bluuebunny/crossref_metadata_2025_split huggingface dataset:
EFFECTS OF PROLOTHERAPY WITH HYPERTONIC DEXTROSE IN PATIENTS WITH KNEE OSTEOARTHRITIS: A RANDOMIZED CLINICAL TRIAL
Authors: Sahebari Maryam , Mirfeizi Zahra , Noorabadi Parisa , Rezaieyazdi Zahra , Khodashahi Mandana , Hashemzadeh Kamila , Nobakht Zohreh , Dadgarmoghaddam Maliheh , Abbasi Bita , Amerizadeh Forouzan , Salari Masoumeh 
Published: March 2024

Background: The role of prolotherapy in the healing process of damaged tissues has been confirmed in patients with degenerative joint disease. Hypertonic dextrose has been introduced as the most common solution in prolotherapy for reducing pain and improving mobility in people with knee osteoarthritis (KOA). This study aimed to compare the KOA patients undergoing hypertonic dextrose prolotherapy (DPT) with the placebo in terms of pain intensity and functional level. Methods: This triple-blind study randomized clinical trial (RCT) was conducted on patients with mild to moderate KOA who were referred to the Rheumatic Diseases Research Center (RDRC), Mashhad University of Medical Sciences, Mashhad, Iran, in the year 2021. Patients were randomly assigned to two groups of the DPT ([Formula: see text] = 47) and normal saline placebo prolotherapy ([Formula: see text] = 50) intra- and peri-articular knee joints. Treatment was monthly for three months. Western Ontario and McMaster Universities’ Arthritis Index (WOMAC) and Anterior Knee Pain Scale (AKPS) were completed before and after intervention (weeks 0, 4, 8, 12, and 16). The variables were compared between the two study groups at a significance level of less than 0.05 ([Formula: see text] < 0.05). Results: The WOMAC score improved significantly compared to the baseline in both groups ([Formula: see text] < 0.005). An increase in WOMAC score (the last follow-up compared to baseline) was 97.4% and 85.7% in DPT and placebo groups, respectively ([Formula: see text]= 0.06). Before the intervention and also after the first injection, the AKPS score in the normal saline group was significantly better than the dextrose group ([Formula: see text]= 0.03). The AKPS score did not differ significantly between the two groups ([Formula: see text] > 0.05) in the next two visits and two-month follow-ups. Improvement of AKPS score in the last follow-up compared to baseline was reported in 66.7% and 68.4% of patients in the normal saline group and dextrose group, respectively, ([Formula: see text]= 0.86). Conclusion: Prolotherapy as intra- and peri-articular injections of hypertonic dextrose could be used to relieve pain and improve functional status in patients with mild to moderate KOA as much as a placebo does. Although no remarkable difference was observed between dextrose and placebo in the outcomes, the rate of improvement (last follow-up compared to the baseline) was relatively higher in the dextrose group than in the normal saline group.
Computational analysis of fractional kinetic equations having Bessel–Maitland function
Authors: Shukla Akanksha , Shekhawat Shalini , Modi Kanak 
Published: March 2024

This paper’s objective is to arrange fractional active conditions while taking into account the Bessel–Maitland capability reported by Khan et al. The solution’s final form is expressed in terms of the Wright hypergeometric function, which allows us to define numerous additional fractional kinetic equation solutions. Generally, fractional kinetic condition is applied to many problems in astronomy and material science.
Abstract 1012: Colorectal cancer in the American Indian and Alaska Native community: A holistic review
Authors: Monetathchi Angela R. , Carson William , Little Alyssa , Cordova-Marks Felina M. , Erdrich Jennifer 
Published: March 2024

Abstract
Colorectal cancer (CRC) is ranked third in the United States for both cancer incidence and mortality. Despite a decline in both categories, CRC continues to be a great concern in American Indian/Alaska Native (AI/AN) communities. AI/AN populations have also experienced the largest increase in early-onset colorectal cancer, have the second highest CRC incidence rates, and the AN community has the highest rates of CRC worldwide. AI/AN populations face numerous barriers and are susceptible to risk factors that may contribute to these findings. Currently, a significant amount of research is on screening efforts. Through conducting a literature review of 63 articles, as well as an additional 11 supplemental sources, this manuscript aims to look at several aspects of CRC including demographics, diet, screening, and the impact of geography. This review presents and organizes available research on CRC in the AI/AN population and explores research beyond screening because a more comprehensive and population-specific fund of knowledge on the totality of the subject is critical to directing more effective prevention, earlier detection, and management. Evaluating different components of CRC honors the holistic approach to health practiced by AI/AN communities.
Citation Format: Angela R. Monetathchi, William Carson, Alyssa Little, Felina M. Cordova-Marks, Jennifer Erdrich. Colorectal cancer in the American Indian and Alaska Native community: A holistic review [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1012.
Abstract 1054: Reciprocal circRNA-miRNA expression axes indicative of early tumor initiation in breast
Authors: Maatouk Nour Abbas , Marei Sarah Hussein , Kurdi Abdallah Bilal , Hamade Nadim Shady , Nasr Rihab Raif , Talhouk Rabih Shakib 
Published: March 2024

