bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving the learning-teaching process through adaptive learning strategy
Authors: Rincon-Flores Elvira G. , Castano Leticia , Guerrero Solis Sadie Lissette , Olmos Lopez Omar , Rodríguez Hernández Carlos Felipe , Castillo Lara Laura Angélica , Aldape Valdés Laura Patricia 
Published: June 2024

AbstractMuch has been written about Adaptive Learning, but does its implementation alone guarantee success? We have found that integrating an Adaptive Learning Strategy with diverse didactic techniques gives better results. The objectives of this exploratory study were to know the impact of the Adaptive Learning Strategy on students’ learning and achievement of disciplinary and transversal sub-competencies in courses supported by an Adaptive Platform in the School of Engineering and Sciences at Tecnologico de Monterrey. The assessment of the students’ and professors’ experience with an Adaptive Learning Strategy evaluated platform’s usability, teaching, learning, and engagement. The study employed a mixed methodological approach, sequential Quant- > Qual, and was quasi-experimental, with control and experimental groups. The courses that participated in the intervention were Computational Thinking, Physics I, Physics II, and Fundamental Mathematical Modeling. The findings indicated that implementing an innovation like Adaptive Learning positively impacts students’ learning and improvement when integrating elements of a flipped classroom, self-regulated learning, and micro-learning into an Adaptive Learning Strategy. The authors also propose an Implementation Model of the Adaptive Learning Strategy that has been designed by the university, implemented, and evaluated successfully.
Influence of surface and material technologies on the loss of lubrication performance of gears
Authors: Morhard B. , Lohner T. , Stahl K. 
Published: June 2024

AbstractEnabling gears to withstand loss of lubrication in gearboxes without secondary oil supply systems can reduce weight and space demand and thus fuel consumption. This study investigates the potential of surface and material technologies on the loss of lubrication performance of gears. Thereby, superfinished, coated, and nitrided gears are compared to ground gears. Systematic experiments under loss of lubrication are performed at a back-to-back gear test rig with circumferential speeds of up to 20 m/s and Hertzian pressures in the pitch point of up to 1723 N/mm2. Torque loss, pinion bulk temperatures, and tooth flank surface are analyzed. The results show that surface and material technologies can greatly influence frictional behavior and damage initiation of gears operating under loss of lubrication. With the materials and conditions tested, superfinishing yields to accelerated rise of frictional losses and thus scuffing. Coatings lead to significantly enhanced service life under loss of lubrication by friction reduction and scuffing avoidance.
Potentiating effect of AMD3100 on bone morphogenetic protein-2 induced bone regeneration
Authors: Shim Gyu-Jo , Lee Chung O. , Lee Jung-Tae , Jung Hong-Moon , Kwon Tae-Geon 
Published: June 2024

Abstract
Background
AMD3100, a CXCR4 antagonist, is currently prescribed for activating the mobilization of hematopoietic stem cells. Recently, AMD3100 was shown to potentiate bone morphogenetic protein-2 (BMP-2)-induced bone formation by stimulating the trafficking of mesenchymal cells. However, optimization of the strategic combination of AMD3100 and BMP-2 has not yet been clearly established. The purpose of this study was to evaluate the effect of AMD3100 on BMP-2-induced bone regeneration in vitro and in a mouse calvarial defect healing model.

Methods
In vitro osteoblastic differentiation and cell migration after sequential treatments with AMD3100 and BMP-2 were analyzed by alkaline phosphatase (ALP) activity, ALP staining, and calcium accumulation. Migration capacity was evaluated after treating mesenchymal cells with AMD3100 and/or BMP-2. A critical-size calvarial defect model was used to evaluate bone formation after sequential or continuous treatment with AMD3100 and BMP-2. The degree of bone formation in the defect was analyzed using micro-computed tomography (micro-CT) and histological staining.

Results
Compared with single treatment using either AMD3100 or BMP-2 alone, sequential treatment with AMD3100 followed by BMP-2 on mesenchymal cells increased osteogenic differentiation. Application of AMD3100 and subsequent BMP-2 significantly activated cell migration on mesenchymal cell than BMP-2 alone or AMD3100 alone.
Micro-CT and histomorphometric analysis showed that continuous intraperitoneal (IP) injection of AMD3100 resulted significantly increased new bone formation in BMP-2 loaded scaffold in calvarial defect than control groups without AMD3100 IP injection. Additionally, both single IP injection of AMD3100 and subsequent BMP-2 injection to the scaffold in calvarial defect showed pronounced new bone formation compared to continuous BMP-2 treatment without AMD3100 treatment.

