bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeted sequencing of DNA/RNA combined with radiomics predicts lymph node metastasis of papillary thyroid carcinoma
Authors: Zhang Runjiao , Hu Linfei , Cheng Yanan , Chang Luchen , Dong Li , Han Lei , Yu Wenwen , Zhang Rui , Liu Pengpeng , Wei Xi , Yu Jinpu 
Published: June 2024

Abstract
Objective
The aim of our study is to find a better way to identify a group of papillary thyroid carcinoma (PTC) with more aggressive behaviors and to provide a prediction model for lymph node metastasis to assist in clinic practice.

Methods
Targeted sequencing of DNA/RNA was used to detect genetic alterations. Gene expression level was measured by quantitative real-time PCR, western blotting or immunohistochemistry. CCK8, transwell assay and flow cytometry were used to investigate the effects of concomitant gene alterations in PTC. LASSO-logistics regression algorithm was used to construct a nomogram model integrating radiomic features, mutated genes and clinical characteristics.

Results
172 high-risk variants and 7 fusion types were detected. The mutation frequencies in BRAF, TERT, RET, ATM and GGT1 were significantly higher in cancer tissues than benign nodules. Gene fusions were detected in 16 samples (2 at the DNA level and 14 at the RNA level). ATM mutation (ATMMUT) was frequently accompanied by BRAFMUT, TERTMUT or gene fusions. ATMMUT alone or ATM co-mutations were significantly positively correlated with lymph node metastasis. Accordingly, ATM knock-down PTC cells bearing BRAFV600E, KRASG12R or CCDC6-RET had higher proliferative ability and more aggressive potency than cells without ATM knock-down in vitro. Furthermore, combining gene alterations and clinical features significantly improved the predictive efficacy for lymph node metastasis of radiomic features, from 71.5 to 87.0%.

Conclusions
Targeted sequencing of comprehensive genetic alterations in PTC has high prognostic value. These alterations, in combination with clinical and radiomic features, may aid in predicting invasive PTC with higher accuracy.
Prognostic value of the tumor-to-liver density ratio in patients with metastatic colorectal cancer treated with bevacizumab-based chemotherapy. A post-hoc study of the STIC-AVASTIN trial
Authors: Mazard Thibault , Mollevi Caroline , Loyer Evelyne M. , Léger Julie , Chautard Romain , Bouché Olivier , Borg Christophe , Armand-Dujardin Paul , Bleuzen Aurore , Assenat Eric , Lecomte Thierry 
Published: June 2024

Abstract
Background
The Response Evaluation Criteria in Solid Tumors (RECIST) are often inadequate for the early assessment of the response to cancer therapy, particularly bevacizumab-based chemotherapy. In a first cohort of patients with colorectal cancer liver metastases (CRLM), we showed that variations of the tumor-to-liver density (TTLD) ratio and modified size-based criteria determined using computed tomography (CT) data at the first restaging were better prognostic criteria than the RECIST. The aims of this study were to confirm the relevance of these radiological biomarkers as early predictors of the long-term clinical outcome and to assess their correlation with contrast-enhanced ultrasound (CEUS) parameters in a new patient cohort.

Methods
In this post-hoc study of the multicenter STIC-AVASTIN trial, we retrospectively reviewed CT data of patients with CRLM treated with bevacizumab-based regimens. We determined the size, density and TTLD ratio of target liver lesions at baseline and at the first restaging and also performed a morphologic evaluation according to the MD Anderson criteria. We assessed the correlation of these parameters with progression-free survival (PFS) and overall survival (OS) using the log-rank test and a Cox proportional hazard model. We also examined the association between TTLD ratio and quantitative CEUS parameters.

Results
This analysis concerned 79 of the 137 patients included in the STIC-AVASTIN trial. PFS and OS were significantly longer in patients with tumor size reduction > 15% at first restaging, but were not correlated with TTLD ratio variations. However, PFS was longer in patients with TTLD ratio > 0.6 at baseline and first restaging than in those who did not reach this threshold. In the multivariate analysis, only baseline TTLD ratio > 0.6 was a significant survival predictor. TTLD ratio > 0.6 was associated with improved perfusion parameters.