Abstract
Cancer prevention and early detection are the most effective tools for cancer control. In this study, we adopt a novel approach of identifying a network of proteins/mRNA-circRNA-miRNA axes. We hypothesize that mutation of oncogenes or tumor suppressor genes during pre-oncogenic stage result in aligned change in levels of circular RNAs-derived genes, as well as, reciprocally, in corresponding sponged miRNAs. These epigenetic risk predictive proteins/mRNA-circRNA-miRNA axes serve as potential tool for early detection of changes leading to breast cancer (BC) and can be further used as non-invasive screening biomarkers of patients’ blood in populations susceptible to cancer. BC patients in GDC Data Portal, TCGA-BRCA project are selected based on several criteria such as their age at diagnosis (20-50 years old), early clinical stage of cancer (stage I) and disease type (ductal and lobular neoplasms). Differentially expressed genes are acquired from mRNA sequencing data by comparing Stage I Breast cancer versus normal primary tissues using R Studio. Then, mRNAs whose expression is aligned with the differentially expressed circRNAs and their host genes acquired from Gene Expression Omnibus (GEO) (GSE182471, Triple Negative Breast cancer tissues versus normal tissues) are selected. Differentially expressed miRNAs, in reciprocal expression with circRNAs, are defined using miRNA sequencing data of the same previously chosen TCGA BRCA patients. Selected miRNAs are hypothesized to be sponged with high confidence by selected circRNAs based on a context percentile binding score in CircInteractome. Using KM Plotter, the survival analysis of corresponding miRNAs in grade I BC patients is examined. The predicted miRNA expression was correlated with lower survival rates among stage I BC patients in KM Plotter. MiRNA-enrichment analysis is used to further validate the involvement of selected miRNAs in early tumorigenic events through exploring in which molecular pathways their downstream genes are enriched. We have constructed more than 20 potential proteins/mRNA-circRNA-miRNA axes for non-invasive screening of patients’ body fluid (i.e. Blood) in populations susceptible to BC using RNA and miRNA sequencing data available in online databases and further validate the proposed axes using in-silico tools. The described axes, once validated in clinical samples could provide a potential tool for early-stage BC prediction and prevention.
Citation Format: Nour Abbas Maatouk, Sarah Hussein Marei, Abdallah Bilal Kurdi, Nadim Shady Hamade, Rihab Raif Nasr, Rabih Shakib Talhouk. Reciprocal circRNA-miRNA expression axes indicative of early tumor initiation in breast [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1054.
Abstract 1109: LINC01770 stabilizes TEAD1 expression to mediates nasopharyngeal cancer radiation resistance rendering tumor cells vulnerable to ferroptosis
Authors: Xu Qingqing , Sun Ciming , Zhang Suixian , Li Xuan , Chen Lei , Chen Ming 
Published: March 2024

