bluuebunny/crossref_metadata_2025 huggingface dataset:
Knowledge Structure and Emerging Trends of Mild Cognitive Impairment with Dyssomnias in Recent 20 Years: A Bibliometric Analysis via CiteSpace and VOSviewer
Authors: Huang Haoyu , Zhuang Zesen , Wan Yiwen , Shi Jiao , Yuan Xu , Wang Dan , Chen Shangjie
Published: January 2024

Background. Mild cognitive impairment (MCI), an intermediate stage between normal aging and dementia, has emerged as a prominent research area in geriatric care due to its heightened propensity for progressing toward dementia. Sleep plays a pivotal role in cognitive function, with dyssomnias not only exacerbating cognitive and affective symptoms associated with neurodegenerative diseases but also contributing to disease progression. Aim. This bibliometric analysis investigates the global research on MCI with dyssomnias over the past two decades, aiming to discern key findings, research domains, and emerging trends in this field. Methods. In this study, a bibliometric analysis was conducted using the search terms “MCI” and “sleep”. Data were extracted from the Web of Science Core Collection database, and visualization and collaborative analysis were performed using CiteSpace and VOSviewer. Results. This study encompassed 546 publications from 2003 to 2023. The publication volume and citation rate consistently increased over time. Neurosciences, Clinical Neurology, and Geriatrics Gerontology emerged as the top three research fields. The Journal of Alzheimer’s Disease had the highest publication count, while Sleep Medicine received the most citations. USA, China, and Italy led in publication output. Collaborative clusters among authors and institutions were identified, but cooperation between clusters was limited. Active cocited reference clusters included “obstructive sleep apnea”, “possible mediating pathways”, and “isolated rapid eye movement sleep behaviour disorder”. The top frequently mentioned keywords, besides “MCI”, were “Alzheimer’s disease”, “dementia”, “risk factor”, and “Parkinson’s Disease”. Notable keyword clusters spanned circadian rhythm, Parkinson’s disease, MCI, dementia with Lewy body, subjective cognitive impairment, Lewy body disease, Alzheimer’s disease, and dietary patterns. Conclusion. The field of MCI with dyssomnias is rapidly expanding, encompassing a wide range of neurodegenerative disorders and sleep disturbances. Current research endeavors are primarily focused on elucidating the underlying pathogenesis, predicting disease progression, and developing innovative treatment strategies for individuals affected by MCI with dyssomnias.
Acoustic Emission Characteristics and Initiation Mechanism of Instantaneous Rock Burst for Beishan Granite
Authors: Wang Chaosheng , Wan Hao , Ma Jianjun , Chen Xianglin
Published: January 2024

In this paper, the instantaneous rock burst test of Beishan granite is carried out by using a deep rock burst simulation test system and an acoustic emission monitoring system. The acoustic emission data were monitored in real time during the test. The variation of the number and energy of acoustic emission events was studied, and the distribution characteristics of rock burst debris were analyzed. Based on plate and shell mechanics, the failure process of surrounding rock is discussed from the perspective of structural stability. The results show that (1) when the vertical stress reaches 171.31 MPa, the specimen is destroyed and the number of acoustic emission events and cumulative absolute energy before the specimen is destroyed increase sharply. (2) The debris generated by rock burst is mainly composed of slab debris, flaky debris, and thin flaky debris, accounting for 93.53% of the total debris. (3) When the length or height of the rock slab is constant, the maximum tensile stress in the rock slab decreases nonlinearly with the increase of rock slab thickness. For the same size of the rock slab, the farther away from the roadway wall, the greater the maximum tensile stress in the rock slab. (4) When the thickness of the rock slab is constant, the maximum tensile stress in the rock slab increases nonlinearly with the increase of height to thickness ratio K. When the ratio of height to thickness K is constant, the maximum tensile stress in the rock slab increases with the increase of rock slab thickness h. (5) With the increase of covering depth, the critical failure thickness of the rock slab decreases nonlinearly and the surplus energy increases nonlinearly.
Colon Lipoma Causing Colo‐Colic Intussusception in an Adult: A Case Report from Tanzania
Authors: Suleiman Jamil , Suleman Mujaheed , Mremi Alex , Sadiq Adnan , Mohamedali Abbas , Machaku Dennis , Lodhia Jay
Published: January 2024

