bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract IA04: Evaluating and mitigating medical misinformation risk in large language models
Authors: Chen Shan , Gao Mingye , Sasse Kuleen , Hartvigsen Thomas , Anthony Brian , Fan Lizhou , Gallifant Jack , Bitterman Danielle D. 
Published: January 2025

Abstract
Background: Large language models (LLMs) are increasingly used to generate medical content, yet their inherent design to follow user instructions may leave them vulnerable to producing misinformation. This risk becomes especially pronounced when LLMs generate incorrect medical information that could adversely affect human health. A propensity to comply with prompts, even when these lead to illogical or false information, highlights a critical gap in their safety, especially in high-stakes fields like healthcare. Methods: We evaluated the behavior of five LLMs—Llama3-8B, Llama3-70B, GPT4o-mini, GPT4o, and GPT-4-0613—by observing their compliance with prompts to generate misleading medical information. Specifically, the LLMs were prompted to suggest that a brand name drug was safer than its generic counterpart, a request with no basis in factual medical reasoning. We tested whether using prompt-based methods and instruction-tuning could enhance the models' ability to detect and resist generating content based on illogical premises. These safety approaches were evaluated in both medical and non-medical contexts to assess generalizability. Results: All five LLMs, despite accurately identifying the equivalence between brand and generic drugs, generated misleading medical content in response to overtly false prompts in over 50% of cases. Instruction-tuning and prompt-based techniques showed promise in reducing misinformation: models became better at detecting logical inconsistencies and were more likely to refuse requests that would result in misinformation, often providing explanations for their refusals. Furthermore, instruction-tuned LLMs showed improved safety behavior not only in medical contexts but also in non-medical domains without compromising performance on standard benchmarks. Conclusions: This study highlights a key vulnerability in LLMs: their tendency to comply with user requests even when it leads to medical misinformation. This compliance, particularly in generating content with flawed or incorrect logic, poses a significant safety issue for both individual and public health. The current safety and performance benchmarks for LLMs fail to account for this harmful behavior, underscoring an urgent need for new development approaches that prioritize logic and factual accuracy. Addressing this issue is essential to creating LLMs that are both useful and safe in medical and other high-stakes applications.
Citation Format: Shan Chen, Mingye Gao, Kuleen Sasse, Thomas Hartvigsen, Brian Anthony, Lizhou Fan, Jack Gallifant, Danielle D. Bitterman. Evaluating and mitigating medical misinformation risk in large language models. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr IA04
Abstract IA09: Radiotherapy immunotherapy interactions: What determines success or failure?
Authors: Weichselbaum Ralph R. 
Published: January 2025

Abstract
Radiation therapy (RT) can both stimulate antitumor immunity and induce immunosuppressive responses, complicating its therapeutic efficacy. Data indicate that certain patient subsets—such as those undergoing combination treatment with radiation and immune-oncology drugs and/or targeted therapies may benefit from strategies that target immunosuppression or metastasis-promoting factors. One of the key challenges is the heterogeneous and context-dependent nature of myeloid suppressive states in the tumor microenvironment, which often leads to resistance to RT and immunotherapy. RT has been shown to skew myeloid plasticity towards immune suppression by expanding myeloid-derived suppressor cell (MDSC) populations, increasing their trafficking into tumor tissues, and promoting the development of suppressive macrophage subsets. Targeting myeloid cell plasticity post-RT presents a promising therapeutic strategy. Interventions that block the systemic induction of immunosuppressive myeloid cells to inhibit their trafficking to tumors, or those that promote the conversion of suppressive myeloid cells into anti-tumor populations could enhance the effectiveness of RT. Additionally, radiation-induced proteins that can be inhibited or amplified may provide a potential avenue to overcome the limitations of RT alone, and in combination with immunotherapy.
Citation Format: Ralph R. Weichselbaum. Radiotherapy immunotherapy interactions: What determines success or failure?. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr IA09
Abstract IA11: FLASH – Where are we and where are we going in the clinical trial future space
Authors: Buchsbaum Jeffrey 
Published: January 2025

Abstract
FLASH is one of the most promising findings in radiation therapy in the last decade. If the FLASH effect takes place, it is thought that normal tissue is spared while tumor tissue is not spared. The biology of FLASH is not fully understood. Exactly when the FLASH effect occurs, if it occurs with every fraction delivered in the same way if it occurs at all, and how to test it in a clinical trial are the real questions that need to be addressed. All of these are complex issues that will be hard to study across OAR’s, populations, and technologies. The first part of the talk will review the published data on clinical trial needs including the quality assurance and other processes needed to open a trial with focus on the NCTN. IROC data and other data will be presented. The second part of the talk will be a review of the clinical data, and pre-clinical data, currently being collected and evaluated. Two P01 grants will be reviewed and discussed (their public components). The talk will conclude with some models for trials that have been proposed as well as a possible thought experiment looking at next steps and moving forward.
Citation Format: Jeffrey Buchsbaum. FLASH – Where are we and where are we going in the clinical trial future space. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr IA11
Abstract IA12: Enhancing radiation-induced anti-tumoral immune responses with PARP inhibitors in PDAC and DIPG
Authors: Morgan Meredith M. 
Published: January 2025

