LncRNA BCYRN1 as a Potential Therapeutic Target and Diagnostic Marker in Serum Exosomes in Bladder Cancer.

Bladder cancer (BC) is a common genitourinary malignancy that exhibits silent morbidity and high mortality rates because of a lack of diagnostic markers and limited effective treatments. Here, we evaluated the role of the lncRNA brain cytoplasmic RNA 1 (BCYRN1) in BC. We performed loss-of-function assays to examine the effects of BCYRN1 downregulation in T24 and BOY BC cells. We found that BCYRN1 downregulation significantly inhibited the proliferation, migration, invasion, and three-dimensional spheroid formation ability and induced apoptosis in BC cells. Additionally, gene set enrichment analysis (GSEA) using RNA sequences from tumor fractions showed that BCYRN1 downregulation decreased the expression of mRNAs associated with the cell cycle. These findings were supported by observations of G2/M arrest in flow cytometry assays. Finally, we examined the expression of serum exosomal BCYRN1 as a biomarker. Clinically, BCYRN1 expression in serum exosomes from patients with BC (n = 31) was significantly higher than that in healthy donors (n = 19; mean difference: 4.1-fold higher, p < 0.01). Moreover, in patients who had undergone complete resection of BC, serum exosomal BCYRN1 levels were significantly decreased (n = 8). Thus, serum exosomal BCYRN1 may be a promising diagnostic marker and therapeutic target in patients with BC.

Targeting metabolic reprogramming to overcome drug resistance in advanced bladder cancer: insights from gemcitabine- and cisplatin-resistant models.

Gemcitabine plus cisplatin (GC) combination chemotherapy is the primary treatment for advanced bladder cancer (BC) with unresectable or metastatic disease. However, most cases develop resistance to this therapy. We investigated whether drug resistance could be targeted through metabolic reprogramming therapies. Metabolomics analyses in our lab's gemcitabine- and cisplatin-resistant cell lines revealed increased phosphoglycerate dehydrogenase (PHGDH) expression in gemcitabine-resistant cells compared with parental cells. Isocitrate dehydrogenase 2 (IDH2) gain of function stabilized hypoxia-inducible factor1α (HIF1α) expression, stimulating aerobic glycolysis. In gemcitabine-resistant cells, elevated fumaric acid suppressed prolyl hydroxylase domain-containing protein 2/Egl nine homolog 1 (PHD2) and stabilized HIF1α expression. PHGDH downregulation or inhibition in gemcitabine-resistant BC cells inhibited their proliferation, migration, and invasion. Cisplatin-resistant cells showed elevated fatty acid metabolism, upregulating fatty acid synthase (FASN) downstream of tyrosine kinase. Using the fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor erdafitinib, we inhibited malonyl-CoA production, which is crucial for fatty acid synthesis, and thereby suppressed upregulated HIF1α expression. Combination treatment with NCT503 and erdafitinib synergistically suppressed tumor cell proliferation and induced apoptosis in vitro and in vivo. Understanding these mechanisms could enable innovative BC therapeutic strategies to be developed.

Development of a deep-learning algorithm for age estimation on CT images of the vertebral column.

PURPOSE: The accurate age estimation of cadavers is essential for their identification. However, conventional methods fail to yield adequate age estimation especially in elderly cadavers. We developed a deep learning algorithm for age estimation on CT images of the vertebral column and checked its accuracy. METHOD: For the development of our deep learning algorithm, we included 1,120 CT data of the vertebral column of 140 patients for each of 8 age decades. The deep learning model of regression analysis based on Visual Geometry Group-16 (VGG16) was improved in its estimation accuracy by bagging. To verify its accuracy, we applied our deep learning algorithm to estimate the age of 219 cadavers who had undergone postmortem CT (PMCT). The mean difference and the mean absolute error (MAE), the standard error of the estimate (SEE) between the known- and the estimated age, were calculated. Correlation analysis using the intraclass correlation coefficient (ICC) and Bland-Altman analysis were performed to assess differences between the known- and the estimated age. RESULTS: For the 219 cadavers, the mean difference between the known- and the estimated age was 0.30 years; it was 4.36 years for the MAE, and 5.48 years for the SEE. The ICC (2,1) was 0.96 (95 % confidence interval: 0.95-0.97, p < 0.001). Bland-Altman analysis showed that there were no proportional or fixed errors (p = 0.08 and 0.41). CONCLUSIONS: Our deep learning algorithm for estimating the age of 219 cadavers on CT images of the vertebral column was more accurate than conventional methods and highly useful.