Intussusception is rarely seen in adulthood but is commonly seen in the pediatric age group. Causes of intussusception in adults are commonly due to tumors and inflammatory diseases. Intussusception in adults accounts for less than 5% of intestinal obstruction. Colonic lipomas are usually asymptomatic and are mostly managed surgically with promising outcomes as seen in our case.
Simulation of Radiation Damage and He Accumulation Induced by 10B(n, α)7Li Reactions in Al‐B4C Neutron Absorbers Used in Spent Fuel Pools
Authors: Kim Geon , Lee Myeongkyu , Jung Yunsong , Yoon Eisung , Ahn Sangjoon
Published: January 2024

Faster than expected surface corrosion and a considerable decrease in the 10B areal density of a non‐clad Al‐B4C neutron absorber were recently reported from surveillance coupons used in a spent fuel pool for about 8 years, which is only approximately one‐fifth of the guaranteed service life of the absorber. Such premature degradation was largely attributed to irradiation‐assisted corrosion since numerous gas bubbles filled with He and H were discovered in the Al alloy matrix near B4C particles, and naturally 10B(n, α)7Li reactions were designated as the underlying mechanism for the porosification that may have expedited the absorber corrosion. In this study, the levels of radiation damage and He concentration in the micrographs published in recent experimental studies were estimated to design ion beam irradiation experiments having appropriate parameters to emulate the status of neutron‐irradiated non‐clad Al‐B4C absorbers. TRITON, CSAS6, and SDTrimSP were coupled with modifications for the calculation of dpa and He concentration in irradiated neutron absorbers. The simulations yielded 3.74–6.71 dpa and 0.71–1.64 at% of He after 99 months of use and 3.82–8.39 dpa and 0.73–2.08 at% of He after 40 years of use. The simulations also demonstrated that the radiation damage and He concentration have a weak correlation with the particle diameter. In terms of radiation damage, these results are in good agreement with the reported experimental data, indicating that they can be referred to in the experimental design. The calculated He concentrations, however, may warrant modification to include leakage of implanted He atoms through irradiation‐induced microcracks in the B4C particles. Because of the high diffusivity of He, full leakage of He from B4C particles to their boundaries with the Al alloy matrix was assumed for further estimations, which revealed that He concentration could be significantly elevated in the Al matrix near B4C particles.
A Different, Nondestructive Method of Investigating In Situ Degradation in Hybrid Perovskite Solar Cells
Authors: Ugokwe Chikezie Williams , Gebremichael Zekarias Teklu , Ogunmoye Kehinde , Onwuzuroha Chibuike , Diegel Marco , Schubert Ulrich S. , Hoppe Harald
Published: January 2024

One of the most significant impediments to the upscaling of hybrid organic‐inorganic perovskite (HOIP) solar cells is poor stability. So, to effectively establish precautionary strategies, it is necessary to have a comprehensive grasp of the mechanisms that contribute to their degradation. Conventional characterization techniques used for in situ degradation assessment of perovskite solar cells either track just universal parameters, which yields poor insights about localized degradation processes, or the technique itself induces degradation, which may confound results. Developed in this study is a nondestructive technique of analyzing in situ active layer degradation in HOIP solar cells’ active layer utilizing a combination of optical modelling and ageing device’s reflectance tracking. The optical dielectric functions of the solar cell’s functional layers were modelled using the layers’ transmitted and reflected light spectra. The transfer matrix approach was used to fit the reflectance spectrum of entire solar cell layer stacks utilizing the computed dielectric functions for individual materials and accounting for the possibility of lead iodide gradient layer formation in the model. Leveraging no other characterization method, the presence of a lead iodide gradient layer was identified within the solar cell layer stack, an unmistakable indicator of methyl ammonium lead iodide perovskite (MAPI) degradation, probing with only photons.
Integrating Network Pharmacology and Metabolomics to Explore the Potential Mechanism of Pinolenic Acid against Atherosclerosis
Authors: Cao Zhanhong , Zhang Zhuang , Yang Qing , Fang Xingyu , Bai Haonan , Li Hui , Chen Shifan , Li Dianyu , An Yu , Liu Jian , Cheng Mengna , Sui Xin , Li Na
Published: January 2024