Abstract
Inhibitors of PARP sensitize cancers to radiation through mechanisms involving DNA damage, replication stress, and PARP trapping. These mechanisms may also activate innate immune signaling leading to Type I Interferon (T1IFN) production. The overall goal of this talk is to explore the hypothesis that PARP inhibitors potentiate radiation-induced T1IFN to activate an anti-tumoral immune response in pancreatic cancer (PDAC) and H3K27 altered-diffuse midline glioma (DMG). Preclinical data supporting this hypothesis will be described including the effects PARP1/2 inhibition (olaparib) as well as PARP1 selective inhibition (AZD5305, AZD4974) in combination with radiation on T1IFN production, modulation of the tumor microenvironment, and the contributions of CD8+ T and NK cells to anti-tumor immune responses in PDAC and DMG, respectively. Furthermore, the translation of these preclinical studies to early phase clinical trials will be discussed.
Citation Format: Meredith M. Morgan. Enhancing radiation-induced anti-tumoral immune responses with PARP inhibitors in PDAC and DIPG. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr IA12
Abstract P010: Monitoring of cancer ferroptosis with [18F]hGTS13, a system xc- specific radiotracer
Authors: Moses Abraham S. , Malek Rim , Kendirli Mustafa T. , Cheung Pierre , Landry Madeleine , Herrera-Barrera Marco , Khojasteh Abbas , Bukhari Syed , Hooper Jody , Hayden-Gephart Melanie , Dixon Scott J. , Recht Lawrence D. , Beinat Corinne 
Published: January 2025

Abstract
Ferroptosis has emerged as a significant process in cancer biology due to its ability to counteract mechanisms of tumor survival and drug resistance. Exploiting this vulnerability is an emerging therapeutic strategy in cancer treatment. System xc- plays a critical role in ferroptosis by regulating the availability of cysteine, a crucial precursor for glutathione synthesis, thereby influencing the cellular antioxidant defense system. We recently reported the development and validation of [18F]hGTS13, a radiolabeled glutamate derivative, as a novel radiopharmaceutical specific for system xc-. We characterized the sensitivity of various cell lines to pro-ferroptotic compounds and evaluated the ability of [18F]hGTS13 to distinguish between sensitive and resistant cell lines and monitor changes in response to ferroptosis-inducing drugs. We then correlated changes in tracer uptake with cellular glutathione content. Furthermore, we performed PET/CT imaging of C6 glioma-bearing rats with [18F]hGTS13, revealing high, sustained uptake within the intracranial glioma, and demonstrated effective blocking of system xc- in vivo using imidazole ketone erastin. In summary, [18F]hGTS13 represents a promising tool for distinguishing cell types that demonstrate sensitivity or resistance to ferroptotic therapies, and monitoring of ferroptosis-inducing drug engagement. Its successful application in preclinical models make it a valuable asset for advancing our understanding of glioma biology and evaluating the efficacy of emerging ferroptosis-targeted therapies. As synergistic ferroptosis/radionuclide therapies are currently under investigation, [18F]hGTS13 represents a valuable tool for identifying patients who would benefit from combinatorial therapy, and monitoring treatment response in glioma and other cancers.
Citation Format: Abraham S. Moses, Rim Malek, Mustafa T. Kendirli, Pierre Cheung, Madeleine Landry, Marco Herrera-Barrera, Abbas Khojasteh, Syed Bukhari, Jody Hooper, Melanie Hayden-Gephart, Scott J. Dixon, Lawrence D. Recht, Corinne Beinat.Monitoring of cancer ferroptosis with [18F]hGTS13, a system xc- specific radiotracer.[abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr P010
Abstract P019: Spatiometabolic mapping of cytoarchitectural changes in lung adenocarcinoma following radiotherapy
Authors: Bouchard Gina 
Published: January 2025

