bluuebunny/crossref_metadata_2025 huggingface dataset:
Ukraine and the Academy: One War, Many Theories
Authors: Platias Athanasios , Trigkas Vasilis
Published: October 2024

Leading theorists of major schools of thought in international relations disagree over the root causes of the ongoing war in Ukraine. This paper examines the merits and bases of the theories or explanations provided by each major IR school. It explores the dominant arguments concerning the nature and trajectory of the ongoing war, the prospects for its resolution, and its strategic effects on the international system with a particular emphasis on China. We argue that scholars’ views on these topics are significantly influenced by their theoretical orientations within international relations. Furthermore, strategic thinkers and policymakers, identified as homines theoretici or feminae theoreticae, are themselves deeply influenced by their theoretical understandings of the world, which in turn shape their normative engagement with world affairs. However, the interplay between theoretical perspectives and practical realities hinges on the dynamics of power and objective material conditions on the ground.
The Transition of International Order: Current Debates and Future Directions
Authors: Sanaei Mehdi
Published: October 2024

The early third millennium AD witnessed the outbreak of global crises and challenges that exposed the weaknesses of the possible unilateral order and the negative aspects of globalization. This led to a widespread debate among international relations thinkers about the transition period and the future of world order. The recent occurrence of two major global crises, namely, the COVID-19 pandemic and the war in Ukraine, has accelerated this transition period, prompting representatives of different schools of international relations to think through various scenarios for the future of world order. These scenarios can be classified into several categories, including the revival of the unipolar order with new characteristics, multipolar order, new bipolar order, non-polar world, and the emergence of multiple regional hegemonies. However, due to the differences and gaps in the consolidation of power centers, as well as the lack of agreement on international norms, it is unlikely that any of these scenarios will be realized in the short term. In the absence of a pervasive, tangible threat or a fundamental shift in political culture, the rules and structures of the old order will persist, albeit in a weakened state. This will prolong the transition period and heighten instability. Thus, it is crucial to manage this transition peacefully by fostering regional alliances, while honoring the cultural and civilizational differences of the key players. Ultimately, a new world order can only emerge through dialog among major powers and consensus on the rules that will shape the international system. Until that time, the global community must prioritize maintaining stability and navigating the transition to ensure a peaceful evolution toward the future order.
Chitosomal Encapsulation Enhances the Anticancer Efficacy of a Theobromine Analogue: An Integrated In Silico and In Vitro Study
Authors: Metwaly Ahmed M. , Abd-El-Azim Heba , Zewail Mariam , Alsfouk Aisha A. , Elkaeed Eslam B. , Eissa Ibrahim H.
Published: October 2024

Aims: This study aims to prepare and investigate the potential of theobromine derivative-loaded chitosomes as an effective anticancer drug. Background: [Formula: see text]-Benzyl-2-(3,7-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1[Formula: see text]-purin-1-yl)acetamide (T-1-BA) exhibited promising anticancer potential. Loaded chitosomes, highlighting their suitability as a drug delivery system. The study builds on the significance of targeted drug delivery systems for enhanced anticancer efficacy. Objectives: To prepare T-1-BA-loaded chitosomes (T-1-BA-PC-CS complex) using the thin film hydration technique. To examine the colloidal characteristics, entrapment efficiency, and stability of the T-1-BA-PC-CS complex. To assess the in vitro anticancer efficacy of the T-1-BA-PC-CS complex against Hct116 and A549 cancer cell lines comparing the free T-1-BA, blank chitosomes, and the standard EGFR inhibitor, Lapatinib. Methods: The T-1-BA-PC-CS complex was prepared through the thin film hydration technique. Colloidal characteristics, including particle size, PDI, and zeta potential, were examined. In vitro anticancer efficacy was assessed through IC[Formula: see text] values, comparative analyses, SI calculations, cell cycle analysis, flow cytometry, and wound healing assays. Results: The T-1-BA-PC-CS complex demonstrated reduced IC[Formula: see text] values against Hct116 and A549 cell lines, indicating enhanced cytotoxicity compared to free T-1-BA and blank chitosomes. Comparative analyses highlighted superior anticancer activity. SI values indicated preferential cytotoxic effects on cancer cell lines. Flow cytometry analysis revealed cell cycle alterations and increased apoptosis. Wound healing assays showed a significant impact on migration and wound healing in A549 cells. Conclusion: The findings suggest that the T-1-BA-PC-CS complex holds great promise as an anticancer therapeutic by efficiently inducing favorable alterations in cell cycle phases and apoptosis, demonstrating its potential for further development in cancer treatment.
Single-Document Abstractive Text Summarization: A Systematic Literature Review
Authors: Rao Abishek , Aithal Shivani , Singh Sanjay
Published: October 2024