Atherosclerosis (AS) is a global disease that causes a heavy economic burden and can significantly impact human health. Pinolenic acid (PLA) has antioxidant, anti-inflammatory, and lipid-lowering effects. However, it is unclear whether PLA holds a therapeutic promise for AS treatment or prevention. This study aims to investigate whether PLA can effectively treat AS and elucidate its therapeutic mechanism. To this end, potential PLA targets in AS treatment were identified by using network pharmacology. Additionally, an in vitro AS cell model was established by H2O2-induced damaging of human coronary artery endothelial cells (HCAECs). Subsequently, endothelial cell function was evaluated by evaluating cell proliferation, oxidative markers, reactive oxygen species (ROS), and nitric oxide (NO) levels. Cellular metabolomics was further employed to assess differential intracellular metabolites following H2O2 injury. In total, 87 overlapping target genes for PLA and AS were detected. PPI network analysis identified 38 hub genes closely associated with oxidative stress and fatty acid metabolism. Moreover, PLA improved cell survival and reduced oxidative stress injury by activating the NRF2/ARE signaling pathway in vitro. Cellular metabolomics confirmed that PLA might help maintain redox homeostasis and reduce endothelial cell injury by upregulating fatty acid β-oxidation. Taken together, our findings suggest that PLA prevents H2O2-induced HCAEC injury by maintaining redox homeostasis and may, therefore, represent a therapeutic potential for AS.
Grewia tenax-Mediated Silver Nanoparticles as Efficient Antibacterial and Antifungal Agents
Authors: Yadav Priyanka , Singhal Monisha , Chatterjee Sreemoyee , Nimesh Surendra , Gupta Nidhi
Published: January 2024

Nanoparticles have gained immense interest as probable drug molecules against microbial infections. Metal nanoparticles synthesized via exploring the reduction potential and capping activity of plants were found to have remarkable antimicrobial activity. The synthesis was conducted without hazardous chemicals and generation of toxic waste products. The focus of the study was, therefore, to investigate the efficacy of silver nanoparticles biosynthesized using Grewia tenax leaf extract as an antibacterial, antibiofilm, and antifungal therapeutic agent. The silver nanoparticles (GTAgNPs) were synthesized using optimized conditions of 2.5 mM AgNO3 and 1 : 10 ratio of 10% extract at 37°C on continuous stirring. The characterization was done by UV-visible spectroscopy, DLS, SEM, zeta potential, and FTIR. The antibacterial activity of GTAgNPs against both Gram (+) Bacillus cereus and Staphylococcus aureus and Gram (−) Escherichia coli and Pseudomonas aeruginosa bacteria via zone of inhibition, MIC, and MBC was analysed. The inhibitory effect of silver nanoparticles on biofilm formation was also observed against these bacteria. These nanoparticles were then evaluated for their potential antifungal activity against Candida albicans and Aspergillus niger by observing fungal growth inhibition. The probable mechanism of antimicrobial activity by GTAgNPs was studied by scanning electron microscopy which showed the significant formation of pores on the cell surface in GTAgNPs-treated microbial cells, leading to the death of the microbial cell. All these studies concluded that GTAgNPs possess the potent antimicrobial potential and can be employed as antimicrobial therapeutic agents.
Point-of-Care Cardiac Ultrasound Training Programme: Experience from the University Hospital Hradec Králové
Authors: Grenar Petr , Nový Jiří , Mědílek Karel , Jakl Martin
Published: January 2024

