Strengthening deep-learning models for intracranial hemorrhage detection: strongly annotated computed tomography images and model ensembles

Background and purposeMultiple attempts at intracranial hemorrhage (ICH) detection using deep-learning techniques have been plagued by clinical failures. We aimed to compare the performance of a deep-learning algorithm for ICH detection trained on strongly and weakly annotated datasets, and to assess whether a weighted ensemble model that integrates separate models trained using datasets with different ICH improves performance.MethodsWe used brain CT scans from the Radiological Society of North America (27,861 CT scans, 3,528 ICHs) and AI-Hub (53,045 CT scans, 7,013 ICHs) for training. DenseNet121, InceptionResNetV2, MobileNetV2, and VGG19 were trained on strongly and weakly annotated datasets and compared using independent external test datasets. We then developed a weighted ensemble model combining separate models trained on all ICH, subdural hemorrhage (SDH), subarachnoid hemorrhage (SAH), and small-lesion ICH cases. The final weighted ensemble model was compared to four well-known deep-learning models. After external testing, six neurologists reviewed 91 ICH cases difficult for AI and humans.ResultsInceptionResNetV2, MobileNetV2, and VGG19 models outperformed when trained on strongly annotated datasets. A weighted ensemble model combining models trained on SDH, SAH, and small-lesion ICH had a higher AUC, compared with a model trained on all ICH cases only. This model outperformed four deep-learning models (AUC [95% C.I.]: Ensemble model, 0.953[0.938–0.965]; InceptionResNetV2, 0.852[0.828–0.873]; DenseNet121, 0.875[0.852–0.895]; VGG19, 0.796[0.770–0.821]; MobileNetV2, 0.650[0.620–0.680]; p < 0.0001). In addition, the case review showed that a better understanding and management of difficult cases may facilitate clinical use of ICH detection algorithms.ConclusionWe propose a weighted ensemble model for ICH detection, trained on large-scale, strongly annotated CT scans, as no model can capture all aspects of complex tasks

Risk stratification of symptomatic brain metastases by clinical and FDG PET parameters for selective use of prophylactic cranial irradiation in patients with extensive disease of small cell lung cancer

Purpose: To identify risk factors for developing symptomatic brain metastases and evaluate the impact of prophylactic cranial irradiation (PCI) on brain metastasis-free survival (BMFS) and overall survival (OS) in extensive disease small cell lung cancer (ED-SCLC). Materials and methods: Among 190 patients diagnosed with ED-SCLC who underwent FDG PET/CT and brain Magnetic Resonance Imaging (MRI) prior to treatment, 53 (27.9%) received PCI while 137 (72.1%) did not. Prognostic index predicting a high risk of symptomatic brain metastases was calculated for the group without receiving PCI (observation group, n = 137) with Cox regression model. Results: Median follow-up time was 10.6 months. Multivariate Cox regression showed that the following three factors were associated with a high risk of symptomatic brain metastases: the presence of extrathoracic metastases (p = 0.004), hypermetabolism of bone marrow or spleen on FDG PET (p < 0.001), and high neutrophil-to-lymphocyte ratio (p = 0.018). PCI significantly improved BMFS in high-risk patients (1-year rate: 94.7% vs. 62.1%, p = 0.001), but not in low-risk patients (1-year rate: 100.0% vs. 87.7%, p = 0.943). However, PCI did not improve OS in patients at high risk for symptomatic brain metastases (1-year rate: 65.2% vs. 50.0%, p = 0.123). Conclusion: Three prognostic factors (the presence of extrathoracic metastases, hypermetabolism of bone marrow or spleen on FDG PET, and high neutrophil-to-lymphocyte ratio) were associated with a high risk of symptomatic brain metastases in ED-SCLC. PCI was beneficial for patients at a high risk of symptomatic brain metastases in terms of BMFS, but not OS. Thus, selective use of PCI in ED-SCLC according to the risk stratification is recommended. (C) 2020 Elsevier B.V. All rights reserved.

A comparative study of rubber band ligation versus BANANA-Clip in grade 1 to 3 internal hemorrhoids

Purpose Rubber band ligation (RBL) for grade 1 to 3 internal hemorrhoids is a well-established modality of choice. But RBL is also a kind of surgical treatment; it is not free from complications (e.g., delayed bleeding [DB], rectal stenosis). This study aimed to investigate the results of the comparative treatment of RBL and BANANA-Clip (BC; Endovision). Methods Study participants were 632 consecutive patients with grade 1 to 3 internal hemorrhoids attended to Department of Colorectal Surgery at Wellness Hospital between January 2010 and May 2019. We retrospectively reviewed the incidence rate of complications, including DB between RBL and BC. Results There were 304 male and 328 female patients, whose ages ranged from 15 to 84 years, with a mean age of 45.7 years. The common symptom and cause of treatment was prolapse (70.1%). The number of ligated sites was 1.49±0.57 in the RBL group and 1.99±0.77 in the BC group. RBL showed a significantly higher incidence of DB (3.5%) compared to BC (0%) (P=0.001). The 1-year success rate was 95.9% in the RBL group and 99.7% in the BC group (P=0.005). Conclusion In our study, BC was more reliable in treating grade 1 to 3 internal hemorrhoids with higher success rates and less postligation complications, especially DB, compared to RBL