Conclusions
Although TTLD ratio variations did not correlate with the long-term clinical outcomes, TTLD absolute values remained a good predictor of survival at baseline and first restaging, and may reflect tumor microvascular features that might influence bevacizumab-based treatment efficiency.

Trial registration
NCT00489697, registration number of the STIC-AVASTIN trial.
The combined effect of leucine-enriched essential amino acid supplements and locomotion training on physical functions and quality of life in hemodialysis patients
Authors: Kitabayashi Kou , Yamamoto Suguru , Katano Yumi , Narita Ichiei 
Published: June 2024

Abstract
Background
Locomotive syndrome (LS) is a condition of reduced mobility (locomotive organ impairment) that is associated with reduced quality of life (QOL) in patients undergoing hemodialysis (HD), and effective interventions for patients with LS undergoing HD are unclear. We conducted a clinical trial to assess the effects of exercise and oral nutritional supplementation (ONS) on QOL in this cohort.

Methods
This study was an open-label, randomized controlled trial. The participants were patients with LS undergoing HD. The intervention period was 3 months. The primary outcome was a change in the physical component summary (PCS) of QOL, and the secondary outcomes were changes in other QOL scores, physical function, body composition, and nutritional status assessed by using the geriatric nutritional risk index. Participants were divided into the locomotion training (LT) and LT + ONS groups. Both groups were instructed on LT that comprised one-leg standing and squats to be carried out four or more times per week. The ONS consisted of 3 g leucin-rich essential amino acids and 800 IU vitamin D per pack, and the participants in the LT + ONS group received one pack of the supplement per day.

Results
In total, 40 individuals undergoing HD were included in the study; 3 patients in the LT + ONS group were excluded from the analysis because of hospitalization and incomplete assessment. The median age was 73 years (interquartile range: 62–80 years), 23 participants were men (62%), and the duration of dialysis treatment was 6 years (interquartile range: 3–16 years). The change in PCS of the LT + ONS group did not differ from that in the LT group [LT + ONS: −1.6 (−5.3, 6.8) versus LT: −0.1 (−5.3, 6.2), p = 0.94]. In contrast, the LT + ONS group showed maintenance in mental health (MH) and improvement of the two-step value.

Conclusions
The LT + ONS group did not show an effect on PCS in QOL compared with only LT in patients with LS undergoing HD. However, maintenance of MH and improvement of two-step value were confirmed in the LT + ONS group. Future research is need to confirm whether leucine-rich essential amino acids and vitamin D help mental health and physical function in patients with LS undergoing HD with larger sample sizes and long-term interventions.
Clinical trial registration University Hospital Medical Information Network Center (UMIN 000032457).
Explore the ancient roots of the Huaxia people and Chinese civilization
Authors: Gao Xing 
Published: June 2024

AbstractChinese civilization, which stands as a shining star in human civilizations, is distinct in its nature and development path. Although it suffered numerous turns of devastation in its 5,000 years of history, it has resiliently remained uninterrupted in its growth and radiance. Characterized by continuity, innovation, unity, inclusiveness, and longstanding commitment to peace, it also exhibits strong cohesion, vitality, flexibility, and adaptability. These characteristics emerged in the Paleolithic Period, indicating that the Chinese civilization did not emerge overnight. Its roots run deep with a long history, sprouting in the Paleolithic Period, breaking ground in the late Neolithic period, and gradually growing into the towering trees it is today. How did the ancient people in China evolve into today’s Chinese nation? How did the ancient culture of prehistoric times develop into the current Chinese civilization? What are the connections between the history buried underground and the society we see today? Obviously, there is no clear answer to these questions. There are still many gaps in prehistoric China that need to be filled, and the process of and reasons for the evolution of ethnic groups and cultures still need to be further interpreted. The author tries to trace the roots of the Chinese nation and its civilization back to the Paleolithic Period, using archaeological materials to connect the survival and reproduction process of ancestors and delve into studying the ancient roots of the Huaxia people and Chinese civilization.
Detecting faults in the cooling systems by monitoring temperature and energy
Authors: Kaushik Keshav , Naik Vinayak 
Published: June 2024