Point-of-care ultrasound examinations performed by physicians of different specialties are a rapidly growing phenomenon, which has led to a worldwide effort to create a standardised approach to ultrasound examination training. The implementation of emergency echocardiography by noncardiologists is mainly aimed at the standardisation of the procedure, a structured training system, and an agreement on competencies. This article summarises the current training programmes for nonechocardiographers at the University Hospital in Hradec Králové. In cooperation with cardiologists specialised in cardiac ultrasound (ECHO), an extended acute echo protocol dedicated to emergency department physicians was developed and validated in daily practice. According to our retrospective evaluation, after one year of clinical practice, we can confirm that point-of-care ultrasound examinations performed using the standardised limited echo protocol are safe and accurate. The observed concordance with comprehensive ECHO was 78%. This trial is registered with NCT05306730.
Data from Direct Medical Spending on Young and Average-Age Onset Colorectal Cancer before and after Diagnosis: a Population-Based Costing Study
Authors: Garg Ria , Sayre Eric C. , Pataky Reka , McTaggart-Cowan Helen , Peacock Stuart , Loree Jonathan M. , McKenzie Michael , Brown Carl J. , Yeung Shirley S.T. , De Vera Mary A.
Published: January 2024

AbstractBackground:
Despite a better understanding of the increasing incidence of young-onset colorectal cancer (yCRC; age at diagnosis <50 years), little is known about its economic burden. Therefore, we estimated direct medical spending on yCRC before and after diagnosis.
Methods:
We used linked administrative health databases in British Columbia, Canada, to create a study population of yCRC and average-age onset colorectal cancer (aCRC; age at diagnosis ≥50 years) cases, along with cancer-free controls. Over the 1-year period preceding a colorectal cancer diagnosis, we estimated direct medical spending on hospital visits, healthcare practitioners, and prescription medications. After diagnosis, we calculated cost attributable to yCRC and aCRC, which additionally included the cost of cancer treatments (e.g., chemotherapy and radiotherapy) across phases of care.
Results:
We included 1,058 yCRC (45.4% females; age at diagnosis 42.4 ± 6.2 years) and 12,619 aCRC (44.8% females; age at diagnosis of 68.1 ± 9.2 years) cases. Direct medical spending on the average yCRC and aCRC case during the year before diagnosis was $6,711 and $8,056, respectively. After diagnosis, the overall average annualized cost attributable to yCRC significantly differed in comparison with aCRC for the initial ($50,216 vs. $37,842; P < 0.001), continuing ($8,361 vs. $5,014; P < 0.001), and end-of-life cancer phase ($86,125 vs. $61,512; P < 0.001) but not end-of-life non-cancer phase ($77,273 vs. $23,316; P = 0.372).
Conclusions:
Reported cost estimates may be used as inputs for future economic evaluations pertaining to yCRC.
Impact:
We provided comprehensive cost estimates for healthcare spending on young-onset colorectal cancer.
Abstract A016: LINC00261 is functionally linked to tumor DNA mutational burden and tumor immune microenvironment composition in lung adenocarcinoma
Authors: Castillo Jonathan , Xue Tianchun , Norwood Mayela , Joseph Samantha , Epstein Alan L. , Wallace W. Dean , Kim Anthony W. , Marconett Crystal N.
Published: January 2024

Immunotherapy has emerged as a breakthrough in the improvement of survival outcomes for lung adenocarcinoma (LUAD), however effective response requires the combination of blocking inhibitory signals on the tumor surface and antigen presentation to the tumor surface for proper immune recognition. Several commercially available and robust methods exist for identification of tumors displaying immune-inhibitory surface receptors, such as PD-L1, however it is currently difficult to predict effectiveness of antigen presentation on the cell surface. To address this, we utilized clinical and next-generation sequencing data from The Cancer Genome Atlas (TCGA) to identify gene signatures that are correlated to tumor mutational burden (TMB) within cancers of epithelial origins as a surrogate for neoantigen signatures. We identified LINC00261 as a top gene correlated to TMB, whose expression activates DNA damage response pathways in vitro along with resistance to cisplatin. LINC00261 expression was also significantly correlated to MHC class I and II genes involved in endogenous neoantigen presentation expression within the TCGA-LUAD cohort. This relationship was confirmed in vitro through ectopic reintroduction of LINC00261 for key MHC class II presentation genes. Interferon gamma-induced MHC gene activation in vitro was also able to induce endogenous expression of LINC00261. The staining of primary human lung cancer sections suggested that loss of LINC00261 is associated with an immunosuppressive tumor microenvironment. Taken together, our results suggest there is a mechanistic relationship in the silencing of LINC00261 in LUAD and compromised DNA repair, accumulation of mutations, and reduced antitumor immune response.