Abstractive text summarization is a task in natural language processing that automatically generates the summary from the source document in a human-written form with minimal loss of information. Research in text summarization has shifted towards abstractive text summarization due to its challenging aspects. This study provides a broad systematic literature review of abstractive text summarization on single-document summarization to gain insights into the challenges, widely used datasets, evaluation metrics, approaches, and methods. This study reviews research articles published between 2011 and 2023 from popular electronic databases. In total, 226 journal and conference publications were included in this review. The in-depth analysis of these papers helps researchers understand the challenges, widely used datasets, evaluation metrics, approaches, and methods. This article identifies and discusses potential opportunities and directions along with a generic conceptual framework and guidelines on abstractive summarization models and techniques for research in abstractive text summarization.
Finding 3-Swap-Optimal Independent Sets and Dominating Sets is Hard
Authors: Komusiewicz Christian , Morawietz Nils
Published: October 2024

Local search problems consist of a set of feasible solutions, an objective function, and a neighborhood relation which assigns to each feasible solution a set of neighbors. A solution 
S
is called
locally optimal
if none of its neighbors has a better objective value than 
S
. For PLS-complete local search problems, there is presumably no polynomial-time algorithm which finds a locally optimal solution, even though determining whether a solution is locally optimal and finding a better one if this is not the case can be done in polynomial time. We study local search for 
Weighted Independent Set
and 
Weighted Dominating Set
with the 3-swap neighborhood. The 3-swap neighborhood of a vertex set 
S
in 
G
is the collection of vertex sets which can be obtained from 
S
by exchanging at most three vertices. On the negative side, the problem of finding a 3-swap-optimal independent set or dominating set is PLS-complete. Using the PLS-completeness for independent sets with the 3-swap-neighborhood, we also show PLS-completeness for a large class of maximum-weight subgraph problems. On the positive side, we show that locally optimal independent sets or dominating sets can be found in polynomial time when allowing all 3-swaps except (a) the swaps that remove two vertices from the current solution and add one vertex to the solution or (b) the swaps that remove one vertex from the current solution and add two vertices to the solution. This result is shown via general algorithms for subset-weight optimization problems with a restricted
k
-swap neighborhood.
A Cascaded ReRAM-based Crossbar Architecture for Transformer Neural Network Acceleration
Authors: Xu Jiahong , Liu Haikun , Peng Xiaoyang , Duan Zhuohui , Liao Xiaofei , Jin Hai
Published: October 2024

Emerging
resistive random-access memory
(ReRAM) based processing-in-memory (PIM) accelerators have been increasingly explored in recent years because they can efficiently perform
in-situ
matrix-vector multiplication
(MVM) operations involved in a wide spectrum of artificial neural networks. However, there remain significant challenges to apply existing ReRAM-based PIM accelerators to the most popular Transformer neural networks. Since Transformers involve a series of
matrix-matrix multiplication
(MatMul) operations with data dependencies, they should write intermediate results of MatMuls to ReRAM crossbar arrays for further processing. Conventional ReRAM-based PIM accelerators often suffer from high latency of ReRAM writes and intra-layer pipeline stalls.

In this paper, we propose ReCAT, a ReRAM-based PIM accelerator designed particularly for Transformers. ReCAT exploits
transimpedance amplifiers
(TIAs) to cascade a pair of crossbar arrays for MatMul operations involved in the self-attention mechanism. The intermediate result of a MatMul generated by one crossbar array can be directly mapped to another crossbar array, avoiding costly analog-to-digital conversions. In this way, ReCAT allows MVM operations to overlap with the corresponding data mapping, hiding the high latency of ReRAM writes. Furthermore, we propose an
analog-to-digital converter
(ADC) virtualization scheme to dynamically share scarce ADCs among a group of crossbar arrays, and thus significantly improve the utilization of ADCs to eliminate the performance bottleneck of MVM operations. Experimental results show that ReCAT achieves 207.3×, 2.11×, and 3.06× performance improvement on average compared with other Transformer acceleration solutions—GPUs, ReBert, and ReTransformer, respectively.
DRL-based Content Caching Strategy With Efficient User Preference Predictions in UAV-assisted VEC
Authors: Li Chunlin , Zhang Yong , Yu Long , Jiang Kun , Luo Youlong , Wan Shaohua
Published: October 2024