Abstract
Understanding how radiotherapy induces metabolic reprogramming and reshapes the cytoarchitecture of the tumor microenvironment (TME) is essential for improving treatment outcomes and overcoming resistance. Despite its importance, no studies have used computational tools to quantitatively assess these cytoarchitectural rearrangements in the TME following radiotherapy. In previous work, we developed a quantitative method called “colocatome analysis,” a spatial -omic approach that catalogs statistically significant colocalizations between pairs of cell subpopulations or states. Through a normalization process, this method enables direct comparisons of spatial features across different conditions, including comparisons between in vitro models and tissue samples. We applied colocatome analysis to multiplexed immunofluorescence images of lung adenocarcinoma specimens, examining differences between naïve and recurrent tumors following radiotherapy using a panel of markers that represent primary tumor compartments (endothelial, malignant, fibroblast, and immune) and include markers for the hexosamine biosynthesis pathway (HBP), glycans, key metabolic enzymes, proliferation, cell death, DNA damage, hypoxia, and EMT. Our preliminary results indicate significant cytoarchitectural differences: tumors that recurred after radiotherapy exhibited a lower epithelial-to-mesenchymal cancer cell ratio and were enriched in FAP+ cancer-associated fibroblasts (CAFs). Although the overall proportions of macrophages and other immune cells remained consistent across samples, their spatial organization differed. In naïve tumors, immune cells were largely segregated from cancer cells, while recurrent tumors showed a more homogeneous mixture of cancer and immune cells. Additionally, CAFs were markedly increased in recurrent tumors. Lastly, cancer cells in naïve tumors displayed high levels of O-GlcNAc, which significantly decreased in recurrent tumors. These findings provide insights into the impact of metabolic reprogramming towards HBP in the TME and highlight its potential role in mediating radioresistance.
Citation Format: Gina Bouchard.Spatiometabolic mapping of cytoarchitectural changes in lung adenocarcinoma following radiotherapy.[abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr P019
Apresentação
Authors: Iazzetta Fernando 
Published: January 2025

É com prazer que apresentamos este novo número da Revista Música. Depois de um processo de retomada do ritmo de publicações após a estabilização da pandemia da Covid-19, tivemos um aumento notável de submissões. Isso nos incentivou a fazer pequenas mudanças no processo editorial visando uma otimização da avaliação dos textos recebidos, tornando o processo mais criterioso, buscando manter a boa qualidade dos textos apresentados.
Este número traz vários artigos sobre aspectos diferentes da cultura musical brasileira, abordando temas como a capoeira, o samba, o carnaval, a cultura dos cocos e do bumba meu boi. Esse bloco se complementa com uma análise dos fã-clubes na projeção da popularidade de uma artista.
Um segundo bloco é composto de quatro textos voltados para a composição. Dois dos artigos trazem reflexões sobre a prática da criação contemporânea. Na sequência, outros dois textos promovem uma abordagem musicológica do campo. O primeiro traz a questão da retórica e da teologia na música Bach, enquanto o segundo coloca a produção de Villa-Lobos em perspectiva.
Fechando este número, temos uma instigante entrevista com Aylton Escobar, um dos músicos brasileiros mais criativos da sua geração.

Desejamos a vocês uma excelente leitura!
Taxonomy, distribution, and ecology of Impatiens violacea (Balsaminaceae) a steno-endemic species in Pettimudi, an area of endemism in southern Western Ghats, India
Authors: Arjun Thomas  , J. Jameson  
Published: January 2025

Impatiens violacea is a steno-endemic species in a valley in Pettimudi forest adjacent to Eravikulam National Park, Kerala, India. Taxonomic treatment, morphology, vertical distribution, ecology, phenology, ethnobotany, threats, and conservation status of the species are provided. Impatiens violaceae is a threatened species under the ‘Vulnerable’ category with substantial anthropogenic stress. The present study on endemic species in Pettimudi forest revealed 13 endemic species of the southern Western Ghats reside at area of (1.87 km2) in a U-shaped valley within the forest of Pettimudi, of which three species, namely, Impatiens violacea, I. johnii, and Cnemaspis anamudiensis were exclusively endemic to this valley whereas I. panduranganii to the Pettimudi forest. The findings suggest that the u-shaped valley in Pettimudi forest is an area of endemism (AoE) and a ‘hot speck’ within the Western Ghats, recognised as one of the global hotspots. Based on the study result, the authors recommend the u-shaped valley in Pettimudi forest be attached to the Eravikulam National Park territory to conserve the endemic species.
Nobiletin restores the intestinal barrier of HFD-induced obese mice by promoting MHC-II expression and lipid metabolism
Authors: Yang Ni , Pang Yue-Shan , Zheng Yali , Gong Yan-Ju , Ding Wei-Jun 
Published: January 2025