Citation Format: Jonathan Castillo, Tianchun Xue, Mayela Norwood, Samantha Joseph, Alan L. Epstein, W. Dean Wallace, Anthony W. Kim, Crystal N. Marconett. LINC00261 is functionally linked to tumor DNA mutational burden and tumor immune microenvironment composition in lung adenocarcinoma [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 A016.
Abstract A023: High glucose increases DNA damage and elevates the expression of multiple DDR genes
Authors: Rahmoon Mai A. , Elghaish Reem A. , Ibrahim Aya A. , Alaswad Zina , Gad Mohamed Z. , El-Khamisy Sherif F. , Elserafy Menattallah
Published: January 2024

The DNA Damage Response (DDR) pathways sense DNA damage and coordinate robust DNA repair and bypass mechanisms. A series of repair proteins are recruited depending on the type of breaks and lesions to ensure overall survival. An increase in glucose levels was shown to induce genome instability, yet the links between DDR and glucose are still not well investigated. In this study, we aimed to identify dysregulation in the transcriptome of normal and cancerous breast cell lines upon changing glucose levels. We first performed bioinformatics analysis using a microarray dataset containing the triple-negative breast cancer (TNBC) MDA-MB-231 and the normal human mammary epithelium MCF10A cell lines grown in high glucose (HG) or in the presence of the glycolysis inhibitor 2-deoxyglucose (2DG). Interestingly, multiple DDR genes were significantly upregulated in both cell lines grown in HG. In the wet lab, we remarkably found that HG results in severe DNA damage to TNBC cells as observed using the comet assay. In addition, several DDR genes were confirmed to be upregulated using qPCR analysis in the same cell line. Our results propose a strong need for DDR pathways in the presence of HG to oppose the severe DNA damage induced in cells.

Citation Format: Mai A. Rahmoon, Reem A. Elghaish, Aya A. Ibrahim, Zina Alaswad, Mohamed Z. Gad, Sherif F. El-Khamisy, Menattallah Elserafy. High glucose increases DNA damage and elevates the expression of multiple DDR genes [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 A023.
Abstract B031: Evaluating the consequence of homologous recombination deficiency in models of pediatric solid tumor
Authors: Savage Evan , Xu Ke , Myer Jason , Rampersaud Evadnie , Hui Yawei , Chang Ti-Cheng , Wu Gang , Tinkle Christopher , Shelat Anang
Published: January 2024

Homologous recombination deficiency (HRD) has been extensively studied in adult cancers where its association with sensitivity to Poly (ADP-ribose) polymerases (PARP) inhibitor sensitivity is well established. In these cancers, HRD is most frequently caused by biallelic inactivation of BRCA1/2 and tumors often exhibit characteristic genomic scars such as elevated HRD.sum score and specific mutational signatures derived from single nucleotide variants, insertions and deletions, and structural variants. Despite its clinical relevance, the therapeutic predictive value of HRD has not been systematically studied in pediatric cancers. Consequently, our team devised a strategy to identify and validate targetable deficiencies in DNA damage response (DDR) genes and assess genomic scars in pediatric tumors. Here, we report evaluation of HRD in a cohort of >200 patient-derived orthotopic xenograft models from the Childhood Solid Tumor Network (CSTN), a freely sharing resource established by our institution to accelerate the development of therapies for children with cancer. We provide an overview of our pipeline and discuss the landscape of genomic scars within our cohort. We profiled somatic and germline variants from over 500 DNA damage response genes and identified TP53 as the most frequently mutated gene with biallelic loss, whereas bi-allelic loss of BRCA1/2 was not found. Overall, our study suggests that HRD exists within solid tumors, but is driven by inactivation of genes other than BRCA1/2, resulting in a different set of genomic scars compared to those in adult cancers where HRD is common. Importantly, the CSTN contains models of pediatric solid tumors that are amenable to in vitro and in vivo interrogation, and therefore, will facilitate examination of the functional consequences of inactivated DDR genes, characterization of the unique genomic scar profiles underlying these inactivation events, and evaluation of novel therapeutic strategies.

