bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-time scheduling of power grid digital twin tasks in cloud via deep reinforcement learning
Authors: Qi Daokun , Xi Xiaojuan , Tang Yake , Zheng Yuesong , Guo Zhengwei 
Published: July 2024

AbstractAs energy demand continues to grow, it is crucial to integrate advanced technologies into power grids for better reliability and efficiency. Digital Twin (DT) technology plays a key role in this by using data to monitor and predict real-time operations, significantly enhancing system efficiency. However, as the power grid expands and digitization accelerates, the data generated by the grid and the DT system grows exponentially. Effectively handling this massive data is crucial for leveraging DT technology. Traditional local computing faces challenges such as limited hardware resources and slow processing speeds. A viable solution is to offload tasks to the cloud, utilizing its powerful computational capabilities to support the stable operation of the power grid. To address the need, we propose GD-DRL, a task scheduling method based on Deep Reinforcement Learning (DRL). GD-DRL considers the characteristics of computational tasks from the power grid and DT system and uses a DRL agent to schedule tasks in real-time across different computing nodes, optimizing for processing time and cost. We evaluate our method against several established real-time scheduling techniques, including Deep Q-Network (DQN). Our experimental results show that the GD-DRL method outperforms existing strategies by reducing response time, lowering costs, and increasing success rates.
Sublingual sufentanil for patient-controlled analgesia during labor induction for pregnancy termination: an effective and well-tolerated approach
Authors: Fierro Giulia , Milan Barbara , Buelli Elena , Bugada Dario , Casarotta Erika , Rizzo Francesco , Ongaro Laura , Gritti Paolo , Previdi Fabio , Lorini Ferdinando Luca 
Published: July 2024

Abstract
Background
Effective pain management during labor induction for pregnancy termination is essential. However, to date, no effective treatment has been identified. The primary aim of this study was to measure the analgesic efficacy of a sufentanil sublingual tablet system during pregnancy termination and patient satisfaction by comparing nulliparous and multiparous women. The secondary aims were to characterize the safety profile by reporting any side effects or adverse events and to determine the need for rescue therapy.

Methods
We conducted an observational, retrospective, single-center study involving 48 women. The data retrieved for analysis included the total and hourly doses of sublingual sufentanil, evaluations of pain management satisfaction using a 5-point rating scale (ranging from 1, indicating “not satisfied” to 5, denoting “completely satisfied”), occurrence of side effects and adverse events, and the rate of rescue analgesic use. Categorical and numerical variables were compared between the two groups, and a correlation analysis was performed.

Results
The median total dose of sufentanil required was 60 mcg. Nulliparous women required a higher dose of sufentanil compared with multiparous women (105 mcg vs. 45 mcg; P = 0.01). Additionally, they underwent a longer labor, indirectly measured by the time of device usage (625 min vs. 165 min; P = 0.05). Regarding satisfaction, 40 patients (83.4%) were satisfied or completely satisfied, whereas only 8 patients (16.6%) reported dissatisfaction. Multiparous women exhibited higher satisfaction levels than did nulliparous women (P = 0.03). No adverse events were reported, and the most common side effects were nausea and vomiting (31.2%). Four patients (12%) required acetaminophen due to insufficient analgesia, with only one patient necessitating a switch to intravenous morphine.

Conclusions
Sublingual sufentanil was effective in both nulliparous and multiparous women with minimal side effects. Therefore, sublingual sufentanil can be considered a valid strategy for analgesia during labor induction for pregnancy termination.
Association between clinical and disease characteristics and detectable or undetectable baseline ctDNA in patients with metastatic uveal melanoma.
Authors: Nathan Paul D. , Collins Laura , Carvajal Richard D. , Thiyagarajah Piruntha , Sullivan Ryan J. , Sacco Joseph J 
Published: July 2024