Conclusion
Our data suggest that single or continuous injection of AMD3100 can potentiate BMP-2-induced osteoblastic differentiation and bone regeneration. This strategic combination of AMD3100 and BMP-2 may be a promising therapy for bone regeneration.
Association of VEGF-2549I/D promoter polymorphism with gastrointestinal tract cancer risk: a meta-analysis
Authors: Mahajan Deepanshi , Sambyal Vasudha , Guleria Kamlesh 
Published: June 2024

Abstract
Background
Gastrointestinal tract (GIT) cancers are complex disorders affecting millions of people worldwide. The vascular endothelial growth factor (VEGF) helps in the development of different GIT cancers by promoting abnormal angiogenesis in cancer cells. The role of VEGF-2549I/D polymorphism in influencing GIT cancer susceptibility has been studied in different populations with inconclusive results. Therefore, the relationship between VEGF-2549I/D polymorphism with GIT susceptibility was studied by performing a meta-analysis study.

Methods
Various online databases were used for identifying the articles. Based on study selection criteria, five studies on different GIT cancers including 1178 patients and 1520 controls were included in the meta-analysis. The accuracy of the study results was determined by performing a trial sequential analysis.

Results
In this study, the VEGF-2549I/D polymorphism did not influence the GIT cancer susceptibility in the overall analysis as well as when stratified according to ethnicity (p > 0.05). Stratification of all the studies based on the different GIT cancers reported an increased susceptibility to gastric cancer under different genetic models including allele contrast (OR = 1.67, CI = 1.294–2.157, p = 0.00008), recessive (OR = 1.68, CI = 1.056–2.660, p = 0.029), dominant (OR = 2.49, CI = 1.617–3.823, p = 0.00003), over-dominant (OR = 1.52, CI = 1.055–2.177, p = 0.025), II vs DD (OR = 2.97, CI = 1.692–5.208, p = 0.00015) and ID vs DD model (OR = 2.35, CI = 1.501–3.669, p = 0.00018).

Conclusion
There was no relationship between VEGF-2549I/D promoter polymorphism and GIT cancer susceptibility in the overall population and also in different ethnic groups. Stratification analysis revealed higher susceptibility towards gastric cancer development with VEGF-2549I/D polymorphism.
Efficiency assessment of a two-stage diagnostic strategy combining CT angiography and fractional flow reserve derived from coronary CT angiography for the detection of myocardial ischemia: a simulation study
Authors: Iwata Kunihiro , Yanagisawa Akira , Ogasawara Katsuhiko 
Published: June 2024

Abstract
Background
The importance of a diagnostic strategy combining coronary computed tomography angiography (CCTA) with fractional flow reserve derived from CCTA (FFRCT) for detecting myocardial ischemia is increasing. However, sensitivity and specificity alone may be insufficient to understand the efficiency characteristics of a diagnostic strategy combining CCTA and FFRCT (DSCCF). Our study aimed to evaluate the overall efficiency of DSCCF in detecting myocardial ischemia and compare it with other diagnostic strategies to determine whether evaluation by DSCCF is currently appropriate.

Results
This simulation study included 1000 patients with stable chest pain and suspected myocardial ischemia. Using a decision tree analysis, assuming a diagnostic strategy of adding FFRCT to CCTA-positive patients, we calculated the following efficiency parameters of DSCCF: (1) true positive (TP), false positive (FP), net false negative (FN), and net true negative (TN) test results; (2) net sensitivity; (3) net specificity; (4) positive predictive value; (5) negative predictive value; (6) post-test probability; (7) diagnostic accuracy; (8) diagnostic odds ratio; and (9) number needed to diagnose. We also calculated the efficiency parameters of other diagnostic strategies and compared them with those of DSCCF. In the basic setting, regarding efficiency parameters (1), the number of TPs, FPs, net FNs, and net TNs were 254, 69, 46, and 631, respectively. Efficiency parameters (2)–(9) were 0.85 (95% confidence interval [CI], 0.80–0.89), 0.90 (95% CI 0.88–0.92), 0.79 (95% CI 0.74–0.83), 0.93 (95% CI 0.91–0.95), 0.07 (95% CI 0.05–0.09), 0.89 (95% CI 0.86–0.90), 50.50 (95% CI 33.83–75.37), and 1.34 (95% CI 1.24–1.48), respectively. Compared with other diagnostic strategies, DSCCF had good efficiency parameters. Moreover, the sensitivity analysis did not reveal any evidence to contradict the findings in the basic setting.