Citation Format: Evan Savage, Ke Xu, Jason Myer, Evadnie Rampersaud, Yawei Hui, Ti-Cheng Chang, Gang Wu, Christopher Tinkle, Anang Shelat. Evaluating the consequence of homologous recombination deficiency in models of pediatric solid tumor [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 B031.
Abstract IA005: PET imaging predictors of response to chemoradiotherapy in cervical cancer
Authors: Schwarz Julie K.
Published: January 2024

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

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

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

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.
Data from The Oncolytic Activity of Zika Viral Therapy in Human Neuroblastoma In Vivo Models Confers a Major Survival Advantage in a CD24-dependent Manner
Authors: Mazar Joseph , Brooks Jeanne K. , Peloquin Matthew , Rosario Rosa , Sutton Emma , Longo Matthew , Drehner Dennis , Westmoreland Tamarah J.
Published: January 2024

Abstract
Neuroblastoma is the most common extracranial tumor, accounting for 15% of all childhood cancer-related deaths. The long-term survival of patients with high-risk tumors is less than 40%, and MYCN amplification is one of the most common indicators of poor outcomes. Zika virus (ZIKV) is a mosquito-borne flavivirus associated with mild constitutional symptoms outside the fetal period. Our published data showed that high-risk and recurrent neuroblastoma cells are permissive to ZIKV infection, resulting in cell type–specific lysis. In this study, we assessed the efficacy of ZIKV as an oncolytic treatment for high-risk neuroblastoma using in vivo tumor models. Utilizing both MYCN-amplified and non-amplified models, we demonstrated that the application of ZIKV had a rapid tumoricidal effect. This led to a nearly total loss of the tumor mass without evidence of recurrence, offering a robust survival advantage to the host. Detection of the viral NS1 protein within the tumors confirmed that a permissive infection preceded tissue necrosis. Despite robust titers within the tumor, viral shedding to the host was poor and diminished rapidly, correlating with no detectable side effects to the murine host. Assessments from both primary pretreatment and recurrent posttreatment isolates confirmed that permissive sensitivity to ZIKV killing was dependent on the expression of CD24, which was highly expressed in neuroblastomas and conferred a proliferative advantage to tumor growth. Exploiting this viral sensitivity to CD24 offers the possibility of its use as a prognostic target for a broad population of expressing cancers, many of which have shown resistance to current clinical therapies.
Significance:
Sensitivity to the tumoricidal effect of ZIKV on high-risk neuroblastoma tumors is dependent on CD24 expression, offering a prognostic marker for this oncolytic therapy in an extensive array of CD24-expressing cancers.
A imprensa Judaica de Livorno e a formação do Judaísmo Marroquino na Amazônia
Authors: Athias Renato
Published: January 2024

Este texto apresenta informações sobre a imprensa e a produção de livros em hebraico, a sua disseminação em vários lugares importantes, onde se entrevê a formação e institucionalização do judaísmo hispano-português na Europa, principalmente após a expulsão dos judeus da Península Ibérica, bem como servira de base para a formação do Judaísmo marroquino na Amazônia Ao problematizar essa institucionalização da produção gráfica de livros judaicos, percebe-se uma relação com a consolidação do Judaísmo marroquino na Amazônia, buscando também apontar observações a partir da realidade amazônica coletadas através de entrevistas com personalidades-chave no judaísmo marroquino na Amazônia. Livorno representou o lugar catalizador, do modus vivendi para o desenvolvimento do judaísmo sefardita na grande diáspora.
Dos números à história: um relato pessoal de refugiados do Nazismo no Brasil
Authors: Krausz Luis Sergio
Published: January 2024

Resenha da obra: GLASBERG, Rubens. Os indesejados: uma história de refugiados no tempo do nazismo. São Paulo: Editora Terceiro Nome, 2023.
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

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”.
Quantized guaranteed cost dynamic output feedback control for uncertain nonlinear networked systems with external disturbance
Authors: Huang Juan , Tang Xiaoming , Xia Zidi , Wei Na , Tan Cheng
Published: January 2024