In vehicular edge computing, Unmanned Aerial Vehicles (UAVs) have become a feasible solution for addressing high deployment costs faced by base stations in congested roads during peak hours. However, UAVs cannot cache all requested content due to limited storage. Hence, we propose a content caching strategy based on user preference predictions. To address resource consumption and user privacy concerns during the training process, we propose a user preference prediction model based on hierarchical federated learning training. Specifically, we employ a hierarchical clustering approach to partition user vehicles and UAVs into multiple clusters and utilize hierarchical federated learning to train prediction models within each cluster. Furthermore, to tackle the joint optimization problem of content caching and bandwidth allocation, we propose I-MADDPG, an improved multi-agent deep deterministic policy gradient algorithm. It determines the next continuous action based on the reward value at the current moment and the average reward value in the iteration period as reference parameters. The experimental results demonstrate that the proposed algorithm has significantly enhanced training efficiency compared to the baselines. Additionally, it has improved cache hit rate and reduced content request delay through effective resource allocation.
Circadian Clocks, Daily Stress, and Neurodegenerative Disease
Authors: Nyamugenda Eugene , Rosensweig Clark , Allada Ravi
Published: October 2024

Disrupted circadian or 24-h rhythms are among the most common early findings in a wide range of neurodegenerative disorders. Once thought to be a mere consequence of the disease process, increasing evidence points toward a causal or contributory role of the circadian clock in neurodegenerative disease. Circadian clocks control many aspects of cellular biochemistry, including stress pathways implicated in neuronal survival and death. Given the dearth of disease-modifying therapies for these increasingly prevalent disorders, this understanding may lead to breakthroughs in the development of new treatments. In this review, we provide a background on circadian clocks and focus on some potential mechanisms that may be pivotal in neurodegeneration.
A Statistical Viewpoint on Differential Privacy: Hypothesis Testing, Representation, and Blackwell's Theorem
Authors: Su Weijie J.
Published: October 2024

Differential privacy is widely considered the formal privacy for privacy-preserving data analysis due to its robust and rigorous guarantees, with increasingly broad adoption in public services, academia, and industry. Although differential privacy originated in the cryptographic context, in this review we argue that, fundamentally, it can be considered a pure statistical concept. We leverage Blackwell's informativeness theorem and focus on demonstrating that the definition of differential privacy can be formally motivated from a hypothesis testing perspective, thereby showing that hypothesis testing is not merely convenient but also the right language for reasoning about differential privacy. This insight leads to the definition of f-differential privacy, which extends other differential privacy definitions through a representation theorem. We review techniques that render f-differential privacy a unified framework for analyzing privacy bounds in data analysis and machine learning. Applications of this differential privacy definition to private deep learning, private convex optimization, shuffled mechanisms, and US Census data are discussed to highlight the benefits of analyzing privacy bounds under this framework compared with existing alternatives.
3-Electrode Setup for the Operando Detection of Side Reactions in Li-Ion Batteries: The Quantification of Released Lattice Oxygen and Transition Metal Ions from NCA
Authors: Reuter Lennart , Reinschlüssel Leonhard J. , Gasteiger Hubert A.
Published: October 2024

Detecting parasitic side reactions is paramount for developing stable cathode active materials (CAMs) for Li-ion batteries. This study presents a method for the quantification of released lattice oxygen and transition metal ions (TMII+ ions). It is based on a 3-electrode cell design employing a Vulcan carbon-based sense electrode (SE) that is held at a controlled voltage against a partially delithiated lithium iron phosphate (LFP) counter electrode (CE). At this SE, reductive currents can be measured while polarizing a CAM working electrode (WE), here a LiNi0.80Co0.15Al0.05O2 (NCA), against the same LFP CE. In voltammetric scans, we show how the SE potential can be selected to specifically detect a given side reaction during CAM charge/discharge, allowing, e.g., to discriminate between lattice oxygen and dissolved TMs. Furthermore, it is shown via online electrochemical mass spectrometry (OEMS) that O2 reduction in the here-used LP47 electrolyte consumes ∼2.3 electrons/O2. Using this value, the lattice oxygen release deduced from the 3-electrode setup upon charging of the NCA WE is in good agreement with OEMS measurements up to NCA potentials >4.65 VLi. At higher potentials, the contributions from the reduction of TMII+ ions can be quantified by comparing the integrated SE current with the O2 evolution from OEMS.
Enhanced Electrocatalytic Performance of Novel d-Ti3CN@CdSe Nanocomposite for Efficient Water Splitting: Achieving Low Overpotential and High Stability
Authors: Bibi Maryam , Asghar Muhammad Asad , Ahmad Saba , Haider Sajjad , Alam Kamran , Khan Shahid Ali , Mansoor Muhammad Adil , Iqbal Mudassir
Published: October 2024