9537 Background: Tebentafusp, a bispecific soluble TCR specific for a gp100 peptide, is licensed for the treatment of metastatic uveal melanoma (mUM) in HLA-A*02:01+ individuals. 82% of patients (pts) with mUM in the IMCgp100-102 (previously treated; 2L+) and 61% in IMCgp100-202 (frontline; 1L) studies, respectively, had detectable baseline ctDNA. There is a strong relationship between decrease in ctDNA by 9 weeks and overall survival (OS) [Carvajal 2022; Hassel & Piperno-Neumann 2023]. Patients with undetectable baseline ctDNA had improved survival despite having macroscopic disease. In this study, we report the characteristics of baseline ctDNA undetectable vs detectable disease. Methods: Disease characteristics of 202 1L (Study 202) and 117 2L+ (Study 102) pts who had baseline undetectable or detectable ctDNA (unDNA vs detDNA) were compared in a post-hoc unplanned analysis. ctDNA detection was analysed at baseline and up to week 9 on tebentafusp using targeted mPCR-NGS assay for mutations in 15 genes including GNAQ, GNA11, SF3B1, CYSLTR2, PLCB4 and EIF1AX. Largest lesion size groups (≤ 3 cm, 3-8 cm, > 8 cm) were defined by American Joint Committee on Cancer 7th Ed. Presence of oncogenic mutations in GNAQ, GNA11, SF3B1 and BAP1 were assessed by WES on metastatic tissue biopsies. Results: Baseline ctDNA levels increased in association with size of largest lesion regardless of number of prior therapies. However, there was an association between disease burden (defined by largest lesion size) and unDNA vs detDNA in both studies, with all pts with largest liver lesion > 8 cm having detDNA. In Study 202, % of the population with unDNA vs detDNA was 50% vs 50% for ≤ 3cm and 27% vs 73% for 3.1-8 cm. While OS was similar for unDNA & detDNA in pts with ≤ 3cm lesions, OS was longer for pts with unDNA vs detDNA who had baseline tumor size 3.1-8 cm in both studies (Table). Within this 3.1-8 cm group, pts with unDNA tended to have lower LDH, AST, and ALP. Initial analysis showed no difference in the frequency of GNAQ, GNA11, SF3B1 or BAP1 mutations between unDNA and detDNA groups. Further data on somatic mutation defined groups and RNAseq gene expression in unDNA and detDNA groups will be presented. Conclusions: Patients with unDNA were more likely to have smaller disease burden than those with detDNA; however, many pts with unDNA had a significant burden of metastatic disease. Baseline unDNA was associated with improved OS outcome vs detDNA in pts with 3.1-8 cm baseline metastatic deposits, but not in pts with ≤ 3cm disease. No association was seen between oncogenic background of GNAQ/GNA11/SF3B1/BAP1 and unDNA vs detDNA. Clinical trial information: NCT02570308 ; NCT03070392 . [Table: see text]
Outcomes of personalized therapy guided by Exacta encyclopedic tumor analysis for women with broadly refractory advanced breast cancer.
Authors: Crook Tim , Limaye Sewanti , Ranade Anantbhushan , Bhatt Amit Dilip , Apurwa Sachin , Patil Darshana , Datar Rajan , Kurzrock Razelle 
Published: July 2024