High-Power and Ultralong-Life Aqueous Zinc-Ion Hybrid Capacitors Based on Pseudocapacitive Charge Storage

© 2019, © 2019, The Author(s). Rechargeable aqueous zinc-ion hybrid capacitors and zinc-ion batteries are promising safe energy storage systems. In this study, amorphous RuO2·H2O for the first time was employed to achieve fast and ultralong-life Zn2+ storage based on a pseudocapacitive storage mechanism. In the RuO2·H2O||Zn zinc-ion hybrid capacitors with Zn(CF3SO3)2 aqueous electrolyte, the RuO2·H2O cathode can reversibly store Zn2+ in a voltage window of 0.4–1.6 V (vs. Zn/Zn2+), delivering a high discharge capacity of 122 mAh g−1. In particular, the zinc-ion hybrid capacitors can be rapidly charged/discharged within 36 s with a very high power density of 16.74 kW kg−1 and a high energy density of 82 Wh kg−1. Besides, the zinc-ion hybrid capacitors demonstrate an ultralong cycle life (over 10,000 charge/discharge cycles). The kinetic analysis elucidates that the ultrafast Zn2+ storage in the RuO2·H2O cathode originates from redox pseudocapacitive reactions. This work could greatly facilitate the development of high-power and safe electrochemical energy storage.[Figure not available: see fulltext.]

Decreased expression of extracellular matrix proteins and trophic factors in the amygdala complex of depressed mice after chronic immobilization stress

BACKGROUND: The amygdala plays an essential role in controlling emotional behaviors and has numerous connections to other brain regions. The functional role of the amygdala has been highlighted by various studies of stress-induced behavioral changes. Here we investigated gene expression changes in the amygdala in the chronic immobilization stress (CIS)-induced depression model. RESULTS: Eight genes were decreased in the amygdala of CIS mice, including genes for neurotrophic factors and extracellular matrix proteins. Among these, osteoglycin, fibromodulin, insulin-like growth factor 2 (Igf2), and insulin-like growth factor binding protein 2 (Igfbp2) were further analyzed for histological expression changes. The expression of osteoglycin and fibromodulin simultaneously decreased in the medial, basolateral, and central amygdala regions. However, Igf2 and Igfbp2 decreased specifically in the central nucleus of the amygdala. Interestingly, this decrease was found only in the amygdala of mice showing higher immobility, but not in mice displaying lower immobility, although the CIS regimen was the same for both groups. CONCLUSIONS: These results suggest that the responsiveness of the amygdala may play a role in the sensitivity of CIS-induced behavioral changes in mice

Development and validation of a prediction model for knee joint line orientation after high tibial osteotomy

Background Maintenance of optimal knee joint line orientation (KJLO) is important after high tibial osteotomy (HTO). No tools, however, are currently available that could predict the value of postoperative KJLO before surgery. First, this study sought to determine the effects of various preoperative anatomical alignment parameters to postoperative KJLO. Based upon these analyses, we aimed to devise an equation that predicts the value of postoperative KJLO. Methods A total of 14 radiographic parameters were measured in preoperative and postoperative full-limb standing anteroposterior radiographs on 50 patients who underwent open-wedge HTO. The parameters were analysed using multivariable linear regression to predict KJLO after HTO. External validation of the equation was done with 20 patients who underwent HTO at another institution. Results After HTO, KJLO increased from − 0.8° to 2.9° (P < 0.001). Based on the multivariable linear regression analysis, an equation was derived that can estimate postoperative KJLO after HTO; postoperative KJLO(°) = 1.029 + 0.560 × preoperative KJLO(°) + 0.310 × preoperative tibia plateau inclination(°) + 0.463 × aimed correction angle(°). The adjusted coefficients of determination value for this equation was 0.721. The equation also showed good calibration and predictability in external validation with predicted squared correlation coefficient of 0.867. Conclusions This study analysed the effects of preoperative anatomical alignment parameters on the postoperative KJLO. An equation which predicts postoperative KJLO with preoperative anatomical alignment factors was devised and validated. This equation would help in selecting optimal patients for HTO and in selecting the optimal target correction angle in HTO

Virus-Host Mucosal Interactions During Early SIV Rectal Transmission

To deepen our understanding of early rectal transmission of HIV-1, we studied virus-host interactions in the rectal mucosa using simian immunodeficiency virus (SIV)-Indian rhesus macaque model and mRNA deep sequencing. We found that rectal mucosa actively responded to SIV as early as 3 days post-rectal inoculation (dpi) and mobilized more robust responses at 6 and 10 dpi. Our results suggests that the failure of the host to contain virus replication at the portal of entry is attributable to both a high-level expression of lymphocyte chemoattractant, proinflammatory and immune activation genes, which can recruit and activate viral susceptible target cells into mucosa; and a high-level expression of SIV accessory genes, which are known to be able to counter and evade host restriction factors and innate immune responses. This study provides new insights into the mechanism of rectal transmission

