bluuebunny/crossref_metadata_2025_split huggingface dataset:
KG-particles in a cosmic string rainbow gravity spacetime in mixed magnetic fields
Authors: Mustafa Omar 
Published: April 2024

AbstractWe investigate and report the effects of rainbow gravity on the spectroscopic structure of KG-oscillators in a mixed magnetic field (in the sense that it has the usually described as a uniform and a non-uniform magnetic fields, each at a time) introduced by the 4-vector potential $$A_\mu =(0,0,A_\varphi ,0)$$

A
μ

=

(
0
,
0
,

A
φ

,
0
)

, where $$A_\varphi =B_1 r^2/2+B_2 r$$

A
φ

=

B
1

r
2

/
2
+

B
2

r

, and $$B_1$$

B
1

and $$B_2$$

B
2

are magnetic field strengths. We also discuss and report the effects of such a mixed magnetic field on the spectra of KG-oscillators in cosmic string rainbow gravity. In so doing, we introduce a new and quite handy conditionally exact solution associated with the truncation of the biconfluent Heun functions into polynomials. Using a loop quantum gravity motivated rainbow functions, we observe interesting effects when the magnetic field strength $$B_2$$

B
2

grows up from zero. Such effects include energy levels crossings which, in this case, turns the spectra of the KG-oscillators upside down. Moreover, Landau-like signature on the spectra are observed and discussed. Yet, interestingly, we also observe that rainbow gravity affects the magnetic field as well, in the sense that the magnetic field becomes probe particle energy-dependent one.
Dynamics of molecules in torsional DNA exposed to microwave and possible impact on its deformation: stability analysis
Authors: Tantawy M. , Abdel-Gawad H. I. 
Published: April 2024

AbstractIn this work, we explore the dynamics of molecules in torsionally stressed DNA subjected to periodic external forces, specifically microwave radiation. Our approach involves constructing a novel continuum model based on a discrete model. Remarkably, this continuum model has not been analytically solved in existing literature, which motivates us to derive analytic solutions for investigating DNA s dynamical behavior. Our primary objective is to examine the impact of an external field (such as microwave radiation) on DNA dynamics, potentially affecting its structural integrity. Scientifically, we know that DNA molecules exposed to microwaves can suffer damage. Here, we focus on stability (or instability) to determine deterministic outcomes. Analytic solutions are essential for this purpose. The model equations governing torsional DNA (TDNA) behavior are non-autonomous and, in some cases, not integrable, meaning no exact solutions exist. Consequently, we rely on approximate solutions. Our chosen method is the extended unified method, allowing us to control errors through parameter selection. We consider two scenarios: when the torsional angle is smaller than one or completely free. Exact solutions emerge only when stacking and chain curvature constants are equal, otherwise, we derive approximate solutions. Numerical results: Numerical representations reveal that the localization of DNA molecules depends significantly on the microwave amplitude (MWA) and damping rate. Additionally, a critical MWA or DA value exists beyond which TDNA undergoes deformation. Stability analysis plays a crucial role in understanding these intricate dynamics. The present study sheds light on the interplay between external fields, DNA stability, and structural changes. Analytic solutions provide valuable insights into this complex system, with potential implications for biological processes and health.
A Cross-Project Defect Prediction Approach Based on Code Semantics and Cross-Version Structural Information
Authors: Zou Yifan , Wang Huiqiang , Lv Hongwu , Zhao Shuai , Tian Haoye 
Published: April 2024

Context: Cross-project defect prediction (CPDP), due to the potential of adaption by industry in realistic scenarios, had gained significant attention from the research community. Currently, existing CPDP studies use static statistical features designed by experts, which might not capture the semantic and structural aspects of software, resulting in low accuracy in defect prediction. Meanwhile, they tend to overlook the valuable iterative information brought about by version updates in mature software projects. Objective: This paper introduces DETECTOR, a novel CPDP approach based on coDE semanTic and cross-vErsion struCTural infORmation to leverage cross-versions features of the software and improve the performance of CPDP. Methods: DETECTOR parses source code to exploit Abstract Syntax Trees (ASTs) and cross-version software network (Cross-SN) that consists of internal class dependency network and cross-version class dependency edges. It utilizes Attention-based Bi-LSTM and simplified graph convolutional neural networks to automatically extract software features from ASTs and Cross-SN. The extracted features are fused using gate(⋅) to generate more effective cross-version features. Finally the source project is selected to carry out the data used to train the classifier to predict the defects. Results: Empirical studies on seven open-source Java projects, the experiment results show that: (1) DETECTOR outperforms the state-of-the-art models in CPDP; (2) our proposed cross-version dependent edges positively contribute to DETECTOR performance; (3) gate(⋅) outperforms existing strategies in fusion features; (4) more multi-versions information enhance DETECTOR’s performance. Conclusion: DETECTOR can predict more defects in CPDP and improve the accuracy and effectiveness of prediction.
Dynamic Effect of Overscreening on Electrochemical and Thermal Properties of EDLC Electrodes during Charging/Discharging Cycles
Authors: Li Jingyu , Hamza Muhammad , Mei Bing-Ang , Feng Huihua , Zuo Zhengxing , Xiong Rui 
Published: April 2024

