Recombinant expression and tryptophan-assisted analysis of human sweet taste receptor T1R3's extracellular domain in sweetener interaction studies.

The human palate can discern multiple tastes; however, it predominantly perceives five fundamental flavors: sweetness, saltiness, sourness, bitterness, and umami. Sweetness is primarily mediated through the sweet taste receptor, a membrane-bound heterodimeric structure comprising T1R2-T1R3. However, unraveling the structural and mechanistic intricacies of the sweet taste receptor has proven challenging. This study aimed to address this knowledge gap by expressing an extracellular N-terminal domain encompassing the cysteine-rich domain of human hT1R3 (hT1R3-TMD) in Escherichia coli. The expressed protein was obtained as inclusion bodies, purified by metal affinity chromatography, and refolded using the dilution-refolding method. Through rigorous analysis, we confirmed the successful refolding of hT1R3-TMD and elucidated its structural characteristics using circular dichroism spectroscopy. Notably, the refolded protein was found to exist as either a monomer or a dimer, depending on its concentration. A tryptophan fluorescence quenching assay revealed that the dissociation constants for sucrose, sucralose, and brazzein were >9500 µM, 2380 µM and 14.3 µM, respectively. Our findings highlight the utility of this E. coli expression system for producing functional hT1R3-TMD for investigations and demonstrate the efficacy of the tryptophan fluorescence quenching assay in revealing complex interactions between sweet taste receptors and various sweeteners.

Exploring the effect of BRCA1/2 status on chemotherapy-induced hematologic toxicity in patients with ovarian cancer.

OBJECTIVE: BRCA1/2 are integral to the DNA repair mechanism and their germline pathogenic variants (gBRCA) result in a high risk for developing breast and ovarian cancer. Patients with gBRCA mutations showed increased sensitivity to DNA cross-linking agent but might have increased treatment-related toxicities. Thus, we hypothesized that gBRCA mutation ovarian cancer patients who underwent platinum-based chemotherapy might be at higher risk of developing chemotherapy-induced hematologic toxicity. METHODS: This study enrolled 160 patients with ovarian cancer who received frontline platinum-based chemotherapy between 2011 and 2019 in Kyungpook National University Chilgok Hospital. Incidence rate and severity of chemotherapy-induced hematologic toxicity (neutropenia, anemia, thrombocytopenia) was compared for BRCA mutation and wild patients. RESULTS: 160 women, including 62 BRCA1/2 (38 BRCA1, and 25 BRCA2) mutation group, and 98 noncarriers, were analyzed. A higher frequency of G2 anemia was noted in the BRCA -mutant group (22% vs. 1%, p = 0.07). Furthermore, G3 anemia was significantly common among BRCA group (12.9% vs. 3%, p = 0.02). In the subgroup analysis according to BRCA1/2 status, BRCA1 mutated patients showed a significantly higher frequency of G1 anemia than BRCA2 (89% vs. 60%, p = 0.01). In terms of neutropenia and thrombocytopenia, BRCA mutated patients and noncarriers had similar hematologic toxicity. CONCLUSION: Germline BRCA mutations were associated with a higher frequency of G2/3 anemia in ovarian cancer patients who underwent first-line platinum-based chemotherapy. Moreover, the BRCA1 mutation appeared to be more strongly associated with the incidence of chemotherapy-induced anemia. Our findings warrant further investigation in larger, prospective studies to confirm these current findings and determine whether preventive interventions may be necessary.

A Comparative Investigation of Functional Connectivity Utilizing Electroencephalography in Insomnia Patients with and without Restless Leg Syndrome

