bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B109: Drug repurposing for T315I mutation in CML through virtual screening and md simulation
Authors: Zulfiqar Nimra 
Published: February 2025

Abstract
Currently, many health incidentals are allocated to diagnosing and treating cancer. Even with the significant advancements in cancer research, there are still many challenges in treating the drug resistance issue. Drug resistance is typically the result of target molecular changes that cause non-response to recommended therapy. Drug resistance to TKIs can be increased by mutations in the kinase domain, impairing the effectiveness of treatment. In the same way, Chronic myeloid Leukemia (CML) is a tumor that obeys this rule. All relevant medicines target BCR-ABL since it has been demonstrated to play a key role in the pathogenesis of CML. Some alterations in the BCR-ABL, such as Y253H, and T315I, reduce the efficiency of treatments in patients. Therefore, more accurate and effective alternative therapies are urgently needed. To address this issue, we screened FDA-approved drugs by virtual screening, MD simulation, binding free energy calculations, ADMET assessment, and Toxicity prediction to identify new inhibitors for this mutant ABL1 protein. Research studies conclude that Tepotinib could inhibit the T315I mutant ABL1. Using this newly identified drug is not just a simple hypothesis in drug discovery. After a simple kinase selectivity assay, this drugs can be evaluated in phase 2 clinical trials. Notably, safety concerns underscore the potential of Tepotinib as a safer and potentially more effective alternative, pending successful phase 2 trial validation.
Citation Format: Nimra Zulfiqar1. Drug repurposing for T315I mutation in CML through virtual screening and md simulation [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr B109.
Abstract B113: Does targeted long read sequencing allow classification of tumor reactive T cells using predicTCR?
Authors: Neuhoff Marie-Therese , Green Edward , Tan Chin Leng , Platten Michael 
Published: February 2025

Abstract
Tumor-reactive T cells can be identified based on their transcriptomic profile using ML tools such as predicTCR. Sequencing cost remains high as single cell sequencing of not only the receptor information but also the whole transcriptome meaning &gt; 20k genes/cell is needed. Here we propose that targeted sequencing of only a minor fraction of the transcriptome may be sufficient to be able to classify a T cell as tumor reactive or not thus massively reducing sequencing cost. This is tested using targeted long read sequencing.
Citation Format: Marie-Therese Neuhoff, Edward Green, Chin Leng Tan, Michael Platten. Does targeted long read sequencing allow classification of tumor reactive T cells using predicTCR? [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr B113.
Abstract B120: Therapeutic cancer vaccine targeting the endogenous retroviral envelope protein ERVMER34-1 facilitates expansion of neoepitope specific T cells and improves responsiveness to PD-L1 blockade
Authors: Hamilton Duane H , Maldonado Maria , Gracia-Hernandez Maria , Donahue Renee N , Palena Claudia M , Schlom Jeffrey 
Published: February 2025