Assessing antiviral treatment efficacy and risk factors for severe COVID-19 in kidney transplant recipients during the Omicron subvariant-dominant period: a retrospective study.

BACKGROUND: Kidney transplant recipients (KTRs) are at risk of severe coronavirus disease 2019 (COVID-19), and even now that Omicron subvariants have become dominant, cases of severe disease are certain to occur. The aims of this retrospective study were to evaluate the efficacy of antiviral treatment for COVID-19 and to identify risk factors for severe disease in KTRs during Omicron subvariant-dominant periods. METHODS: A total of 65 KTRs diagnosed with COVID-19 who received antiviral treatment between July 2022 and September 2023 were analyzed. Mild cases received oral molnupiravir (MP) as outpatient therapy, while moderate or worse cases received intravenous remdesivir (RDV) as inpatient therapy. In principle, mycophenolate mofetil was withdrawn and switched to everolimus. We investigated the efficacy of antiviral treatment and compared the clinical parameters of mild/moderate and severe/critical cases to identify risk factors for severe COVID-19. RESULTS: Among 65 cases, 49 were mild, 6 were moderate, 9 were severe, and 1 was of critical severity. MP was administered to 57 cases; 49 (86%) improved and 8 (14%) progressed. RDV was administered to 16 cases; 14 (87%) improved and 2 (13%) progressed. Seventeen (26%) cases required hospitalization, and none died. Comparisons of the severe/critical group (n = 10) with the mild/moderate group (n = 55) demonstrated that the severe/critical group had a significantly higher median age (64 vs. 53 years, respectively; p = 0.0252), prevalence of diabetes (70% vs. 22%, respectively; p = 0.0047) and overweight/obesity (40% vs. 11%, respectively; p = 0.0393), as well as a significantly longer median time from symptom onset to initial antiviral therapy (3 days vs. 1 day, respectively; p = 0.0026). Multivariate analysis showed that a longer time from symptom onset to initial antiviral treatment was an independent risk factor for severe COVID-19 (p = 0.0196, odds ratio 1.625, 95% confidence interval 1.081-2.441). CONCLUSION: These findings suggest that a longer time from symptom onset to initial antiviral treatment is associated with a higher risk of severe COVID-19 in KTRs. Initiating antiviral treatment as early as possible is crucial for preventing severe outcomes; this represents a valuable insight into COVID-19 management in KTRs.

Performance of postmortem CT in the diagnosis of natural death from out-of-hospital cardiac arrest.

PURPOSE: Postmortem CT (PMCT) is used widely to identify the cause of death. However, its diagnostic performance in cases of natural death from out-of-hospital cardiac arrest (OHCA) may be unsatisfactory because the cause tends to be cardiogenic and cannot be detected on PMCT images. We retrospectively investigated the diagnostic performance of PMCT in the diagnosis of natural death from OHCA and compared it to that of unnatural death. MATERIALS AND METHODS: Our series included 450 cases; 336 were natural- and 114 were unnatural death cases. Between 2018 and 2022 all underwent non-contrast PMCT to identify the cause of death. Two radiologists reviewed the PMCT images and categorized them as diagnostic (PMCT alone sufficient to determine the cause of death), suggestive (the cause of death was suggested but additional information was needed), and non-diagnostic (the cause of death could not be determined on PMCT images). The diagnostic performance of PMCT was defined by the percentage of diagnosable and suggestive cases and compared between natural- and unnatural death cases. Interobserver agreement for the cause of death on PMCT images was also assessed with the Cohen kappa coefficient of concordance. RESULTS: The diagnostic performance of PMCT for the cause of natural- and unnatural deaths from OHCA was 30.3% and 66.6%, respectively (p < 0.01). The interobserver agreement for the cause of natural- and unnatural deaths on PMCT images was very good with kappa value 0.92 and 0.96, respectively. CONCLUSION: As PMCT identified the cause of natural death by OHCA in only 30% of cases, its diagnostic performance must be improved.

Chest CT findings in severe acute respiratory distress syndrome requiring V-V ECMO: J-CARVE registry.