The escalating global demand for clean and sustainable energy has ignited significant interest in hydrogen production through water splitting. A major challenge in this pursuit is the development of efficient and cost-effective electrocatalysts for the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). Here, we present the synthesis of a novel two-dimensional d-Ti3CN @CdSe nanocomposite, designed as a high-performance electrocatalyst for overall water splitting. Synthesized via hydrothermal methods, the nanocomposite was characterized using advanced characterization techniques viz. Raman spectroscopy, XRD, XPS, and SEM/EDS. Electrochemical evaluations demonstrate that the d-Ti3CN @CdSe nanocomposite significantly enhances catalytic performance compared to its individual components, achieving a low overpotential of 232 mV for HER at 10 mA cm−2 and reducing the OER overpotential from 498.3 mV for d-Ti3CN MXene to 382.2 mV in the nanocomposite at 30 mA cm−2. Additionally, it exhibits excellent stability, retaining about 75.37% of its current density after 36 h of continuous operation. This remarkable performance is attributed to the synergistic interactions between CdSe nanoparticles and Ti3CN MXene layers, which prevent restacking, increase the electrochemically active surface area, and enhance charge transfer efficiency. These features position the d-Ti3CN @CdSe nanocomposite as a promising candidate for scalable and sustainable water-splitting applications.
The Effect of Electrochemical Ageing of Glassy Carbon Electrodes on VII-VIII and VIV-VV Kinetics
Authors: Alhajji M. , Bourke A. , Buckley D. N. , Lynch R. P.
Published: October 2024

Electrode activity towards the negative and positive half-cell reactions of a vanadium flow battery were investigated. Cyclic voltammetry and electrochemical impedance spectroscopy were employed to monitor electrode activity of glassy carbon electrodes towards VII-VIII and VIV-VV redox reactions during electrochemical ageing through repeated anodic and cathodic treatments. Electrode activity is found to increase with number of treatment steps, showing little difference initially between anodised and cathodised electrodes. However, after several treatments, a potential-differentiated behaviour emerges, with distinct enhanced and inhibited states. For VII-VIII, anodised electrodes showed enhanced activity, while cathodised electrodes were inhibited. Conversely, for VIV-VV, cathodised electrodes had enhanced activity. In almost all cases, the activity is greater than that of an untreated electrode. Eventually, electrode activities stabilise in a steady-state region where activity depends on the final treatment potential rather than the number of steps. In this region, activity can be toggled reproducibly between enhanced and inhibited states. Therefore, it can be concluded that functional groups, rather than surface roughening or defect formation, are responsible for this toggling capability. Furthermore, for VIV-VV, steady-state activity levels and the number of treatment steps required to reach this region are found to be dependent on the upper and lower treatment potentials.
Serial and regional assessment of the right ventricular molecular and functional response to pressure loading
Authors: Yazaki Kana , Dewar Michael , Dauz John , Akazawa Yohei , Hui Lucy , Sun Mei , Hui Wei , Kabir Golam , Dejardin Jean-Francois , Connelly Kim A. , Heximer Scott P. , Friedberg Mark K.
Published: October 2024

Exploring the dynamics of right ventricular remodeling: unveiling the intricate interplay between inflammation, metabolic shifts, and fibrotic signaling in response to pressure loading. Through a comprehensive study spanning from initiation to 6 wk post-pressure loading, our research sheds light on the early onset of crucial molecular processes preceding overt hypertrophy and dysfunction. These findings challenge conventional intervention timing, advocating for early, targeted therapeutic strategies to mitigate adverse remodeling in right ventricular pressure loading.
Cardiac surgery-associated acute kidney injury in cardiopulmonary bypass: a focus on sex differences and preventive strategies
Authors: Kulthinee Supaporn , Warhoover Matthew , Puis Luc , Navar L. Gabriel , Gohar Eman Y.
Published: October 2024