In this article, the guaranteed cost control problem for a class of nonlinear networked control systems (NCSs) with dynamic quantization, external bounded disturbance, and data dropout is investigated via the dynamic output feedback. The Takagi–Sugeno (T-S) fuzzy model is used to represent the discrete-time nonlinear system discussed in this paper. Under the dynamic quantization strategy, two quantizers with dynamic parameters are used to quantize the measured output and control input, and the data dropout process is described by introducing the Bernoulli stochastic variable. By using the quadratic boundedness technique, the quadratic stability of the quantized NCS with external disturbance is described. Furthermore, the sufficient condition for the global design approach are proposed, that is, not only the dynamic output feedback controller but parameters of the quantizers are designed synchronously with strict linear matrix inequalities. Eventually, a simulation of nonlinear mass-spring-damper mechanical system is carried out to verify the effectiveness of the provided algorithm.
Simultaneous attitude fault detection and control of the six-rotor UAV based on event trigger mechanism
Authors: Huang Qingnan , Zhang Enze , Dai Xisheng , Qi Jingru , Wu Qiqi
Published: January 2024

This paper analyzes the problem of simultaneous fault detection and control of the six-rotor unmanned aerial vehicle control system, considering external disturbance, measurement disturbance, and actuator fault. The integral event trigger mechanism is introduced in the control side and sensor side of the system. Based on Lyapunov stability and H∞ control theory, the sufficient conditions to make the fault system asymptotically stable and have certain performance indexes are given by means of linear matrix inequalities; at the same time, the design criteria of event trigger parameters are also given. The linear matrix inequality is decoupled, and the calculation method of gain matrix of simultaneous fault detection and control module is given. The effectiveness of the proposed method is verified by simulation experiments.
Predefined-time sliding mode control based on exact time disturbance observer for second-order systems with matched and mismatched disturbances
Authors: Cai Zhongze , Sun Guhao , Zeng Qingshuang
Published: January 2024

This paper’s primary motivation is to present a globally predefined-time sliding mode control (PtSMC) strategy to stabilize a class of second-order systems subjected to matched and mismatched disturbances. To achieve this, the paper proposes a new exact time disturbance observer (DOB) based on a terminal time regulator, which accurately estimates the disturbances within a prescribed time, effectively preventing the system state from escaping to infinity due to high gains and overestimation. In addition, a new predefined-time sliding mode variable with the estimation of DOB is developed to ensure a predefined-time convergence on the sliding mode phase against mismatched disturbances. The proposed DOB-based technique can alleviate the chattering resulting from the use of an overestimated gain, in contrast to the controller without employing a DOB. Furthermore, a predefined-time reaching law is introduced to guarantee a global predefined-time convergence. This paper establishes the stability of the disturbed second-order system under the proposed controller through strict Lyapunov analysis. The novelty of the proposed method lies in its global predefined-time convergence, chattering-reduced properties and robustness against matched and mismatched disturbances. Finally, numerical simulations and application examples validate the proposed methodology’s effectiveness.
Prescribed-time leader-following consensus and containment control for second-order multiagent systems with only position measurements
Authors: Ren Yuanhong , Li Zhiwei , Sun Yuqing
Published: January 2024

The problems of prescribed-time leader-following consensus and prescribed-time containment control for double-integrator multiagent systems (MASs) with only position measurements are investigated in this paper. An observer-based prescribed-time control protocol is proposed, in which the two groups of observers for estimating the consensus errors of each follower both converge to zero within a specified time. Furthermore, the proposed controller only relies on its own observers and does not need to obtain the data from observers embedded in its neighbor nodes. The sufficient conditions for the MASs to achieve the defined prescribed-time consensus and to fulfill the goal of prescribed-time containment control are, respectively, given. The effectiveness of the proposed control protocol is further verified by computer simulations.
LuGre model–based robust adaptive control for a pump-controlled hydraulic actuator experiencing friction
Authors: Wang Bing-Long , Cai Yan , Song Jin-Chun , Sepehri Nariman
Published: January 2024