e13124 Background: Following the failure of three lines of systemic treatments in breast cancers, Standard of Care guidelines typically recommend palliative care or participation in clinical trials for such patients. Breast cancer remains a global health threat, impacting lives worldwide. For refractory patients, the outlook is grim, with limited treatment options post multiple failures. Dismal outcomes underscore the urgency for innovative approaches, as traditional interventions often fall short. Methods: The Resilient trial was a Phase-II, single-arm, open-label clinical trial. Its primary objective was to assess the effectiveness of Exacta ETA-guided treatments across a spectrum of solid organ cancers in advanced refractory cancer patients. Exacta Encyclopedic Tumor Analysis (ETA) comprising the interrogation of gene alterations, gene expression, immunohistochemistry (IHC), and in vitro chemoresistance profiling (CRP) of viable tumor cells was performed on freshly obtained tumor tissue from 21 breast cancer patients with broadly refractory advanced breast cancers who had failed multiple lines of treatment. Six (29%) patients had metastasis to the brain, 11 (52%) patients had metastasis to the liver, 9 (43%) patients had metastasis to the lungs, and 15 (71%) patients had skeletal metastasis. The findings obtained through Exacta ETA were integrated to formulate patient-specific therapy recommendations. Personalized treatment plans were devised, and organ- and label-agnostic treatment regimens were administered to each patient. Patients were monitored to ascertain Overall Survival (OS). Results: Median overall survival (OS) was not reached at the time of analysis. By considering the OS values censored at the interim (most recent follow-up), the median OS in the entire cohort (n = 21) was 11.5 months (95% CI 4.5 to 16.9). The median OS was 11.4 months (95% CI 4.0 to 15.1) among patients with brain metastases, 14.5 months (95% CI 2.6 to 22.8) among patients with liver metastases, 11.9 months (95% CI 3.7 to 22.3) among patients with pulmonary metastases and 11.4 months (95% CI 3.7 to 22.3) among patients with skeletal metastases, respectively. No grade IV adverse events or treatment-related deaths were reported in the cohort. Conclusions: Exacta Encyclopedic Tumor Analysis (ETA) guided treatments provide a viable and meaningful treatment option for patients with advanced refractory breast cancers with metastatic deposits. The observed high OS in this heavily pretreated population underscores the value of multi-analyte guided of Exacta ETA as a valuable approach to managing these challenging clinical cases. Clinical trial information: CTRI/2018/02/011808.
Clinical validation of Northstar response: A novel methylated ctDNA therapy response monitoring assay in patients with advanced gastrointestinal cancers.
Authors: Sahin Ilyas , Kahramangil Doga , Kim George P. , Rogers Sherise C. , Ramnaraign Brian Hemendra , Manda Pravalika , Varga Matthew Gordon , Palmer Gary A. , Ye Patrick Peiyong , George Thomas J. 
Published: July 2024

e16000 Background: Circulating tumor DNA (ctDNA) offers a non-invasive method to comprehensively assess tumors. While most assays for therapy response monitoring rely on variant allele frequencies, methylated ctDNA has shown promise. However, accuracy has been limited by quantification precision. The CLIA-approved Northstar Response assay quantifies over 550 hyper-methylated loci and has demonstrated a 10-fold increase in detection signal over tissue-informed assays. Methods: We present an interim analysis from an ongoing prospective, observational study designed to assess the clinical validity of Northstar Response as a tool to monitor therapeutic response without prior tumor tissue. Our study aims to include 100 advanced GI cancer patients undergoing systemic therapies for advanced disease. Serial ctDNA measurements are collected at baseline, approximately every 30 days post-treatment initiation, and with imaging assessments. The primary endpoint is concordance between ctDNA and RECISTv1.1 criteria for disease response until progression or death. Results: Baseline ctDNA characteristics were examined from 44 patients, with 23 undergoing at least two longitudinal blood collections and subsequent imaging. The median age in this cohort was 65.5 years, with a male predominance (70.5%) and a majority identifying as White (79.5%). Cancers included esophageal (18.2%), hepatocellular (29.5%), biliary (15.9%) and colorectal (15.9%), among others. A majority (59.1%) had both primary and metastatic lesions. Baseline methylation scores ranged from 280 in biliary cancers to 100,000 in colorectal cancers. Those on second-line treatments had lower scores than first or third-line therapies. Methylation scores decreased in patients responding to treatment, indicating that these scores have the potential to serve as indicators of therapeutic efficacy. Conclusions: Baseline methylation scores differ across GI tumor types, disease burdens, and treatment lines, reflecting the complexity of using methylation as a biomarker. Northstar Response has shown initial promise in monitoring therapy response in GI cancers. More mature data, which will further elucidate the assay's clinical utility, will be presented at the meeting.
Trends and disparities in the incidence and mortality of stomach cancer in the United States.
Authors: Ajibawo Temitope 
Published: July 2024

