bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract IA005: PET imaging predictors of response to chemoradiotherapy in cervical cancer
Authors: Schwarz Julie K. 
Published: January 2024

Abstract
Although HPV transformed tumors are presumed to be radiation sensitive, approximately one third of locally advanced cervical cancer patients fail the current standard of care (concurrent cisplatin and radiation therapy). Work in our laboratory has combined the results of functional imaging with 18F-fluoro-deoxy-glucose positron emission tomography (FDG-PET) imaging together with bioinformatic analyses of associated translational correlates to define new predictors of resistance to DNA damaging therapies. Results of this work demonstrate that cervical tumors with increased FDG uptake on pretreatment FDG-PET imaging are characterized by myeloid predominant inflammatory infiltrates, including immature monocytes and macrophages. Co-culture of cervical tumor cells with macrophages is associated with increased glucose uptake and pro-survival signaling in tumor cells mediated through macrophage derived IL-6 and signaling through the JAK-STAT pathway. We are currently using a combination of single cell sequencing and spatially resolved approaches to further define PET associated and chemoradiation induced changes in cervix tumor cell metabolism and the immune tumor microenvironment with the goal of defining new targets for personalized therapies. Importantly, cervical cancers retain and transcribe portions of the HPV genome. At the end of the talk, we will review recent work in our lab that highlights the impact of HPV associated gene expression, including splice variants, on the response to DNA damaging agents.
Citation Format: Julie K. Schwarz. PET imaging predictors of response to chemoradiotherapy in cervical cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr IA005.
Abstract IA020: Micronuclei are a nexus of DNA damage signaling and genomic instability
Authors: Harding Shane M. 
Published: January 2024

Abstract
Micronuclei have classically been considered inert biomarkers of genomic instability arising from failed DNA damage repair and chromosome segregation errors in mitosis. Work from several groups including our own have now demonstrated that micronuclei are active contributors to the cellular response to DNA damage by driving chromothripsis and through induction of anti-viral gene expression programs mediated by the cGAS-STING pathway. We now show that the specific DNA damage type leading to micronuclei formation influences the capacity for cGAS localization and activation. This arises in part due to discrete chromatin features, present prior to DNA damage induction, that are retained in micronuclei several days after their formation. Together these data demonstrate that micronuclei connect the pre-damage chromatin status and the chromatin context of micronuclei-inciting lesions to the long-term signaling outcomes important for anti-tumor immunity. This finding implies that micronuclei represent archives for the nature of DNA repair failure and downstream signaling consequences. Based on this premise we will present our efforts in micronuclear proteomics where we uncover common features of micronuclei including splicing deficiencies. Such deficiencies presage exacerbated MN-associated DNA damage that is upstream of chromothripsis. These studies have direct implications for how cells sense the aftermath of DNA damage and how micronuclei contribute to ongoing genomic instability.
Citation Format: Shane M. Harding. Micronuclei are a nexus of DNA damage signaling and genomic instability [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr IA020.
Abstract IA022: Uracil DNA glycosylase activity limits deoxyuridine contamination in genomic DNA and is essential for the type-1 interferon response in cells treated with ATR kinase inhibitors
Authors: Pandya Pinakin , Vendetti Frank P. , Ghoubaira Joseph A. , Pathak Sudipta , Deppas Joshua J. , Jones Reyna E. , Zhang Yunqi , Ivanov Daniel , Buj Raquel , Aird Katherine M. , Beumer Jan H. , Sobol Robert W. , Bakkenist Christopher J. 
Published: January 2024