Overscreening was commonly observed during charging/discharging cycles of electric double layer capacitors(EDLCs). This study presented a two-dimensional continuum electrochemical thermal model with a distribution function for concentration considering overscreening to investigate how overscreening affected the dynamic formation of electric double layer (EDL) near electrodes in macroscale. The results indicated that ion distribution was co-affected by EDL formation and overscreening near the electrode. Correspondingly, layered space charge density distribution resulted in a thicker diffuse layer, whose thickness was determined by the sum of co-ion and counter-ion diameters. Additionally, the diffuse layer capacitance was proportional to the reciprocal of counter-ion diameter, while the total capacitance was proportional to a linear combination of counter-ion and the larger ion diameters. Moreover, the shift from endothermic to exothermic for the total heat generation rate was dominated by heat of mixing, and was caused by the local ion mixing due to overscreening, resulting in local entropy increase. The results of this study can be used to further investigate the effect of overscreening on ion transient transport dynamic and heat generation rates.
Safety and Preliminary Efficacy of Pembrolizumab Following Transarterial Chemoembolization for Hepatocellular Carcinoma: The PETAL Phase Ib Study
Authors: Pinato David J. , D'Alessio Antonio , Fulgenzi Claudia Angela Maria , Schlaak Alexandra Emilia , Celsa Ciro , Killmer Saskia , Blanco Jesus Miguens , Ward Caroline , Stikas Charalampos-Vlasios , Openshaw Mark R. , Acuti Nicole , Nteliopoulos Georgios , Balcells Cristina , Keun Hector C. , Goldin Robert D. , Ross Paul J. , Cortellini Alessio , Thomas Robert , Young Anna-Mary , Danckert Nathan , Tait Paul , Marchesi Julian R. , Bengsch Bertram , Sharma Rohini 
Published: April 2024

Abstract

Purpose:
Transarterial chemoembolization (TACE) may prime adaptive immunity and enhance immunotherapy efficacy. PETAL evaluated safety, preliminary activity of TACE plus pembrolizumab and explored mechanisms of efficacy.

Patients and Methods:
Patients with liver-confined hepatocellular carcinoma (HCC) were planned to receive up to two rounds of TACE followed by pembrolizumab 200 mg every 21 days commencing 30 days post-TACE until disease progression or unacceptable toxicity for up to 1 year. Primary endpoint was safety, with assessment window of 21 days from pembrolizumab initiation. Secondary endpoints included progression-free survival (PFS) and evaluation of tumor and host determinants of response.

Results:
Fifteen patients were included in the safety and efficacy population: 73% had nonviral cirrhosis; median age was 72 years. Child-Pugh class was A in 14 patients. Median tumor size was 4 cm. Ten patients (67%) received pembrolizumab after one TACE; 5 patients after two (33%). Pembrolizumab yielded no synergistic toxicity nor dose-limiting toxicities post-TACE. Treatment-related adverse events occurred in 93% of patients, most commonly skin rash (40%), fatigue, and diarrhea (27%). After a median follow-up of 38.5 months, objective response rate 12 weeks post-TACE was 53%. PFS rate at 12 weeks was 93% and median PFS was 8.95 months [95% confidence interval (CI): 7.30–NE (not estimable)]. Median duration of response was 7.3 months (95% CI: 6.3–8.3). Median overall survival was 33.5 months (95% CI: 11.6–NE). Dynamic changes in peripheral T-cell subsets, circulating tumor DNA, serum metabolites, and in stool bacterial profiles highlight potential mechanisms of action of multimodal therapy.