e16102 Background: Stomach cancer is the fifth most common cancer worldwide and has one of the lowest survival rates across all malignancies. There is a constant need to define current stomach cancer incidence and incidence-based mortality (IBM) rates among different population groups for improved clinical practice. We aimed to investigate the trends of stomach cancer incidence and IBM by population characteristics of age groups, gender and ethnic groups. Methods: Data obtained from the National Cancer Institute’s Surveillance, Epidemiology, and End results (SEER) Registry 12 were obtained to determine the incidence and IBM rate of stomach incidence from 1992 to 2020. Joinpoint Regression Analysis program was used to calculate the annual percent change (APC) for trend analysis. Results: A total of 82,810 stomach cancer patients were identified from the dataset. Most of the patients were males; N = 49,909(60.27%) and Non-Hispanic Whites, N = 40,894 (49.38%). The overall incidence rate was 8.00 (95% Confidence Interval [CI]: 7.95 to 8.06) and the overall IBM rate was 6.44 (95%CI: 6.39 to 6.49). The incidence rate of stomach cancer decreased significantly by 1.28 % per year from 1992 to 2020; however the degree of decline from 1992 to 2017, APC (-1.18, 95% CI: -1.27 to -1.04, p < .001) was lower compared to between 2017 and 2020, APC (-3.42, 95% CI: -6.08 to -1.69, p = 0.01). Conversely, IBM rate increased significantly from 1992 to 1994, APC (36.59, 95% CI: 22.51 to 52.29, p < .001) followed by a significant decrease from 1994 to 2020, APC (-1.29, 95%CI: -1.43 to -1.15, p < .001).Incidence rates reduced significantly from 1992 to 2020 for all gender, ethnic and age groups except among the Non-Hispanic Asian Indian or Alaska Native (NHAIAN) population with APC (-0.67, 95 CI% -1.93 to 0.61, p = 0.29) and < 60 years age group with APC (0.03, 95 CI % : 0.18 to 0.25, p = 0.76). Significant decline in IBM rate was observed from 2000 to 2020 across all gender, ethnicities and age groups except among the NHAIAN, APC (-0.21, 95 CI%: -1.26 to 0.84, p = 0.68) and the < 60 years age group, APC (0.16, 95 CI%: -0.33 to -0.65, p = 0.52). Conclusions: Stomach cancer incidence and IBM rates have decreased significantly over the last 20 years except in NHAIAN and < 60 years age populations. These findings suggest the need for further research focused efforts in these potentially high-risk groups.
Safety and efficacy of intensified preoperative management of locally advanced gastrorsophageal junction cancer (INPROVE).
Authors: Torresan Sara , Bortolot Martina , de Scordilli Marco , Innocente Roberto , Fumagalli Arianna , Foltran Luisa , Guardascione Michela , Di Nardo Paola , Ongaro Elena , Noto Claudia , Rota Simone , Pastò Brenno , Cannizzaro Renato , Navarria Federico , Vecchiato Massimo , Ubiali Paolo , Belluco Claudio , Petri Roberto , Guglielmi Alessandra , Puglisi Fabio 
Published: July 2024