Abstract
Most chemotherapies target DNA replication, and their efficacy depends on the DNA damage response that integrates DNA repair with the cell cycle. Widely used standard-of-care antimetabolites inhibit thymidylate synthase and increase the incorporation of deoxyuridine (dU) into DNA by polymerases. Contamination of dU in DNA is limited by the DNA damage response kinase ATR that induces cell cycle checkpoints and reduces the rate of DNA replication. ATR inhibitors (ATRi) induce origin firing across active replicons and cause ribonuclease reductase degradation in otherwise unperturbed cells. This increases both the amount of DNA replication and the amount of free dUTP in cells. Thus, ATRi increase the incorporation of dU into DNA by polymerases. Since ATRi also inhibit cell cycle checkpoints, ATRi induce more dU contamination than antimetabolites. ATRi-induced dU contamination in DNA is associated with an innate immune response. We showed this with the simple observation that ATRi-induced dU contamination and IFN-α/β expression is reversed by low doses of thymidine. Here we show that ATRi-induced IFN-α/β response is dependent on uracil DNA glycosylase (UNG) which removes dU from DNA. Our data are consistent with a model in which UNG-dependent base excision repair (BER) removes dU from DNA, ultimately generating cytoplasmic dsDNA that induces IFN-α/β. We propose that ATRi-induced dU contamination contributes to dose-limiting leukocytopenia and inflammation in the clinic and CD8+ T cell dependent anti-tumor responses in mouse models of cancer treated with radiation therapy.
Citation Format: Pinakin Pandya, Frank P. Vendetti, Joseph A. Ghoubaira, Sudipta Pathak, Joshua J. Deppas, Reyna E. Jones, Yunqi Zhang, Daniel Ivanov, Raquel Buj, Katherine M. Aird, Jan H. Beumer, Robert W. Sobol, Christopher J. Bakkenist. Uracil DNA glycosylase activity limits deoxyuridine contamination in genomic DNA and is essential for the type-1 interferon response in cells treated with ATR kinase inhibitors [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr IA022.
Abstract PR008: Elucidating the mechanistic role of the MRE11-NDRG1 interaction in DNA repair and chemoresistance
Authors: Doh Hanna M , Kozlova Nina , Muranen Taru 
Published: January 2024

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with limited treatment options. PDAC patients are commonly treated with chemotherapeutic drugs to induce DNA damage in rapidly dividing tumor cells, however tumors frequently develop resistance to chemotherapies, underscoring the need for more effective therapeutic strategies. The DNA damage response (DDR) is required for detecting and repairing chemotherapy-induced DNA damage, and DDR alterations have been shown to contribute to chemoresistance. Another key factor driving chemoresistance in PDAC is the dense stroma, which is composed of a variety of non-tumor cell types including cancer associated fibroblasts (CAFs). We have recently identified a novel CAF-induced resistance mechanism involving NDRG1 (N-myc downstream regulated gene 1), a protein that plays a role in stress responses. CAF-induced signaling cascade results in the phosphorylation of NDRG1 and NDRG1-dependent DNA repair and protection from chemotherapies in pancreatic cancer cells. Specifically, inhibition of SGK1-mediated phosphorylation of NDRG1 and NDRG1 knockout both resulted in increased chemotherapy-induced DNA damage assessed via comet assay, and decreased replication fork speed and recovery after fork stalling assessed via DNA fiber spreading assay. To gain insight into the molecular mechanism of NDRG1-mediated DNA repair and replication, we performed a BioID screen to identify binding partners of NDRG1 and we have identified meiotic recombination 11 (MRE11), a nuclease involved in critical DNA repair pathways, as a novel binding partner of NDRG1. We have found that the interaction between MRE11 and NDRG1 is enriched during late S/early G2 cell cycle phases and under hydroxyurea-induced replication stress. Furthermore, we have found that the interaction is weakened when SGK1-mediated phosphorylation is inhibited. Interestingly, using the fork protection fiber spreading assay, we have found that blocking SGK1-mediated NDRG1 phosphorylation and blocking MRE11 exonuclease activity using mirin both result in increased protection of nascent DNA at stalled forks. However, in NDRG1 knockout cells, treatment with mirin leads to decreased protection of nascent DNA, suggesting that NDRG1 and MRE11 may be acting in the same pathway and that NDRG1 is required for MRE11’s activity at stalled forks. In summary, our work has uncovered a novel protein interaction that may play a key role in pancreatic cancer chemoresistance due to its role in the processing of stalled replication forks.
Citation Format: Hanna M Doh, Nina Kozlova, Taru Muranen. Elucidating the mechanistic role of the MRE11-NDRG1 interaction in DNA repair and chemoresistance [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr PR008.
The Legacy of Loet Leydesdorff to the Triple Helix as a Theory of Innovation
Authors: Amaral Marcelo , Cai Yuzhuo , Perazzo Anne Rocha , Rapetti Carina , Piqué Josep Miquel 
Published: January 2024