AbstractThe cooling systems contribute to 40% of overall building energy consumption. Out of which, 40% is wasted because of faulty parts that cause anomalies in the cooling systems. We propose a three-stage, non-invasive part-level anomaly detection technique to identify anomalies in both cooling systems, a ducted-centralized and a ductless-split. We use COTS sensors to monitor temperature and energy without invading the cooling system. After identifying the anomalies, we find the cause of the anomaly. Based on the anomaly, the solution recommends a fix. If there is a technical fault, our proposed technique informs the technician regarding the faulty part, reducing the cost and time needed to repair it. In the first stage, we propose a domain-inspired time-series statistical technique to identify anomalies in cooling systems. We observe an AUC-ROC score of more than 0.93 in simulation and experimentation. In the second stage, we propose using a rule-based technique to identify the cause of the anomaly. We classify causes of anomalies into three classes. We observe an AUC-ROC score of 1. Based on the anomaly classification, we identify the faulty part of the cooling system in the third stage. We use the Nearest-Neighbour Density-Based Spatial Clustering of Applications with Noise (NN-DBSCAN) algorithm with transfer learning capabilities to train the model only once, where it learns the domain knowledge using the simulated data. The trained model is used in different environmental scenarios with both types of cooling systems. The proposed algorithm shows an accuracy score of 0.82 in simulation deployment and 0.88 in experimentation. In the simulation we used both ducted-centralized and ductless-split cooling systems and in the experimentation we evaluated the solution with ductless-split cooling systems. The overall accuracy of the three-stage technique is 0.82 and 0.86 in simulation and experimentation, respectively. We observe energy savings of up to 68% in simulation and 42% during experimentation, with a reduction of ten days in the cooling system’s downtime and up to 75% in repair cost.
Characteristics and effectiveness of deep and ultradeep tight sandstone fractures: Insights from geologic and geophysical data analysis
Authors: Zhang Guanjie , Liu Jingshou , Xu Ke , Jiang Shu , Zhang Binxin , Shi Ning 
Published: June 2024

Effective natural fractures are those that contribute to reservoir storage and conductivity. In this study, the effectiveness of fractures in deep and ultradeep reservoirs (depths > 6 km) is evaluated by using geophysical image logs, cores, microstructures, mechanical tests, and geologic evidence of the tectonic context (including current in situ stress) and sedimentary faces and diagenesis. Intraformational open-mode fractures are the most common fracture type in this tectonically active region, and their effectiveness is affected by the coupling between past tectonic activity, in situ stress, and chemical reactions such as mineral precipitation or dissolution (diagenesis). Our results show that the effectiveness of fractures is mainly related to the aperture and filling, and fractures formed by early tectonic movement are more likely to be filled by minerals, reducing their effectiveness. Strata near orogenic belts in strongly cemented, tight diagenetic facies exhibit a greater abundance of mineral-filled fractures, whereas dissolution increases the fracture apertures, produces secondary pores in host rocks, and roughens the fracture walls. The effective normal stress acting on the fracture surface decreases when the fracture is parallel to the maximum horizontal stress component, so the fracture has a large aperture and, therefore, is more effective. The results of our laboratory measurements reveal that the contribution of fractures to the reservoir space is limited, and the reservoir space provided by fractures accounts for only 13% of all types of reservoir space, whereas the presence of fractures increases reservoir permeability by 1–2 orders of magnitude. Fractures improve the effectiveness of the reservoir by connecting the dispersed pores in the reservoir matrix. Fractures with a low angle to the maximum horizontal stress component have greater apertures and permeabilities and are the main channels for fluid flow.
CD8 radiomics signature to assess inter-lesion spatial heterogeneity and cold liver lesions in advanced non-small cell lung cancers treated with durvalumab.
Authors: Sun Roger , Emeriau Yanis , Achkar Samir , Mitrea Diana , Laville Adrien , Deny Nicolas , Bockel Sophie , Chaffai Ines , Mrissa Linda , Cifliku Vjona , Talebi Fereshteh , Wu Wenxia , Le Pechoux Cecile , Barlesi Fabrice , Robert Charlotte , Levy Antonin , Deutsch Eric 
Published: June 2024