BACKGROUND: Chest computed tomography findings are helpful for understanding the pathophysiology of severe acute respiratory distress syndrome (ARDS). However, there is no large, multicenter, chest computed tomography registry for patients requiring veno-venous extracorporeal membrane oxygenation (V-V ECMO). The aim of this study was to describe chest computed tomography findings at V-V ECMO initiation and to evaluate the association between the findings and outcomes in severe ARDS. METHODS: This multicenter, retrospective cohort study enrolled patients with severe ARDS on V-V ECMO, who were admitted to the intensive care units of 24 hospitals in Japan between January 1, 2012, and December 31, 2022. RESULTS: The primary outcome was 90-day in-hospital mortality. The secondary outcomes were the successful liberation from V-V ECMO and the values of static lung compliance. Among the 697 registry patients, of the 582 patients who underwent chest computed tomography at V-V ECMO initiation, 394 survived and 188 died. Multivariate Cox regression showed that traction bronchiectasis and subcutaneous emphysema increased the risk of 90-day in-hospital mortality (hazard ratio [95% confidence interval] 1.77 [1.19-2.63], p = 0.005 and 1.97 [1.02-3.79], p = 0.044, respectively). The presence of traction bronchiectasis was also associated with decreased successful liberation from V-V ECMO (odds ratio: 0.27 [0.14-0.52], p < 0.001). Lower static lung compliance was associated with some chest computed tomography findings related to changes outside of pulmonary opacity, but not with the findings related to pulmonary opacity. CONCLUSIONS: Traction bronchiectasis and subcutaneous emphysema increased the risk of 90-day in-hospital mortality in patients with severe ARDS who required V-V ECMO.

Perioperative proximal splenic artery embolization in cirrhotic patients with splenomegaly.

INTRODUCTION: The purpose of this study was to determine the effect of proximal splenic artery embolization (SAE) in cirrhotic patients with splenomegaly who underwent surgical laparotomy. MATERIAL AND METHODS: This retrospective observational study included 8 cirrhotic patients with splenomegaly. They underwent proximal SAE before- (n = 6) or after (n = 2) laparotomy. Vascular plugs or coils were placed in the proximal splenic artery. The diameter of the portal vein and the splenic volume were recorded. Clinical outcome assessments included platelet counts, the model for end-stage liver disease (MELD) score, and complications. RESULTS: After embolization, the portal venous diameter was significantly smaller (pre: 13.6 ± 2.7 mm, post: 12.5 ± 2.3 mm, p = 0.023), the splenic volume was significantly decreased (pre: 463.2 ± 145.7 ml, post: 373.3 ± 108.5 ml, p = 0.008) and the platelet count was significantly higher (pre: 69.6 ± 30.8 × 103/µl, post: 86.8 ± 27.7 × 103/µl, p = 0.035). Before embolization, the median MELD score was 12; after embolization, it was 11 (p = 0.026). No patient developed post-treatment complications after embolization. CONCLUSIONS: The reduction of hypersplenism by perioperative proximal SAE may be safe and reduce the surgical risk in cirrhotic patients with splenomegaly.

Potential therapeutic target secretogranin II might cooperate with hypoxia-inducible factor 1α in sunitinib-resistant renal cell carcinoma.

Multitargeted receptor tyrosine kinase inhibitors, including vascular endothelial growth factor (VEGF) inhibitors, such as sunitinib, have been used as the primary targeted agents for patients with recurrent or distant metastasis of advanced renal cell carcinoma (RCC). However, endogenous or acquired sunitinib resistance has become a significant therapeutic problem. Therefore, we focused on mechanisms of sunitinib resistance in RCC. First, we undertook RNA sequencing analysis using previously established sunitinib-resistant RCC (SUR-Caki1, SUR-ACHN, and SUR-A498) cells. The results showed increased expression of secretogranin II (SCG2, chromogranin C) in SUR-RCC cells compared to parental cells. The Cancer Genome Atlas database showed that SCG2 expression was increased in RCC compared to normal renal cells. In addition, the survival rate of the SCG2 high-expression group was significantly lower than that of the RCC low-expression group. Thus, we investigated the involvement of SCG2 in sunitinib-resistant RCC. In vitro analysis showed that migratory and invasive abilities were suppressed by SCG2 knockdown SUR cells. As SCG2 was previously reported to be associated with angiogenesis, we undertook a tube formation assay. The results showed that suppression of SCG2 inhibited angiogenesis. Furthermore, coimmunoprecipitation assays revealed a direct interaction between SCG2 and hypoxia-inducible factor 1α (HIF1α). Expression levels of VEGF-A and VEGF-C downstream of HIF1α were found to be decreased in SCG2 knockdown SUR cells. In conclusion, SCG2 could be associated with sunitinib resistance through VEGF regulation in RCC cells. These findings could lead to a better understanding of the VHL/HIF/VEGF pathway and the development of new therapeutic strategies for sunitinib-resistant RCC.