Abstract
Background: Long noncoding RNAs (lncRNAs) regulate various essential biological processes, including cell proliferation, differentiation, apoptosis, migration, and invasion. However, in nasopharyngeal carcinoma (NPC), the clinical significance and mechanisms of lncRNAs in malignant progression are unknown.
Methods: LINC01770 expression was determined using quantitative real-time reverse transcription PCR, and its prognostic value was evaluated using Kaplan-Meier survival analysis. RNA sequencing and bioinformatic analysis were used to determine the potential function of LINC01770, and its biological effects were investigated using in vitro and in vivo experiments. Mass spectrometry-coupled RNA pull-down assays and western blotting identified LINC01770 interacting proteins, followed by confirmation using RNA immunoprecipitation (RIP) assays. Ferroptosis and lipid peroxidation were detected using flow cytometry.
Results: LINC01770 was overexpressed in NPC tissues according to microarray screening. Patients with NPC showing high LINC01770 expression experienced shorter survival and worse prognosis. In vitro and in vivo experiments suggested that knockdown of LINC01770 expression significantly inhibited the proliferation, migration, and invasion of NPC cells. Sequencing and functional complementation experiments showed that LINC01770 regulates the proliferation and metastasis of NPC through TEA domain transcription factor 1 (TEAD1). Meanwhile, RIP and PCR experiments suggested that LINC01770 and TEAD1 were common targets of microRNAs miR-615-5p and miR-1293. Overexpression of LINC01770 promoted ferroptosis in vitro and in vivo through the TEAD1/Acyl-CoA synthetase long chain family member 4 (ACSL4)/transferrin receptor (TFRC) pathway.
Conclusions: LINC01770 is a prognostic biomarker for NPC and participates in the regulation of TEAD1 signaling pathway through competitive binding to miRNA-615-5p and miRNA-1293, resulting in NPC metastasis and progression. Radiation resistant cells are in a delicate balance between lipid peroxidation and increased vulnerability to ferroptosis, suggesting that ferroptosis could be used to kill NPC cells and reverse their radiotherapy resistance during the malignant progression of NPC caused by high expression of LINC01770. Thus, inducing ferroptosis could be used to treat recurrent and refractory NPC.
Citation Format: Qingqing Xu, Ciming Sun, Suixian Zhang, Xuan Li, Lei Chen, Ming Chen. LINC01770 stabilizes TEAD1 expression to mediates nasopharyngeal cancer radiation resistance rendering tumor cells vulnerable to ferroptosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1109.
Abstract 1144: Glioblastoma cells increase expression of neurodevelopmental programs and synaptic connectivity in the tumor periphery
Authors: Harwood Dylan , Pedersen Vilde , Bager Nicolai S. , Schmidt Ane Y. , Stannius Tobias O. , Areskeviciute Ausrine , Josefsen Knud , Nørøxe Dorte S. , Scheie David , Rostalski Hannah E. , Lassen Ulrik , Bagger Frederik O. , Weischenfeldt Joachim , Heiland Dieter H. , Vitting-Seerup Kristoffer , Michaelsen Signe R. , Kristensen Bjarne W. 
Published: March 2024

Abstract
Glioblastoma remains one of the deadliest brain malignancies. First-line therapy consists of maximal surgical tumor resection, accompanied by concomitant and adjuvant temozolomide chemotherapy and radiotherapy. Malignant cells escape surgical resection by migrating into the brain parenchyma, where they give rise to the recurrent tumor. Based on gene expression, the tumor core can be subtyped into mesenchymal, proneural and classical areas, each being associated with differences in genetic alterations and cellular composition. In contrast, the tumor periphery where migrating tumor cells infiltrate brain parenchyma is less characterized in patients. Using spatial transcriptomics (n = 11), we show that specific malignant states colocalize in tumor core areas with necrosis and microvascular proliferation. Malignant cells within proneural or mesenchymal subtyped cores displayed, as expected, many differences in genetic expression, although such differences disappeared in the tumor periphery. Malignant cells residing in the tumor periphery had increased expression of genes related to neurodevelopmental pathways and synaptic connectivity. Our findings show similarities in cellular states across tumor subtypes with implications for post-operative treatment and provide an updated view of the spatial landscape of glioblastomas.
Citation Format: Dylan Harwood, Vilde Pedersen, Nicolai S. Bager, Ane Y. Schmidt, Tobias O. Stannius, Ausrine Areskeviciute, Knud Josefsen, Dorte S. Nørøxe, David Scheie, Hannah E. Rostalski, Ulrik Lassen, Frederik O. Bagger, Joachim Weischenfeldt, Dieter H. Heiland, Kristoffer Vitting-Seerup, Signe R. Michaelsen, Bjarne W. Kristensen. Glioblastoma cells increase expression of neurodevelopmental programs and synaptic connectivity in the tumor periphery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1144.
Abstract 116: Generation of humanized PD-1/PD-L1/CD94/NKG2A mice for evaluating novel combination therapies
Authors: He Fang , Yuan Jiangfeng , Shan Yawen , Bahetiyaer Huwatibieke , Xu Qingqing , Frame Jenna , Lin Qingcong , Zhou Xiaofei , Shang Chengzhang 
Published: March 2024