2511 Background: The objective of this study was to assess whether a validated CD8 radiomics signature may help to evaluate patient inter-lesion heterogeneity and to predict the clinical outcome of advanced non-small cell lung cancers (NSCLC) patients treated with durvalumab in Study 1108 phase I/II trial (NCT01693562). Methods: Clinical data and imaging data from patients with naïve and pretreated advanced NSCLC who received durvalumab monotherapy were used. Radiomic features were extracted on contrast-enhanced CT scans and a validated CD8 radiomics signature was applied. A progressive lesion was defined by an increase in lesion longest diameter of 20% at 8 weeks. Dispersion metrics of the radiomics signature were estimated to evaluate the impact of inter-lesion heterogeneity on patient’s response. Results: A total of 188 patients were included in this study, accounting for a total of 1137 lesions (median [IQR] = 4 [3 - 9] lesions per patient) evaluated at baseline using a radiomics approach. A low CD8 radiomics score at baseline was associated with a significantly higher risk of progression at the lesion-level (AUC=0.59, P-value<0.0001), and was especially performant for liver lesions (AUC=0.66, P-value=0.0002). At the patient level, the least infiltrated lesion of a patient according to the radiomics score of CD8 T-cells was positively associated with OS (HR=0.70, P-value=0.029) and PFS (HR=0.68, P-value=0.014), the highest values being associated with the best outcomes. 55 patients had liver lesions, with worse prognosis than patients without liver lesion (HR=2 for OS and PFS, P-value = 0.00012 and 0.00022 respectively). In these patients, the CD8 radiomic score enabled the stratification of patients according to hot and cold liver metastasis (HR=0.6, P-value=0.072 and HR=0.54, P-value=0.038 for OS and PFS respectively). A 4-class stratification of the whole cohort based on the least infiltrated (cold/hot) and liver or non-liver lesion was independently associated with clinical outcomes. These radiomics approaches have shown independent prognostic values when adjusting for PD-L1 status in multivariate analyses (Table). Conclusions: These results confirm the predictive value at a lesion level and the patient level of the biologically inspired CD8 radiomics score for advanced NSCLC patients treated with durvalumab. It has shown interesting results in discriminating outcomes of patients with liver lesions by identifying hot and cold lesions. [Table: see text]
Clinical landscape of precision oncology for rare cancers among diverse Asian populations: Insights from the MASTER KEY registry.
Authors: Mizoguchi Chiharu , Okuma Hitomi Sumiyoshi , Muto Manabu , Kinoshita Ichiro , Baba Eishi , Takahashi Masanobu , Ando Masashi , Soo Hoo Hwoei Fen , Yusak Suhana , Voon Pei Jye , Ramachandran Rangasamy , Thiagarajan Muthukkumaran , Imasa Marcelo Severino Bulauitan , Malik Rozita Abdul , Choi Wonyoung , Dao Tu Van , Chen Tom Wei-Wu , Yonemori Kan , Nakamura Kenichi , Yamamoto Noboru 
Published: June 2024