Characteristics of the pulmonary opacities on chest CT associated with difficulty in short-term liberation from veno-venous ECMO in patients with severe ARDS.

BACKGROUND: It is clinically important to predict difficulty in short-term liberation from veno-venous extracorporeal membrane oxygenation (V-V ECMO) in patients with severe acute respiratory distress syndrome (ARDS) at the time of initiation of the support. The aim of this study was to identify the characteristics of pulmonary opacities on chest CT that is associated with difficulty in short-term liberation from V-V ECMO (< 14 days). METHODS: This multicenter retrospective study was conducted in adult patients initiated on V-V ECMO for severe ARDS between January 2014 and June 2022. The pulmonary opacities on CT at the time of initiation of the ECMO support were evaluated in a blinded manner, focusing on the following three characteristics of the opacities: (1) their distribution (focal/diffuse on the dorso-ventral axis or unilateral/bilateral on the left-right axis); (2) their intensity (pure ground glass/pure consolidation/mixed pattern); and (3) the degree of fibroproliferation (signs of traction bronchiectasis or reticular opacities). RESULTS: Among the 153 patients, 72 (47%) were successfully liberated from ECMO in the short term, while short-term liberation failed in the remaining 81 (53%) patients. Multivariate logistic regression analysis showed that the presence of mixed-pattern pulmonary opacities and signs of traction bronchiectasis, but not the distribution of the opacities, were independently associated with difficulty in short-term liberation (OR [95% CI]; 4.8 [1.4-16.5] and 3.9 [1.4-11.2], respectively). CONCLUSIONS: The presence of a mixed pattern of the pulmonary opacities and signs of traction bronchiectasis on the chest CT were independently associated with difficulty in short-term liberation from V-V ECMO in severe ARDS patients.

Age estimation using post-mortem computed tomography and fetal dental radiographic findings in an early to mid-pregnancy fetus: A case report.

Parameters for body size growth are essential to evaluate the relationship between fetal growth and accurate age estimation in forensics. Size values measured postmortem are also affected by the postmortem environment. On the contrary, when using hard tissue maturation criteria, age estimation remains unaffected by the degree of fetal preservation. In Japan, a fetus dying 12 weeks after pregnancy must be reported as a stillbirth. A Japanese stillborn infant buried without reporting to the authorities underwent a forensic autopsy. The gestational age was 4-5 months, based on the mother's description. The body was not fixed, and it was macerated and flattened along the sagittal plane; therefore it was difficult to correctly measure indicators involving soft tissue. The bone size and tooth development were evaluated using postmortem computed tomography (CT) images and intraoral radiography to estimate the age. Considering all the information, including age estimation based on bone sizes referenced in a Japanese study, calcified upper central incisors, we estimated fetal gestational age for our sample as 14-17 gestational weeks finally. However, there were discrepancies between age estimations based on bone size (20-25 gestational weeks, bone radiographic imaging standards; or 4-6 gestational months, an average of the extremity-bones by a Japanese study) and tooth development (14-17 gestational weeks). Deep discussions based on multiple indices with professionals should be applied to forensic age estimation since existing methods may be based on data for different races, use other measurement tools, or apply different sample conditions even if the targets are the same.

Iodine maps derived from sparse-view kV-switching dual-energy CT equipped with a deep learning reconstruction for diagnosis of hepatocellular carcinoma.