Objective: The current study aimed to identify distinctive functional brain connectivity characteristics that differentiate patients with restless legs syndrome (RLS) from those with primary insomnia. Methods: Quantitative electroencephalography (QEEG) was employed to analyze connectivity matrices using the phaselocking value technique. A total of 107 patients with RLS (RLS group) and 17 patients with insomnia without RLS (primary insomnia group) were included in the study. Demographic variables were compared using t tests and chi-square tests, while differences in connectivity were examined through multiple analyses of covariance. Correlation analysis was conducted to explore the relationship between connectivity and the severity of RLS. Results: The results indicated significant differences in the primary somatosensory cortex (F = 4.377, r = 0.039), primary visual cortex (F = 4.215, r = 0.042), and anterior prefrontal cortex (F = 5.439, r = 0.021) between the RLS and primary insomnia groups. Furthermore, the connectivity of the sensory cortex, including the primary somatosensory cortex (r = -0.247, p = 0.014), sensory association cortex (r = -0.238, p = 0.028), retrosplenial region (r = -0.302, p = 0.002), angular gyrus (r = -0.258, p = 0.008), supramarginal gyrus (r = -0.230, p = 0.020), primary visual cortex (r = -0.275, p = 0.005) and secondary visual cortex (r = -0.226, p = 0.025) exhibited an inverse association with RLS symptom severity. Conclusion: The prefrontal cortex, primary somatosensory cortex, and visual cortex showed potential as diagnostic biomarkers for distinguishing RLS from primary insomnia. These findings indicate that QEEG-based functional connectivity analysis shows promise as a valuable diagnostic tool for RLS and provides insights into its underlying mechanisms. Further research is needed to explore this aspect further.

Primary Invasive Ductal Carcinoma Arising in Axillary Accessory Breast: A Case Report.

Ectopic breast tissue can develop along the mammary ridge from the axilla to the groin, and the most common site is the axillae. Primary carcinoma of ectopic breast tissue is extremely rare. We report a rare case of a 61-year-old woman with a palpable mass in her left axilla who had a history of surgical excision of accessory breast tissue in the same area. Mammography (MMG), including axillary tail view, ultrasound (US), and breast MRI were performed. We evaluated the extent and characteristics of the microcalcifications in the axillary tail view. A US-guided biopsy was done, and histopathology revealed an invasive ductal carcinoma. Enhanced abdominal CT revealed multiple hepatic masses consistent with metastases, and the patient received palliative chemotherapy. Herein, we present a rare case of breast cancer arising from accessory breast tissue in the axilla, best appreciated on the axillary tail view of the patient's MMG.

Driving towards digital biomanufacturing by CHO genome-scale models.

Genome-scale metabolic models (GEMs) of Chinese hamster ovary (CHO) cells are valuable for gaining mechanistic understanding of mammalian cell metabolism and cultures. We provide a comprehensive overview of past and present developments of CHO-GEMs and in silico methods within the flux balance analysis (FBA) framework, focusing on their practical utility in rational cell line development and bioprocess improvements. There are many opportunities for further augmenting the model coverage and establishing integrative models that account for different cellular processes and data for future applications. With supportive collaborative efforts by the research community, we envisage that CHO-GEMs will be crucial for the increasingly digitized and dynamically controlled bioprocessing pipelines, especially because they can be successfully deployed in conjunction with artificial intelligence (AI) and systems engineering algorithms.

Metabolism of phenolic compounds catalyzed by Tomato CYP736A61.

Cytochrome P450s (CYPs) regulate plant growth and stress responses by producing diverse primary and secondary metabolites. However, the function of many plant CYPs remains unknown because, despite their structural similarity, predicting the enzymatic activity of CYPs is difficult. In this study, one member of the CYP736A subfamily (CYP736A61) from tomatoes was isolated and characterized its enzymatic functions. CYP736A61 was successfully expressed in Escherichia coli through co-expression with molecular chaperones. The purified CYP736A61 showed hydroxylation activity toward 7-ethoxycoumarin, producing 7-hydroxycoumarin or 3-hydroxy 7-ethoxycoumarin. Further substrate screening revealed that dihydrochalcone and stilbene derivates (resveratrol and polydatin) are the substrates of CYP736A61. CYP736A61 also mediated the hydroxylation of resveratrol and polydatin, albeit with low activity. Importantly, CYP736A61 mediated the cleavage of resveratrol and polydatin as well as pinostilbene and pterostilbene. Interestingly, CY736A61 also converted phloretin to naringenin chalcone. These results suggest that CYP736A61 is a novel CYP enzyme with stilbene cleavage activity.

Impact of extracorporeal membrane oxygenation-related complications on in-hospital mortality.

