bluuebunny/crossref_metadata_2025 huggingface dataset:
Passenger origin–destination estimation in public transit using boarding count data
Authors: Saeidi Tara , Abolfazli Mostafa , Mehran Babak
Published: October 2024

Passenger boarding and alighting data are critical for understanding travel patterns in transit systems, yet many systems only record boarding, making it difficult to track alighting. This study introduces a method to estimate alighting counts from boarding data using transit symmetry at a cluster level. Bus stops are grouped into clusters, assuming equal inflow and outflow, and a gravity model is calibrated to estimate an origin–destination (OD) matrix. Using data from three bus routes in Regina, Canada (2017), the method achieved a symmetry ratio of 60% across clusters and a mean structural similarity measure score of 0.84, validating the accuracy of the OD estimates. This approach provides a practical solution to the challenge of missing alighting data. While effective for single-mode transit systems, future research will expand its application to multi-modal systems and address factors like seasonal and land-use variations, offering a cost-effective alternative for OD estimation.
Testing and results of an open-source radiation epidemiology model using the Goiânia accident
Authors: Quaranta Riccardo , Ludovici Gian Marco , Romano Luca , Manenti Guglielmo , Malizia Andrea
Published: October 2024

In the event of dispersed radioactive materials, whether from accidental orphan sources or deliberate use of radiological dispersal devices (RDD) or radiological exposure devices (RED), free open-source modelling codes can greatly assist in forecasting the dispersion of the radiation following the event. Several codes are currently available to quickly calculate the progression of radiological dispersion. However, most of these codes can only simulate the evolution of the threat for limited times after the event and over relatively short distances from the location. In order to predict the transport of radioactive material over long distances and for long times, and thus prevent its expected effects on the exposed population, specific epidemiological codes can be used, taking into account the characteristic of the radiation. If it is considered that radioactive material can be deposited on unsuspecting people who continue their daily activities after exposure, it can be assumed that these people unintentionally carry this radioactive material over long distances. This scenario is comparable to viral vectors of a hypothetical virus designed to mimic the physical characteristics of radiation. In this work, the free open-source spatio-temporal epidemiological modeller (STEM) tool is used to simulate the spread of a chimeric viral agent with specific characteristics of Ebola and COVID-19, designed to replicate the biological conditions caused by exposure to a Cs-137 source for an individual unaware of the risk. The goal is to predict the territorial spread of radioactive material caused by a CBRNe event, such as orphan sources or the use of a RDD or a RED, and its possible effects on the affected population. This supports decision-makers in forecasting the consequences of radioactive material spread and thus helps in reducing the risk. The code was tested comparing its results with the real case of the famous 1987 Goiânia radiological accident. The results show that the developed code was indeed able to accurately represent the number of contaminated individuals and the number of casualties within a month of the initial exposure, with a distribution of radioactive material in the territory similar to that actually caused by the Goiânia accident.
Accelerating Neural Network Inference in Handwritten Digit Recognition — Comparative Study
Authors: Thomas Winnie , Singh Virendra
Published: October 2024

In deep learning, one of the popular subclasses of multilayer perceptron is the Convolutional Neural Networks (CNNs), optimized for image and semantic segmentation tasks. With a large number of floating-point operations and relatively less data transfer in the training phase, CNNs are well suited to be handled by parallel architectures. The high accuracy of CNNs comes at the cost of consequential compute and memory demands. In this article, we present a comparative analysis of a pre-trained CNN framework for recognizing a handwritten digit on different processing platforms. The performance of the neural network as the function of the parallel processing platforms offers parametric insights and factors that influence the inference on state-of-the-art Graphics Processing Units (GPUs) and systolic arrays such as Eyeriss and Tensor Processing Unit (TPU). Through inference time analysis, we observed that the systolic arrays can outperform upto 58.7 times better than a Turing architecture powered GPU. We show that while the efficiency with which the available resources are utilized is higher in the existing GPUs (upto 32%) than the TPUs, the efficiency of application-specific systolic arrays can be on par with that of GPUs. We present the results obtained from three different customized systolic array-based platforms which can be adopted by the designers to decide the hardware optimization goal.
Biracks and switch braid quivers
Authors: Chao-Haft Max , Nelson Sam
Published: October 2024

We consider birack and switch colorings of braids. We define a switch structure on the set of permutation representations of the braid group and consider when such a representation is a switch automorphism. We define quiver-valued invariants of braids using finite switches and biracks and use these to categorify the birack 2-cocycle invariant for braids. We obtain new polynomial invariants of braids via decategorification of these quivers.
Testing consistency of cosmological parameters in spatially flat ΛCDM model from observational data in different redshift regions
Authors: Tang Dan , Liu Yang , Yu Hongwei , Wu Puxun
Published: October 2024

The Hubble tension has become the most significant crisis in modern cosmology, suggesting that the [Formula: see text]CDM model may not accurately describe cosmic evolution. In this paper, we test the spatially flat [Formula: see text]CDM model by comparing constraints on cosmological parameters from observational data across different redshift regions. Utilizing Pantheon[Formula: see text] SN Ia sample, cosmic chronometer data, and baryon acoustic oscillation data, we derive six distinct sets of constraints within the redshift range [Formula: see text]. At the first three and the last redshift points, the observed values of the present matter density parameter, [Formula: see text], are consistent with those from the full dataset within [Formula: see text] confidence level (CL), whereas values at [Formula: see text] and [Formula: see text] are not, and the maximum deviation occurring at [Formula: see text] reaches [Formula: see text]. The data indicate a decreasing trend in the Hubble constant, [Formula: see text], and the SN Ia absolute magnitude, M, with increasing redshift. Despite the variation of both [Formula: see text] and [Formula: see text] across different redshifts, the values of [Formula: see text] remain consistent within [Formula: see text] CL across all regions.
Analytic primordial power spectrum in the dressed metric approach to loop quantum cosmology and thermodynamics of spacetime
Authors: Alonso-Serrano Ana , Marugán Guillermo A. Mena , Vicente-Becerril Antonio
Published: October 2024