Abstract
This paper is an in memoriam tribute to the distinguished scholar Loet Leydesdorff written by some of his academic collaborators, including the editors of the Triple Helix journal and representatives of the Triple Helix Association. The paper revisits Loet Leydesdorff’s seminal contributions and legacy in innovation studies, particularly his work on the Triple Helix model and the measurement of Triple Helix synergies. Additionally, we highlight that Loet was not only a prolific author and outstanding scholar but also a humble person who played a crucial role in the community formed around Triple Helix ideas. The paper also serves as the editorial for the special issue of Triple Helix journal, titled “Legacy of Leydesdorff and the Triple Helix”.
Hippocampal region avoidance in whole brain radiotherapy in brain metastases: For all or for some? A real-world feasibility report
Authors: Corrao Giulia , Bergamaschi Luca , Eleonora Pierini Vanessa , Gaeta Aurora , Volpe Stefania , Pepa Matteo , Zaffaroni Mattia , Vincini Maria Giulia , Fodor Cristiana Iuliana , Piperno Gaia , Emiro Francesca , Ferrari Annamaria , Gandini Sara , Cattani Federica , Orecchia Roberto , Marvaso Giulia , Jereczek-Fossa Barbara Alicja 
Published: January 2024

Purpose: Hippocampal sparing whole-brain radiotherapy (HS-WBRT) showed significantly lower long-term side effects compared to standard WBRT. Aim of this study is to describe a HS-WBRT real-world monoinstitutional experience within a retrospective cohort. Methods: Patients who completed HS-WBRT course, with Karnofsky Performance Status ⩾ 60 and radiological diagnosis of brain metastases (BMs) were enrolled. Treatment was performed using helical Tomotherapy scheduled in 30 Gy in 10 or 12 fractions or 25 Gy in 10 fractions. Oncological outcomes were clinically and radiologically assessed every three months. Toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events 4.3. Results: One hundred and nineteen patients from 2016 to 2020 met inclusion criteria; after a median follow-up of 18 months, 29 patients were alive; 6- and 12-months overall survival rates were 66% and 41%, respectively. HS-WBRT response was assessed for 72 patients. Median time to any progression and intracranial failure (IF) was 4.5 and 13.7 months, respectively. The 6- and 12-month IF rates were 85% and 57%. Among 40 patients (34%) who experienced IF, 17 (42%) were oligometastatic, 23 (58%) polymetastatic and 15/40 developed IF within the hippocampi avoidance zone. No grade (G) ⩾ 2 acute toxicities were reported and one G2 (dizziness) late toxicity was described. Conclusions: HS-WBRT is well tolerated, and despite the hippocampal sparing region, the oncological control is satisfying. Further investigation is warranted to find patients who could most benefit from a HS-WBRT approach.
Artificial Intelligence Chatbots’ Understanding of the Risks and Benefits of Computed Tomography and Magnetic Resonance Imaging Scenarios
Authors: Patil Nikhil S. , Huang Ryan S. , Caterine Scott , Yao Jason , Larocque Natasha , van der Pol Christian B. , Stubbs Euan 
Published: January 2024