Conclusions:
TACE plus pembrolizumab was tolerable with no evidence of synergistic toxicity, encouraging further clinical development of immunotherapy alongside TACE.
Abstract CT288: Brightline-4: A phase 3 open-label, single-arm, multicenter study to assess the safety and efficacy of brigimadlin (BI 907828) treatment in patients with treatment-naïve or pretreated advanced dedifferentiated liposarcoma
Authors: Schuetze Scott , Jayadeva Girish , Santoro Michael 
Published: April 2024

Abstract
Background Current treatment options for dedifferentiated liposarcoma (DDLPS) are associated with suboptimal efficacy and substantial toxicities.
Purpose Brigimadlin (BI 907828) is a highly potent, orally available MDM2-p53 antagonist that binds to MDM2 and blocks its interaction with p53, thereby restoring p53 function, leading to cell cycle arrest and apoptosis in TP53 wild-type tumors. Brigimadlin has been evaluated in a phase 1a/1b study in patients with solid tumors (NCT03449381) and has shown encouraging preliminary efficacy in patients with DDLPS. Based on these data, brigimadlin is being investigated for the first-line treatment of advanced DDLPS in the randomized phase 2/3 Brightline-1 trial (NCT05218499). The Brightline-4 trial will generate additional safety and efficacy data in a broader DDLPS patient population.
Experimental design Brightline-4 (NCT06058793) is an open-label, single-arm, global, multicenter phase 3 study that aims to assess the safety and efficacy of brigimadlin in patients with treatment-naïve or pretreated advanced DDLPS. Approximately 240 patients with treatment-naïve (Cohort A) or pre-treated (Cohort B) advanced DDLPS will be enrolled. All patients will receive brigimadlin 45 mg orally once every 3 weeks. Key inclusion criteria include: ≥18 years of age; locally advanced/metastatic, unresectable, histologically confirmed DDLPS; tumor MDM2 expression by immunohistochemistry or MDM2 amplification (via fluorescence in situ hybridization or next-generation sequencing); ≥1 measurable target lesion (RECIST v1.1); and ECOG PS 0/1. Key exclusion criteria include: prior treatment with an MDM2-p53 antagonist; known mutation in TP53; receiving treatment for brain metastases or leptomeningeal disease. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoints are the occurrence of treatment-emergent adverse events (TEAEs) and grade ≥3 TEAEs according to NCI CTCAE v5. Secondary endpoints include objective response, progression-free survival, overall survival, duration of response, disease control and further assessment of safety. All analyses will be descriptive; no hypothesis testing is planned.
Citation Format: Scott Schuetze, Girish Jayadeva, Michael Santoro. Brightline-4: A phase 3 open-label, single-arm, multicenter study to assess the safety and efficacy of brigimadlin (BI 907828) treatment in patients with treatment-naïve or pretreated advanced dedifferentiated liposarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT288.
Abstract LB069: Repurposing anti-mesothelin CAR-NK immunotherapy against colorectal cancer
Authors: Torchiaro Erica , Cortese Marco , D'Andrea Alice , Petti Consalvo , Medico Enzo 
Published: April 2024