Cardiac surgery-associated acute kidney injury (CSA-AKI) is a high-risk complication with well-recognized increased morbidity and mortality after cardiac surgery attributable in large part to cardiopulmonary bypass (CPB)-associated factors contributing to AKI including hemodilution, hypothermia, hypotension, and exposure to artificial surfaces. These conditions disrupt the renal microcirculation and activate local and systemic inflammatory responses to nonpulsatile flow and low perfusion pressure. The underlying mechanisms of CSA-AKI in CPB are not fully understood, and the incidence of CSA-AKI remains high at around 30%. Furthermore, women appear to be more vulnerable than men to the renal injury associated with CPB even though the overall incidence of cardiovascular and kidney diseases is lower in premenopausal women. Nevertheless, estrogen elicits renoprotective effects in several ways including mitigating inflammation, promoting natriuresis, and endothelial protection as shown in preclinical studies. However, women have higher rates of CSA-AKI and these are exacerbated in postmenopausal women. This leads to the conundrum of whether sex, age, and hormonal status differences influence CSA-AKI. In this review, we briefly discuss the pathophysiology of CSA-AKI in CPB and sex differences in kidney functions with a focus on the possible role of estrogen-specific effects in CPB and also possible differences in CPB in women including greater hemodilution. Furthermore, we review strategies to prevent CSA-AKI in CPB with a highlight for potential sex-specific strategies. Improving our understanding of the impact of sex and sex hormones on CSA-AKI initiation and development will allow us to better manage the CPB strategies delivered to all patients.
Chronic kidney disease amplifies severe kidney injury and mortality in a mouse model of skin arsenical exposure
Authors: Srivastava Ritesh Kumar , Traylor Amie Mark , Muzaffar Suhail , Esman Stephanie K. , Soliman Reham H. , Khan Jasim , Warren Phoebe , Bolisetty Subhashini , George James F. , Agarwal Anupam , Athar Mohammad
Published: October 2024

Preexisting chronic kidney disease (CKD) predisposes experimental animals to augmented morbidity and mortality following cutaneous vesicant exposure. The mechanism underlying increased susceptibility to renal injury and associated morbidity involves the DNA damage-regulated p53 signaling pathway.
5/6 Nephrectomy impairs acute kaliuretic responses and predisposes to postprandial hyperkalemia
Authors: Wei Kuang-Yu , Gritter Martin , Danser A. H. Jan , Vogt Liffert , de Borst Martin H. , Rotmans Joris I. , Imenez Silva Pedro Henrique , Hoorn Ewout J.
Published: October 2024

Rats who underwent 5/6 nephrectomy demonstrate a reduced ability to excrete an acute K+ load with the development of postprandial hyperkalemia. 5/6 Nephrectomy attenuates K+-induced natriuresis and impairs ENaC regulation despite intact NCC dephosphorylation and increased plasma aldosterone. This offers a potential explanation for why patients with chronic kidney disease are predisposed to postprandial hyperkalemia.
Cadence-based energy expenditure in able-bodied male people comparing cadence-based energy expenditure and oxygen cost indices in able-bodied male people
Authors: Hong Juntaek , Yu Jehyeon , Lee Juyeon , Shim Dain , Choi Tae Young , Cho Ye Bin , Lee Jeuhee , Rha Dong-Wook
Published: October 2024

We proposed cEEI as a reliable metric for estimating energy expenditure under various walking conditions. Its demonstrated accuracy and potential for real-time individualized feedback could revolutionize personalized exercise prescriptions for diverse sexes and age groups, as well as individuals with disabilities requiring real-time physical monitoring and home care.
The influence of sex on the effects of inorganic nitrate supplementation on muscular power and endurance
Authors: Ortiz de Zevallos Joaquin , Hogwood Austin C. , Kruse Ka’eo , De Guzman Jeison , Buckley Meredith , DeJong Lempke Alexandra F. , Weltman Arthur , Allen Jason D.
Published: October 2024

Recent data have suggested that inorganic nitrate ([Formula: see text]) supplementation may benefit males; however, females may experience worsened endurance capacity. This study revealed a potential differentiated effect of [Formula: see text] supplementation on outcomes of muscle contractile function between healthy, young males and females. The specific responses of [Formula: see text] supplementation in females and across sexes remain understudied and require further investigation.
The effects of inorganic nitrate supplementation on muscular power and endurance across the menstrual cycle
Authors: Hogwood Austin C. , Ortiz De Zevallos Joaquin , Kruse Ka’eo , Buckley Meredith , De Guzman Jeison , DeJong Lempke Alexandra , Weltman Arthur , Allen Jason D.
Published: October 2024

Recent data have suggested that inorganic nitrate ([Formula: see text]) supplementation may benefit males, however, females may experience worsened endurance capacity independent of menstrual cycle phase. This study revealed neither [Formula: see text] supplementation nor the follicular phase of the menstrual cycle influenced maximal isometric voluntary contraction or endurance capacity in healthy, young, naturally menstruating females, whereas [Formula: see text] supplementation significantly worsened estimated peak power (Pmax) and velocity (Vmax) independent of the menstrual cycle phase.
Quantification and interpretation of nitric oxide-dependent cutaneous vasodilation during local heating
Authors: Wolf S. Tony , Dillon Gabrielle A. , Alexander Lacy M. , Kenney W. Larry , Stanhewicz Anna E.
Published: October 2024

