Artificial intelligence algorithm for neoplastic cell percentage estimation and its application to copy number variation in urinary tract cancer.

Background: Bladder cancer is characterized by frequent mutations, which provide potential therapeutic targets for most patients. The effectiveness of emerging personalized therapies depends on an accurate molecular diagnosis, for which the accurate estimation of the neoplastic cell percentage (NCP) is a crucial initial step. However, the established method for determining the NCP, manual counting by a pathologist, is time-consuming and not easily executable. Methods: To address this, artificial intelligence (AI) models were developed to estimate the NCP using nine convolutional neural networks and the scanned images of 39 cases of urinary tract cancer. The performance of the AI models was compared to that of six pathologists for 119 cases in the validation cohort. The ground truth value was obtained through multiplexed immunofluorescence. The AI model was then applied to 41 cases in the application cohort that underwent next-generation sequencing testing, and its impact on the copy number variation (CNV) was analyzed. Results: Each AI model demonstrated high reliability, with intraclass correlation coefficients (ICCs) ranging from 0.82 to 0.88. These values were comparable or better to those of pathologists, whose ICCs ranged from 0.78 to 0.91 in urothelial carcinoma cases, both with and without divergent differentiation/ subtypes. After applying AI-driven NCP, 190 CNV (24.2%) were reclassified with 66 (8.4%) and 78 (9.9%) moved to amplification and loss, respectively, from neutral/minor CNV. The neutral/minor CNV proportion decreased by 6%. Conclusions: These results suggest that AI models could assist human pathologists in repetitive and cumbersome NCP calculations.

Two-channel EEG based diagnosis of panic disorder and major depressive disorder using machine learning and non-linear dynamical methods.

The current study aimed to investigate the possibility of rapid and accurate diagnoses of Panic disorder (PD) and Major depressive disorder (MDD) using machine learning. The support vector machine method was applied to 2-channel EEG signals from the frontal lobes (Fp1 and Fp2) of 149 participants to classify PD and MDD patients from healthy individuals using non-linear measures as features. We found significantly lower correlation dimension and Lempel-Ziv complexity in PD patients and MDD patients in the left hemisphere compared to healthy subjects at rest. Most importantly, we obtained a 90% accuracy in classifying MDD patients vs. healthy individuals, a 68% accuracy in classifying PD patients vs. controls, and a 59% classification accuracy between PD and MDD patients. In addition to demonstrating classification performance in a simplified setting, the observed differences in EEG complexity between subject groups suggest altered cortical processing present in the frontal lobes of PD patients that can be captured through non-linear measures. Overall, this study suggests that machine learning and non-linear measures using only 2-channel frontal EEGs are useful for aiding the rapid diagnosis of panic disorder and major depressive disorder.

Dynamic changes in circulating PD-1+CD8+ T lymphocytes for predicting treatment response to PD-1 blockade in patients with non-small-cell lung cancer.

BACKGROUND: The predictive value of immune monitoring with circulating CD8+ T lymphocytes for treatment response to programmed cell death protein 1 (PD-1) inhibitors has not been explored in non-small-cell lung cancer (NSCLC), prompting us to investigate whether dynamic changes in PD-1+CD8+ T lymphocytes have predictive value for durable clinical benefit (DCB) and survival after PD-1 blockade. METHODS: Patients with recurrent and/or metastatic NSCLC treated with PD-1 inhibitors were enrolled (discovery cohort; n = 94). Peripheral blood was obtained immediately before and after one cycle of treatment with PD-1 blockade. Phenotyping of circulating CD8+ T lymphocytes was conducted using multi-colour flow cytometry. Predictive values of dynamic changes in circulating PD-1+CD8+ T lymphocytes during the first cycle were validated in an independent cohort (validation cohort; n = 54) of a prospective trial with a PD-1 inhibitor (NCT03486119). RESULTS: Circulating PD-1+CD8+ T lymphocytes were enriched with effector/memory populations with elevated expression of activation- and exhaustion-related markers. Reduction in the frequency of PD-1+ cells among CD8+ T lymphocytes after one cycle of treatment was associated with a higher probability of DCB and superior survival outcomes in the discovery cohort. Similar results were obtained in the analysis of tumour antigen NY-ESO-1-specific CD8+ T lymphocytes and the validation cohort. Mechanistically, PD-1 molecule expression on CD8+ T lymphocytes suppresses the effector functions of tumour antigen-specific CD8+ T lymphocytes. CONCLUSIONS: Dynamic changes in circulating PD-1+CD8+ T lymphocytes predict clinical, and survival benefit from PD-1 blockade treatment in NSCLC, providing a useful tool to identify patient subgroups who will optimally benefit from PD-1 inhibitors.

