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As both the role and clinical application of adjuvant chemotherapy (CTx) for pT3N0M0 gastric cancer after curative gastrectomy have fluctuated chronologically, the oncological benefit of adjuvant CTx in patients should be elucidated. Between 2000 and 2018, 1083 patients underwent radical gastrectomy for pT3N0M0 gastric cancer and were subsequently divided into two groups: the surgery-alone group (n = 471) and the adjuvant CTx group (n = 612). Chronological changes in adjuvant CTx and various chemotherapeutic regimens were evaluated and disease-free survival was compared between the two groups. Risk factors for tumor recurrence were also analyzed. The proportion of patients in the surgery-alone group was more than 60% until 2001, whereas in the CTx group this increased to over 80%, especially after publication of the American Joint Committee on Cancer (AJCC) 7th edition staging manual. The main chemotherapeutic agents were tegafur-uracil (UFT) and 5-fluorouracil with leucovorin until 2008, whereas tegafur/gimeracil/oteracil (TS-1) has been the main agent since 2009. The 5-year disease-free survival was 89.2% in the surgery-alone group and 89.9% in the CTx group, which was not significantly different (p = 0.694). In multivariate analysis, larger tumor size (≥ 4.5 cm) and venous invasion were significant risk factors for tumor recurrence. In addition, adjuvant CTx did not improve the oncological outcome, even in the large tumor size group (p = 0.760) and the venous invasion group (p = 0.753). As adjuvant CTx did not show any oncological benefit in pT3N0M0 gastric cancer in this large-scale study, it might be unnecessary for these patients after curative gastrectomy.

Pancreatic cancer is a devastating disease with a poor prognosis. It is usually symptom-free during development and is advanced by the time of diagnosis. PANC-1 is a pancreatic ductal carcinoma cell derived from a 56-year-old male with adenocarcinoma in the head of the pancreas and metastasized to the duodenal wall. Apoptosis is a controlled program cell death process that the body uses to combat cancer development. Scutellaria barbata (SB) has been used in traditional Chinese medicine for treating liver, lung, and rectal cancers. SB and Oldenlanida diffusa (OD) are included in most of the herbal cancer treatment formulas in Taiwan hospitals. We previously showed that aqueous extracts of SB and OD selectively induced apoptosis in colon HCT 116 cancer cells but not in colon CCD 841 CoN normal epithelial cells by modulating the pro-apoptotic and anti-apoptotic proteins. These two herbs also effectively modulated apoptosis in MDA-MB-157 and 93B breast cancer cells. Green synthesis of gold nanoparticles (AuNPs) of SB demonstrated effective anticancer activity against this PANC-1 cell. This study used the green/red/blue fluorescent Apoptosis/Necrosis Detection Kit and the Human Apoptosis Antibody Array - Membrane [43 Targets] Test (Abcam). Our fluorescent apoptosis data showed that a 2-hour treatment with 1.5 mg and 3.0 mg aqueous extract of SB and OD induced a statistically significant percentage of apoptosis in PANC-1 cells (SB: 57.5 ± 2.5%, 68.0 ± 0.0% > 11.5% ± 3.5%, p < 0.05; OD: 62.0 ± 9.0%, 67.0 ± 11.0%> 11.5% ± 3.5%, p < 0.05) as compared to the negative control respectively. Similar results were obtained with the 4-hour incubation period (SB: 73.5 ± 0.5%, 72.0 ± 2.0% > 18.2% ± 2.0%, p < 0.05; OD: 59.0 ± 1.0%, 73.5 ± 13.5%> 18.2% ± 2.0%, p < 0.05). From the antibody array-membrane experiments, modulation of various apoptosis markers by SB and OD such as the pro-apoptotic proteins Bid, Bim, Bad, Bax, p27, and p53 as compared to the negative controls were observed; and regulation of anti-apoptotic proteins Bcl-2, FasL, IGF-I, and p21 were also revealed. These results suggest that SB and OD contain phytochemicals that induce apoptosis in pancreatic ductal carcinoma PANC-1 cells via the modulation of various apoptotic protein productions. Further study of their specific modulation effects of apoptosis is warranted to reveal their potential chemopreventive and therapeutic properties against pancreatic and other cancers. Citation Format: MinSeo Kang, Allana Benjamin, Christine Choi, Rekha Isaac, Sarah Wolf, Jasmine Cha, Elim Choi, Jessica Yi, Padma T. Uppala, Ryan Hayes, Brian Yuen Yau Wong. Induction and modulation of apoptosis in pancreatic ductal carcinoma PANC-1 cells by Chinese medicinal herbs Scutellaria barbata and Oldenlandia diffusa [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6125.