Abstract
Purpose: Endogenous retroviruses (ERVs) are remnants of retrovirus germline infections that occurred over the course of evolution and constitute between 5-8% of the human genome. While ERVs tend to be epigenetically silenced in normal adult human tissues, they are often overexpressed in carcinomas and may represent novel immunotherapeutic targets. However, therapeutic cancer vaccines targeting ERVs have not been assessed clinically. For the first time, this study characterizes the ERV envelope protein ERVMER34-1 as target for a therapeutic cancer vaccine. Experimental Design: The expression of ERVMER34-1 in multiple healthy adult and cancer tissues was assessed, as was its immunogenicity to ascertain whether specific T-cells could lyse human carcinoma cell lines expressing ERVMER34-1. Furthermore, the ability of a rationally designed ERVMER34-1 targeted therapeutic vaccine to induce tumor clearance in two murine carcinoma models expressing ERVMER34-1 was examined either as a monotherapy or in combination with immune-oncology agents. Results: The ERVMER34-1 protein is overexpressed in several types of human carcinomas while being absent in most healthy adult tissues. ERVMER34-1 specific T-cells were detected in PBMCs of cancer patients but not healthy donors following an overnight stimulation. However, reactive T-cells are readily expanded from both healthy donor and cancer patient PBMCs following a 7-day in-vitro stimulation. Furthermore, specific T-cells selectively kill human carcinoma cell lines expressing ERVMER34-1. A novel, rationally designed, therapeutic cancer vaccine targeting ERVMER34-1 mediated tumor control in established syngeneic murine tumors expressing ERVMER34-1 and promoted expansion of neoepitope-reactive T cells, which was enhanced when combined with rationally selected immune-oncology agents. Conclusions: This study supports the potential clinical development of a therapeutic cancer vaccine targeting the retroviral envelope protein ERVMER34-1, which would represent a new class of therapeutic cancer vaccine targeting ERVs.
Citation Format: Duane H Hamilton, Maria Maldonado, Maria Gracia-Hernandez, Renee N Donahue, Claudia M Palena, Jeffrey Schlom. Therapeutic cancer vaccine targeting the endogenous retroviral envelope protein ERVMER34-1 facilitates expansion of neoepitope specific T cells and improves responsiveness to PD-L1 blockade [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr B120.
Abstract IA02: Developing and manufacturing next generation cell therapies in the academic setting
Authors: Shy Brian R 
Published: February 2025

Abstract
The UCSF Investigational Cell Therapy Program streamlines preclinical development, regulatory interactions, and GMP manufacturing to accelerate the translation of cutting-edge cell and gene therapy technologies within the academic setting. This presentation will highlight our experience developing and manufacturing a range of experimental cellular therapies, leveraging next-generation genome and epigenome engineering strategies. I will showcase current and upcoming products incorporating targeted CRISPR-based approaches, multiplexed engineering, pooled T cell therapies, multi-receptor logic circuits, and platform technologies for rare diseases. Additionally, I will discuss the unique strengths and challenges of advancing these therapies in an academic environment and explore opportunities to expand access and bring these transformative treatments to more patients.
Citation Format: Brian R Shy. Developing and manufacturing next generation cell therapies in the academic setting [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr IA02.
Abstract IA03: Towards personalized minimally-invasive T-cell therapies
Authors: Gros Alena 
Published: February 2025

Abstract
Ex vivo expansion of tumor-infiltrating lymphocytes can lead to durable tumor regression in patients with metastatic melanoma. Accumulating evidence suggests that TIL frequently recognize neoantigens and that neoantigen reactive TIL play an important role in the antitumor responses of patients treated with immune checkpoint blockade and TIL therapy. These are optimal targets for cancer immunotherapy as their expression is exquisitely confined to the tumor site, and T cells targeting these antigens have not undergone negative selection in the thymus. Despite the promising efficacy of TIL therapy against melanoma tumors, current research in the field focuses on trying to extend this efficacy to other tumor types. We will discuss the existing possibilities to develop personalized T-cell therapies targeting neoantigens for solid cancers, with particular emphasis on minimally invasive T-cell therapies.
Citation Format: Alena Gros. Towards personalized minimally-invasive T-cell therapies [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr IA03.
Abstract IA06: Isotype-Switched Antibodies Produced in Tertiary Lymphoid Structures Antagonize Human Cancer Progression
Authors: Conejo-Garcia Jose R 
Published: February 2025

Abstract
Many epithelial cancers orchestrate prognostically significant intra-tumoral tertiary lymphoid structures (TLS), yet the mechanisms behind their antitumor activity remain unclear. Here we show that intra-tumoral TLS in human cancers contain highly oligoclonal B cells and plasma cells expressing IgA or IgG, which are not found outside the TLS. We demonstrate that these antibodies antagonize the progression of the autologous tumor. Accordingly, TLS enlargement and de novo formation in response to the injection of an oncolytic virus in muscle-invasive, cisplatin-ineligible bladder cancers is associated with complete clincial responses and the production of IgA and IgG antibodies at tumor beds. Our data show that TLS inhibit malignant progression through in situ production of isotype-switched anti-tumor antibodies , underscoring the importance of coordinated cellular and humoral responses in human cancer.
Citation Format: Jose R Conejo-Garcia. Isotype-Switched Antibodies Produced in Tertiary Lymphoid Structures Antagonize Human Cancer Progression [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr IA06.
Growth performance and carcass characteristics of Bonga sheep fed on noug seed cake, mulberry and Vernonia amygdalina leaf meal
Authors: Aleme M. , Mengistu G. , Tulu D. , Bogale A. , Walelign M. , Besufkad S. 
Published: February 2025