Deep learning-based spectral CT imaging (DL-SCTI) is a novel type of fast kilovolt-switching dual-energy CT equipped with a cascaded deep-learning reconstruction which completes the views missing in the sinogram space and improves the image quality in the image space because it uses deep convolutional neural networks trained on fully sampled dual-energy data acquired via dual kV rotations. We investigated the clinical utility of iodine maps generated from DL-SCTI scans for assessing hepatocellular carcinoma (HCC). In the clinical study, dynamic DL-SCTI scans (tube voltage 135 and 80 kV) were acquired in 52 patients with hypervascular HCCs whose vascularity was confirmed by CT during hepatic arteriography. Virtual monochromatic 70 keV images served as the reference images. Iodine maps were reconstructed using three-material decomposition (fat, healthy liver tissue, iodine). A radiologist calculated the contrast-to-noise ratio (CNR) during the hepatic arterial phase (CNRa) and the equilibrium phase (CNRe). In the phantom study, DL-SCTI scans (tube voltage 135 and 80 kV) were acquired to assess the accuracy of iodine maps; the iodine concentration was known. The CNRa was significantly higher on the iodine maps than on 70 keV images (p < 0.01). The CNRe was significantly higher on 70 keV images than on iodine maps (p < 0.01). The estimated iodine concentration derived from DL-SCTI scans in the phantom study was highly correlated with the known iodine concentration. It was underestimated in small-diameter modules and in large-diameter modules with an iodine concentration of less than 2.0 mgI/ml. Iodine maps generated from DL-SCTI scans can improve the CNR for HCCs during hepatic arterial phase but not during equilibrium phase in comparison with virtual monochromatic 70 keV images. Also, when the lesion is small or the iodine concentration is low, iodine quantification may result in underestimation.

Improvement of Spatial Resolution on Coronary CT Angiography by Using Super-Resolution Deep Learning Reconstruction.

RATIONALE AND OBJECTIVES: Our objective was to compare the image quality of coronary CT angiography reconstructed with super-resolution deep learning reconstruction (SR-DLR) and with hybrid iterative reconstruction (IR) images. MATERIALS AND METHODS: This retrospective study included 100 patients who underwent coronary CT angiography using a 320-detector-row CT scanner. The CT images were reconstructed with hybrid IR and SR-DLR. The standard deviation of the CT number was recorded and the CT attenuation profile across the left main coronary artery was generated to calculate the contrast-to-noise ratio (CNR) and measure the edge rise slope (ERS). Overall image quality was evaluated and plaque detectability was assessed on a 4-point scale (1 = poor, 4 = excellent). For reference, invasive coronary angiography of 14 patients was used. RESULTS: The mean image noise on SR-DLR was significantly lower than on hybrid IR images (15.6 vs 22.9 HU; p < 0.01). The mean CNR was significantly higher and the ERS was steeper on SR-DLR- compared to hybrid IR images (CNR: 32.4 vs 20.4, p < 0.01; ERS: 300.0 vs 198.2 HU/mm, p < 0.01). The image quality score was better on SR-DLR- than on hybrid IR images (3.6 vs 3.1; p < 0.01). SR-DLR increased the detectability of plaques with < 50% stenosis (p < 0.01). CONCLUSION: SR-DLR was superior to hybrid IR with respect to the image noise, the sharpness of coronary artery margins, and plaque detectability.

Understanding CT imaging findings based on the underlying pathophysiology in patients with small bowel ischemia.

Because acute small bowel ischemia has a high mortality rate, it requires rapid intervention to avoid unfavorable outcomes. Computed tomography (CT) examination is important for the diagnosis of bowel ischemia. Acute small bowel ischemia can be the result of small bowel obstruction or mesenteric ischemia, including mesenteric arterial occlusion, mesenteric venous thrombosis, and non-occlusive mesenteric ischemia. The clinical significance of each CT finding is unique and depends on the underlying pathophysiology. This review describes the definition and mechanism(s) of bowel ischemia, reviews CT findings suggesting bowel ischemia, details factors involved in the development of small bowel ischemia, and presents CT findings with respect to the different factors based on the underlying pathophysiology. Such knowledge is needed for accurate treatment decisions.

Exosomal microRNA-1 and MYO15A as a target for therapy and diagnosis in renal cell carcinoma.