INTRODUCTION: Although extracorporeal membrane oxygenation (ECMO) is a well-established treatment for supporting severe cardiopulmonary failure, the morbidity and mortality of patients requiring ECMO support remain high. Evaluating and correcting potential risk factors associated with any ECMO-related complications may improve care and decrease mortality. This study aimed to assess the predictors of ECMO-related vascular and cerebrovascular complications among adult patients and to test the hypothesis that ECMO-related complications are associated with higher in-hospital mortality rates. METHODS: This single-center, retrospective study included 856 ECMO runs administered via cannulation of the femoral vessels of 769 patients: venoarterial (VA) ECMO (n = 709, 82.8%) and venovenous (VV) ECMO (n = 147, 17.2%). The study outcomes included the occurrence of ECMO-related vascular and cerebrovascular complications and in-hospital death. The association of ECMO-related complications with the risk of in-hospital death was analyzed. RESULTS: The incidences of ECMO-related vascular and cerebrovascular complications were 20.2% and 13.6%, respectively. The overall in-hospital mortality rate was 48.7%: 52.8% among VA ECMO runs and 29.3% among VV ECMO runs. Multivariable analysis indicated that age (P < 0.01), cardiopulmonary cerebral resuscitation (P < 0.01), continuous renal replacement therapy (P < 0.01), and initial platelet count [<50×103/µL (P = 0.02) and 50-100(×103)/µL (P < 0.01)] were associated with an increased risk of in-hospital death. ECMO-related vascular and cerebrovascular complications were not independently associated with higher in-hospital mortality rates for VA or VV ECMO runs. CONCLUSION: ECMO-related vascular and cerebrovascular complications were not associated with an increased risk of in-hospital death among adult patients.

Decoding cellular mechanism of recombinant adeno-associated virus (rAAV) and engineering host-cell factories toward intensified viral vector manufacturing.

Recombinant adeno-associated virus (rAAV) is one of the prominent gene delivery vehicles that has opened promising opportunities for novel gene therapeutic approaches. However, the current major viral vector production platform, triple transfection in mammalian cells, may not meet the increasing demand. Thus, it is highly required to understand production bottlenecks from the host cell perspective and engineer the cells to be more favorable and tolerant to viral vector production, thereby effectively enhancing rAAV manufacturing. In this review, we provided a comprehensive exploration of the intricate cellular process involved in rAAV production, encompassing various stages such as plasmid entry to the cytoplasm, plasmid trafficking and nuclear delivery, rAAV structural/non-structural protein expression, viral capsid assembly, genome replication, genome packaging, and rAAV release/secretion. The knowledge in the fundamental biology of host cells supporting viral replication as manufacturing factories or exhibiting defending behaviors against viral production is summarized for each stage. The control strategies from the perspectives of host cell and materials (e.g., AAV plasmids) are proposed as our insights based on the characterization of molecular features and our existing knowledge of the AAV viral life cycle, rAAV and other viral vector production in the Human embryonic kidney (HEK) cells.

Prognostic value of CT-based radiomics in grade 1-2 pancreatic neuroendocrine tumors.