Abstract
The objective of this study was to evaluate the growth performance and carcass characteristics of the Bonga sheep supplemented with noug seed cake (NSC; Guizotia abyssinica) with dried mulberry leaf meal (DMLM; Morus indica) and higher protein Vernonia amygdalina leaf (DVLM) meal mixtures maintained on Desho (Penisetum glaucifolium) grass hay ad libitum. The five experimental diets were 100% NSC (T1), 75% DMLM+25% DVLM (T2), 100% DMLM (T3), 50% DVLM+25% NSC (T4) and 100% DVLM (T5). Thirty lambs at the age of eight months with an initial body weight (BW) 15.63±1.4 kg were assigned in randomised complete block design with six replications to each experimental diet. The intake of crude protein, ash, neutral detergent fibre, and acid detergent lignin were significantly (P<0.0001) different for animals fed T2, and dry matter intake (DMI), total dry matter intake (TDMI), total dry matter intake as % of body weight (TDMI %BW) and total dry matter intake of metabolic body weight was relatively higher for T3 (P<0.0001). There was a significant (P<0.05) effect on slaughter body weight among treatments which was higher for sheep fed T2 and T3, at 25.7 kg each. There was no effect (P>0.05) on other carcass traits, edible or non-edible offal components. Total DMI was strongly and positively correlated with carcass traits and crude protein intake was positively correlated with body weight. Total replacement with DMLM and the mix of 75% DMLM + 25% NSC with Desho grass hay can be used to give better growth performance and carcass yield of lambs.
Health Utilities in People with Hepatitis C Virus Infection: A Study Using Real-World Population-Level Data
Authors: Saeed Yasmin A. , Mitsakakis Nicholas , Feld Jordan J. , Krahn Murray D. , Kwong Jeffrey C. , Wong William W. L. 
Published: February 2025

Background Hepatitis C virus (HCV) infection is associated with reduced quality of life and health utility. It is unclear whether this is primarily due to HCV infection itself or commonly co-occurring patient characteristics such as low income and mental health issues. This study aims to estimate and separate the effects of HCV infection on health utility from the effects of clinical and sociodemographic factors using real-world population-level data. Methods We conducted a cross-sectional retrospective cohort study to estimate health utilities in people with and without HCV infection in Ontario, Canada, from 2000 to 2014 using linked survey data from the Canadian Community Health Survey and health administrative data. Utilities were derived from the Health Utilities Index Mark 3 instrument. We used propensity score matching and multivariable linear regression to examine the impact of HCV infection on utility scores while adjusting for clinical and sociodemographic factors. Results There were 7,102 individuals with hepatitis C status and health utility data available (506 HCV-positive, 6,596 HCV-negative). Factors associated with marginalization were more prevalent in the HCV-positive cohort (e.g., household income <$20,000: 36% versus 15%). Propensity score matching resulted in 454 matched pairs of HCV-positive and HCV-negative individuals. HCV-positive individuals had substantially lower unadjusted utilities than HCV-negative individuals did (mean ± standard error: 0.662 ± 0.016 versus 0.734 ± 0.015). The regression model showed that HCV positivity (coefficient: −0.066), age, comorbidity, mental health history, and household income had large impacts on health utility. Conclusions HCV infection is associated with low health utility even after controlling for clinical and sociodemographic variables. Individuals with HCV infection may benefit from additional social services and supports alongside antiviral therapy to improve their quality of life. Highlights Hepatitis C virus (HCV) infection is associated with reduced quality of life and health utility. There is debate in the literature on whether this is primarily due to HCV infection itself or commonly co-occurring patient characteristics such as low income and mental health issues. We showed that individuals with HCV infection have substantially lower health utilities than uninfected individuals do even after controlling for clinical and sociodemographic variables, based on a large, real-world population-level dataset. Socioeconomically marginalized individuals with HCV infection had particularly low health utilities. In addition to improving access to HCV testing and treatment, it may be beneficial to provide social services such as mental health and financial supports to improve the quality of life and health utility of people living with HCV.
Oculomotor deficits in children with sensory processing difficulties
Authors: Hodgson Timothy L , Cartwright Phoebe , Dodd Joseph , Hippisley Annabelle 
Published: February 2025