Abstract
NKG2A and its co-receptor, CD94, are expressed on the surface of NK cells, and function to send inhibitory signals to NK cells upon recognition of the HLA-E complex on adjacent cells. Blockade of the NKG2A/CD94 complex is a promising strategy for cancer immunotherapy, due to the potential to trigger NK-mediated tumor killing. Previously, we generated humanized NKG2A/CD94 mice for testing novel therapeutics targeting human NKG2A/CD94. To explore the potential that this complex could be targeted as part of a novel combination therapy, we crossed humanized NKG2A/CD94 mice with humanized PD-1/PD-L1 mice, which were previously engineered to express the extracellular regions of human PD-1/PD-L1. Flow cytometric data from splenocytes isolated from the quadruple humanized mice confirmed expression of human NKG2A and CD94 in NK cells and activated CD8 T cells, as well as PD-1/PD-L1 on the surface of T cells. To test the efficacy of antibodies targeting these checkpoints in vivo, B-hHLA-E plus/hPD-L1 MC38 colon cancer cells were subcutaneously implanted into the quadruple humanized mice and treated with antibodies targeting human NKG2A, human PD-L1, or both antibodies. Results indicate that the combination therapy significantly reduced tumor growth when compared to NKG2A single antibody treatment. Together, these data suggest that humanized PD-1/PD-L1/CD94/NKG2A mice are a validated model for further evaluation of novel combination therapies.
Citation Format: Fang He, Jiangfeng Yuan, Yawen Shan, Huwatibieke Bahetiyaer, Qingqing Xu, Jenna Frame, Qingcong Lin, Xiaofei Zhou, Chengzhang Shang. Generation of humanized PD-1/PD-L1/CD94/NKG2A mice for evaluating novel combination therapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 116.
Abstract 1195: Prospective study for the identification of nivolumab biomarkers via analyses of pre-treatment plasma exosome mRNAs from head and neck cancer patients (BIONEXT)
Authors: Masuda Muneyuki , Toh Satoshi , Matsuo Mioko , Sugasawa Masashi , Yamazaki Keisuke , Yushi Ueki , Nakashima Torahiko , Uryu Hideoki , Ono Takeharu , Ueda Tsutomu , Umeno Hirohito , Kano Satoshi , Tsukahara Kiyoaki 
Published: March 2024

Abstract
Nivolumab paved a new way in the treatment of recurrent or metastatic (RM) head and neck squamous cell carcinoma of (HNSCC). However, the limited rates of long-term survivors (&lt; 20%) demand a robust prognostic biomarker. This nationwide multi-centric prospective study aimed to identify a plasma exosome (PEX) mRNA signature, which serves as a companion diagnostic of nivolumab and as well provides a biological clue to develop effective therapies for a majority of non-survivors. Pre-treatment plasmas (N = 104) were subjected to comprehensive PEX mRNA analyses for prognostic marker discovery and validation. In parallel, paired treatment naïve tumor and plasma samples (N = 20) were assayed to elucidate biological implications of the PEX mRNA signature. A combination of 6 candidate PEX mRNAs plus neutrophil-to-lymphocyte ratio precisely (P = 0.000124) distinguished non-survivors from &gt;2-yr survivor (0% vs 57.7%) with a high hazard ratio (2.878; 95% confidence interval 1.639-5.055; P = 0.0002348). In paired samples, high PEX HLA-E mRNA (a non-survivor-predicting marker) reflected the increased HLA-E protein expression (P = 0.0191) and the dense population of tumor-infiltrating NK cells (P = 0.024) in the corresponding tumor. It is estimated that the effects of PD-1blockade is canceled by the HLA-E-NKG2A immune checkpoint in patients with high PEX HLA-E mRNA. The combination of NKG2A antibody (i.e., monalizumab) and nivolumab may be a promising strategy for non-survivors predicted by a RT-qPCR-based pre-treatment measurement of PEX mRNAs. A candidate companion diagnostic of nivolumab that indicates a possible treatment option is identified.
Citation Format: Muneyuki Masuda, Satoshi Toh, Mioko Matsuo, Masashi Sugasawa, Keisuke Yamazaki, Ueki Yushi, Torahiko Nakashima, Hideoki Uryu, Takeharu Ono, Tsutomu Ueda, Hirohito Umeno, Satoshi Kano, Kiyoaki Tsukahara. Prospective study for the identification of nivolumab biomarkers via analyses of pre-treatment plasma exosome mRNAs from head and neck cancer patients (BIONEXT) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1195.
Abstract 1205: Inferring allele-specific copy number aberrations and tumor phylogeography from spatially resolved transcriptomics
Authors: Ma Cong , Balaban Metin , Liu Jingxian , Chen Siqi , Ding Li , Raphael Benjamin J. 
Published: March 2024