BACKGROUND: Surgically resected grade 1-2 (G1-2) pancreatic neuroendocrine tumors (PanNETs) exhibit diverse clinical outcomes, highlighting the need for reliable prognostic biomarkers. Our study aimed to develop and validate CT-based radiomics model for predicting postsurgical outcome in patients with G1-2 PanNETs, and to compare its performance with the current clinical staging system. METHODS: This multicenter retrospective study included patients who underwent dynamic CT and subsequent curative resection for G1-2 PanNETs. A radiomics-based model (R-score) for predicting recurrence-free survival (RFS) was developed from a development set (441 patients from one institution) using least absolute shrinkage and selection operator-Cox regression analysis. A clinical model (C-model) consisting of age and tumor stage according to the 8th American Joint Committee on Cancer staging system was built, and an integrative model combining the C-model and the R-score (CR-model) was developed using multivariable Cox regression analysis. Using an external test set (159 patients from another institution), the models' performance for predicting RFS and overall survival (OS) was evaluated using Harrell's C-index. The incremental value of adding the R-score to the C-model was evaluated using net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: The median follow-up periods were 68.3 and 59.7 months in the development and test sets, respectively. In the development set, 58 patients (13.2%) experienced recurrence and 35 (7.9%) died. In the test set, tumors recurred in 14 patients (8.8%) and 12 (7.5%) died. In the test set, the R-score had a C-index of 0.716 for RFS and 0.674 for OS. Compared with the C-model, the CR-model showed higher C-index (RFS, 0.734 vs. 0.662, p = 0.012; OS, 0.781 vs. 0.675, p = 0.043). CR-model also showed improved classification (NRI, 0.330, p < 0.001) and discrimination (IDI, 0.071, p < 0.001) for prediction of 3-year RFS. CONCLUSIONS: Our CR-model outperformed the current clinical staging system in prediction of the prognosis for G1-2 PanNETs and added incremental value for predicting postoperative recurrence. The CR-model enables precise identification of high-risk patients, guiding personalized treatment planning to improve outcomes in surgically resected grade 1-2 PanNETs.

Exploring metabolic effects of dipeptide feed media on CHO cell cultures by in silico model-guided flux analysis.

There is a growing interest in perfusion or continuous processes to achieve higher productivity of biopharmaceuticals in mammalian cell culture, specifically Chinese hamster ovary (CHO) cells, towards advanced biomanufacturing. These intensified bioprocesses highly require concentrated feed media in order to counteract their dilution effects. However, designing such condensed media formulation poses several challenges, particularly regarding the stability and solubility of specific amino acids. To address the difficulty and complexity in relevant media development, the biopharmaceutical industry has recently suggested forming dipeptides by combining one from problematic amino acids with selected pairs to compensate for limitations. In this study, we combined one of the lead amino acids, L-tyrosine, which is known for its poor solubility in water due to its aromatic ring and hydroxyl group, with glycine as the partner, thus forming glycyl-L-tyrosine (GY) dipeptide. Subsequently, we investigated the utilization of GY dipeptide during fed-batch cultures of IgG-producing CHO cells, by changing its concentrations (0.125 × , 0.25 × , 0.5 × , 1.0 × , and 2.0 ×). Multivariate statistical analysis of culture profiles was then conducted to identify and correlate the most significant nutrients with the production, followed by in silico model-guided analysis to systematically evaluate their effects on the culture performance, and elucidate metabolic states and cellular behaviors. As such, it allowed us to explain how the cells can more efficiently utilize GY dipeptide with respect to the balance of cofactor regeneration and energy distribution for the required biomass and protein synthesis. For example, our analysis results uncovered specific amino acids (Asn and Gln) and the 0.5 × GY dipeptide in the feed medium synergistically alleviated the metabolic bottleneck, resulting in enhanced IgG titer and productivity. In the validation experiments, we tested and observed that lower levels of Asn and Gln led to decreased secretion of toxic metabolites, enhanced longevity, and elevated specific cell growth and titer. KEY POINTS: • Explored the optimal Tyr dipeptide for the enhanced CHO cell culture performance • Systematically analyzed effects of dipeptide media by model-guided approach • Uncovered synergistic metabolic utilization of amino acids with dipeptide.

The Relationship between Depression Severity and Prefrontal Hemodynamic Changes in Adolescents with Major Depression Disorder: A Functional Near-infrared Spectroscopy Study.

Objective: : Numerous studies have identified hemodynamic changes in adults with major depressive disorder (MDD) by using functional near-infrared spectroscopy (fNIRS). However, studies on adolescents with MDD are limited. As adolescence is a stage of rapid brain development, differences may occur depending on age. This study used fNIRS as an objective tool to investigate hemodynamic changes in the frontal lobe according to depression severity and age in adolescents with MDD. Methods: : Thirty adolescents (12 aged 12-15 years and 18 aged 16-18 years) were retrospectively investigated. The Children's Depression Inventory was used as a psychiatric evaluation scale, fNIRS was used as an objective brain function evaluation tool, and the Verbal Fluency Test was performed. Results: : During the Verbal Fluency Test, in the younger MDD group, oxygenated-hemoglobin concentration increased in the right dorsolateral prefrontal cortex region as the severity of depression increased. In the older MDD group, the oxygenated-hemoglobin concentration decreased in the right dorsolateral prefrontal cortex region as the severity of depression increased. Conclusion: : These results suggest that fNIRS may be an objective tool for identifying age differences among adolescents with MDD. To generalize the results and verify fNIRS as a potential biomarker tool, follow-up studies with a larger sample group should be conducted.