Purpose: Patients may seek online information to better understand medical imaging procedures. The purpose of this study was to assess the accuracy of information provided by 2 popular artificial intelligence (AI) chatbots pertaining to common imaging scenarios’ risks, benefits, and alternatives. Methods: Fourteen imaging-related scenarios pertaining to computed tomography (CT) or magnetic resonance imaging (MRI) were used. Factors including the use of intravenous contrast, the presence of renal disease, and whether the patient was pregnant were included in the analysis. For each scenario, 3 prompts for outlining the (1) risks, (2) benefits, and (3) alternative imaging choices or potential implications of not using contrast were inputted into ChatGPT and Bard. A grading rubric and a 5-point Likert scale was used by 2 independent reviewers to grade responses. Prompt variability and chatbot context dependency were also assessed. Results: ChatGPT’s performance was superior to Bard’s in accurately responding to prompts per Likert grading (4.36 ± 0.63 vs 3.25 ± 1.03 seconds, P < .0001). There was substantial agreement between independent reviewer grading for ChatGPT (κ = 0.621) and Bard (κ = 0.684). Response text length was not statistically different between ChatGPT and Bard (2087 ± 256 characters vs 2162 ± 369 characters, P = .24). Response time was longer for ChatGPT (34 ± 2 vs 8 ± 1 seconds, P < .0001). Conclusions: ChatGPT performed superior to Bard at outlining risks, benefits, and alternatives to common imaging scenarios. Generally, context dependency and prompt variability did not change chatbot response content. Due to the lack of detailed scientific reasoning and inability to provide patient-specific information, both AI chatbots have limitations as a patient information resource.
Outlier speakers and apparent effects: The case of variable subject placement in Spanish
Authors: Limerick Philip P. 
Published: January 2024

Aims and objectives: The current paper utilizes corpus data to examine variation and potential language contact effects regarding pronominal subject placement among first-generation immigrants in Atlanta, with particular attention paid to the individual speaker. The research questions that guide the study are the following: What linguistic and social predictors govern subject placement in Mexican Spanish spoken in Roswell, GA? What role, if any, does English contact play in the overall preverbal rates and/or constraints that govern subject placement? Do the data show any substantial individual differences with regard to rates of subject placement? If so, how might the inclusion versus exclusion of these speakers influence the overall interpretation of the results? Design and data: This study employs a variationist sociolinguistic framework, and the speakers comprise 20 first-generation Mexican immigrants living in Georgia. Analysis: Descriptive statistics are employed for purposes of overall as well as individual usage rates of postverbal subjects. In addition, linguistic (e.g., person/number, priming) and social predictors (e.g., sex, English proficiency, preferred media language) were incorporated into logistic regression analyses using Rbrul. Findings: Pronominal subject placement is most strongly influenced by person/number. Third-person singular pronouns favor postverbals while other pronouns favor preverbal position. Regarding social predictors, both sex and preferred media language appeared to play significant roles in the initial analysis; however, upon considering outlier speaker effects, the apparent effect of sex disappeared. The media language effect shows that those with a preference for English media favor preverbal subjects, suggesting a potential language contact effect. Originality and implications: The current study is the first to analyze this phenomenon in southeastern U.S. Spanish. The findings have implications for the study of language contact and change, demonstrating the importance of considering how individual speakers could misrepresent the overall data, interpretations of results, and conclusions in sociolinguistic studies of bilingualism.
A comparison of in situ and impedance eduction experimental techniques for acoustic liners with grazing flow and high sound pressure level
Authors: Bonomo Lucas A , Quintino Nicolas T , Spillere André M N , Murray Paul B , Cordioli Julio A 
Published: January 2024