Exosomes are 40-100 nm nano-sized extracellular vesicles and are receiving increasing attention as novel structures that participate in intracellular communication. We previously found that miRNA-1 (miR-1) functions as a tumor suppressor in renal cell carcinoma (RCC). In this study, we investigated the function of exosomal miR-1 and the possibility that the exosome constitutes a tumor maker in RCC. First, we established the method to collect exosomes from cell lysates and human serum by a spin column-based method. Next, we assessed exosomes using Nanosight nanoparticle tracking analysis and Western blot analysis with exosome marker CD63. We confirmed that exosomes labeled with PKH26 fused with recipient cells. Moreover, miR-1 expression was elevated in RCC cells treated with exosomes derived from miR-1-transfected cells. Functional analyses showed that exosomal miR-1 significantly inhibited cell proliferation, migration and invasion compared to control treatment. Our analyses with TCGA database of RCCs showed that miR-1 expression was significantly downregulated in clinical RCC samples compared to that in normal kidney samples, and patients with low miR-1 expression had poorer overall survival in comparison to patients with high expression. Furthermore, RNA sequence analyses showed that expression levels of several genes were altered by exposure to exosomal miR-1. The analyses with TCGA database indicated that high expression of MYO15A was associated with a poorer outcome in RCC. In addition, RT-qPCR analysis of exosomes from clinical patients' sera showed that MYO15A was significantly upregulated in RCC patients compared to that in healthy controls. This study showed that treatment with exosomal miR-1 might be an effective approach to treating RCCs. In addition, exosomal MYO15A could be a diagnostic tumor marker in RCCs.

Four cases of cytokine storm after COVID-19 vaccination: Case report.

The global coronavirus disease 2019 (COVID-19) pandemic has led to the rapid development of vaccines against this disease. Despite the success of the international vaccination program, adverse events following vaccination, and the mechanisms behind them, remain poorly understood. Here we present four cases of death following receipt of a second dose of COVID-19 vaccine, with no obvious cause identified at autopsy. Using RNA sequencing, we identified genes that were differentially expressed between our post-vaccination cases and a control group that died of blood loss and strangulation. Three hundred and ninety genes were found to be upregulated and 115 genes were downregulated in post-vaccination cases compared with controls. Importantly, genes involved in neutrophil degranulation and cytokine signaling were upregulated. Our results suggest that immune dysregulation occurred following vaccination. Careful observation and care may be necessary if an abnormally high fever exceeding 40°C occurs after vaccination, even with antipyretic drugs.

Cranio-caudal puncture with computed tomography-guided drainage of a deep pelvic abscess.

Purpose: Computed tomography (CT)-guided percutaneous drainage has been used to address pelvic abscesses because it is safe and minimally invasive. However, CT-guided drainage has the limitation that the puncture route should be on the same axial slice. A technique for puncturing in the cranio-caudal direction under CT fluoroscopy is needed. Case report: An 82-year-old man with an abscess due to rectal cancer was scheduled for CT-guided drainage to improve his general condition before radical surgery. Drainage was performed via a perineal approach to localize the drainage tract in the resection area to avoid dissemination of cancer cells. To perform a puncture in the cranio-caudal direction we controlled the needle like a joystick and advanced it under CT fluoroscopy while moving the CT gantry cranially to follow the needle tip throughout the puncture. Our unique technique yielded successful CT-guided puncture in the cranio-caudal direction. Conclusions: Our unique technique overcomes the limitations of CT-guided cranio-caudal puncture and may allow the drainage of abscesses whose treatment was heretofore difficult.

Targeting of the glutamine transporter SLC1A5 induces cellular senescence in clear cell renal cell carcinoma.

In recent years, cancer metabolism has attracted attention as a therapeutic target, and glutamine metabolism is considered one of the most important metabolic processes in cancer. Solute carrier family 1 member 5 (SLC1A5) is a sodium channel that functions as a glutamine transporter. In various cancer types, SLC1A5 gene expression is enhanced, and cancer cell growth is suppressed by inhibition of SLC1A5. However, the involvement of SLC1A5 in clear cell renal cell carcinoma (ccRCC) is unclear. Therefore, in this study, we evaluated the clinical importance of SLC1A5 in ccRCC using The Cancer Genome Atlas database. Our findings confirmed that SLC1A5 was a prognosis factor for poor survival in ccRCC. Furthermore, loss-of-function assays using small interfering RNAs or an SLC1A5 inhibitor (V9302) in human ccRCC cell lines (A498 and Caki1) showed that inhibition of SLC1A5 significantly suppressed tumor growth, invasion, and migration. Additionally, inhibition of SLC1A5 by V9302 in vivo significantly suppressed tumor growth, and the antitumor effects of SLC1A5 inhibition were related to cellular senescence. Our findings may improve our understanding of ccRCC and the development of new treatment strategies for ccRCC.