Local heating protocols are commonly used in conjunction with intradermal microdialysis for assessing nitric oxide (NO)-dependent microvascular function in humans, but various methods used to quantify and describe NO-dependent vasodilation may impact data interpretation. We compared four approaches for quantifying NO-dependent cutaneous vasodilation during local heating at 39°C and 42°C. We identify discrepancies in calculated NO-dependent dilation responses that are dependent upon the mathematical approach and meaningfully impact data interpretation and reproducibility.
Design of a mindfulness intervention to reduce risk factors for colorectal cancer among at-risk Black women in Chicago
Authors: Lima Oliveira Manoela , Lima Natalia Salvatierra , Khara Renaud Garcelle , Estrada Andy , Buitrago Diana , Hamm Alyshia , Nadeem Saba , Naylor Keith B. , Chen Zhengjia , Yanez Betina , Booms Emily , Searcy Jasmin , Biggers Alana , Tussing-Humphreys Lisa Marie
Published: October 2024

We propose to evaluate an 8-wk mindfulness intervention delivered in a hybrid format (synchronous and asynchronous sessions) among 40 Black women at elevated risk of CRC who reside in vulnerable communities and who report moderate to high perceived stress. The specific aims are to assess the feasibility and acceptability of the intervention and explore changes on stress, weight, fasting glucose, inflammation markers, and the gut microbiota—risk markers and risk pathways associated with CRC.
Antimicrobial Resistance Profiles of E. coli Isolated From Pooled Samples of Sick, Farm, and Market Chickens in Nairobi County, Kenya
Authors: Deng Tino A. , Bebora Lilly C. , Odongo Mahacla O. , Muchemi Gerald M. , Karuki Samuel , Gathumi Peter K.
Published: October 2024

Bacterial antimicrobial resistance (AMR) is a global threat to both human and animal health. This is mainly because the same antimicrobial molecules are used for the treatment and prophylaxis of bacterial diseases in both cases, and about 60% of human pathogens are shared with animals. For effective control of AMR in any country, the current situation has to be established; this is done through surveillance exercises. In Kenya, there is scanty data on the prevailing AMR situation, especially in animals. This paper reports on AMR profiles of 54 E. coli strains isolated from chickens in a cross‐sectional study, out of which 36/54 (72%) were from clinically ill chickens, 11/54 (22%) were from farm chickens, and 7/54 (9.7%) were from slaughtered chicken, respectively. All 54 isolates exhibited varying antimicrobial resistance profiles with the majority showing resistance to Ampicillin (85.22%), Tetracycline (66.7%), Co‐trimoxazole (57.4%), and Streptomycin (40.7%). Very few isolates were resistant to Amoxicillin and Gentamicin (each at 3.7%), Ampicillin (11.1%), and Nalidixic acid (24.1%). A total of 44/54 (81.5%) showed multiple resistance to up to 6 antimicrobial agents. This information will augment current data on the AMR status of bacteria harbored by chickens in Kenya. It will also inform policymakers in their fight against AMR.
Magnitude and Associated Factors of Herbal Medicine Use During Pregnancy Among Women Attending Antenatal Care in Public Health Institutions of Central Tigray, Northern Ethiopia (2020): Facility‐Based Cross‐Sectional Study
Authors: Gebrekidan Hailemikael , Kidanemariam Gebregziabher
Published: October 2024

Introduction: Herbal medicine is described by the World Health Organization (WHO) as plant‐derived compounds, either raw or processed, that are thought to have therapeutic advantages. Herbal medication is becoming more and more popular worldwide, particularly during pregnancy. The WHO estimates that 80% of people utilize herbal remedies. In Ethiopia, grandmothers and grandfathers frequently use herbal medicine at home to treat common health issues. Instead of using medically proven treatments during their pregnancy, the majority of expectant mothers trust herbal remedies.

Objective: The aim of this study was to assess the magnitude and associated factors of herbal medicine use during pregnancy among women attending antenatal care in public health institutions of central Tigray, northern Ethiopia.

Methods: Facility‐based cross‐sectional study was conducted from March 01 to May 15, 2020. Data were collected using a structured and pretested questionnaire. Data were entered into Epi‐data manager version 7.2.5 and analyzed using SPSS version 23. Both binary and multivariate logistic regression analyses were carried out to assess the associated factors. Variables with p value less the 0.2 in bivariate analysis were transferred to multivariate analysis, and variables with p value ≤ 0.05 were considered as significant.

Result: Out of the total 333 respondents, making a response rate of 100%, 176 (52.9%) used herbal medicine during current pregnancy. The most common medicines used during pregnancy were garlic (59.4%) and ginger (51.7%). Occupation that is housewife had educational status (AOR = 11.816, 95% CI 1.848–35.535), illiterate (AOR = 1.886, 95% CI 1.586–2.241), residency/rural (AOR = 2.905, 95% CI 1.173–7.197), and average monthly income less than 500 Ethiopian birrs (AOR = 7.621, 95% CI 2.691–21.585) were factors that are significantly associated with the use of herbal medicine during pregnancy.