Clinical Role of Upfront F-18 FDG PET/CT in Determining Biopsy Sites for Lung Cancer Diagnosis.

PURPOSE: This study aimed to investigate the impact of FDG PET/CT timing for biopsy site selection in patients with stage IV lung cancer regarding complications and diagnostic yield. METHODS: This retrospective analysis was performed on 1297 patients (924 men and 373 women with a mean age of 71.4 ± 10.2 years) who underwent percutaneous needle biopsy (PNB) for stage IV lung cancer diagnosis in two hospitals. Data collected included the patient's characteristics, order date of the biopsy and PET/CT exams, biopsy target site (lung or non-lung), guidance modality, complications, sample adequacy, and diagnostic success. Based on the order date of the PNB and PET/CT exams, patients were categorized into upfront and delayed PET/CT groups. RESULTS: PNB for non-lung targets resulted in significantly lower rates of minor (8.1% vs. 16.2%), major (0.2% vs. 3.4%), and overall complications (8.3% vs. 19.6%) compared to PNB for lung targets (p < 0.001 for all types of complications). Compared to the delayed PET/CT group, the upfront PET/CT group exhibited a lower probability of lung target selection of PNB (53.9% vs. 67.1%, p < 0.001), including a reduced incidence of major complications (1.0% vs. 2.9%, p = 0.031). Moreover, there was no significant difference in the occurrence of minor and total complications between the two groups. Upfront PET/CT and delayed PET/CT groups showed no significant difference regarding sample adequacy and diagnostic success. CONCLUSIONS: Upfront PET/CT may have an impact on the selection of the biopsy site for patients with advanced lung cancer, which could result in a lower rate of major complications with no change in the diagnostic yield. Upfront PET/CT demonstrates potential clinical implications for enhancing the safety of lung cancer diagnosis in clinical practice.

Achieving imaging and computational reproducibility on multiparametric MRI radiomics features in brain tumor diagnosis: phantom and clinical validation.

OBJECTIVES: The Image Biomarker Standardization Initiative has helped improve the computational reproducibility of MRI radiomics features. Nonetheless, the MRI sequences and features with high imaging reproducibility are yet to be established. To determine reproducible multiparametric MRI radiomics features across test-retest, multi-scanner, and computational reproducibility comparisons, and to evaluate their clinical value in brain tumor diagnosis. METHODS: To assess reproducibility, T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), and diffusion-weighted imaging (DWI) were acquired from three 3-T MRI scanners using standardized phantom, and radiomics features were extracted using two computational algorithms. Reproducible radiomics features were selected when the concordance correlation coefficient value above 0.9 across multiple sessions, scanners, and computational algorithms. Random forest classifiers were trained with reproducible features (n = 117) and validated in a clinical cohort (n = 50) to evaluate whether features with high reproducibility improved the differentiation of glioblastoma from primary central nervous system lymphomas (PCNSLs). RESULTS: Radiomics features from T2WI demonstrated higher repeatability (65-94%) than those from DWI (38-48%) or T1WI (2-92%). Across test-retest, multi-scanner, and computational comparisons, T2WI provided 41 reproducible features, DWI provided six, and T1WI provided two. The performance of the classification model with reproducible features was higher than that using non-reproducible features in both training set (AUC, 0.916 vs. 0.877) and validation set (AUC, 0.957 vs. 0.869). CONCLUSION: Radiomics features with high reproducibility across multiple sessions, scanners, and computational algorithms were identified, and they showed higher diagnostic performance than non-reproducible radiomics features in the differentiation of glioblastoma from PCNSL. CLINICAL RELEVANCE STATEMENT: By identifying the radiomics features showing higher multi-machine reproducibility, our results also demonstrated higher radiomics diagnostic performance in the differentiation of glioblastoma from PCNSL, paving the way for further research designs and clinical application in neuro-oncology. KEY POINTS: • Highly reproducible radiomics features across multiple sessions, scanners, and computational algorithms were identified using phantom and applied to clinical diagnosis. • Radiomics features from T2-weighted imaging were more reproducible than those from T1-weighted and diffusion-weighted imaging. • Radiomics features with good reproducibility had better diagnostic performance for brain tumors than features with poor reproducibility.