Comparison of Long-Term Outcomes of Infliximab versus Adalimumab Treatment in Biologic-Naïve Patients with Ulcerative Colitis.

BACKGROUND/AIMS: The tumor necrosis factor-α inhibitors infliximab and adalimumab are standard treatments for moderate to severe ulcerative colitis (UC). However, there has been no headto- head comparison of treatment efficacy and outcomes between the two agents. The aim of this study was to compare the efficacy and long-term outcomes of infliximab versus adalimumab treatment in biologic-naïve patients with UC. METHODS: We retrospectively analyzed the records of 113 biologic-naïve patients with UC who were treated between September 2012 and December 2017 (the infliximab group [n=83] and the adalimumab group [n=30]). We compared remission and response rates between these groups at 8 and 52 weeks. We used Kaplan-Meier curves to compare long-term outcomes, and logistic regression analysis and Cox-proportional hazard regression models to assess factors affecting outcomes. RESULTS: The median follow-up duration was 25.8 months. Baseline clinical characteristics were similar between groups. There were no significant differences between the two groups in the rate of clinical remission or clinical response at 8 or 52 weeks. Multivariate analyses also showed that long-term outcomes were not significantly different (adjusted hazard ratio [HR], 1.45; 95% confidence interval [CI], 0.81 to 2.56; p=0.208). An elevated C-reactive protein level (greater than 5 mg/L) was a significant predictive factor for poor outcomes (adjusted HR, 2.25; 95% CI, 1.37 to 3.70; p=0.001). During the follow-up period, the rates of adverse event were not significantly different between the two groups (p=0.441). CONCLUSIONS: In our study, infliximab and adalimumab had similar treatment efficacy and longterm outcomes in biologic-naïve patients with moderate to severe UC.

A review of high-resolution X-ray computed tomography applied to petroleum geology and a case study.

High-resolution X-ray computed tomography (micro-CT) has been widely used as a non-destructive technique, allowing 3D imaging and analysis of internal features of various objects. This paper briefly describes this technique used in the field of petroleum geology, with an example of its applications for tight-gas sandstone reservoirs. Reservoir quality controls the storage, distribution, and flow of fluids within tight-gas sandstone reservoirs, however, it remains difficult to predict. Although our earlier work has reported that reservoir quality of non-marine tight-gas sandstones in the Lower Cretaceous Denglouku Formation in the Songliao Basin, China is controlled by sedimentary texture, depositional facies, and diagenesis, there is lack of information on the effectiveness of pore-lining clay minerals on pore preservation and pore connectivity. Micro-CT is performed on two representative sandstone samples from the studied Denglouku sandstones, (1) to quantify the internal architecture in 3D and (2) to carry out fluid-flow modelling to determine the effective transport capacity. The quantitative 3D imaging and modelling by means of micro-CT provides a better insight of pore network connectivity and pore preservation characteristics at the pore scale. Here, we develop a procedure that integrates pore-scale imaging and modelling with depositional and diagenetic processes in the context of non-marine tight-gas sandstones. Micro-CT data are compared with results derived from core and wireline log interpretation as well as laboratory measurements on the same core samples, which results in good agreement and supports the prediction of pore preservation effectiveness of the sandstones containing pore-lining chlorite and illite with relatively high grain-surface coverage. It opens a potential opportunity for a pore-to-core upscaling approach to predict reservoir quality for tight-gas sandstones.

Characteristics of Particulate Matter and Volatile Organic Compound Emissions from the Combustion of Waste Vinyl.