In this paper, a LuGre model–based robust adaptive control (RAC) approach is presented for a pump-controlled hydraulic actuator. We first decompose the LuGre friction model into its steady-state model and a lumped dynamic part applying the mean value theorem, which are compensated by a feedforward term and a robust adaptive term, respectively. The robust adaptive term also plays a part in mismatched disturbance attenuation. In addition, parametric uncertainties and matched disturbances are handled by σ-modified adaptation laws and a robust control law, respectively. The stability of the closed-loop system is proved via the Lyapunov analysis. The efficacy and robustness of the proposed approach are validated by comparative experiments. Compared with common adaptive friction compensation methods, the proposed method has a simpler structure, less computational burden, better control performance, and stronger robustness. Moreover, since the available information is separated from the LuGre model and acts as a model-based compensation term, the design conservativeness of RAC is effectively reduced.
Event-triggered finite-time neural control for uncertain nonlinear systems with unknown disturbances and its application in SVC
Authors: Pi Wenbo , Liu Wenhui
Published: January 2024

In this article, an event-triggered finite-time neural control strategy is proposed for nonlinear power systems with unknown disturbances and static var compensator (SVC). We first transform the power system with SVC into a three-dimensional uncertain nonlinear system and then extend it to an [Formula: see text]-dimensional uncertain nonlinear system. The disturbance observer is established to estimate external disturbances and the unknown nonlinear terms are approximated by the radial basis function neural networks. Moreover, to avoid the complexity explosion problem in the traditional backstepping method, the command filtering technique is adopted, and the error caused by the command filters is compensated. The adaptive event-triggered finite-time controller ensures that all signals are bounded in finite time and excludes Zeno phenomena. In the end, the simulation for the two-area interconnected power system with SVC is presented to verify the availability and feasibility of the proposed approach.
Passing on the “whistle”: Users’ creative engagement with platform censorship in an online relay campaign in China
Authors: Wu Xiaoping
Published: January 2024

The advances and proliferation of social media technologies have not only empowered Chinese users with more opportunities for opinion expression and public participation, but also provided the censors with increasingly sophisticated means to monitor and control the public discourse. In this game of cat and mouse, Chinese censors and users are intertwined with each other as new forms of censorship and counter-censorship stimulate both sides to further develop tactics to compete with each other. Drawing on (social) media discourse analysis, this study examines the strategies users adopted in an online relay campaign to keep a censored article alive on WeChat Public Accounts. The analysis highlights three major forms of creative strategies including textual reproductions, multi-semiotic and multimodal reproductions, and technically encoded forms. It also underscores platform censorship as a particular level of censorship where the platform takes responsibility for removing sensitive or perceived sensitive posts and content. This study adds to the growing literature that examines creative strategies of censorship engagement and a more nuanced understanding of the multi-layered online censorship mechanism in China.
Longitudinal associations among adult attachment orientations, emotion regulation tendencies, and transdiagnostic anxiety and depression symptoms in young adults
Authors: Metts Allison V. , Zinbarg Richard E. , Nusslock Robin , Tabak Benjamin A. , Craske Michelle G.
Published: January 2024

Adult attachment orientations can influence emotion regulation. Such influence on the tendency to employ two strategies, cognitive reappraisal (which aims to modify emotional experiences) and expressive suppression (which inhibits emotional expression) and later symptoms is understudied. This longitudinal study evaluated indirect associations between adult attachment orientations—with a focus on the dimension of security—and transdiagnostic anxiety and depression symptoms (General Distress; GD) through reappraisal and suppression. Correlational analyses examined cross-sectional associations among constructs across four timepoints. A cross-lagged panel model was fit to examine prospective hypotheses using 30-month longitudinal data from young adults ( N = 270 at baseline). Correlational evidence provided support for expected cross-sectional associations. In prospective analyses, there was a significant unique effect of attachment-related avoidance on expressive suppression such that higher attachment-related avoidance predicted higher use of subsequent expressive suppression. There were significant unique effects of emotion regulation on symptoms such that higher reappraisal predicted lower subsequent GD and higher suppression predicted higher subsequent GD. There was no evidence for significant direct or indirect effects of attachment orientations on GD. Results suggest that adult attachment orientation may inform how one expresses emotions in the future, and how one regulates emotions may inform subsequent shared symptoms of depression and anxiety. There was no evidence that attachment orientations informed future transdiagnostic symptoms of depression and anxiety.