Conclusions
This study demonstrated the diagnostic ability characteristics of DSCCF by assessing various efficiency parameters. Compared with other diagnostic strategies, DSCCF had good efficiency. In terms of efficiency, evaluation using DSCCF for detecting myocardial ischemia appears to be appropriate.
Overexpression of heat shock protein 47 is associated with increased proliferation and metastasis in gastric cancer
Authors: Lee Jieun , Hwang Jung-Ah , Hong Seung-Hyun , Kim Seon-Young , Seol Donghyeok , Choi Il Ju , Lee Yeon-Su 
Published: June 2024

AbstractHere, we investigated that the heat shock protein 47 (HSP47) plays a crucial role in the progression of gastric cancer (GC). We analyzed HSP47 gene expression in GC cell lines and patient tissues. The HSP47 mRNA and protein expression levels were significantly higher in GC cell lines and tumor tissues compared to normal gastric mucosa. Using siRNA to silence the expression of HSP47 in GC cells resulted in a significant reduction in their proliferation, wound healing, migration, and invasion capacities. Additionally, we also showed that the mRNA expression of matrix metallopeptidase-7 (MMP-7), a metastasis-promoting gene, was significantly reduced in HSP47 siRNA-transfected GC cells. We confirmed that the HSP47 promoter region was methylated in the SNU-216 GC cell line expressing low levels of HSP47 and in most non-cancerous gastric tissues. It means that the expression of HSP47 is regulated by epigenetic regulatory mechanisms. These findings suggest that targeting HSP47, potentially through its promoter methylation, could be a useful new therapeutic strategy for treating GC.
Extracting Systemic Anticancer Therapy and Response Information From Clinical Notes Following the RECIST Definition
Authors: Zuo Xu , Kumar Ashok , Shen Shuhan , Li Jianfu , Cong Grace , Jin Edward , Chen Qingxia , Warner Jeremy L. , Yang Ping , Xu Hua 
Published: June 2024

PURPOSE The RECIST guidelines provide a standardized approach for evaluating the response of cancer to treatment, allowing for consistent comparison of treatment efficacy across different therapies and patients. However, collecting such information from electronic health records manually can be extremely labor-intensive and time-consuming because of the complexity and volume of clinical notes. The aim of this study is to apply natural language processing (NLP) techniques to automate this process, minimizing manual data collection efforts, and improving the consistency and reliability of the results. METHODS We proposed a complex, hybrid NLP system that automates the process of extracting, linking, and summarizing anticancer therapy and associated RECIST-like responses from narrative clinical text. The system consists of multiple machine learning–/deep learning–based and rule-based modules for diverse NLP tasks such as named entity recognition, assertion classification, relation extraction, and text normalization, to address different challenges associated with anticancer therapy and response information extraction. We then evaluated the system performances on two independent test sets from different institutions to demonstrate its effectiveness and generalizability. RESULTS The system used domain-specific language models, BioBERT and BioClinicalBERT, for high-performance therapy mentions identification and RECIST responses extraction and categorization. The best-performing model achieved a 0.66 score in linking therapy and RECIST response mentions, with end-to-end performance peaking at 0.74 after relation normalization, indicating substantial efficacy with room for improvement. CONCLUSION We developed, implemented, and tested an information extraction system from clinical notes for cancer treatment and efficacy assessment information. We expect this system will support future cancer research, particularly oncologic studies that focus on efficiently assessing the effectiveness and reliability of cancer therapeutics.
Updated safety and efficacy data of combined KRAS G12C inhibitor (glecirasib, JAB-21822) and SHP2 inhibitor (JAB-3312) in patients with KRAS p.G12C mutated solid tumors.
Authors: Zhao Jun , Fang Jian , Yu Yan , Chu Qian , Li Xiaoyan , Chen Jiayan , Liu Zhe , Zhang Li , Wu Lin , Zhuang Wu , Li XingYa , Zhao Yanqiu , Xing Ligang , Liu Lian , Bai Chunmei , Dong Xiaorong , Song Qibin , Pan Pinghua , Fang Xuefeng , Wang Jie 
Published: June 2024

