 to 2022. The statistical software Statistical Package for Social Sciences (SPSS) 20.0 (SPSS Inc., Chicago, IL, USA) was used to analyze the data. RESULTS: Five patients with brain metastases from DTC were revealed by MRI, 18F-FDG PET/CT with contrast enhancement, and 131I-SPECT/CT. The median time of overall survival (OS) was 15 months, ranging from 10 to 65 months. Two out of the five patients underwent surgery, and futher 2 patients were treated with stereotactic surgery (SRS). All patients are still alive. CONCLUSIONS: Brain metastases from DTC are rare. MRI is the preferred imaging mobility to screen brain lesions in DTC. The primary treatment modalities are surgery and SRS.

Custom gene expression panel for evaluation of potential molecular markers in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide. It is a highly heterogeneous disease with poor prognosis and limited treatment options, which highlights the need for reliable biomarkers. This study aims to explore molecular markers that allow stratification of HCC and may lead to better prognosis and treatment prediction. MATERIALS AND METHODS: We studied 20 candidate genes (HCC hub genes, potential drug target genes, predominant somatic mutant genes) retrieved from literature and public databases with potential to be used as the molecular markers. We analysed expression of the genes by RT-qPCR in 30 HCC tumour and adjacent non-tumour paired samples from Vietnamese patients. Fold changes in expression were then determined using the 2-∆∆CT method, and unsupervised hierarchical clustering was generated using Cluster v3.0 software. RESULTS: Clustering of expression data revealed two subtypes of tumours (proliferative and normal-like) and four clusters for genes. The expression profiles of the genes TOP2A, CDK1, BIRC5, GPC3, IGF2, and AFP were strongly correlated. Proliferative tumours were characterized by high expression of the c-MET, ARID1A, CTNNB1, RAF1, LGR5, and GLUL1 genes. TOP2A, CDK1, and BIRC5 HCC hub genes were highly expressed (> twofold) in 90% (27/30), 83% (25/30), and 83% (24/30) in the tissue samples, respectively. Among the drug target genes, high expression was observed in the GPC3, IGF2 and c-MET genes in 77% (23/30), 63% (19/30), and 37% (11/30), respectively. The somatic mutant Wnt/ß-catenin genes (CTNNB1, GLUL and LGR5) and TERT were highly expressed in 40% and 33% of HCCs, respectively. Among the HCC marker genes, a higher percentage of tumours showed GPC3 expression compared to AFP expression [73% (23/30) vs. 43% (13/30)]. CONCLUSION: The custom panel and molecular markers from this study may be useful for diagnosis, prognosis, biomarker-guided clinical trial design, and prediction of treatment outcomes.

Pretreatment 18F-FDG PET/CT-Derived Parameters in Predicting Clinical Outcomes of Locally Advanced Upper Third Esophageal Squamous Cell Carcinoma After Definitive Chemoradiation Therapy.

Purpose: The aim of this study was to investigate whether standard uptake values (SUVs) of pretreatment 18F-FDG PET/CT were the surrogate parameters for predicting the outcomes in locally advanced esophageal squamous cell carcinoma patients treated with definitive chemoradiotherapy. Materials and Methods: Sixty patients with esophageal squamous cell carcinoma underwent pretreatment 18F-FDG PET/CT and received definitive chemoradiotherapy. 18F-FDG metabolic parameters including SUVmax, SUVmean, SULpeak, total lesion glycolysis (TLG), and metabolic tumor volume (MTV) of primary tumor were calculated. The receiver-operating characteristic (ROC) curve was used to determine the optimal cutoff value of FDG PET/CT-derived parameters that associated with treatment response. Estimating progression-free survival (PFS) and overall survival (OS) was analyzed by using Kaplan-Meier methods. Univariate and multivariate analysis for PFS and OS was performed using Cox regression. Results: Complete response was achieved in 38.3%. The 4-year OS and PFS rates were 48.6% and 44.4%, respectively. SUVmean with a cutoff value of 6.1 could predict complete response with sensitivity of 69.6%, specificity of 78.4%, and accuracy of 75%. Cox multi-factor regression analyses revealed SUVmean > 6.1 as an independent prognostic factor for OS (HR = 6.74, p = 0.02) and PFS (HR = 6.53, p < 0.001). Conclusions: Our study suggests that SUVmean of the primary tumor in pretreatment 18F-FDG PET/CT may be used as an independent predictor in esophageal squamous cell carcinoma patients treated with definitive chemoradiotherapy.

CRISPR-Cas12a combination to alleviate the false-positive in loop-mediated isothermal amplification-based diagnosis of Neisseria meningitidis.

BACKGROUND: Loop isothermal amplification (LAMP) has recently been proposed as a point-of-care diagnostic tool to detect acute infectious pathogens; however, this technique embeds risk of generating false-positive results. Whereas, with abilities to accurately recognize specific sequence, the CRISPR/Cas12a can forms complexes with cognate RNA sensors and cleave pathogen's DNA targets complimerntary to its cognate RNA, afterward acquiring the collateral activity to unbiasedly cut nearby off-target fragments. Therefore, if relevant fluorescent-quencher-nucleic probes are present in the reaction, the non-specific cleavage of probes releases fluorescences and establish diagnostic read-outs. METHODS: The MetA gene of N. meningitidis was selected as target to optimize the LAMP reaction, whereas pseudo-dilution series of N. meningitidis gemonics DNA was used to establish the detection limit of LAMP/Cas12a combination assay. The diagnostic performance of established LAMP/Cas12a combination assay was validated in comparation with standard real-time PCR on 51 CSF samples (14 N. meningitidis confirmed patients and 37 control subjects). RESULTS: In relevant biochemical conditions, CRISPR-Cas12a and LAMP can work synchronously to accurately identify genetics materials of Nesseria menitigistis at the level 40 copies/reaction less than 2 h. CONCLUSIONS: In properly optimized conditions, the CRISPR-Cas12a system helps to alleviate false positive result hence enhancing the specificity of the LAMP assays.