In this paper, we investigate the primordial power spectrum of cosmological tensor perturbations in the dressed metric approach to Loop Quantum Cosmology. We compute the background-dependent effective mass that affects their propagation using the effective description of Loop Quantum Cosmology and show that this mass can be approximated in different cosmological epochs by appropriate analytic functions. Moreover, in each of those epochs we can analytically solve the propagation of the perturbations, then obtaining the general solution globally by continuity requirements. On the other hand, since there are regimes far away from slow roll in the considered background evolution, the Bunch–Davies state does not provide a privileged choice of vacuum that would pick out a specific solution for the perturbations. Instead, we select the state of these perturbations by a recently proposed criterion that removes unwanted oscillations in the power spectrum. We compute the spectrum of this vacuum and compare it with other spectra obtained in the literature, especially with one corresponding to the hybrid approach to Loop Quantum Cosmology. Finally, we notice that the same type of background dynamics is found in a phenomenological approach to quantum gravity based on thermodynamics, allowing in this case a free value for the tantamount of the critical density. Extending the dressed metric proposal to this phenomenological model, one might expect a similar form for the associated primordial power spectrum.
The equivariant K- and KO-theory of certain classifying spaces via an equivariant Atiyah–Hirzebruch spectral sequence
Authors: Fuentes Mario
Published: October 2024

In this paper, we compute the [Formula: see text]- and [Formula: see text]-theory for the classifying [Formula: see text]-spaces [Formula: see text] for proper actions of certain infinite discrete groups [Formula: see text] via the equivariant Atiyah–Hirzebruch spectral sequence.
Noiseless homomorphic encryption for complex numbers and fully homomorphic encryption with modular arithmetic
Authors: Chun Jonghee , Han Hee , Kang Stefano V. , Wang Hyo Keun
Published: October 2024

In this paper, we construct a new noiseless homomorphic encryption scheme based on the hardness of AGCD problem. We give a succinct and efficient algorithm that produces necessary secret keys for homomorphic evaluation of higher degree polynomial circuits. We also show that our scheme can homomorphically evaluate all the integer polynomials, real polynomials and complex polynomials. Moreover, using Fermat’s Little Theorem, we prove that the size of secret key is bounded above and hence it is a FHE in itself without having to rely on any bootstrapping procedure.
Characterization of Lie n-isomorphisms of certain algebras
Authors: Zhao Xingpeng , Gao Meilian , Yang Jing
Published: October 2024

In this paper, Lie [Formula: see text]-isomorphisms on nest algebras and von Neumann algebras are constructed, which can be viewed as a common generalization of Lie isomorphisms and Lie triple isomorphisms. Besides, several 2-local Lie [Formula: see text]-isomorphisms and 2-local Lie [Formula: see text]-∗-isomorphisms on certain von Neumann algebras are studied.
THE EFFECT OF THE SHADOW ECONOMY AND ECONOMIC FREEDOM ON ENTREPRENEURSHIP: AN EMPIRICAL STUDY IN ASIAN COUNTRIES
Authors: DANG BUU KIEM , NGUYEN KHOI DINH
Published: October 2024

This study examines the effect of the shadow economy, economic freedom and other macroeconomic factors on formal entrepreneurship in Asian countries. The dataset encompasses 28 countries over the period from 1995 to 2018. The Fixed Effect Model (FEM) and Generalized Least Squares (GLS) methodologies are employed for regression analysis. The results indicate a nonlinear relationship between the shadow economy and formal entrepreneurship. Economic freedom, particularly trade freedom, significantly enhances entrepreneurship. Positive macroeconomic influences on formal entrepreneurship include financial development, political stability, GDP per capita growth and foreign direct investment net inflows, while government spending and unemployment negatively affect entrepreneurship. The findings suggest that a substantial shadow economy does not inherently impede formal entrepreneurship. Consequently, governments should prudently consider the role of the shadow economy in fostering entrepreneurial growth. Moreover, policies aimed at improving economic freedom, especially trade freedom, can create a conducive environment for boosting formal entrepreneurship.
ORGANISATIONAL CREATIVITY AND ARTIFICIAL INTELLIGENCE: INTRODUCTION OF A CREATIVITY ASSESSMENT FOR IDEATION
Authors: HÖRAUF DOMINIK , BREM ALEXANDER
Published: October 2024