Abstract
Tumors evolve through the acquisition of somatic mutations over time and across space. While the temporal aspects of tumor evolution can be inferred by applying phylogenetic techniques to bulk or single-cell DNA sequencing data, the spatial aspects of tumor evolution remain understudied. Spatially resolved transcriptomics (SRT) measures gene expression at thousands of spatial locations in a tumor, but does not directly measure genetic aberrations. Thus, SRT data has not yet been fully utilized for tumor evolution studies. We introduce CalicoST, an algorithm that simultaneously infers allele-specific copy number aberrations (CNAs) and derives a phylogeographic model of tumor evolution from SRT data. By modeling CNA-induced perturbations in both gene expression and allele frequencies, CalicoST identifies important types of CNAs - including copy-neutral loss of heterozygosity (CNLOH) and mirrored subclonal CNAs - that are invisible to total copy number analysis. On SRT data from nine patients from the Human Tumor Atlas Network (HTAN), CalicoST achieves an average accuracy of 86%, approximately 21% higher than existing methods. On two of these patients with multiple adjacent slices, CalicoST reconstructs a tumor phylogeography that describes the spread of cancerous clones in three-dimensional space. CalicoST analysis of multiple SRT slices from a cancerous prostate organ reveals five spatially coherent clones, with mirrored subclonal CNAs distinguishing clones on the two sides of the prostate, and a bifurcating phylogeography in both genetic and physical space that suggests a polyclonal cancer.
Citation Format: Cong Ma, Metin Balaban, Jingxian Liu, Siqi Chen, Li Ding, Benjamin J. Raphael. Inferring allele-specific copy number aberrations and tumor phylogeography from spatially resolved transcriptomics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1205.
Abstract 1216: Pan-RAS inhibition by a tumor-targeted biotherapeutic
Authors: Beilhartz Greg L. , Liang Huazhu , Udaskin Molly , Ng Christine , Radulovich Nikolina , Melnyk Roman A. 
Published: March 2024

Abstract
Oncogenic RAS signaling drives tumor growth in about 30% of human malignancies. In recent years the first mutant-specific inhibitors of KRAS G12C (sotorasib and adagrasib) entered the clinic. While some durable responses were noted in KRAS-mutant non-small cell lung cancer, the clinical experience of KRAS G12C inhibitors is marked by rapid drug resistance, either intrinsic or acquired, causing re-activation of the MAPK pathway. Common resistance mechanisms include compensatory signaling through the related RAS isoforms NRAS and HRAS, as well as the selection of non-G12C KRAS mutations, among others. The bacterial peptidase RRSP potently cleaves all RAS mutants and isoforms in the conserved Switch I region. We have shown that receptor-mediated intracellular delivery of RRSP using an engineered protein delivery system (RASx) can inactivate all RAS signaling in a cell, causing apoptosis in RAS-addicted tumor cells in vitro and in vivo. Since systemic pan-RAS inhibition is not likely to be tolerated therapeutically, precise tumor targeting is a necessary feature of a true pan-RAS inhibitor. Here, we describe the unique ability of the RASx system to specify the cell surface receptor used by RRSP to enter cells, allowing exquisite targeting and killing of KRAS, NRAS and HRAS-driven tumor cells while sparing healthy tissues. We screened a panel of patient-derived tumor organoids (PDOs), to demonstrate broad tumor cell killing across pancreatic and colorectal cancer-derived PDOs. 97% of KRAS mutant organoids were sensitive to RASx, independent of the specific mutation. Intriguingly, 46% of wildtype RAS PDOs were sensitive to RASx, including organoids with activating mutations in EGFR. In contrast, PDOs with mutations downstream of RAS such as BRAF V600E were resistant to RASx. Indeed, RASx is effective not only against RAS-addicted tumors, but also wildtype RAS tumors driven by upstream receptor tyrosine kinases, potentially expanding the clinical utility of this platform. RASx is a first-in-class, tumor-targeted pan-RAS inhibitor that represents a unique entry into the growing armamentarium against oncogenic RAS.
Citation Format: Greg L. Beilhartz, Huazhu Liang, Molly Udaskin, Christine Ng, Nikolina Radulovich, Roman A. Melnyk. Pan-RAS inhibition by a tumor-targeted biotherapeutic [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1216.