Abstract
Colorectal cancer (CRC) is the third most common cancer worldwide, with highly variable prognosis and response to treatment. A large subset of patients does not respond to standard treatments or develops resistance. As an alternative, adoptive immunotherapy based on chimeric antigen receptor (CAR)-transduced immune cells has been proposed, however with significant adverse events. We therefore evaluated alternative CAR targets already tested in other tumour types, and employed the natural killer cell line NK-92 for CAR transduction because of its more favourable toxicity profile.
As an alternative antigen, we considered mesothelin (MSLN), the most represented in CAR-based clinical studies for solid tumours. MSLN RNA expression was analysed in large series of CRC patient-derived xenografts (PDXs, n=500), cell lines (n=150) and tumours (n=640), to evaluate its distribution and to identify MSLN-overexpressing models. NK-92 cells were transduced with anti-MSLN CAR, and subsequently sorted and cloned. Activity of CAR-NK-92 cells against target-expressing ovarian and CRC cells was assessed in vitro and in vivo. Statistical significance of efficacy was evaluated by t-test.
The large-scale expression analysis highlighted that about 10% of CRCs overexpress MSLN at levels comparable to those of ovarian cancer, a typical target of MSLN-CAR-based therapy. Intriguingly, MSLN overexpression is more frequent in the CRIS-B poor prognosis subtype and KRAS/BRAF-mutant CRC. Lentiviral transduction of NK-92 cells with the MSLN-CAR, followed by sorting and cloning, led to the identification of one clone, NK-92cl45, stably expressing the CAR and retaining the NK phenotype. As expected, the clone demonstrated significant in vitro and in vivo activity against ovarian cancer cells. When repurposed against models of CRC expressing high MSLN levels, it displayed comparable efficacy, both in vitro and in vivo. Specificity of NK-92cl45 was confirmed by the absence of activity on control models with low or absent MSLN.
Our results provide preclinical evidence that a subset of colorectal cancers expressing high mesothelin levels can be effectively targeted by MSLN-CAR-based immunotherapy. The potential therapeutic impact of these findings is enhanced by the fact that frequently MSLN-overexpressing CRCs display worse prognosis and resistance to standard care.
Citation Format: Erica Torchiaro, Marco Cortese, Alice D'Andrea, Consalvo Petti, Enzo Medico. Repurposing anti-mesothelin CAR-NK immunotherapy against colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB069.
Abstract LB080: iOTarg screening platform reveals novel mechanisms of colorectal cancer evasion from antigen-specific tumor cell killing by T cells
Authors: Michels Tillmann , Volpin Valentina , Amerhauser Carmen , Tschulik Claudia , Majunke Leonie , Weglarz Aleksandra , Baritz Kilian , Sudan Kritika , Bak-Kiss Szilvia , Huth Alina , Strobl Carolin , Turqueti-Neves Adriana , Khandelwal Nisit 
Published: April 2024

Abstract
While immune checkpoint therapies have revolutionized cancer treatment, their efficacy remains limited in colorectal cancer (CRC) and other malignancies. Tumors employ diverse strategies to evade immune-mediated destruction, hindering the success of immunotherapies. We introduce iOTarg, a robust high-throughput screening platform designed to uncover resistance pathways against T cell-mediated tumor killing within the tumor microenvironment. Focusing on CRC, we utilized iOTarg to dissect evasion mechanisms against antigen-specific T cell (TC) killing. In a representative CRC cell line co-culture system (SW480, HCT116 or COLO-678) with various TC sources, we gained key insights of tumor resistance towards killing. Survivin-specific TCs induce strong tumor lysis while tumor-infiltrating lymphocyte 412 (TIL412) represent a weaker basal killing representative of the situation in the tumor. Knockout of β₂-microglobulin abrogated TC-mediated killing, while c-FLIP knockout significantly enhanced tumor lysis. Intriguingly, PD-L1 blockade had no impact on TC activation or killing, underlining its lack of efficacy in CRC. Screening over 6000 druggable genes revealed several critical candidates, including anti-apoptotic BIRC family members (BIRC2, 3), apoptosis regulators (Bcl-xL, XIAP), TNF signaling regulators (TRAF2, MAP3K7), and genes recently described as sensitization mediators (B3GNT3, CHMP4B). Caspase-8 knockout prevented TC-mediated killing of CRC cells, confirming its crucial role in immune-mediated tumor cell clearance. Further validation in secondary screenings reinforced a subset of genes as strong regulators of tumor cell killing, uncovering an array of CRC resistance mechanisms. Our findings present a pioneering platform delineating resistance mechanisms against T cell-mediated colorectal tumor killing. We identify established and novel targets, offering prospects for novel therapeutics and expanding immune oncology treatment options. This platform holds promise for developing first-in-class therapies targeting the tumor microenvironment, potentially transforming CRC treatment paradigms.
Citation Format: Tillmann Michels, Valentina Volpin, Carmen Amerhauser, Claudia Tschulik, Leonie Majunke, Aleksandra Weglarz, Kilian Baritz, Kritika Sudan, Szilvia Bak-Kiss, Alina Huth, Carolin Strobl, Adriana Turqueti-Neves, Nisit Khandelwal. iOTarg screening platform reveals novel mechanisms of colorectal cancer evasion from antigen-specific tumor cell killing by T cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB080.
Abstract LB166: Discovery of CT3021, a novel potent adenosine A2a/A2b/A1 receptor triple antagonist
Authors: Han Sandong , Kim Nam Hee , He Hongmei , Chu Zhi Liang 
Published: April 2024