The assessment of creativity is both elaborating and challenging with today’s tools and methods in organisational creativity. This study presents the result of an AI-based model for the originality assessment of creative ideas using an artificial intelligence (AI) tool (Word2Vec). First, we define everyday creativity and outline the relevance and challenges of its evaluation. Then, the Word2Vec algorithm is introduced and used to develop three different models for originality assessment by calculating a semantic distance between ideas. We conclude with an empirical validation of the three models. While results indicate that all three models can be used to measure idea originality, they further point out that merely human-based assessments may be task-dependent. The paper closes with implications for research and practice to integrate AI in creative idea originality measurement. Managers can use the methods presented in this study to benefit from AI-supported creativity within their companies. Furthermore, idea managers of companies with large idea databases can implement the algorithms to analyse employee ideas regarding specific contexts or topics within their innovation management processes.
RPEPL: Tibetan Sentiment Analysis Based on Relative Position Encoding and Prompt Learning
Authors: Kong Chunwei , Lv Xueqiang , Zhang Le , Zhao Haixing , Cai Zangtai , Chen Yuzhong
Published: October 2024

Sentiment analysis is a critical task for natural language processing. Much research has been done for high-resource languages such as English and Chinese. However, Tibetan is an extremely low resource language with less reference information. According to the practical demands, this article proposes RPEPL, a Tibetan sentiment analysis method based on relative position encoding and prompt learning. First, word information is introduced to syllable sequences by converting the directed acyclic lattice into a squashed structure. Second, a relative position encoding is used to encode the position information of syllables and words. Third, the association relations and semantic information of tokens are identified by leveraging the multi-attention. Finally, the sentiment category of the Tibetan sentence is obtained through a prompt learning framework. Experimental results demonstrate that RPEPL significantly outperforms the baseline methods on the TUSA dataset and TNEC (Tibetan News Event Comments) dataset. Additionally, traditional recurrent neural networks cannot perform large-scale parallel computation and convolutional neural networks have difficulty modeling long-distance dependencies in Tibetan text, both of which are resolved using RPEPL. Furthermore, the use of multi-attention not only enriches the association relations between syllables and words but also enhances the understanding of sentence semantic and syntactic structure information, and improves the performance of Tibetan sentiment analysis.
Reproducibility in the Classroom
Authors: Dogucu Mine
Published: October 2024

Difficulties in reproducing results from scientific studies have lately been referred to as a reproducibility crisis. Scientific practice depends heavily on scientific training. What gets taught in the classroom is often practiced in labs, fields, and data analysis. The importance of reproducibility in the classroom has gained momentum in statistics education in recent years. In this article, we review the existing literature on reproducibility education. We delve into the relationship between computing tools and reproducibility through visiting historical developments in this area. We share examples for teaching reproducibility and reproducible teaching while discussing the pedagogical opportunities created by these examples as well as challenges that the instructors should be aware of. We detail the use of teaching reproducibility and reproducible teaching practices in an introductory data science course. Lastly, we provide recommendations on reproducibility education for instructors, administrators, and other members of the scientific community.
Exosomal PDL1 Suppresses the Anticancer Activity of CD8+ T Cells in Hepatocellular Carcinoma
Authors: Hu Qi , Chen Shuai , Deng Rilin , Deng Hongyu , Peng Mingjing , Wang Xiaohong , Deng Shun , Wang Jinfeng , Xu Biaoming , Xu Yan , Zhu Haizhen , Zheng Jinhai , Xia Man , Zuo Chaohui
Published: October 2024

Tumor microenvironment (TME) is essential for the development and progression of hepatocellular carcinoma (HCC). Exosomes participate in constructing TME by passing biological information, but the regulatory effect of PDL1 in exosomes on anticancer activity of CD8+ T cells in HCC still needs to be further explored. In this study, high level of PDL1 was found in plasma exosomes of HCC patients, which turned out to be significantly associated with the increased number of tumor nodules, the upregulated level of serum AFP, the raised tendency of TNM stage, and the poor prognosis of HCC. The expression of CD8 may be inhibited in HCC that is characterized with high level of PDL1, and the protein level of exosomal PDL1 was determined by intracellular PDL1 abundance. High level of exosomal PDL1 inhibited the proliferation and activation of CD8+ T cells, but exhibited limited effect on the proliferation of hepatic cancer cells. Moreover, the growth of tumors formed by hepatic cancer cells Hepa1–6 in C57L mice was significantly promoted by the exosomal PDL1, which might be caused by the inhibitory effect of exosomal PDL1 on CD8+ T cells. Thus, exosomal PDL1 promotes the development and progression of HCC through inhibiting the anticancer activity of CD8+ T cells. This study provides sights for understanding the oncogenic role of PDL1 and a reasonable explanation for the low efficacy of anti‐PD1/PDL1 immunotherapies in HCC.
Influence of Permeable Wellbore on Formation Testing While Drilling and Mobility Inversion
Authors: Wu Lejun , Chen Ming , Liu Jianxin , Zhang Zhiqiang , Li Xiaodong , Peng Nian , Ma Tianshou
Published: October 2024