Vinyl samples were burned in a controlled environment to determine the characteristics of particulate matter (PM) and volatile organic compound (VOC) emissions during the combustion process. Open burning of plastic or vinyl products poses several environmental and health risks in developed and developing countries, due to the release of high concentrations of harmful pollutants. The production of fine and ultrafine particles was significant. At a heat flux of 25 kW/m², the production of PM of 0.35 µm in size was highest at 63.0 µg/m³. In comparison, at fluxes of 35 and 50 kW/m², the production of PM of 0.45 µm in size was highest with values of 67.8 and 87.7 µg/m³, respectively. Benzene, acetone, and other toxic compounds were also identified in the analyses.

Character drawing style in cartoons on empathy induction: an eye-tracking and EEG study.

In its most basic form, empathy refers to the ability to understand another person's feelings and emotions, representing an essential component of human social interaction. Owing to an increase in the use of mass media, which is used to distribute high levels of empathy-inducing content, media plays a key role in individual and social empathy induction. We investigated empathy induction in cartoons using eye movement, EEG and behavioral measures to explore whether empathy factors correlate with character drawing styles. Two different types of empathy-inducing cartoons that consisted of three stages and had the same story plot were used. One had an iconic style, while the other was realistic style. Fifty participants were divided into two groups corresponding to the individual cartoon drawing styles and were presented with only one type of drawing style. We found that there were no significant differences of empathy factors between iconic and realistic style. However, the Induced Empathy Score (IES) had a close relationship with subsequent attentional processing (total fixation length for gaze duration). Furthermore, iconic style suppressed the fronto-central area more than realistic style in the gamma power band. These results suggest that iconic cartoons have the advantage of abstraction during empathy induction, because the iconic cartoons induced the same level of empathy as realistic cartoons while using the same story plot (top-down process), even though lesser time and effort were required by the cartoon artist to draw them. This also means that the top-down process (story plot) is more important than the bottom-up process (drawing style) in empathy induction when viewing cartoons.

Terrestrial biome distribution in the Late Neogene inferred from a black carbon record in the northeastern equatorial Pacific.

The appearance and expansion of C4 plants in the Late Cenozoic was a dramatic example of terrestrial ecological change. The fire hypothesis, which suggests fire as a major cause of C4 grassland is gaining support, yet a more detailed relationship between fire and vegetation-type change remains unresolved. We report the content and stable carbon isotope record of black carbon (BC) in a sediment core retrieved from the northeastern equatorial Pacific that covers the past 14.3 million years. The content record of BC suggests the development process of a flammable ecosystem. The stable carbon isotope record of BC reveals the existence of the Late Miocene C4 expansion, the 'C4 maximum period of burned biomass' during the Pliocene to Early Pleistocene, and the collapse of the C4 in the Late Pleistocene. Records showing the initial expansion of C4 plants after large fire support the role of fire as a destructive agent of C3-dominated forest, yet the weak relationships between fire and vegetation after initial expansion suggest that environmental advantages for C4 plants were necessary to maintain the development of C4 plants during the late Neogene. Among the various environmental factors, aridity is likely most influential in C4 expansion.

Concomitant Statin Use Has a Favorable Effect on Gemcitabine-Erlotinib Combination Chemotherapy for Advanced Pancreatic Cancer.

PURPOSE: Erlotinib-gemcitabine combined chemotherapy is considered as the standard treatment for unresectable pancreatic cancer. This study aimed to determine the clinical factors associated with response to this treatment. MATERIALS AND METHODS: This retrospective study included 180 patients with unresectable pancreatic cancer who received ≥2 cycles of gemcitabine-erlotinib combination therapy as first-line palliative chemotherapy between 2006 and 2014. "Long-term response" was defined as tumor stabilization after >6 chemotherapy cycles. RESULTS: The median progression-free survival (PFS) and overall survival (OS) were 3.9 and 8.1 months, respectively. On univariate analysis, liver metastasis (p=0.023) was negatively correlated with long-term response. Locally advanced stage (p=0.017), a history of statin treatment (p=0.01), and carcinoembryonic antigen levels <4.5 (p=0.029) had a favorable effect on long-term response. On multivariate analysis, a history of statin treatment was the only independent favorable factor for long-term response (p=0.017). Prognostic factors for OS and PFS were significantly correlated with liver metastasis (p=0.031 and 0.013, respectively). A history of statin treatment was also significantly associated with OS after adjusting for all potential confounders (hazard ratio, 0.48; 95% confidence interval, 0.26-0.92; p=0.026). CONCLUSION: These results suggest that statins have a favorable effect on "long-term response" to gemcitabine-erlotinib chemotherapy in unresectable pancreatic cancer patients. Statins may have a chemoadjuvant role in stabilizing long-term tumor growth.