Conclusion and Recommendation: Based on our results, herbal medicine use during pregnancy is highly practiced in this study, and occupation, residency, educational status, and average monthly income were the significantly associated factors of herbal medicine use during pregnancy. There is a need to educate and counsel pregnant women on the harmful effects of herbal medicine use during pregnancy by the health care personnel and health extension worker.
Genomic Biomarkers Predict Response to Combined ATR Inhibition and Radiotherapy
Authors: Schrank Benjamin R. , Colbert Lauren E.
Published: October 2024

For decades, chemoradiosensitization with checkpoint kinase inhibitors has been proposed but largely unexplored. A recent study reports that the novel ataxia telangiectasia and Rad3-related kinase inhibitor RP-3500 synergizes with radiation to control Atm−/− tumors in vivo. RP-3500 did not radiosensitize wild-type or Brca-1–deficient tumors, highlighting the need for a genotype-tailored approach.

See related article by Ng et al., p. 5643
Abstract A008: Better outcomes for ovarian cancer associated with the detection of anti-EBV TCR CDR3s: Potential relevance to diffuse large B-cell lymphoma
Authors: Goel Nandini , Baker Madeline C , Blanck George , Jain Rahul , Diaz Michael J , Huda Taha I , Chobrutskiy Andrea , Chobrutskiy Boris I , Song Joanna J , Priya Vangala Veda Naga
Published: October 2024

Given the ongoing challenges regarding the specific roles of viral infections in cancer etiology, or as cancer co-morbidities, this study assessed potential associations between anti-viral, T-cell receptor (TCR) complementarity domain region-3 (CDR3s) and clinical outcomes for ovarian cancer. Analyses revealed that patients with exact matches of anti-Epstein-Barr virus (EBV) CDR3 amino acid sequences exhibited better outcomes for both overall and disease-specific survival. However, better outcomes were not observed when assessing anti-viral CDR3s representing cytomegalovirus, influenza A, or Sars-CoV-2. Due to previous occurrences of the occasional misdiagnoses of lymphoma as ovarian cancer, the frequency of anti-EBV CDR3s in lymphoma patients was determined. These frequencies were relatively high, particularly in diffuse large B-cell lymphoma. These findings (i) underscore the potential value of anti-EBV immune responses in terms of patient outcomes; (ii) raise questions about the potential value of anti-EBV immunotherapies; and (iii) support further inquiry into the relationship between EBV infection and previously reported cases of ovary-resident lymphoma.

Citation Format: Nandini Goel, Madeline C Baker, George Blanck, Rahul Jain, Michael J Diaz, Taha I Huda, Andrea Chobrutskiy, Boris I Chobrutskiy, Joanna J Song, Veda Naga Priya Vangala. Better outcomes for ovarian cancer associated with the detection of anti-EBV TCR CDR3s: Potential relevance to diffuse large B-cell lymphoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr A008.
Abstract A013: Transcription initiation and its regulation in mouse L1s
Authors: Saha Karabi , An Wenfeng
Published: October 2024

Long interspersed elements type 1 (LINE-1s or L1s) are highly abundant non-LTR retrotransposons in mammalian genomes. Apart from an evolutionary role in altering the genomic landscape and gene expression, recent discoveries have revealed the scale and impact of active movement by L1, both in the germline and in somatic niches (e.g., the brain and many cancers). As transcriptional activation is a prerequisite for L1 retrotransposition, it is important to understand how L1 transcription is regulated. L1 transcription is controlled by an internal promoter contained in the 5’ untranslated region (5’UTR) of a full-length element. It has been shown that transcription start sites (TSSs) of human L1 are clustered at the beginning of its 5’UTR and the precision of transcription initiation is controlled by transcription factor YY1. The laboratory mouse is an essential model for investigating L1 retrotransposition and the associated consequences in vivo. However, mouse L1 5’UTRs are distinctly different from human L1’s: the former are organized into tandem repeats called monomers and separated from the open reading frames by a nonmonomeric sequence called tether. Unlike the human L1 promoter, transcription initiation and its regulation in mouse L1 subfamilies remain unknown. In this study, we streamlined the cloning of different types of mouse L1 promoters. TSSs were determined using RNA ligation-mediated 5’ rapid amplification of cDNA ends (RLM-5’RACE) incorporating a highly efficient reverse transcriptase enzyme followed by Nanopore sequencing. In the context of two monomer promoter reporter construct, transcription could initiate from either monomer or the tether sequence. While mouse L1 TSSs are distributive, a higher number of transcripts were initiated from the inner monomer. Surprisingly, a significant fraction of transcripts was also initiated from the tether sequence. In addition, we showed that YY1 transcriptionally activates mouse L1 5’UTR and is responsible for the synergy between the monomers. As transcription initiation is a major determinant for the proportion of active L1 loci in the next round of retrotransposition, these findings have important implications on L1 biology in the mouse model.