Formation pressure and mobility represent two fundamental parameters that are essential for the development of oil and gas resources. These parameters can be obtained in real time through the process of formation testing while drilling (FTWD). It is highly probable that the drilling fluid will invade the formation during the FTWD process. Nevertheless, the prevailing theory regarding FTWD assumes that the wellbore is impermeable, thereby rendering its potential impact on FTWD and mobility inversion unclear. Therefore, to clarify the influence of the permeable wellbore on FTWD and mobility inversion, a mathematical model of FTWD seepage was first proposed by involving the permeable wellbore. Secondly, the finite element method was used to solve this model, and this model was verified by using the analytical models. The pressure response curves and isobaric surface near the FTWD probe were then compared for both the permeable and impermeable wellbores, and the influence of the permeable wellbore on the pressure response curves of FTWD was analyzed. Finally, the method of integral area was used to invert mobility, and the compressive influence of different factors on both the pressure response curves and mobility inversion was discussed for both the permeable and impermeable wellbores. The results indicated that the permeable wellbore has a significant impact on the pressure response curves and isobaric surface near the probe due to the limited pressure sweeping range around the probe and the invasion of drilling fluid. In the case of a permeable wellbore, the invasion of the drilling fluid into the formation can cause a supercharge effect around the well. This effect can cause an initial increase followed by a decrease in the pressure buildup phase. The pressure buildup always exceeds the original formation pressure, which can lead to an overestimation of the measured formation pressure compared to the original. Meanwhile, the permeable wellbore can also lead to an overestimation of the inversion mobility, but the impermeable wellbore has much less influence on the mobility inversion. To improve inversion accuracy, it is recommended to increase the rubber packer radius, lengthen the suction period, reduce the storage volume of the pipeline, and decrease the overbalanced pressure. However, these measures cannot mitigate the impact of the supercharge effect on formation pressure testing. This paper provides theoretical guidelines for the use of FTWD tools and data interpretation.
Loss of PI5P4Kα Slows the Progression of a Pten Mutant Basal Cell Model of Prostate Cancer
Authors: Triscott Joanna , Lehner Marika , Benjak Andrej , Reist Matthias , Emerling Brooke M. , Ng Charlotte K.Y. , de Brot Simone , Rubin Mark A.
Published: October 2024

Although early prostate cancer depends on the androgen receptor signaling pathway, which is predominant in luminal cells, there is much to be understood about the contribution of epithelial basal cells in cancer progression. Herein, we observe cell type–specific differences in the importance of the metabolic enzyme phosphatidylinositol 5-phosphate 4-kinase alpha (PI5P4Kα; gene name PIP4K2A) in the prostate epithelium. We report the development of a basal cell–specific genetically engineered mouse model targeting Pip4k2a alone or in combination with the tumor suppressor phosphatase and tensin homolog (Pten). PI5P4Kα is enriched in basal cells, and no major histopathologic changes were detectable following gene deletion. Notably, the combined loss of Pip4k2a slowed the development of Pten mutant mouse prostatic intraepithelial neoplasia. Through the inclusion of a lineage tracing reporter, we utilize single-cell RNA sequencing to evaluate changes resulting from in vivo downregulation of Pip4k2a and characterize cell populations influenced in the established Probasin-Cre– and cytokeratin 5-Cre–driven genetically engineered mouse model. Transcriptomic pathway analysis points toward the disruption of lipid metabolism as a mechanism for reduced tumor progression. This was functionally supported by shifts of carnitine lipids in LNCaP prostate cancer cells treated with siPIP4K2A. Overall, these data nominate PI5P4Kα as a target for PTEN mutant prostate cancer.

Implications: PI5P4Kα is enriched in prostate basal cells, and its targeted loss slows the progression of a model of advanced prostate cancer.
Supplemental Figure 7 from Chemotherapy Enriches for Proinflammatory Macrophage Phenotypes that Support Cancer Stem-Like Cells and Disease Progression in Ovarian Cancer
Authors: Cruz Luisjesus S. , Robinson Mikella , Stevenson Denay , Amador Isabella C. , Jordan Gregory J. , Valencia Sofia , Navarrete Carolina , House Carrie D.
Published: October 2024

Mouse Immune Panel
Supplemental Figure 5 from Chemotherapy Enriches for Proinflammatory Macrophage Phenotypes that Support Cancer Stem-Like Cells and Disease Progression in Ovarian Cancer
Authors: Cruz Luisjesus S. , Robinson Mikella , Stevenson Denay , Amador Isabella C. , Jordan Gregory J. , Valencia Sofia , Navarrete Carolina , House Carrie D.
Published: October 2024

Flow cytometry analysis of ip TAMs
Prevalence, Incidence, and Mortality of Myasthenia Gravis and Myasthenic Syndromes: A Systematic Review
Authors: Sciancalepore Francesco , Lombardi Niccolò , Valdiserra Giulia , Bonaso Marco , Cappello Emiliano , Hyeraci Giulia , Crescioli Giada , Celani Maria Grazia , Cantisani Teresa Anna , Brunori Paola , Vecchi Simona , Bacigalupo Ilaria , Locuratolo Nicoletta , Lacorte Eleonora , Vanacore Nicola , Kirchmayer Ursula
Published: October 2024

Introduction: No systematic reviews were published in the last years investigating epidemiological data, involving myasthenia gravis (MG) and related myasthenic syndromes. This systematic review aimed to estimate the prevalence, incidence, and mortality of all MG types and myasthenic syndromes worldwide. Methods: All literature published up to February 2024 was retrieved by searching the databases “Medline,” “Embase,” “ISI Web of Science” and “CINAHL” using the following search terms: (epidemiolog* OR frequency OR prevalence OR incidence OR mortality) AND (myasth* OR “anti-acetylcholine receptor antibody” OR “AChR” OR “MuSK” OR “anti-muscle specific kinase antibody” OR “LRP4” OR “seronegative MG”). Results: A total of 94 studies, performed between 1952 and 2022, were included. Prevalence of MG ranged from 20 to 475 cases per million, with a mean prevalence of 173.3 (95% confidence interval [CI]: 129.7–215.5) cases per million and a median prevalence of 129.6 cases per million. Incidence rates ranged from 2.3 to 61.3 cases per million person-years, with a mean incidence of 15.7 (95% CI: 11.5–19.9) and a median of 13.3 cases. Mortality rates showed a mean of 1.4 (95% CI: 0.8–2.1) cases per million person-years. Acetylcholine receptor (AChR)-MG was the clinical subtype more frequent in terms of prevalence and incidence. Discussion: The prevalence and incidence of MG have significantly increased over the last years worldwide, probably due to the improvement of epidemiological methodologies and current advances in diagnosis. However, we observed a significant variation in frequencies of MG between and within countries because of methodological biases and complex heterogeneity of the disease characterized by several phenotypes and different clinical responses.
Cancer Epithelial Cells Participate in the Self-Organization of Lung Tumor Spheroids: A Morphological Approach
Authors: Monleón-Guinot Irene , Bravo-Baranda Lucía , Milián Lara , Sancho-Tello María , Llop-Miguel Mauro , Galbis José Marcelo , Cremades Antonio , Carda Carmen , Mata Manuel
Published: October 2024