e16110 Background: The optimal management of locally advanced gastroesophageal junction adenocarcinoma (LAGEJad) is not fully established yet. Both neoadjuvant chemoradiotherapy (CRT) and perioperative taxane-based triplet chemotherapy (CT) are acknowledged treatment options for Siewert I and II cancers. In this retrospective study, we aimed to assess the safety and outcomes of an intensified preoperative regimen combining taxane-based triplet CT and CRT. Methods: We conducted a retrospective analysis of a cohort comprising 16 consecutive HER2 negative patients (pts) with LAGEJad treated at the Centro di Riferimento Oncologico of Aviano between 2019 and 2022. All pts received induction CT (iCT) consisting of fluoropyrimidine, oxaliplatin and docetaxel, followed by CRT (45Gy/25Fr) with simultaneous boost and concomitant CT. Surgery (Ivor-Lewis or McKeown) was performed 8 weeks post-CRT. Clinico-pathological (CP) and treatment features were analyzed using logistic regression to assess their association with response to iCT-CRT. The association of iCT-CRT with survival outcomes was investigated using the Kaplan-Meier method. Results: Key CP data are summarized in Table 1. Median age was 59 years, all pts were male. At diagnosis, 81.2% of pts exhibited cT3+ and cN+ disease. All pts received iCT and CRT. The rate of partial responses was 50% after iCT and 68.8% after CRT. Overall, 12 pts underwent surgery, all achieving R0 resections within a median timeframe of 9 [8.5;11] weeks post-CRT. Among them, 25% had a pathologic complete response, while 62.5% attained a Mandard tumor regression grade (TRG) of 1-2. No new safety signals emerged from iCT (only 2 pts had ≥G3 diarrhea) or CRT (≥G3 mucositis occurred in 6.2% and anemia in 6.2% of pts). No significant surgical delays were observed, although 5 pts experienced post-operative complications (4 grade I, 1 grade IIa). There were no statistically significant associations between CP variables and response to the iCT-CRT. Relapses were seen in 8 pts (2 locoregionally); 3-year survival was 46%. Median event-free survival was 5 [5;11] months, while median overall survival 34 [14;NR] months. Conclusions: The intensification of preoperative treatment in pts with LAGEJad is active and safe: the surgical schedule was not significantly delayed, and the safety profile remained comparable to standard regimens, with no major complications reported. Randomized clinical trials are ongoing to assess the clinical benefits of this approach. [Table: see text]
High versus standard radiation dose of definitive chemoradiotherapy combined with immunotherapy for inoperable esophageal squamous cell carcinoma: A multicenter propensity score matching analysis.
Authors: Chen Baoqing , Chen Biqi , Zhang Hao , Wang Bingyi , Cheng Qi , Chen Wenyan , Cheng Xingyuan , Cen Peiying , Liu Shiliang , Xi Mian , Li Qiaoqiao 
Published: July 2024

e16118 Background: There is no consensus of the radiation dose for esophageal squamous cell carcinoma (ESCC) in the setting of definitive chemoradiotherapy (dCRT) combined with immunotherapy. This study aimed to compare the efficacy and safety of high-dose (HD) versus standard-dose radiotherapy (SD) for locally inoperable ESCC. Methods: Patients with locally advanced unresectable ESCC or advanced ESCC with supraclavicular lymph node metastases only who received high-dose (≥ 60Gy) or standard-dose (50-50.4Gy) radiation in dCRT combined with anti-PD-1 antibody as the first-line treatment from four academic cancer centers were enrolled. Propensity score matching (PSM) was conducted to minimize the potential confounding effects. Results: Between March 2019 and July 2022, 328 patients were enrolled from four cancer centers in China, with 163 patients in the HD and 165 patients in the SD groups, respectively. The median follow-up time in the HD and SD groups were 28.9 and 25.9 months, respectively. There was no significant difference in overall survival (OS) (median OS: not reached in both, P = 0.080), progression-free survival (PFS) (median PFS: not reached vs. 30.3 months, P = 0.073), locoregional progression-free survival (LRPFS) and distant metastasis survival (DM) between the HD and SD groups. After 1:2 PSM, 156 patients in the HD and 78 patients in the SD groups were selected for further analyses. The results remained consistent and showed that the HD group had no significant benefits in OS (hazard ratio [HR] = 0.87, 95% confidence interval [CI] = 0.50-1.51, P = 0.624), PFS (HR = 0.79, 95%CI = 0.51-1.23, P = 0.300), LRPFS (HR = 0.75, 95%CI = 0.47-1.19, P = 0.228) and DM (HR = 1.05, 95%CI = 0.64-1.73, P = 0.849), compared with the SD group. In terms of failure patterns, the incidences of locoregional failure only (13.5% vs. 16.7%, P = 0.512), distant failure only (10.9% vs. 9.0%, P = 0.648) and synchronous locoregional and distant failure (2.6% vs. 6.4%, P = 0.164) were similar between two groups. No significant difference was found in the incidences of hematological toxicities, esophagitis, pneumonia (12.2% vs. 10.3%, P = 0.664) and fistula (7.1% vs 9.0%, P = 0.603) between the HD and SD groups. Conclusions: Compared with a radiation dose of 50-50.4Gy, the increase in radiation dose (≥60Gy) did not result in survival benefits for inoperable ESCC patients receiving dCRT combined with immunotherapy. Furthermore, similar failure patterns and toxicities were observed between the two treatment groups.
Preclinical antitumor efficacy of ETN101, a novel oral anticancer agent with Wnt/ß-catenin signaling inhibition, TME modulation, and VEGFR2 targeting for advanced hepatocellular carcinoma treatment.
Authors: Yang HyeJin , Kim Yeoun-Hee , Choi Garam , Park Hyun Jin , Kim Yesl , Choi Min-Jin , Jang Eunbee , Jo Sang Heon , Kim Sarah , Hwang Seonghwan , Kwon Tae-Jun , Kim Dongkyu 
Published: July 2024