TRAIL sensitize MDR cells to MDR-related drugs by down-regulation of P-glycoprotein through inhibition of DNA-PKcs/Akt/GSK-3β pathway and activation of caspases

<p>Abstract</p> <p>Background</p> <p>The development of new modulator possessing high efficacy, low toxicity and high selectivity is a pivotal approach to overcome P-glycoprotein (P-gp) mediated multidrug resistance (MDR) in cancer treatment. In this study, we suggest a new molecular mechanism that TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) down-regulates P-glycoprotein (P-gp) through inhibition of DNA-PKcs/Akt/GSK-3β pathway and activation of caspases and thereby sensitize MDR cells to MDR-related drugs.</p> <p>Results</p> <p>MDR variants, CEM/VLB_10-2, CEM/VLB_55-8and CEM/VLB₁₀₀cells, with gradually increased levels of P-gp derived from human lymphoblastic leukemia CEM cells, were gradually more susceptible to TRAIL-induced apoptosis and cytotoxicity than parental CEM cells. The P-gp level of MDR variants was positively correlated with the levels of DNA-PKcs, pAkt, pGSK-3β and c-Myc as well as DR5 and negatively correlated with the level of c-FLIPs. Hypersensitivity of CEM/VLB₁₀₀cells to TRAIL was accompanied by the activation of mitochondrial apoptotic pathway as well as the activation of initiator caspases. In addition, TRAIL-induced down-regulation of DNA-PKcs/Akt/GSK-3β pathway and c-FLIP and up-regulation of cell surface expression of death receptors were associated with the increased susceptibility to TRAIL of MDR cells. Moreover, TRAIL inhibited P-gp efflux function via caspase-3-dependent degradation of P-gp as well as DNA-PKcs and subsequently sensitized MDR cells to MDR-related drugs such as vinblastine and doxorubicin. We also found that suppression of DNA-PKcs by siRNA enhanced the susceptibility of MDR cells to vincristine as well as TRAIL via down-regulation of c-FLIP and P-gp expression and up-regulation of DR5.</p> <p>Conclusion</p> <p>This study showed for the first time that the MDR variant of CEM cells was hypersensitive to TRAIL due to up-regulation of DR5 and concomitant down-regulation of c-FLIP, and degradation of P-gp and DNA-PKcs by activation of caspase-3 might be important determinants of TRAIL-induced sensitization of MDR cells to MDR-related drugs. Therefore, combination of TRAIL and chemotherapeutic drugs may be a good strategy for treatment of cancer with multidrug resistance.</p

Tolerability and Outcomes of First-Line Pemetrexed-Cisplatin Followed by Gefitinib Maintenance Therapy Versus Gefitinib Monotherapy in Korean Patients with Advanced Nonsquamous Non-small Cell Lung Cancer: A Post Hoc Descriptive Subgroup Analysis of a Randomized, Phase 3 Trial

Purpose We recently reported on a randomized, open-label, phase 3 trial comparing pemetrexedcisplatin chemotherapy followed by gefitinib maintenance therapy (PC/G) with gefitinib monotherapy in patients with non-small cell lung cancer (NSCLC). Here, we report on a post hoc subgroup analysis of that study assessing the demographics and disposition of the Korean patient subgroup, and comparing the tolerability of PC/G and gefitinib monotherapy and the tumor response with respect to epidermal growth factor receptor (EGFR) status. Materials and Methods Patients, who were 18 years, chemonalve, Korean, light ex-smokers/never-smokers with advanced NSCLC, were randomly assigned (1:1) to PC/G or gefitinib monotherapy. Treatment-emergent adverse events (TEAEs) were graded, and tumor response was measured as change in lesion sum from baseline at best response. The study was registered with ClinicalTrials.gov, NCT01017874. Results Overall, 111 Korean patients were treated (PC/G, 51; gefitinib, 60). Between-arm characteristics were balanced and similar to those of the overall population. Treatment discontinuations due to adverse events were low (PC/G: 1, 2.0%; gefitinib: 7, 11.7%). Overall, 92 patients (82.9%) reported >= 1 TEAE (PC/G, 44; gefitinib, 48); few patients (PC/G, 16; gefitinib, 7) reported severe TEAEs; the most frequent was neutropenia (PC/G arm) and elevated alanine aminotransferase (gefitinib arm). The lesion sum was decreased by PC/G treatment in most patients, regardless of EGFR mutation status, while gefitinib monotherapy reduced the lesion sum in EGFR-positive patients but had no effect in EGFR-negative patients. Conclusion Our results confirm that both PC/G and gefitinib were well tolerated in Korean patients, regardless of EGFR status; however, patients with EGFR wild-type NSCLC may not benefit from gefitinib monotherapy.