Background and objectivesWhile pattern identification (PI) is an essential process for diagnosis and treatment in traditional Asian medicine (TAM), it is difficult to objectify since it relies heavily on implicit knowledge. Here, we propose a machine learning-based analysis tool to objectify and evaluate the clinical decision-making process of PI in terms of explicit and implicit knowledge.MethodsClinical data for the development of the analysis tool were collected using a questionnaire administered to allergic rhinitis (AR) patients and the diagnosis and prescription results of TAM doctors based on the completed AR questionnaires. Explicit knowledge and implicit knowledge were defined based on the explicit and implicit importance scores of the AR questionnaire, which were obtained through doctors’ explicit scoring and feature evaluations of machine learning models, respectively. The analysis tool consists of eight evaluation indicators used to compare, analyze and visualize the explicit and implicit knowledge of TAM doctors.ResultsThe analysis results for 8 doctors showed that our tool could successfully identify explicit and implicit knowledge in the PI process. We also conducted a postquestionnaire study with the doctors who participated to evaluate the applicability of our tool.ConclusionsThis study proposed a tool to evaluate and compare decision-making processes of TAM doctors in terms of their explicit and implicit knowledge. We identified the differences between doctors’ own explicit and implicit knowledge and the differences among TAM doctors. The proposed tool would be helpful for the clinical standardization of TAM, doctors’ own clinical practice, and intern/resident training.

Scutellaria barbata (SB) and Oldenlandia diffusa (OD) have been used in Traditional Chinese Medicine for treating colon cancer, glioblastoma, and ovarian cancer liver, lung, and rectal cancers. These two herbs are included in most of the herbal cancer treatment formulas in China and Taiwan hospitals. We previously demonstrated that aqueous extracts of SB and OD inhibited mutagenesis, DNA binding, and metabolism of aflatoxin B1 and benzo[a]pyrene in carcinogenesis. In studies by Hugo (2006) and Perez (2010), the efficacy of BZL 101 (an extract of SB) has been demonstrated in preliminary Phase Ia and Ib clinical trials in metastatic breast cancer patients. It is also shown to induce an S phase arrest of the cell cycle by affecting the Cycline A2 and CDK2 expression in estrogen-sensitive MCF7 and estrogen insensitive MDA-MB-231 breast cancer cells. MeOH and BuOH extract of OD have been illustrated to reduce MCF7 invasion via the inhibition of MMP-9 and ICAM-1 apoptotic proteins expression. Ursolic acid of OD could inhibit breast cancer metastasis by suppressing glycolytic metabolism through activating SP1/Caveolin-1 signaling. In this study, the effectiveness of aqueous extract of SB and OD in the modulation of apoptosis of breast cancer cell lines MDA-MB-157 and 93B (a drug-resistant APC-mutant of it) were investigated. Assessments were performed using green/red/blue fluorescent Apoptosis/Necrosis Detection Test and the Human Apoptosis Antibody Array - Membrane [43 Targets] Test (Abcam). Our fluorescent apoptosis data showed that 3-hours treatment with 2.5 mg aqueous extract of SB induced a statistically significant percentage of apoptosis in MDA-MB-157 (46.5 ± 7.5% > 16%± 1.0%, p < 0.05) and 93B (46.5 ± 7.5% > 16%± 1.0%, p < 0.05) as compared to the negative control. Similar results were obtained with the OD treatment. From the antibody array-membrane experiments, modulation of various apoptosis markers by SB such as the pro-apoptotic proteins BID and BIM (p=0.019; p=0.007) in MDA-MB-157 and Bad (p=0.002), Bax (p=0.020), BID (p=0.001), p27 (p=0.004), p53 (p=0.022) in 93B as compared to the negative controls; and anti-apoptotic markers BcL-2, FasL, IGF-I, and p21 were also observed. OD treatment also induced similar significant production of these two types of proteins. These results suggest that SB and OD contain phytochemicals that induce apoptosis in MDA-MB-157 and 93B via the modulation of these pro-apoptotic and anti-apoptotic proteins. Citation Format: MinSeo Kang, Nathaly Manrique, Rekha Issac, Sarah Wolf, Jasmine Cha, SungBeen Han, Hugo Jie Qin, Lun Kim, Padma P. Uppala, Brian Yuen Yau Wong. Chinese medicinal herbs Scutellaria barbata and Oldenlandia diffusa modulate apoptosis via induction of pro-apoptotic and anti-apoptotic proteins in MDA-MB-157 and 93B breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6261A.