Introduction/aims: The tumor microenvironment is known to play an important role in tumor progression. However, the specific mechanisms underlying this process are still not known in detail and more research is needed on the elements that control tumor progression in lung cancer. In this work, we aimed to investigate the involvement of epithelial and stromal cancer cells in growth, cell migration, and epithelial-to-mesenchymal transition (EMT) in a 3D in vitro model consisting of cell spheroids cultured in a type I collagen scaffold. Methods: Spheroids were manufactured using different combinations of epithelial cells, particularly H460 and H1792 cell lines, with cancer-associated fibroblasts and normal fibroblasts, both isolated from adenocarcinoma patients. We evaluated the morphology of the spheroids by analysis of F-actin and pankeratin with confocal microscopy. We determined the ultrastructure of cells in the spheroids by transmission electron microscopy and the expression of CDH1, CDH2, and VIM by RT-PCR. Results: We observed that, on the one hand, the type of epithelial cell influences the morphology of spheroids. Stromal cells stimulated spheroid growth and cell dissemination through the collagen matrix, either alone or organized in branches with a nucleus of epithelial cells preceded by fibroblast cells. They also induced the appearance of new cell groups in the scaffold and the presence of EMT markers. Conclusion: The results presented here indicate the participation of both epithelial and stromal cells in the control of spheroid self-organization. The experimental model proposed here, although preliminary, is useful for the study of some aspects related to tumor progression in lung cancer.
Virus-Induced Voracity: Uncovering Hyperphagia Post-Herpes Simplex Virus Type 1
Authors: Mitra Arpan , Bhuyan Nayana , Vivek Ankur , Jain Akansha , Mishra Vijaya Nath , Pathak Abhishek
Published: October 2024

Introduction: Herpes simplex virus type 1 (HSV-1) is the leading cause of sporadic fatal encephalitis, typically presenting with temporal lobe abnormalities. It usually manifests as fever, headache, seizure, altered sensorium, and focal neurological deficit. Hyperphagia as a sole complication of HSV-1 encephalitis is a rare presentation. Case Presentation: We report a 25-year-old woman with a 10-day history of fever, headache, and vomiting, progressing to confusion, visual hallucinations, and drowsiness. She had a history of meningoencephalitis at age 8 and well-controlled focal seizures. Upon admission, magnetic resonance imaging showed T2/fluid-attenuated inversion recovery hyperintensities in both temporal lobes with diffusion restriction. Electroencephalography indicated generalized slowing and cerebrospinal fluid (CSF) analysis revealed lymphocytic pleocytosis with elevated protein levels. Viral encephalitis was suspected, and intravenous acyclovir was initiated. CSF polymerase chain reaction (PCR) confirmed HSV-1. With treatment, she gradually improved but developed hyperphagia during hospital stay. Hyperphagia, a rare complication of herpes simplex virus (HSV) encephalitis, is a part of Kluver-Bucy syndrome typically associated with other cognitive dysfunctions. Despite early treatment, voracious appetite remained partially, emphasizing the need for rapid diagnosis and treatment to prevent severe outcomes. Conclusion: The case highlights that acute onset hyperphagia can be an isolated complication of HSV encephalitis, requiring tailored therapeutic strategies. Follow-up showed significant weight gain with partial improvement in hyperphagia, underscoring the challenges in managing this condition.
Systemic Factors Contributing to Gender Differences in Living Kidney Donation: A Systematic Review and Meta-Synthesis Using the Social-Ecological Model Lens
Authors: Loban Katya , Wong-Mersereau Chloe , Cates Ferrer Jewy , Hales Lindsay , Przybylak-Brouillard Antoine , Cantarovich Marcelo , Kute Vivek B. , Bhalla Anil K. , Morgan Rosemary , Sandal Shaifali
Published: October 2024