Triaging of COVID-19 patients using low dose chest CT: Incidence and factor analysis of lung involvement on CT images.

INTRODUCTION: Despite an increase in CT studies to evaluate patients with coronavirus disease 2019 (COVID-19), their indication in triage is not well-established. The purpose was to investigate the incidence of lung involvement and analyzed factors related to lung involvement on CT images for establishment of the indication for CT scans in the triaging of COVID-19 patients. METHODS: Included were 192 COVID-19 patients who had undergone CT scans and blood tests for triaging. Two radiologists reviewed the CT images and recorded the incidence of lung involvement. The prediction model for lung involvement on CT images using clinico-laboratory variables [age, gender, body mass index, oxygen saturation of the peripheral artery (SpO2), comorbidities, symptoms, and blood data] were developed by multivariate logistic regression with cross-validation. RESULTS: In 120 of the 192 patients (62.5%), CT revealed lung involvement. The patient age (odds ratio [OR]; 4.95, 95% confidence interval [CI]; 0.93-26.49), albumin (OR; 4.66, 95%CI; 1.37-15.84), lactate dehydrogenase (OR; 5.79, 95%CI; 1.43-23.38) and C-reactive protein (OR; 8.93, 95%CI; 4.13-19.29) were selected for the final prediction model for lung involvement on CT images. The cross-validated area under the receiver operating characteristics (ROC) curve was 0.83. CONCLUSIONS: The high incidence of lung involvement (62.5%) was confirmed on CT images. The proposed prediction model that includes the patient age, albumin, lactate dehydrogenase, and C-reactive protein may be useful for predicting lung involvement on CT images and may assist in deciding whether triaged COVID-19 patients should undergo CT.

Global illumination rendering versus volume rendering for the forensic evaluation of stab wounds using computed tomography.

We compared three-dimensional (3D) CT images of stabbing victims subjected to volume-rendering (VR) or global illumination-rendering (GIR), a new technique now available for the reconstruction of 3D CT images. It simulates the complete interactions of photons with the scanned object, thereby providing photorealistic images. The diagnostic value of the images was also compared with that of macroscopic photographs. We used postmortem 3D CT images of 14 stabbing victims who had undergone autopsy and CT studies. The 3D CT images were subjected to GIR or VR and the 3D effect and the smoothness of the skin surface were graded on a 5-point scale. We also compared the 3D CT images of 37 stab wounds with macroscopic photographs. The maximum diameter of the wounds was measured on VR and GIR images and compared with the diameter recorded at autopsy. The overall image-quality scores and the ability to assess the stab wounds were significantly better on GIR than VR images (median scores: VR = 3 vs GIR = 4, p < 0.01). The mean difference between the wound diameter measured on VR and GIR images and at autopsy were both 0.2 cm, respectively. For the assessment of stab wounds, 3D CT images subjected to GIR were superior to VR images. The diagnostic value of 3D CT GIR image was comparable to that of macroscopic photographs.

microRNA-99a-5p induces cellular senescence in gemcitabine-resistant bladder cancer by targeting SMARCD1.

Patients with advanced bladder cancer are generally treated with a combination of chemotherapeutics, including gemcitabine, but the effect is limited due to acquisition of drug resistance. Thus, in this study, we investigated the mechanism of gemcitabine resistance. First, gemcitabine-resistant cells were established and resistance confirmed in vitro and in vivo. Small RNA sequencing analyses were performed to search for miRNAs involved in gemcitabine resistance. miR-99a-5p, selected as a candidate miRNA, was downregulated compared to its parental cells. In gain-of-function studies, miR-99a-5p inhibited cell viabilities and restored sensitivity to gemcitabine. RNA sequencing analysis was performed to find the target gene of miR-99a-5p. SMARCD1 was selected as a candidate gene. Dual-luciferase reporter assays showed that miR-99a-5p directly regulated SMARCD1. Loss-of-function studies conducted with si-RNAs revealed suppression of cell functions and restoration of gemcitabine sensitivity. miR-99a-5p overexpression and SMARCD1 knockdown also suppressed gemcitabine-resistant cells in vivo. Furthermore, ß-galactosidase staining showed that miR-99a-5p induction and SMARCD1 suppression contributed to cellular senescence. In summary, tumor-suppressive miR-99a-5p induced cellular senescence in gemcitabine-resistant bladder cancer cells by targeting SMARCD1.