Background: Atypically developing children often present with a variety of sensory processing difficulties which have been proposed to reflect abnormal development of pathways integrating sensation and action. A brain system in which the process of sensorimotor integration is particularly well understood is the oculomotor system, but no studies to date have used computerised eye tracking to assess eye movements in children with sensory processing difficulties. Method: Ten children with sensory processing difficulties completed a battery of oculomotor tasks comprising pro-saccades, anti-saccades, smooth pursuit tracking and sustained fixation. Eye movements were recorded using a high-resolution eye tracker. Results: Compared to age-matched controls, children with sensory processing difficulties were found to make more directional errors in the anti-saccade task and less-accurate smooth pursuit and sustained fixation. Conclusion: Consistent differences were found in oculomotor ability in children with sensory processing difficulties which are likely to impact children’s ability to process and respond to visual information within home and school contexts. Further research is needed to understand the relationship between oculomotor deficits in children with sensory processing difficulties and the presence/absence of neurodevelopmental diagnoses. Eye tracking may be of value in the future for assessment and objective evaluation of interventions for sensory processing difficulties such as sensory integration therapy.
Localized paclitaxel delivery using a novel hyaluronic acid-coated fibrous carrier produced via needle-less electrospinning
Authors: Lubasova Daniela , Mayoral Safont Mireia , McCormack Emmet 
Published: February 2025

Pancreatic cancer remains one of the most challenging malignancies to treat due to its dense stromal microenvironment and resistance to conventional therapies. This study introduces a novel localized drug delivery system design to target residual cancer cells following surgery. Electrospun fibrous carriers were fabricated using needle-less electrospinning from polycaprolactone (PCL), silk fibroin (SF), and their blend. Among these, PCL carriers (average fiber diameter: 141 ± 28 nm) exhibited the highest and most sustained paclitaxel (PTX) release in vitro. Coating the PCL carrier with hyaluronic acid (HA) increased the fiber diameter to 535 ± 116 nm and modulated PTX release, shifting from an initial rapid release phase in uncoated carrier to a more gradual and sustained release over 120 hours. PTX-loaded HA-coated electrospun PCL carriers significantly reduced MiaPaCa cell viability, with only 13% viability at 96 hours compared to 22% for the non-coated carrier. This HA-coated electrospun PCL carrier offers a scalable and efficient solution for localized PTX delivery, providing sustained drug release, prolonged cytotoxic efficacy, and reduced off-target effects. Its industrial scaleability, combined with its potential for post-surgical pancreatic cancer management, presents an innovative approach to minimizing reliance on systemic chemotherapy and its associated toxicities. The use of needle-less NanospiderTM electrospinning technology further emphasizes its clinical potential, with future in vivo studies needed to confirm carrier’s safety, pharmacokinetics, and therapeutic benefits.
Efficacy and Safety of Herbal Medicine Bojungikki-Tang in Combination with Pembrolizumab versus Pembrolizumab Monotherapy for Stage IV Non-Small Cell Lung Cancer: Study Protocol for a Randomized, Open-Label, Double-Arm, Multicenter Trial
Authors: Cho Eunbyul , Yi Jin-Mu , Chun Jaemoo , Jang Ho , Yoon Seong Hoon , Lee Seung Hyeun , Jang Seung Hun , Park Dong Won , Kim Seung Joon , Um Sang-Won , Lee Sung Yong , Jeong Mi-Kyung 
Published: February 2025