Introduction: The field of living kidney donation is profoundly gendered contributing to a predominance of women, mothers, and wives as living kidney donors (LKDs). Individual factors have traditionally been emphasized, and there is a limited appreciation of relational, community, and sociocultural influences in decision-making. We aimed to comprehensively capture existing evidence to examine the relative importance of these factors. Methods: This was a systematic review of existing literature that has explored the motivation of different genders to become LKDs. Of the 3,188 records screened, 16 studies from 13 counties were included. Data were synthesized thematically using the Social-Ecological Model lens. Results: At the individual level, themes related to intrinsic motivation; thoughtful deliberation; and attitudes, fears, and beliefs; however, evidence demonstrating differences between men and women was minimal. Greater variation between genders emerged along the relational (coercion from family/network, relationship with the intended recipient, self-sacrifice within the family unit, and stability/acceptance within family); community (economic value and geographic proximity to recipient); and sociocultural (gendered societal roles, social norms and beliefs, social privilege, and legislation and policy) dimensions. The relative importance of each factor varied by context; cultural components were inferred in each study, and economic considerations seemed to transcend the gender divide. Conclusions: A complex interplay of factors at relational, community, and sociocultural levels influences gender roles, relations, and norms and manifests as gender disparities in living kidney donation. Our findings suggest that to address gender disparities in living donation, dismantling of deep-rooted systemic contributors to gender inequities is needed.
Abstract Mo004: The Protective Effects of Empagliflozin in Carfilzomib-induced Cardiotoxicity in Mice: Unveiling the Crosstalk between Oxidative Stress, Inflammation, Endoplasmic Reticulum Stress, and Autophagy Axes.
Authors: George Mina Y. , Dabour Mohamed , Rashad Eman , Zordoky Beshay
Published: October 2024

Introduction:
Multiple myeloma ranks as the second most prevalent hematologic cancer in the US. Survival rates have significantly improved owing to advances in chemotherapy treatment. Carfilzomib, an irreversible proteasome inhibitor, has been used globally for the treatment of multiple myeloma. Unfortunately, its clinical use has been linked to cardiovascular complications. Empagliflozin is a sodium glucose co-transporter-2 inhibitor with potential cardioprotective activities, for which it is approved for heart failure management.

Aims:
The current study determined the beneficial effects of Empagliflozin against Carfilzomib-induced cardiotoxicity in C57BL/6 mice and the possible underlying mechanisms.

Methods:
Thirty-two mice were randomly divided into four groups and treated for two days as follows: Control (vehicle), Empagliflozin (10 mg/kg, oral), Carfilzomib (8 mg/kg, i.p.), and Carfilzomib + Empagliflozin groups.

Results:
The impact of Carfilzomib and Empagliflozin treatment on markers of cardiotoxicity and heart tissue architecture was assessed. Empagliflozin corrected histological alterations, CK-MB activity, and troponin I level induced by Carfilzomib. Additionally, Empagliflozin mitigated Carfilzomib-induced oxidative deficits via its effect on catalase activity, reduced glutathione level, and superoxide dismutase activity, restoring the balance of redox circuit. Moreover, Empagliflozin averted Carfilzomib-induced inflammatory response as evidenced by reducing nuclear factor-κB (p65), tumor necrosis factor-α, and interleukin-1β levels. Mechanistically, a substantial amelioration in the activating transcription factor 6-mediated endoplasmic reticulum stress was demonstrated with Empagliflozin treatment owing to its effect on glucose regulated protein-78, activating transcription factor-6, and C/EBP homologous protein. Intriguingly, the induction of autophagy by Carfilzomib was notably amplified following Empagliflozin administration as evidenced by higher mRNA expression of LC3B and beclin-1, and lower expression of p62. Accordingly, the apoptotic marker cleaved caspase-3 expression was markedly reduced following Empagliflozin treatment. Importantly, Empagliflozin did not alter the cytotoxic effect of Carfilzomib on human U266B1 myeloma cell line.

Conclusion:
This research suggests Empagliflozin could offer cardioprotection against Carfilzomib-induced cardiotoxicity in multiple myeloma patients.
Abstract Mo007: Molecular Basis of Sepsis-Induced Cardiomyopathy Under Anthracycline Treatment: Insights from Mouse Model
Authors: Markandran Kasturi , Wang Rina , Lim Yi Peng , Chen Ching Kit
Published: October 2024

Anthracyclines constitute a fundamental component in numerous paediatric chemotherapy regimens. However, its myelosuppressive & cardiotoxic nature put patients at risk of sepsis and sepsis-induced cardiomyopathy (SIC). When anthracycline-treated patients develop SIC, successful treatment of sepsis is sufficient for the restoration of cardiac function, giving rise to the 'transient cardiac dysfunction' phenomenon. Although transient it poses compromised clinical outcomes & the mechanism driving this phenomenon remains elusive.

We hypothesise that the molecular regulators of the phenomenon lie within cardiac cell populations & is controlled by transcriptional activation. Thus, we aim to model 'transient cardiac dysfunction' in mice and conduct transcriptomics on their heart tissues.

‘Transient cardiac dysfunction’ was modelled in male juvenile C57BL6 mice treated with a cumulative of 10mg/kg doxorubicin followed by sepsis induction via cecal ligation & perforation (CLP) to induce SIC. To recapitulate ‘transient cardiac dysfunction’, antibiotics were administered 20h post-CLP to treat sepsis & restore cardiac function. Controls against doxorubicin (saline treatment) was established. Echocardiography and biological sample curation were conducted at pre-SIC (before CLP), onset-SIC (10h post-CLP) & post-SIC (60h post-CLP).

Sepsis was verified based on procalcitonin fold change as compared to pre-SIC (n=3-6). Procalcitonin was 15±1.6 folds higher in dox- (n=3) & 10±0.39 folds higher in saline-treated (n=3) mice at onset-SIC. The infection was more aggressive in dox-treated mice as procalcitonin remained elevated at post-SIC (17.1±2.0, n=4), whereas in saline-treated mice, procalcitonin was reduced by post-SIC (7.9±1.0, n=3). In saline-treated mice, LVEF(%) was reduced at onset-SIC (49.0%±3.0, n=7) from pre-SIC (58.1±1.1, n=7) and recovered to baseline by post-SIC (61.8±1.7, n=5). In the contrary, LVEF in dox-treated mice (n=7) was increased at onset-SIC (62.5±1.7) from pre-SIC (56.0±0.8) & sustained till post-SIC (60.1±1.0), suggesting cardioprotection. Normal distribution was verified before statistical hypothesis testing.