Suboptimal hepatobiliary phase image in gadoxetic acid-enhanced liver MRI for the evaluation of the HCC: Predictive factors.

To determine the relevant laboratory values for hepatobiliary phase (HBP) imaging and predictive factors for suboptimal HBP images on gadoxetic acid-enhanced liver magnetic resonance imaging (MRI) for the evaluation of hepatocellular carcinoma (HCC) in patients with chronic liver disease (CLD). This study included 307 patients with CLD who underwent gadoxetic acid-enhanced liver MRI for HCC evaluation. The liver-portal vein contrast ratio and liver-spleen contrast ratio were calculated from the measurements of the HBP images. In this study, a suboptimal HBP image was defined as the presence of a bright portal vein or a liver-spleen contrast ratio of <1.5. Correlation, comparison, and receiver operating characteristic analyses were performed between the measured parameters on the HBP images and hepatic and renal function tests. The estimated glomerular filtration rate did not correlate with any measured or calculated values on the HBP images. On receiver operating characteristic analysis, the optimal cutoff value for the bright portal vein was an albumin level of 4.05 g/dL (area under the curve, 0.971; sensitivity, 65%; specificity, 82%). The optimal cutoff value of the suboptimal HBP image was a serum direct bilirubin level of 0.83 mg/dL (area under the curve, 0.830; sensitivity, 69%; specificity, 84%). On gadoxetic acid-enhanced MRI for the evaluation of HCC in patients with CLD, suboptimal HBP images were most strongly correlated with serum direct bilirubin levels. Renal function was not associated with suboptimal HBP imaging. Although the sensitivity is low, suboptimal HBP images can be predicted before gadoxetic acid-enhanced liver MRI can be performed.

Efficacy of Bronchial Artery Embolization for Clinically Suspected Bronchial Dieulafoy's Disease.

BACKGROUND: The efficacy of bronchial artery embolization (BAE) for bronchial Dieulafoy's disease (BDD) has not been well established. OBJECTIVE: This study aimed to evaluate the safety and efficacy of BAE in patients with clinically suspected BDD presenting with major hemoptysis, and to describe angiographic findings. METHODS: 17 patients (all men; mean age, 53.5 years) diagnosed with clinically suspected BDD by bronchoscopy (n = 7) or CT angiography (CTA) (n = 10) and who underwent BAE after directional and segmental localization of the target bronchus were enrolled. BAE was performed at the culprit bronchial artery traveling toward the target bronchus, regardless of the pathologic angiographic findings. Angiographic findings and clinical outcomes of BAE, including technical and clinical success, complication, recurrent hemoptysis, and follow-up imaging, were retrospectively reviewed. RESULTS: Representative angiographic findings included parenchymal hypervascularity prominent in the lobe where the BDD was located (82.4%), bronchial artery hypertrophy (70.6%), and contrast extravasation into the bleeding bronchus (17.6%). BAE was technically successful in all patients. All hemoptysis ceased within 24 h. No procedure-related complications occurred. During a mean follow-up of 491.9 days, 1 (6%) patient experienced recurrent hemoptysis. Follow-up bronchoscopy or CT performed in 10 (58.8%) patients showed the disappearance of pre-existing lesions (n = 9) or glue cast within the target bronchial artery (n = 1). CONCLUSION: Bronchial angiography showed pathologic findings in most patients with clinically suspected BDD. BAE assisted by bronchoscopy or CTA localization is a safe and effective treatment for patients with clinically suspected BDD with excellent short- to mid-term results.

Reducing false positives in deep learning-based brain metastasis detection by using both gradient-echo and spin-echo contrast-enhanced MRI: validation in a multi-center diagnostic cohort.