Endoscopic Submucosal Dissection of an Inverted Early Gastric Cancer-Forming False Gastric Diverticulum.

Endoscopic submucosal dissection (ESD) is a standard treatment for early gastric cancer (EGC) that does not have any risk of lymph node or distant metastases. Here, we report a case of EGC resembling a diverticulum. Diverticular formation makes it difficult for endoscopists to determine the depth of invasion and to subsequently perform ESD. Because the false diverticulum does not have a muscular layer, this lesion can be treated with ESD. Our case was successfully treated with ESD. After ESD, the EGC was confined to the submucosal layer without vertical and lateral margin involvement. This is the first case in which ESD was successfully performed for a case of EGC that coexisted with a false gastric diverticulum. An additional, larger study is needed to determine the efficacy of ESD in various types of EGC, such as a false gastric diverticulum.

Addition of tumor multiplicity improves the prognostic performance of the hepatoma arterial-embolization prognostic score.

BACKGROUND & AIMS: The hepatoma arterial-embolization prognostic (HAP) score predicts survival outcome in patients with hepatocellular carcinoma (HCC) treated with trans-arterial chemoembolization (TACE). We validated the HAP score in Korean subjects with HCC and investigated whether its prognostic performance is improved with additional parameters. METHODS: A total of 280 patients with HCC treated with TACE between 2003 and 2009 were included. Validation and modification of HAP score were performed based on multivariate Cox regression models. RESULTS: The median age of the study population (211 men, 69 women) was 60 years. Viral etiology of HCC accounted for 80.4% (n = 181 for hepatitis B, 44 for hepatitis C). The median overall survival (OS) was 40.5 months. On multivariate analysis, together with the original components of the HAP score (serum albumin <3.6 g/dl, total bilirubin >0.9 mg/dl, alpha-foetoprotein >400 ng/ml, and tumor size >7 cm), tumor number ≥2 was selected as an independent unfavorable prognostic factor for OS (hazard ratio 2.3; P < 0.001). Accordingly, a modified HAP-II (mHAP-II) score was established by adding tumor number ≥2. Although both HAP and mHAP-II scores discriminated the four different risk groups (log-rank test, all P < 0.001), the mHAP-II score performed significantly better than the HAP score, as per the areas under receiver-operating curves predicting OS at 3 years (0.717 vs. 0.658) and 5 years (0.728 vs. 0.645), respectively (all P < 0.05). CONCLUSIONS: Although the HAP score predicted OS for Korean subjects with HCC undergoing TACE, the addition of tumor number significantly improved the prognostic performance. The mHAP-II score can be used for accurate prognostication and selection of optimal candidates for TACE.

Adsorption and isotope effects by ion exchange with 1-aza-12-crown-4 bonded Merrifield peptide resin.

Magnesium isotope effects were investigated by chemical ion exchange with synthesized 1-aza-12-crown-4 bonded Merrifield peptide resin using elution chromatography. The capacity of azacrown ion exchanger was 0.89 meq/g dry resin. The heavier isotopes of magnesium were enriched in the resin phase, while the lighter isotopes were enriched in the solution phase. The hydration effect is less than the complexation and isotope mass effects. The single stage separation factor was determined according to the method of Glueckauf from the elution curve and isotopic assays. The separation factors of 24Mg(2+)-25Mg(2+), 24Mg(2+)-26Mg(2+), and 25Mg(2+)-26Mg(2+) were 1.012, 1.023, and 1.011, respectively.