In conclusion, ‘transient cardiac dysfunction’ was modelled in saline-treated mice, & novel cardio protective effect was observed in dox-treated mice. Moving forward, longitudinal snRNA-seq will be conducted on whole hearts to identify cardiac cell populations & genes responsible for ‘transient cardiac dysfunction’ & cardioprotection.
Abstract Mo012: Optimizing Mouse Models of Doxorubicin Cardiomyopathy
Authors: Curtin Casie , Liu Jing , Basu Sandeep , Weitzman Benjamin , Wieke Jakob , Asnani Aarti
Published: October 2024

Introduction:
Anthracyclines such as doxorubicin (Dox) are effective chemotherapies that treat various cancers, including breast, lymphoma, and leukemia. While effective, their use is limited due to cardiac toxicity, leading to cardiomyopathy and heart failure.

Background:
Several Dox treatment regimens in mice have been reported in the literature, from acute high-dose models to chronic low-dose models. Many of these regimens cause fulminant cardiomyocyte apoptosis and heart failure within days, and they do not accurately recapitulate the human toxicity phenotype.

Objective:
Our goal was to identify a Dox dosing regimen in mice that causes the most consistent subacute/chronic cardiomyopathy, as seen in patients, with the least systemic toxicity.

Methods:
We administered four different Dox dosing regimens to C57BL/6N female and male mice, based on published protocols and our laboratory’s prior studies (
Fig. 1
):

#1: Dox 3mg/kg intraperitoneally (IP) every other day for two weeks (cumulative dose of 24mg/kg) or saline

#2: Dox 5mg/kg IP twice a week for two and a half weeks (cumulative dose of 25mg/kg) or saline

#3: Dox 5mg/kg IP once a week for five weeks (cumulative dose of 25mg/kg) or saline

#4: Dox 5mg/kg intravenously (IV) once a week for four weeks (cumulative dose of 20mg/kg) or saline

Cardiac function was assessed after five to seven weeks by echocardiography, prior to sacrifice. Hearts and blood were isolated for molecular analyses. Regimens were compared using a one-way ANOVA and multiple comparisons analysis.

Results:
Protocol #3 (Dox 5mg/kg IP once a week for five weeks; cumulative dose of 25mg/kg) demonstrated the most consistent difference in fractional shortening between male mice treated with saline compared to those treated with Dox, as assessed by echocardiography (
Fig. 2
). This protocol resulted in the lowest mortality, as well as the least amount of systemic toxicity (
Fig. 3
). Protocol #1 (Dox 3mg/kg IP every other day for two weeks; cumulative dose of 24mg/kg) was the only protocol that elicited a decline in fractional shortening in female mice treated with Dox compared to those treated with saline, as assessed by echocardiography.

Conclusion:
Going forward, protocol #3 (5mg/kg IP once a week for five weeks) will be implemented as the standard dosing regimen in our laboratory. Ensuring consistency in cardiac phenotypes will allow us to better understand the effects of modulating cardioprotective pathways on the development of Dox cardiac toxicity.
Abstract Mo019: Angiotensin II Links Cardiovascular Disease With Enhanced Cancer Growth
Authors: van Berlo Benji , Civati Celine , Esposito Pierangela , De Keulenaer Gilles , Guns Pieter-Jan , Segers Vincent
Published: October 2024

Introduction:
It has been demonstrated that CVD promote tumor growth in mouse models of breast, lung, and colon cancer, suggesting a causal relationship between both diseases. Cancer and CVD share several risk factors and pathophysiological mechanisms, e.g. inflammation and oxidative stress, that could explain why patients with CVD are prone to develop cancer. Recent reports also suggest a link between hypertension, hypertrophy and lung cancer. Angiotensin II (ANGII) is a hormone involved in blood pressure regulation, vascular hemostasis and hypertrophy development. Moreover, ANGII is cancerogenic by increasing proliferation of several cancer cell types. Hence, ANGII could be a link in CVD-induced enhancement of cancer growth.

Hypothesis:
We hypothesized that ANGII treatment, and subsequent hypertension and cardiac hypertrophy, could promote cancer growth.

Methods:
ANGII (2000 ng.kg
-1
.min
-1
; 4w) was administered to 10w old C57B6/J mice using osmotic minipumps. After 4w, pumps were removed and 5*10
5
Lewis lung carcinoma (LLC) cells injected onto the right flank. To study the direct impact of the ANGII peptide on the cancer growth mice were treated with ANGII as mentioned above and LLC cells were injected after 3w to allow concomitant ANGII treatment and cancer growth. A similar experiment was performed by injecting 2*10
5
MC38 colon cancer cells. Tumor growth was monitored for 21d after which the mice were sacrificed. Results are expressed as mean ± SEM.

Results:
ANGII treatment concomitantly with cancer growth resulted in significantly larger tumors as shown by post-mortem tumor volume (881 ± 111 control vs. 1467 ± 154 mm^3 ANGII, P=0.013). In contrast, no increased tumor growth was observed when ANGII was administered non-concomitant with cancer growth. Interestingly, MC38 tumor growth significantly decreased in the ANGII treated group as portrayed by tumor volume (462 ± 65 control vs. 227 ± 81 mm^3 ANGII).