Background: Non-small cell lung cancer (NSCLC) exhibits low survival rates. Although immune checkpoint inhibitors (ICIs) have become first-line treatment for NSCLC, their limited response to ICI monotherapy has led to exploration of combination treatments. However, the high incidence of treatment-related adverse events associated with conventional drug combinations has highlighted the need for alternative herbal therapy. Bojungikki-tang (BJIKT), a traditional herbal medicine, has been used to treat gastrointestinal disorders and enhance immune function. Our preclinical studies have demonstrated that BJIKT combined with anti-PD-1 or anti-PD-L1 antibodies exhibits significant efficacy in suppressing tumor growth by modulating the immunosuppressive tumor microenvironment. Building on these preclinical findings, this study aims to evaluate the efficacy and safety of BJIKT with pembrolizumab combination therapy compared to pembrolizumab monotherapy in advanced NSCLC patients. Methods: 70 individuals with stage IV NSCLC scheduled for first-line pembrolizumab monotherapy will be randomly assigned to intervention or control groups. The primary outcome will be progression-free survival, with secondary outcomes including disease control rate, overall survival, and quality of life assessment. Adverse events will be monitored for safety. This study will explore the synergistic mechanism of combinatorial therapy using immune profiling and multi-omics analysis, and the possibility for personalized integrative therapy based on cold-heat syndrome differentiation (SD) types in East Asian medicine. Discussion: This study will provide novel evidence regarding survival outcomes, quality of life, and safety profiles of combined ICI and BJIKT therapy for advanced NSCLC. The exploratory data will contribute to tailoring treatments to immune-based SD types in NSCLC patients.
Application of causal forests to randomised controlled trial data to identify heterogeneous treatment effects: a case study
Authors: Van Vogt Eleanor , Gordon Anthony C. , Diaz-Ordaz Karla , Cro Suzie 
Published: February 2025

Abstract

Background
Classical approaches to subgroup analysis in randomised controlled trials (RCTs) to identify heterogeneous treatment effects (HTEs) involve testing the interaction between each pre-specified possible treatment effect modifier and the treatment effect. However, individual significant interactions may not always yield clinically actionable subgroups, particularly for continuous covariates. Non-parametric causal machine learning approaches are flexible alternatives for estimating HTEs across many possible treatment effect modifiers in a single analysis.

Methods
We conducted a secondary analysis of the VANISH RCT, which compared the early use of vasopressin with norepinephrine on renal failure-free survival for patients with septic shock at 28 days. We used classical (separate tests for interaction with Bonferroni correction), data-adaptive (hierarchical lasso regression), and non-parametric causal machine learning (causal forest) methods to analyse HTEs for the primary outcome of being alive at 28 days. Causal forests comprise honest causal trees, which use sample splitting to determine tree splits and estimate treatment effects separately. The modal initial (root) splits of the causal forest were extracted, and the mean value was used as a threshold to partition the population into subgroups with different treatment effects.

Results
All three models found evidence of HTE with serum potassium levels. Univariable logistic regression OR 0.435 (95%CI [0.270, 0.683]. p = 0.0004), hierarchical lasso logistic regression standardised OR: 0.604 (95% CI 0.259, 0.701), lambda = 0.0049. Hierarchical lasso kept the interaction between the treatment and serum potassium, sodium level, minimum temperature, platelet count and presence of ischemic heart disease. The causal forest approach found some evidence of HTE (p = 0.124). When extracting root splits, the modal split was on serum potassium (mean applied threshold of 4.68 mmol/L). When dividing the patient population into subgroups based on the mean initial root threshold, risk differences in being alive at 28 days were 0.069 (95%CI [-0.032, 0.169]) and − 0.257 (95%CI [-0.368, -0.146]) with serum potassium ≤ 4.68 and > 4.68 respectively.

Conclusions
The causal forest agreed with the data-adaptive and classical method of subgroup analysis in identifying HTE by serum potassium. Whilst classical and data-adaptive methods may identify sources of HTE, they do not immediately suggest subgroup splits which are clinically actionable. The extraction of root splits in causal forests is a novel approach to obtaining data-derived subgroups, to be further investigated.