Abstract
In a CD73-positive tumor microenvironment (TME), ATP released from apoptotic tumor cells converts to adenosine, generating an adenosine-rich immunosuppressive environment. Adenosine activates G-protein coupled receptors expressed on immune cells to achieve immune suppression, with a mechanism of action involving 1) dampening antitumor effector cells (T eff and NK cells) via adenosine engagement on A2a receptor, (2) reducing dendritic cell antigen presentation and promoting MDSC differentiation by activating A2b and A2a receptors, and (3) inducing chemotactic migration of immature plasmacytoid dendritic cells to infiltrate tumor tissue via A1 receptor. Furthermore, A1 receptor expression in certain tumors mediates an adenosine-driven tumor cell proliferation, likely through A1 receptor Gi coupling to the Hippo-YAP signal transduction pathway. Thus, pharmacologic inhibition of A2a, A2b, and A1 receptors by a triple antagonist in the context of adenosine-rich TME may represent an attractive strategy to achieve a better outcome in treating solid tumors. We discovered and characterized a novel adenosine receptor antagonist CT3021. CT3021 exhibits high binding affinity to A2a, A2b, and A1, with a Ki value of 0.37 nM, 1.76 nM, and 1.26 nM, respectively, and is selective against the A3 receptor and other 84 pharmacologically and/or toxicologically relevant targets. Schild analysis demonstrated that CT3021 is a competitive antagonist with a calculated KB value of 0.18 nM on A2a receptor in a whole cell cAMP assay in transfected HEK293 cells. In functional antagonist assays, CT3021 maintains its high potency full antagonism under an adenosine-rich TME-like condition (10-100 µM adenosine) both in transfected HEK293 cells and in isolated human T lymphocytes. CT3021 has a high oral bioavailability, a limited CNS exposure, and a favorable ADME profile. CT3021 is well tolerated in rats after repeat dosing. Further toxicology and efficacy studies are underway to explore the potential of CT3021 as a best-in-class adenosine receptor antagonist immunotherapy for the treatment of CD73 positive and A1 receptor positive solid tumors.
Citation Format: Sandong Han, Nam Hee Kim, Hongmei He, Zhi Liang Chu. Discovery of CT3021, a novel potent adenosine A2a/A2b/A1 receptor triple antagonist [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB166.
Abstract LB175: Discovery of HP567, a highly potent, brain-penetrating, and H1047R-selective PI3Kα inhibitor for the treatment of tumors bearing H1047R mutation
Authors: Li Jing , Fan Lei , Liu Chengcheng , Luo Yao , Chu Xiaohui , Yu Hua , Wang Fei , Li Xinghai 
Published: April 2024

Abstract
The phosphoinositide 3 kinase (PI3K)-protein kinase B (PKB/AKT) is one of the most altered pathways in human cancer and its hyperactivation promotes tumor growth and survival. H1047R increases kinase activity and is the most common PI3Kα mutation with a mutation rate of 7.8% in all cancers, and 21%, 5% and 3% in breast cancer, endometrium, and ovarian cancer, respectively. Alpelisib is an FDA approved PI3Kα inhibitor targeting both wild-type (WT) and mutant PI3Kα, yet its clinical benefit is limited by the toxicities including hyperglycemia and rash (which are considered on target effects of WT- PI3Kα inhibition). Here, we report an allosteric and brain-penetrating PI3Kα inhibitor, HP567 that is 14-fold selective for PI3Kα H1047R over PI3Kα WT and is 80-fold selective over other PI3K isoforms. HP567 strongly inhibits proliferation and p-AKT (S473) in H1047R mutant cell lines with an average IC50 of 138 nM and 8 nM, respectively, and has no activity against PI3Kα WT cell lines. HP567 strongly inhibits growth of tumors bearing H1047R in multiple CDX models including breast cancers (MDA-MB-453, T47D, and CAL-148), ovarian cancer (SK-OV-3), tongue squamous cell carcinoma (CAL-33), and a brain-metastatic breast cancer (MDA-MB-453), without causing hyperglycemia or increases in plasma insulin levels. In conclusion, HP567 is a novel, potent, and brain-penetrating PI3Kα H1047R selective inhibitor. The pre-clinical data supports the clinical development of HP567 for the treatment of tumors bearing PI3Kα H1047R mutations. Structure of HP567 will not be disclosed.
Citation Format: Jing Li, Lei Fan, Chengcheng Liu, Yao Luo, Xiaohui Chu, Hua Yu, Fei Wang, Xinghai Li. Discovery of HP567, a highly potent, brain-penetrating, and H1047R-selective PI3Kα inhibitor for the treatment of tumors bearing H1047R mutation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB175.