3008 Background: Resistance to KRAS G12C inhibitor in non-small cell lung cancer (NSCLC) can be overcome by SHP2 blockade. This concept was tested in Phase I study of glecirasib combined with JAB-3312 in patients (pts) with KRAS p.G12C mutated tumors. Promising preliminary data of safety and response were reported at the 2023 ESMO (653O). Here, we present the updated safety and efficacy data with treatment response and progression-free survival (PFS) of the combination therapy in front-line NSCLC. Methods: The phase 1/2a study [NCT05288205] evaluated glecirasib plus JAB-3312 in patients with KRAS p.G12C mutated solid tumors. The primary objective of the dose-escalation phase was to assess the safety and tolerability of the combination therapy, and the primary objective of the dose-expansion phase was to assess efficacy. Efficacy endpoints included objective response rate (ORR), disease control rate (DCR), duration of response (DoR), PFS by investigator per RECIST1.1 and overall survival. Glecirasib 400 mg or 800 mg daily was combined with various JAB-3312 doses and schedules. Results: As of December 1st, 2023, 179 pts were enrolled, including 157 with NSCLC, 17 with colorectal cancer, and five with other tumor types. Treatment-related adverse events (TRAE) ≥ grade 3 occurred in 41.9% of all pts. There were no treatment-related deaths. Discontinuation of either glecirasib or JAB-3312 due to TRAE occurred in 7.8% of all pts. The AE profile was unchanged from the last ESMO report. The most common ( > 20%) TRAEs included anemia, ALT/AST increased, hypertriglyceridemia, bilirubin increased, neutropenia/leukopenia, creatine kinase increased, and edema. No overlapped toxicity was observed for this combination therapy. Amongst all pts enrolled, 88 had NSCLC and received the combination therapy as front-line treatment in seven dosing groups. The median follow-up duration was 6.1 (range:0.5-16.7) months. Eighty pts had at least once post-treatment efficacy assessment. The ORR was 72.5% (58/80) and DCR was 96.3% (77/80). In the group of glecirasib 800mg QD + JAB-3312 2mg one week on/one week off, the ORR was 77.8% (21/27) and DCR was 92.6% (25/27). The median PFS was not mature by the data cut-off date. The 6-month and 12-month PFS rate were 67.3% and 53.7%, respectively. Additional safety and efficacy data will be presented at the meeting. Conclusions: Glecirasib plus JAB-3312 has a manageable safety profile and a promising ORR and PFS as a front-line treatment for patients with KRAS p.G12C NSCLC. This combination will be further evaluated in a randomized phase III trial in NSCLC. Clinical trial information: NCT05288205 .
Ipatasertib in patients with AKT1/2/3 mutation-positive (AKTmut) tumors: TAPISTRY study.
Authors: Thomas David Morgan , Daniele Gennaro , Kim Jeong Eun , Gadgeel Shirish M. , Ahn Eugene R. , Paz-Ares Luis G. , Prenen Hans , Chen David , Fang Junhan , Wilson Timothy R. , Simmons Brian P. , Barlesi Fabrice 
Published: June 2024