Conclusion:
Our data suggest a role for ANGII in CVD-enhanced cancer growth, but also that this effect is not universal, illustrated by a differential effect of ANGII on distinct cancer types. Although further investigation is required to unravel the role of ANGII, screening cancer patients with CVD comorbidities for ANGII involvement might be warranted.
Abstract Mo021: Role of Estrogen and Testosterone in promoting Sex Dimorphism in Doxorubicin Cardiotoxicity.
Authors: Trampel Katy , De Melo Amaral Paloma , Efimov Igor , George Sharon Ann
Published: October 2024

Background:
Doxorubicin (DOX), a cancer chemotherapeutic agent, causes sex-specific cardiotoxicity. Lower cardiotoxicity in females compared to males is typically attributed to the cardioprotective effects of estrogen (E2). However, the role of the sex hormones, E2 and testosterone (T), in modulating DOX induced cardiac dysfunction and its underlying mechanisms are not known.

Methods:
C57BL/6J mice were divided into four groups, 1) Control, 2) DOX (5 mg/kg/week for 6 weeks), 3) Reverse hormone profile (RevH, castrated males+E2 and ovariectomized females+T), and 4) RevH + DOX. Mouse morbidity was tracked daily. Total body weight and cardiac function was assessed biweekly for 6 weeks by echocardiography, ECG and optical mapping. Dependence on fatty acid versus glucose for metabolism was measured by seahorse analysis.

Results:
DOX treatment reduced total body weight (11%) in males, and increased morbidity in males and females. This was associated with reduced mechanical function (15% decrease in stroke volume) in males and electrical remodeling (29% action potential duration prolongation) in females.

In RevH mice, no changes in morbidity or cardiac function were observed compared to Control.

In RevH+DOX males, the onset of morbidity was delayed by two weeks compared to DOX males. This cardioprotective effect was associated with preserved mechanical and electrical function. On the other hand, in RevH+DOX females, morbidity was increased, and this correlated with mechanical (20% reduction in cardiac output) and electrical remodeling (22% increase in action potential duration). Comparing RevH+DOX males to females, males had greater fatty acid dependency while females had greater glucose dependency for metabolism.

Conclusions:
These results suggest that sex hormones play a significant role in modulating specific aspects of DOX cardiotoxicity. While E2 has a critical role in preserving cardiac mechanics during DOX therapy, high T levels were associated with mechanical dysfunction in both males and RevH females. Switching of metabolic substrates with greater preference for fatty acid metabolism in mice with higher E2 could underlie cardiac mechanics preservation. Finally, DOX induced electrical remodeling was not altered by sex hormones.
Abstract Mo023: Inhibition of Cyp1a Protects Mice against Anthracycline Cardiomyopathy
Authors: Liu Jing , Curtin Casie , Ariza Abul , Wieke Jakob , Sejour Leinal , Vlachos Ioannis , Asnani Aarti
Published: October 2024

Background:
Anthracyclines such as doxorubicin (Dox) are highly effective anti-tumor agents, but their use is limited by dose-dependent cardiomyopathy. Our laboratory previously reported that activation of cytochrome P450 family 1 (Cyp1) enzymes contributes to acute doxorubicin (Dox) cardiotoxicity in zebrafish and in mice, and that potent Cyp1 inhibitors prevent cardiotoxicity. However, the role of Cyp1 enzymes in chronic Dox cardiomyopathy, as well as the mechanisms underlying cardioprotection associated with Cyp1 inhibition, have not been fully elucidated.

Objective:
This study aims to define the role of Cyp1 inhibition in mouse models that more accurately recapitulates the chronic cardiomyopathy seen in patients.

Methods:
The function of Cyp1 enzymes was evaluated using a small molecule Cyp1 inhibitor in wild-type (WT) mice, or Cyp1-null mice (

Cyp1a1/1a2
-/-

,

Cyp1b1
-/-

, and

Cyp1a1/1a2/1b1
-/-

). Low-dose Dox was administered by serial intraperitoneal or intravenous injections, respectively. Expression of Cyp1 isoforms was measured by RT-qPCR, and myocardial tissue was isolated from the left ventricle for RNA sequencing. Cardiac function was evaluated by transthoracic echocardiography.

Results:
In WT mice, Dox treatment was associated with a decrease in
Cyp1a2
and an increase in
Cyp1b1
expression in the heart and in the liver. Co-treatment of WT mice with Dox and the potent Cyp1 inhibitor YW-130 protected against cardiac dysfunction compared to Dox treatment alone.

Cyp1a1/1a2
-/-

and

Cyp1a1/1a2/1b1
-/-

mice were protected from Dox cardiomyopathy compared to WT mice. Male, but not female,

Cyp1b1
-/-

mice had increased cardiac dysfunction following Dox treatment compared to WT mice. RNA sequencing of myocardial tissue showed upregulation of
Fundc1
and downregulation of
Ccl21c
in

Cyp1a1/1a2
-/-

mice treated with Dox, implicating changes in mitophagy and chemokine-mediated inflammation as possible mechanisms of Cyp1a-mediated cardioprotection.

Conclusions:
Taken together, this study highlights the potential therapeutic value of Cyp1a inhibition in mitigating anthracycline cardiomyopathy.