OBJECTIVES: To develop a deep learning (DL) for detection of brain metastasis (BM) that incorporates both gradient- and turbo spin-echo contrast-enhanced MRI (dual-enhanced DL) and evaluate it in a clinical cohort in comparison with human readers and DL using gradient-echo-based imaging only (GRE DL). MATERIALS AND METHODS: DL detection was developed using data from 200 patients with BM (training set) and tested in 62 (internal) and 48 (external) consecutive patients who underwent stereotactic radiosurgery and diagnostic dual-enhanced imaging (dual-enhanced DL) and later guide GRE imaging (GRE DL). The detection sensitivity and positive predictive value (PPV) were compared between two DLs. Two neuroradiologists independently analyzed BM and reference standards for BM were separately drawn by another neuroradiologist. The relative differences (RDs) from the reference standard BM numbers were compared between the DLs and neuroradiologists. RESULTS: Sensitivity was similar between GRE DL (93%, 95% confidence interval [CI]: 90-96%) and dual-enhanced DL (92% [89-94%]). The PPV of the dual-enhanced DL was higher (89% [86-92%], p < .001) than that of GRE DL (76%, [72-80%]). GRE DL significantly overestimated the number of metastases (false positives; RD: 0.05, 95% CI: 0.00-0.58) compared with neuroradiologists (RD: 0.00, 95% CI: - 0.28, 0.15, p < .001), whereas dual-enhanced DL (RD: 0.00, 95% CI: 0.00-0.15) did not show a statistically significant difference from neuroradiologists (RD: 0.00, 95% CI: - 0.20-0.10, p = .913). CONCLUSION: The dual-enhanced DL showed improved detection of BM and reduced overestimation compared with GRE DL, achieving similar performance to neuroradiologists. CLINICAL RELEVANCE STATEMENT: The use of deep learning-based brain metastasis detection with turbo spin-echo imaging reduces false positive detections, aiding in the guidance of stereotactic radiosurgery when gradient-echo imaging alone is employed. KEY POINTS: •Deep learning for brain metastasis detection improved by using both gradient- and turbo spin-echo contrast-enhanced MRI (dual-enhanced deep learning). •Dual-enhanced deep learning increased true positive detections and reduced overestimation. •Dual-enhanced deep learning achieved similar performance to neuroradiologists for brain metastasis counts.

A Radiation Induced Low-Grade Myofibroblastic Sarcoma in the Retropectoral Area After Breast Conserving Surgery: A Case Report.

Low-grade myofibroblastic sarcoma (LGMFS) is a rare type of sarcoma, and its manifestation as a radiotherapy (RT)-induced sarcoma following RT for breast cancer is even more unusual. To date, only one case of RT-induced mammary myofibroblastic sarcoma (MFS) has been reported. Here we present the case of a 49-year-old woman with LGMFS after undergoing breast-conserving surgery for invasive ductal carcinoma (IDC), and with a history of RT 16 years prior. Due to the rarity of this disease, previous studies have focused primarily on the pathological findings of MFS. In this report however, we present the clinical and radiological features of LGMFS in the retro pectoral area as a rare type of RT-induced sarcoma.

Assessment of diagnostic performance of risk factors affecting extraprostatic extension: Role of zonal level of prostate cancer.

OBJECTIVE: Extraprostatic extension (EPE) serves as a crucial marker of prostate cancer aggressiveness and independently predicts the likelihood of biochemical recurrence (BCR), exhibiting a strong correlation with the histologic severity of EPE. Therefore, this study aimed to investigate the probability of EPE along the zonal level of the prostate by measuring tumor contact length (TCL) using multiparametric magnetic resonance imaging (mpMRI). MATERIALS AND METHODS: Records of 308 patients who had undergone radical prostatectomy (RP) were identified. Tumor levels in the prostate were categorized as apex, mid-gland, and base, after which the correlation between TCL measured using MRI and microscopic EPE on pathologic specimens was evaluated. Univariable and multivariable logistic regression analyses were performed to assess the association among tumor origin, index tumor diameter, and TCL measured using MRI and microscopic EPE in RP specimens. RESULTS: Among the 214 patients included, 45 apical cancers (21%), 87 mid-gland cancers (41%), and 82 base cancers (38%) were observed. Pathological reports revealed that 18 (40.0%) apex, 31 (35.6%) mid-gland, and 50 (61.0%) base tumors were pT3a. Multivariable analysis demonstrated that the zonal level of the tumor, especially the base level, was an independent predictive factor for EPE (P < 0.001), and the AUC value of the base tumor was 0.858. CONCLUSION: Prostate cancers arising from the base were more likely to exhibit EPE than those arising from the mid-gland and apex of the prostate gland. Therefore, identifying the origin of the zonal level of prostate cancer may help guide treatment decisions and predict clinical prognosis.