3092 Background: AKT1/2/3 point mutations are found in ~1% of all solid tumors, with varying prevalence across different tumor types. Ipatasertib is an inhibitor of the AKT kinase, but its antitumor activity as monotherapy in patients with AKTmut tumors is unknown. We present efficacy and safety data of ipatasertib in patients with advanced/metastatic AKTmut solid tumors from Cohort E of the TAPISTRY trial (NCT04589845). Methods: TAPISTRY is a phase II, global, open-label, multi-cohort trial evaluating the efficacy and safety of different therapies in patients with advanced/metastatic solid tumors. Patients in Cohort E were aged ≥12 years and had solid tumors harboring an AKT1/2/3mutation identified by next-generation sequencing and measurable disease by RECIST v1.1. Oral ipatasertib 400 mg was administered once daily. Tumor assessments were performed at screening, every eight weeks from Day 1/Cycle 1 for one year, and every 12 weeks after that. The primary endpoint was objective response rate (ORR) by independent review committee (IRC). Key secondary endpoints included ORR by investigator, duration of response, progression-free survival, overall survival and safety. Results: At data cut-off (16 Jul 2023), 50 patients were safety evaluable and 48 were efficacy evaluable. In the safety-evaluable population, median age was 59 years (range, 30–79); 98% of patients (n/N = 49/50) had an AKT1 mutation ( AKT1 E17K, n=47) and 2% (n/N = 1/50) had an AKT2 E17K mutation; 41/50 patients (82%) had received ≥2 prior lines of treatment. Efficacy-evaluable patients had 10 different tumor types, the most common being breast cancer (n/N = 21/48; 44%). Key outcomes are summarized in the Table. After a median follow-up of 11.3 months, ORR by IRC in efficacy-evaluable patients was 31.3% (n/N = 15/48; 95% CI 18.7–46.3), driven by responses in three tumor types: breast (n/N = 7/21; 33%), endometrial (n/N = 7/7; 100%), and head and neck (n/N = 1/2; 50%). The most frequent adverse event was diarrhea (n/N = 39/50; 78%). Safety was consistent with the known profile of ipatasertib; no new safety signals were identified. Conclusions: Treatment with ipatasertib led to a marked and durable antitumor activity in some tumor types such as endometrial cancer, but not in the overall tumor-agnostic cohort. Further studies are needed to understand the relevance of AKT inhibition in these tumor types. Clinical trial information: NCT04589845 . [Table: see text]
FCN-159, a MEK1/2 inhibitor, in patients with advanced melanoma harboring NRAS or NF1mutations: A phase 1B dose-expansion study.
Authors: Gu Junjie , Mao Lili , Guo Jun , Jiang Yu , Zhu Lingjun , Zhang Xiaoshi , Yan Wangjun , Chen Yu , Tan Chang , Zhu Weiyou , Zhang Jian , Liu Jie , Lin Jing , Wu Zhuli , Wang Xingli , Yang Yuchen , Li Ben , Si Lu 
Published: June 2024

3095 Background: In phase 1A dose-escalation study, preliminary anti-tumor activity of FCN-159 was observed in advanced melanoma patients harboring NRAS mutations (ORR: 19.0%, mPFS: 3.8 months) with tolerable safety profile, which was posted during AACR 2022 (No.: 22-LB-7398-AACR). Here, we report the results from phase 1B dose-expansion study in advanced NRAS- or NF1-mutant melanoma patients at RP2D predetermined at 12 mg. Methods: This open-label, dose-expansion, phase 1B study (NCT03932253) consists of two cohorts, which enrolled patients with unresectable stage III/IV melanoma harboring NRAS or NF1 mutations, respectively. Patients received FCN-159 orally at 12 mg once daily (QD) continuously in 28-day cycles. The primary endpoint was anti-tumor activity. Results: As of July 17, 2023, 46 patients (32 patients with NRASmutations in Cohort 1 and 14 patients with NF1mutations in Cohort 2) were enrolled and received 12 mg FCN-159 QD. The median follow-up time was 8.6 months. Among 25 patients who failed in previous anti-PD-1 therapy in Cohort 1, 6 had confirmed partial responses (ORR, 24.0%; 95% confidence interval [CI], 9.4–45.1). Median DOR was 6.5 months (95% CI, 2.7–NE). Median progression-free survival (mPFS) was 3.6 months (95% CI, 1.8–5.5). Among 14 patients in Cohort 2, 1 had PR (ORR, 7.1%; 95% CI, 0.2-33.9) and mPFS was 2.8 months (95% CI, 1.8-5.5) (Table). Grade≥3 FCN-159-related treatment-emergent adverse events (TEAEs) were reported in 10 (21.7%) patients in both cohorts; the most common was blood creatine phosphokinase increased (13.0%). FCN-159–related serious AEs (SAEs) were reported in 3 (6.5%) patients, which were edema lower limb, cellulitis and pneumonia. Two (4.3%) patients discontinued treatment due to FCN-159 related TEAEs, including serous retinal detachment and herpes zoster. No FCN-159-related TEAEs led to death. Conclusions: FCN-159 showed encouraging efficacy data with well tolerated safety profile in patients with NRAS-mutant advanced melanoma, especially those who failed in previous anti-PD-1 therapy. Clinical trial information: NCT03932253 . [Table: see text]