Abstract
The incidence of obesity is increasing annually worldwide. A high-fat diet (HFD) causes intestinal barrier damage, but effective interventions are currently unavailable. Our previous work demonstrated the therapeutic effect of nobiletin on obese mice; thus, we hypothesized that nobiletin could reverse HFD-induced damage to the intestinal barrier. Male C57BL/6 J mice were orally administered nobiletin for 14 d. After identification, the obese mice were equally divided into three groups: the HFD group, the low-dose (NOL, 100 mg/kg/d) group and the high-dose nobiletin (NOH, 200 mg/kg/d) group. A normal control group (CON) was also included. Hematoxylin and eosin (HE) staining and immunofluorescence were used to observe the intestinal barrier. RT-qPCR was used to determine the transcriptomic levels of genes involved in intestinal barrier integrity and lipid metabolism. The results revealed that intestinal tight proteins, including ZO-1 and Occludin, were significantly reduced in HFD-fed mice but markedly restored after nobiletin intervention, particularly in NOH mice. Improvements in the intestinal barrier and lipid metabolism associated with major histocompatibility complex class II (MHC-II) and relevant elements were revealed after nobiletin intervention. Enrichment analysis revealed that MHC-II plays an important role in the restoration of the intestinal barrier. Taken together, nobiletin restored intestinal barrier integrity and lipid metabolism by regulating MHC-II expression.
VEXAS, Chediak–Higashi syndrome and Danon disease: myeloid cell endo-lysosomal pathway dysfunction as a common denominator?
Authors: Savy Coline , Bourgoin Maxence , Cluzeau Thomas , Jacquel Arnaud , Robert Guillaume , Auberger Patrick 
Published: January 2025

Abstract
Vacuolization of hematopoietic precursors cells is a common future of several otherwise non-related clinical settings such as VEXAS, Chediak–Higashi syndrome and Danon disease. Although these disorders have a priori nothing to do with one other from a clinical point of view, all share abnormal vacuolization in different cell types including cells of the erythroid/myeloid lineage that is likely the consequence of moderate to drastic dysfunctions in the ubiquitin proteasome system and/or the endo-lysosomal pathway. Indeed, the genes affected in these three diseases UBA1, LYST or LAMP2 are known to be direct or indirect regulators of lysosome trafficking and function and/or of different modes of autophagy. Furthermore, all three genes are highly expressed in the more mature myeloid cells pointing out their likely important function in these cells. LAMP2 deficiency for instance is known to be associated with alterations of lysosome architecture and function. It is thus well established that different cell types from Danon disease patients that harbor invalidating mutations in LAMP2 exhibit giant lysosomes containing undigested materials characteristic of defects in the fusion of lysosomes with autophagosomes, a feature also found in VEXAS and CHS. Other similarities regarding these three diseases include granulocyte and monocyte dysfunctions and a recurrent inflammatory climate. In the present review we discuss the possibility that some common clinical manifestations of these diseases, notably the hematopoietic ones are consecutive to a dysfunction of the endo-lysosomal pathway in myeloid/erythroid progenitors and in mature myeloid cells including neutrophiles, monocytes and macrophages. Finally, we propose reacidification as a way of reinducing lysosome functionalities and autophagy as a potential approach for a better management of these diseases.
Early effects of LT3 + LT4 combination therapy on quality of life in hypothyroid patients: a randomized, double-blind, parallel-group comparison trial
Authors: Hajtalebi Fatemeh , Alaei-Shahmiri Fariba , Golgiri Fatemeh , Shahini Najmeh , Akbari Hamideh , Assadian Kasra , Mosalamiaghili Seyedarad 
Published: January 2025

Abstract

Background
This study aimed to evaluate the impact of combined levothyroxine (LT4) and triiodothyronine (LT3) therapy on quality of life in patients with primary hypothyroidism.

Methods
In a randomized, double-blind, parallel-group trial, 151 Iranian patients diagnosed with primary hypothyroidism between 2020 and 2021 were enrolled. One group received LT4 alone (n = 80), while the other received LT4 and LT3 (n = 71) for a minimum of six months. The primary outcome was quality of life assessed using the SF-36V1 questionnaire, and the secondary endpoints included clinical and laboratory measurements.

Results
In the LT4 + LT3 group, a significant reduction in TSH levels (p < 0.05) was observed compared to baseline. While no significant differences emerged between the groups in terms of blood pressure, lipid profiles (except for low-density lipoprotein cholesterol), or body weight, there were notable improvements in physical functioning and bodily pain in the LT4 + LT3 group compared to the LT4 + placebo group. Compared with baseline, combination therapy significantly increased the physical component summary score after six months, but the difference was not significant.

Conclusion
Combination therapy may benefit patients with primary hypothyroidism, particularly those experiencing body pain or physical function issues. However, the overall impact on quality of life remains inconclusive, as evidenced by the scores for the mental component. Further research is needed to determine the broader implications of this therapy. This study provides valuable insights into the potential advantages of combining LT4 and LT3 in the management of primary hypothyroidism.

Trial registration
The study was registered with the Iranian Registry of Clinical Trials (IRCT) and assigned the registration number IRCT20200410047012N1 on 2022–08-07.
Trial registration number: IRCT20200410047012N1.
Date of registration: 2020–06-12.