Modeling and investigation of swelling kinetics of sodium carboxymethyl cellulose/starch/citric acid superabsorbent polymer.

Crosslinked hydrophilic polymers with high water absorption rates are known as superabsorbent polymers (SAPs). Most commercial superabsorbent polymers are made with acrylic acid, which is difficult to biodegrade. So, in this investigation, carboxymethyl cellulose (CMC) was utilized as a significant component in the synthesis of polysaccharide-based SAPs. Citric acid (CA) and starch were chosen as crosslinking agents because they are more eco-friendly, non-toxic, and biodegradable than traditional crosslinking agents. FTIR analysis revealed that the superabsorbent polymer product contains a crosslinked structure of CMC and starch with side chains that carry carboxylate functional groups. Superabsorbent weight loss and grafting data were satisfactorily studied using the TGA approach. Under optimum circumstances, the SAP2 water absorbency capacity in distilled water was 287.37 g.g-1 and SAP1 absorbency capacity in a solution containing 0.9 wt% NaCl was 52.18 g.g-1. Moreover, Schott's pseudo-second-order model was used to determine the kinetic swelling of the superabsorbent. The initial swelling rate of SAPs can be calculated using the Q∞ data acquired in the following order: SAP2 > SAP1 > SAP3 > SAP4 in distilled water and SAP1 > SAP2 > SAP3 > SAP4 in 0.9 wt% NaCl solution, respectively. The findings suggested that a small amount of citric acid introduced into the SAPs matrix could enhance the swelling rate of SAPs. The results of the cytotoxicity tests show that the extraction liquid of composite hydrogel fibers is less cytotoxic than the positive control. As well, SAP underwent in silico docking investigations on the DNA Gyrase enzyme. As the ligand is a monomer of SAP, it was a long chain of carbohydrate molecules with alcoholic groups, esters groups, and keto groups forms a strong binding interaction with DNA gyrase.

Debottlenecking and reformulating feed media for improved CHO cell growth and titer by data-driven and model-guided analyses.

Designing and selecting cell culture media along with their feeding are a key strategy to maximize culture performance in biopharmaceutical processes. However, the sensitivity of mammalian cells to their culture environment necessitates specific nutritional requirements for their growth and the production of high-quality proteins such as antibodies, depending on the cell lines and operational conditions employed. In this regard, previously we developed a data-driven and in-silico model-guided systematic framework to investigate the effect of growth media on Chinese hamster ovary (CHO) cell culture performance, allowing us to design and reformulate basal media. To expand our exploration for media development research, we evaluated two chemically defined feed media, A and B, using a monoclonal antibody-producing CHO-K1 cell line in ambr15 bioreactor runs. We observed a significant impact of the feed media on various aspects of cell culture, including growth, longevity, viability, productivity, and the production of toxic metabolites. Specifically, the concentrated feed A was inadequate in sustaining prolonged cell culture and achieving high titers when compared to feed B. Within our framework, we systematically investigated the major metabolic bottlenecks in the tricarboxylic acid cycle and relevant amino acid transferase reactions. This analysis identified target components that play a crucial role in alleviating bottlenecks and designing highly productive cell cultures, specifically the addition of glutamate to feed A and asparagine to feed B. Based on our findings, we reformulated the feeds by adjusting the amounts of the targeted amino acids and successfully validated the effectiveness of the strategy in promoting cell growth, life span, and/or titer.