Several techniques are available to characterize acoustic liners when subject to grazing flow and high sound pressure level (SPL). Although the in situ technique started as the primary experimental procedure, impedance eduction techniques have gained popularity over the past years. However, there is a lack of comparison between these group of methods, especially at conditions typically found in turbofan engines. In this work, in situ and impedance eduction techniques are compared at high flow velocities and SPL using typical acoustic liner test samples and considering uniform flow. Both upstream and downstream acoustic wave propagation will also be considered in view of the discrepancies recently observed by eduction methods. A new method to compensate the instrumentation effect in the in situ technique is proposed and validated. Results are obtained for bulk Mach numbers up to 0.5 and SPLs up to 145 dB for both in situ and two eduction techniques. The three methods presents good agreement in the absence of flow. Unexpected results are observed with higher flow Mach numbers using the eduction technique.
Single-Port Laparoscopic Extraperitoneal Repair of Pediatric Inguinal Hernias and Hydroceles by Using Hernia Crochet Needle With a Cannula
Authors: Lin Zhixiong , Yan Lei , Fang Zhihao , Wu Dianming , Liu Mingkun , Fang Yifan 
Published: January 2024

Purpose Numerous modifications laparoscopic techniques have mushroomed in recent years. Here we describe a modified technique of extracorporeal ligation of processus vaginalis in children using a hernia crochet needle with a cannula. Methods Processus vaginalis repair was carried out on patients diagnosed with inguinal hernia or hydroceles using this novel technique between June 2021 and June 2022. The processus vaginalis was closed extracorporeally using a hernia crochet needle with a cannula. In the presence of patent processus vaginalis, the same procedure would be performed on the contralateral side. The primary outcomes was the safety and efficiency of this modified procedure, and the secondary outcomes was the post operative complications. Results A total of 212 (165 inguinal hernia and 47 hydroceles) children were corrected by this novel technique. The mean operation time was 27.49 min for unilateral inguinal hernia cases and 36.55 min for bilateral cases. The unilateral hydrocele median operation time was 27.83 min and that for the bilateral cases was 37.30 min. During the mean of 10.92 months of follow-up, there was only a boy subject to a metachronous contralateral occurrence of hernia 10 months after surgery, and no other complications (knot reactions, testicular atrophy, postoperative hydrocele or iatrogenic) have been observed yet. Conclusion This study shown a unique procedure with using a hernia crochet needle with a cannula to be simple, safe, and effective in managing inguinal hernias and hydroceles in the pediatric population.
Género, infodemia y desinformación en salud. Revisión de alcance global, vacíos de conocimiento y recomendaciones
Authors: Moyano Daniela Luz , Agulló-Tomás María Silveria , Zorrilla-Muñoz Vanessa 
Published: January 2024

Objetivo: explorar el estado de la literatura científica sobre los aspectos de infodemia y desinformación en salud vinculados al género y a la interseccionalidad, detectar vacíos de conocimiento y brindar recomendaciones. Métodos: revisión de alcance global, con la detección de vacíos de conocimiento y recomendaciones. Se buscó en ocho bases de datos: MEDLINE (Pubmed), Anthropological Index Online, Studies on Women & Gender Abstracts, LILACS, Scielo, Global Index Medicus, Web of Science, Google académico y se hizo una búsqueda manual en Google de documentos de los últimos 10 años, sin restricciones de idioma y geográficas. Se realizó un análisis de contenido de los estudios incluidos. Resultados: 855 registros fueron identificados y 21 cumplieron con los criterios de inclusión. Predominan los estudios que tuvieron como primer autor/a una mujer (13/21), aunque en la autoría global se destacaron los hombres (10/21). El modelo binario fue el enfoque principal (16/21). La mayoría (18/21) se publicaron a partir del 2020. Se abordaron principalmente temas relacionados con la COVID-19 y la salud sexual y reproductiva (antes de la pandemia), y en menor medida la salud mental. Se identificaron interacciones entre diferencias de sexo/género en la desinformación/infodemia en salud especialmente en mujeres, colectivos de género diverso, personas mayores y población de bajo nivel socioeducativo. Conclusiones: existen brechas de conocimiento en el tema explorado, con escaso número de estudios, y limitaciones de alcances y del enfoque de género y/o feminista (más allá del binario). No obstante, los resultados tentativos constatan la presencia de inequidades de género e interseccionalidad en la desinformación en salud. Palabras clave: infodemia, desinformación, género, COVID-19, revisión sistemática