Automatic scan range for dose-reduced multiphase CT imaging of the liver utilizing CNNs and Gaussian models.

Multiphase CT scanning of the liver is performed for several clinical applications; however, radiation exposure from CT scanning poses a nontrivial cancer risk to the patients. The radiation dose may be reduced by determining the scan range of the subsequent scans by the location of the target of interest in the first scan phase. The purpose of this study is to present and assess an automatic method for determining the scan range for multiphase CT scans. Our strategy is to first apply a CNN-based method for detecting the liver in 2D slices, and to use a liver range search algorithm for detecting the liver range in the scout volume. The target liver scan range for subsequent scans can be obtained by adding safety margins achieved from Gaussian liver motion models to the scan range determined from the scout. Experiments were performed on 657 multiphase CT volumes obtained from multiple hospitals. The experiment shows that the proposed liver detection method can detect the liver in 223 out of a total of 224 3D volumes on average within one second, with mean intersection of union, wall distance and centroid distance of 85.5%, 5.7 mm and 9.7 mm, respectively. In addition, the performance of the proposed liver detection method is comparable to the best of the state-of-the-art 3D liver detectors in the liver detection accuracy while it requires less processing time. Furthermore, we apply the liver scan range generation method on the liver CT images acquired from radiofrequency ablation and Y-90 transarterial radioembolization (selective internal radiation therapy) interventions of 46 patients from two hospitals. The result shows that the automatic scan range generation can significantly reduce the effective radiation dose by an average of 14.5% (2.56 mSv) compared to manual performance by the radiographer from Y-90 transarterial radioembolization, while no statistically significant difference in performance was found with the CT images from intra RFA intervention (p = 0.81). Finally, three radiologists assess both the original and the range-reduced images for evaluating the effect of the range reduction method on their clinical decisions. We conclude that the automatic liver scan range generation method is able to reduce excess radiation compared to the manual performance with a high accuracy and without penalizing the clinical decision.

Association Between Soluble Notch Ligand Delta-like Ligand 1 and Bleeding Complications in Patients With Dengue Fever Infection.

Bleeding associated with endothelial damage is a key feature of severe dengue fever. In the current study, we investigated whether Notch ligands were associated with bleeding in 115 patients with confirmed dengue infection in Vietnam. Soluble Notch ligands were determined by means of enzyme-linked immunosorbent assay. Seventeen of 115 patients (14.8%) experienced bleeding manifestations. High soluble delta-like ligand 1 (sDLL1) plasma levels was associated with bleeding (median, 15 674 vs 7117 pg/mL; P < .001). Receiver operating characteristic (ROC) curve analysis demonstrated that sDLL1 had the best test performance (area under the ROC curve, 0.852), with 88% sensitivity and 84% specificity. The combination with alanine aminotransferase and aspartate aminotransferase slightly increased sDLL1 performance. sDLL1 may be useful to guide clinical management of patients with patients in endemic settings.

PSMA-based 18F-DCFPyL PET: a better choice than multiparametric MRI for prostate cancer diagnosis?

Owing to the high tissue contrast, multiparametric MRI (mpMRI) has already been the most widely applied imaging method for prostate cancer. Recently, prostate-specific membrane antigen (PSMA) ligands for nuclear imaging are emerging as a promising modality in prostate cancer, especially since the 2 PET/CT agents (68Ga-PSMA-11 and 18F-DCFPy) approved by U.S. Food and Drug Administration (FDA). However, limited studies have performed the comparison of mpMRI versus recently approved 18F-DCFPyL PET/CT. In this issue of AJNMMI, Lu et al. compared the performance of 18F-DCFPyL PET/CT and pelvic mpMRI in intermediate-high risk and biochemical recurrent prostate cancer patients. The results demonstrated the two modalities have a good concordance rate for patient-based analysis, and 18F-DCFPyL PET/CT has a better diagnostic performance in detecting lymph node metastases and bone metastases for lesion-based analysis. The use of 18F-DCFPyL PET/CT provides more diagnostic confidence to better assess prostate cancer lesions.

Circulating miR-147b as a diagnostic marker for patients with bacterial sepsis and septic shock.

BACKGROUND: Early diagnosis, precise antimicrobial treatment and subsequent patient stratification can improve sepsis outcomes. Circulating biomarkers such as plasma microRNAs (miRNAs) have proven to be surrogates for diagnosis, severity and case management of infections. The expression of four selected miRNAs (miR-146-3p, miR-147b, miR-155 and miR-223) was validated for their prognostic and diagnostic potential in a clinically defined cohort of patients with sepsis and septic shock. METHODS: The expression of plasma miRNAs was quantified by quantitative PCR (qPCR) in patients with bacterial sepsis (n = 78), in patients with septic shock (n = 52) and in patients with dengue haemorrhagic fever (DHF; n = 69) and in healthy controls (n = 82). RESULTS: The expression of studied miRNA was significantly increased in patients with bacterial sepsis and septic shock. The plasma miR-147b was able to differentiate bacterial sepsis from non-sepsis and septic shock (AUC = 0.77 and 0.8, respectively, p≤ 0.05), while the combination of plasma miR-147b and procalcitonin (PCT) predicted septic shock (AUC = 0.86, p≤ 0.05). CONCLUSIONS: The plasma miR-147b may be an useful biomarker independently or in combination with PCT to support clinical diagnosis of sepsis and equally prognosis of patients with septic shock.