Introduction: Gwakhyangjeonggi-san (GJS) is an herbal formula with anti-inflammatory and anti-allergic properties that is broadly used to treat a wide range of diseases including gastrointestinal disorders and allergic diseases. There have been several clinical studies conducted on its effects on atopic dermatitis (AD). So far, no randomized controlled trials have been conducted. Here, we describe the protocol for a randomized controlled study designed to investigate the efficacy and safety of GJS for treating patients with AD that have gastrointestinal symptoms. Methods and analysis: A randomized, double-blind, placebo-controlled, parallel-group, clinical trial has been designed to investigate the clinical efficacy and safety of GJS on patients with AD that have gastrointestinal symptoms. A total of 58 participants with AD will be recruited and randomly allocated to the GJS or placebo group in a 1:1 ratio. The participants will be administered GJS or placebo granules 3 times a day for 8 weeks. Data will be collected from the participants at baseline and after 4 and 8 weeks. The primary outcome measure will be the mean change in the SCORing of Atopic Dermatitis (SCORAD) index from baseline to 8 weeks. The secondary outcomes will include the eczema area and severity index (EASI), dermatology life quality index (DLQI), EuroQoL 5 dimensions 5 levels (EQ-5D-5L), and immunological factors. The Korean Gastrointestinal Symptom Rating Scale (KGSRS), Nepean Dyspepsia Index will also be obtained for assessing the gastrointestinal status. Discussion: The findings of this study are expected to provide evidence on the safety and effectiveness of GJS and for treating patients with AD that have gastrointestinal symptoms. Additionally, the study will explore the mechanism of GJS action via gut microbiome. This study will provide new perspectives on approaching treatment for AD. Ethics and dissemination: The study protocol was approved by the Institutional Review Board of Kyung Hee University Korean Medicine Hospital at Gangdong (KHNMCOH2019-06-002-001). Trial registration number: This study has been registered at the Korean National Clinical Trial Registry, Clinical Research Information Service (KCT0004299).

We report a simple method to produce work-function-tuned graphene nanosheets based on the nucleophilic substitution of the epoxy groups on graphene oxide. The electrical property of the graphene oxide is controlled dramatically, which results in the apparent work functions in a broad range between 3.73 eV and 5.1 eV, by attaching various functional groups on the graphene surface. As a proof of concept, we successfully demonstrated organic field effect transistors incorporating the functionalized graphene nanosheet interlayers. Here, when nanosheets were applied in an organic transistor as the interlayer material between electrodes and organic channel, the device performance was significantly improved. Our approach can be utilized to increase the performance and the flexibility of various advanced carbon-material-based hybrid electrical devices.

This work proposes sliding window fall detection match (SW-FDM), a rule-based fall detection method based on event pattern matching from human body posture event streams. Fall and post-fall (long lie) rules are expressed as patterns, and complex event processing (CEP) systems are adopted to quickly find these patterns. They can be detected with event selection strategies such as Skip Till Next Match and Skip Till Any Match. However, existing strategies generate either duplicate or missing alarms; even worse, their processing cost is very high when the size of event streams is large. Since SW-FDM uses a concept of sliding window, it is able to detect correct matches constantly and reduce the processing cost without duplicate computation. The experiments demonstrate that SW-FDM results in both higher accuracy and efficiency. Also, it is shown that the improvement of efficiency becomes greater as the data size increases, which is an indeed preferable property.

Rationale: The rate of spontaneous recovery of sudden sensorineural hearing loss (SSNHL) has been reported to be as high as 32% to 65%. Although the majority of spontaneous recoveries occur within 2 weeks, treatment of refractory SSNHL failing conventional therapy is difficult. In particular, it is more difficult to treat children—who have a worse prognosis than adults—with SSNHL refractory to conventional therapy. No studies reported delayed recovery of pediatric SSNHL later than 3 months after onset, or delayed recovery treated with acupuncture. Patient concerns: A 15-year-old girl experienced hearing loss after acquiring a cold. Diagnosis: She did not undergo audiometry and only took medicine for a common cold after diagnosis by an internal medicine doctor. Ninety-three days after onset, she visited an otorhinolaryngology clinic and was diagnosed with SSNHL. Seven rounds of intratympanic steroid (ITS) treatment were performed 93 to 135 days after onset; audiogram at 149 days did not demonstrate improvement. Interventions: Two-hundred sixty-six days after onset, she visited to TKM hospital and was admitted for 21 days and received outpatient treatment for 1 month after discharge. She was treated acupuncture, transcutaneous electrical nerve stimulation, and moxibustion. Outcomes: She experienced improvement in experienced improvement in pure tone average, speech recognition threshold, and word recognition scores after acupuncture treatment. Delayed ITS treatment at 93 to 135 days after onset did not improve the patient's hearing loss. However, slight recovery was achieved at the conclusion of treatment. Lessons: Acupuncture may be a therapeutic option for individuals who do not experience improvement after the use of steroids or miss early treatment.

Counting triangles in networks is a fundamental problem in network science. In addition, because we are forced to manage very large real-world networks, current triangle counting algorithms naturally require a distributed computing system. In this paper, we propose a distributed triangle counting algorithm based on both the vertex-centric and node-iterator models and using the multi-level branching technique. Multi-level branching is a method that constructs an ordered graph structure based on levels. This method not only facilitates an efficient triangle counting process, but also guarantees the computational integrity of each split in the distributed triangle counting process. First, we describe a level-based triangle counting algorithm based on both the vertex-centric model and the node-iterator algorithm. Then, we develop a distributed implementation of the proposed algorithm using GraphChi. The main advantages of the proposed algorithm are that the execution is simple yet effective, and thus its parallelization is efficient. Experiments on real-world networks verify its performance, particularly, its near-linear parallelization scalability.