e16138 Background: Hepatocellular carcinoma (HCC) is an important cancer in worldwide with over 900,000 new cases and approximately 830,000 deaths were reported in 2020. It ranks sixth in global cancer incidence and third in mortality, highlighting its worldwide significance. The high frequency of occurrence and elevated mortality rates contribute to a significant socio-economic burden. However, most patients are diagnosed in the middle and late stages, missing the optimal treatment. Therefore, it is necessary to develop novel, safe, and effective drugs for HCC inhibition, elucidating their mechanisms of action. Methods: Evaluation of ETN101 was utilized in subcutaneous xenograft and orthotopic animal models with human HCC cell lines. ETN101 was administered orally. The tumor volume, tumor weight, and bodyweight were measured, and cancer cell proliferation and apoptosis were also analyzed. The toxicity of ETN101 was investigated through GOT/GPT and histological analysis in the liver and kidney. The signaling mechanism of ETN101 was analyzed through kinase analysis, phosphorylation, in silico docking analysis, and RNA sequencing, both in vitro and in vivo. Results: ETN101 demonstrated approximately 30% tumor inhibition at 10 mg/kg group compared to control. Moreover, 20 mg/kg treatment group also showed significant tumor reduction in all individuals with one complete response (CR). Interestingly, all individuals exhibited CR from 40 to 82 mg/kg treatment groups. During the 10 administrations of Nexavar and Lenvatinib, individuals who showed proliferated tumors persistently were selected, followed by the administration of ETN101. All individuals exhibited either CR or significant reduction in tumor volume upon ETN101. After tracking complete responders for two months, there were no signs of tumor recurrence or metastasis. These results suggested that ETN101 has anticancer effect by regulating Wnt/ß-catenin pathway in tumor microenvironment (TME) with increasing the infiltration of cytotoxic T cells into the tumor. Furthermore, it targets VEGFR2, blocking angiogenesis-related signals to improve therapeutic effects in advanced HCC. Conclusions: Due to lack of effective single drugs for advanced HCC patients, combination therapy is used clinically. We developed ETN101, a monotherapy that targets VEGFR2 and modulates the TME with the same mechanism as the combination therapy. ETN101 also showed excellent efficacy in preclinical study and secured a broad safety margin relative to the effective dose. In addition, ETN101 was effective in those who are not responded to conventional targeted cancer therapies. It is anticipated that ETN101 could serve as a novel therapeutic strategy for advanced HCC patients.