3024 Background: Despite considerable strides in novel cancer treatments, disparities in access and care persist globally. This is particularly pronounced for rare cancers and among Asian patient cohorts, presenting a dual challenge. Methods: We conducted an analysis on clinical and biomarker data from the MASTER KEY Study, a multi-regional, prospective, observational precision oncology initiative encompassing 3,764 rare cancer patients across Asia. Clinical treatment and biomarker data, inclusive of DNA/RNA sequencing, were scrutinized to compare precision oncology adoption across various countries. Results: Within the Japanese cohort (3,268 patients), predominant rare cancer types included soft tissue sarcomas (22.0%), CNS/brain tumors (12.8%), and head and neck tumors (9.2%). The broader Asian cohort (496 patients) included soft tissue sarcomas (14.6%), liver/biliary tract tumors (14.4%), and head and neck tumors (13.8%), drawing patients from Malaysia, Korea, Taiwan, Philippines, Thailand, and Vietnam. Clinical trial participation for these rare cancers was notably higher in Taiwan (8.2%), followed by Japan (6.5%) and Malaysia (2.0%). The utilization of molecular target agents and/or immune checkpoint inhibitors was highest in Japan (20.3%), trailed by Taiwan (18.9%) and Korea (12.8%). DNA/RNA targeted sequencing data was available for 1,852 patients in Japan (56.7%) and 321 patients (64.7%) across the rest of Asia. 19.5% and 7.0% received on-target therapy in Japan and the rest of Asia, respectively. Notably, in Japan, patients harboring detectable targetable genes like BRAF V600E, BRCA1, and BRCA2 received BRAF/MEK inhibitors and PARP inhibitors at rates of 78.3%, 37.8%, and 25.0%, respectively, with varying response rates of 33.3%, 18.2%, and 20.2% each. Intriguingly, TP53 mutation acted as a negative predictor for response to BRAF/MEK inhibitors. Notably, no patients in the Asian cohort received BRAF/MEK inhibitors or PARP inhibitors despite the detection of these genes. Conclusions: The MASTER KEY Study demonstrates the feasibility of a prospective precision oncology platform, spotlighting rare cancers and enabling on-label targeted therapy as well as off-label targeted therapy for a subset of patients through trials. However, the broader Asian population outside Japan encounters heightened limitations in accessing precision oncology. Urgent expansion of clinical trials throughout Asia is crucial to effectively address the disparity that lies within Asian rare cancer patients.
Selpercatinib in non-MTC, RET-mutated tumors: Efficacy in MEN-associated and other tumors.
Authors: Cassier Philippe Alexandre , De Braud Filippo G. , Ryder Mabel M. , Robinson Bruce , Tomasini Pascale , Morise Masahiro , Lakhani Nehal J. , Szymczak Sylwia , Peterson Patrick , Barker Scott , Sukrithan Vineeth 
Published: June 2024

3150 Background: Selpercatinib, a first-in-class highly selective and potent RET kinase inhibitor with CNS activity, is approved in multiple countries for the treatment of RET-activated cancers. Current indications for RET mutant disease are limited to MTC. This analysis examined if selpercatinib was effective in non-MTC, RET mutation positive tumors and whether certain RET mutations demonstrated better activity (n=23; data cut-off: 13Jan2023). Methods: The phase 1/2 LIBRETTO-001 trial (NCT03157128) enrolled pts with locally advanced/metastatic RET-altered solid tumors, including pts with RET mutations in tumors other than MTC. Mutations must be known to be activating based on activity in MTC or other published evidence. Primary endpoint was objective response rate (ORR) by independent review committee (IRC). Secondary endpoints included ORR by investigator (INV), duration of response (DoR), progression-free survival (PFS), and safety. Results: Fourteen different tumor types were identified among the 23 pts with non-MTC RET-mutated tumors. This included 8 tumors from the Multiple Endocrine Neoplasia (MEN) syndrome spectrum; adrenal (pheochromocytoma; n=5), paraganglioma (n=2), neuroendocrine (n=1) (Table). Most of the mutations were located in extracellular cysteine-rich domain (CRD) and in the tyrosine kinase domain (TKD) of RET. In 23 efficacy-evaluable pts, confirmed ORR by IRC was 21.7% (5/23, 95% CI: 7.5, 43.7). ORR by IRC for pts with MEN-associated tumors (n=8) was 37.5% while five of these pts (62.5%) had stable disease lasting at least 16 weeks (SD16+). ORR by IRC for the sub-population with pheochromocytoma (n=5) was 40.0% and for pts with tumors manifesting RET extracellular cysteine mutations (n=5) was 60.0%. Of the 15 pts with non-MEN-associated tumors, 2 pts (8.7%; mutation in TKD) had a partial response (both with NSCLC adenocarcinoma, of which one had co-existent MTC). For the overall pts, the median DoR was 12.2 months (95% CI: 3.8, NE) and median PFS was 5.5 months (95% CI: 1.8, 19.4). No new safety signals were identified compared to previous reports. One grade 5 AE, general physical health deterioration, was observed and deemed by INV as not related to selpercatinib. Conclusions: This study suggests that RET-mutated, MEN-associated cancers (adrenal, paraganglioma, neuroendocrine) may benefit from selpercatinib treatment, which could be mediated through mutations in the extracellular CRD. The non-MTC RET-mutated tumor types appear not to derive benefit from selpercatinib. Clinical trial information: NCT03157128 . [Table: see text]