Citation Format: Karabi Saha, Wenfeng An. Transcription initiation and its regulation in mouse L1s [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr A013.
Abstract A024: POSTPRANDIAL CHANGES TO SYSTEMIC METABOLISM IMPRINT DURABLE CHANGES ON T CELL IMMUNE RESPONSES
Authors: Kumar Alok , Rivadeneira Dayana B , Kohan Alison , Delgoffe Greg
Published: October 2024

While nutrient availability and intrinsic metabolic pathways play key roles in T cell function and fate, systemic nutrient availability waxes and wanes with every meal. How postprandial metabolism affects T cell function and fate are unstudied. Here we show short periods of fasting and refeeding can have long-lasting effects on T cell immunity. Mouse or human T cells from fed hosts have higher mitochondrial quality and respiratory capacity than those from fasted hosts ex vivo. These metabolic phenotypes persist after activation and expansion, both in vitro culture and in vivo in response to vaccination. Fed T cells outcompete fasted T cells in a co-transfer model, such that T cells from fasted hosts form far fewer memory T cells. Serum profiling revealed triglycerides as a driver of postprandial metabolic reprogramming: chylomicrons enriched from the lymphatics of fed mice were sufficient to enhance mitochondria of fasted T cells. LDLR-deficient T cells had the metabolic phenotype of fasted T cells and were insensitive to fed serum, confirming the role of triglyceride uptake in postprandial T cell metabolic programming. Transcriptomic analysis revealed higher expression of LDLR, OXPHOS proteins, and fatty acid metabolism enzymes in fed T cells over fasted T cells. Finally, human CAR T cells manufactured from the same donor after a meal show a therapeutic advantage over T cells collected in the fasted state. In summary, postprandial metabolism imparts durable metabolic and functional advantage on T cells. Our study highlights the need to consider diet content and timing as key factors in immune cell analysis, vaccination strategies, and the generation of cellular therapies for cancer.

Citation Format: Alok Kumar, Dayana B Rivadeneira, Alison Kohan, Greg Delgoffe. POSTPRANDIAL CHANGES TO SYSTEMIC METABOLISM IMPRINT DURABLE CHANGES ON T CELL IMMUNE RESPONSES [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr A024.
Abstract A038: Antigen Presentation By Cancer-Associated Fibroblasts
Authors: Kina Eralda , Côté Caroline , Larouche Jean-David , Durette Chantal , Lanoix Joel , Bonneil Eric , Laverdure Jean-Philippe , Lavallée Gabriel Ouellet , Buchanan Margaret , Aguilar Adriana , Mechta-Grigoriou Fatima , Thibault Pierre , Basik Mark , Perreault Claude
Published: October 2024

Introduction: Immunotherapy has shown promise in treating some patients with metastatic diseases, but the effectiveness of the immune system in controlling cancer is hampered by a suppressive tumor microenvironment (TME), in which cancer-associated fibroblasts (CAFs) play a key role. Developing new and highly specific immunotherapeutic tools targeting CAFs may have a significative impact on tumor control. For this purpose, we aim to investigate antigen presentation characteristics by MHC-I molecules in CAFs and identify targetable CAF-specific antigens. Methods and Results: Analysis of existing single-cell datasets revealed higher expression of MHC-I in CAFs compared to normal fibroblasts (p<0.05) in various tumor types. In melanoma, higher MHC-I expression was linked to resistance to immune checkpoint blockade (ICB). Additionally, we found a positive correlation between MHC-I expression and immunosuppressive molecules such as galectin-9 and HVEM. These observations were supported by initial flow cytometry analyses in CAF cell lines derived from patients. Furthermore, prolonged and severe hypoxia further elevated MHC-I protein levels in CAF cell lines. Using a proteogenomic approach with mass spectrometry, we identified over 10,000 antigens in five patient-derived CAF cell lines from primary breast cancer tumors and one normal fibroblast cell line. By integrating single-cell and bulk RNA sequencing data from various tumors and normal tissues, we identified more than 20 CAF-specific or fibroblast-specific antigens. Conclusion: CAFs exhibit high MHC-I expression, which is amplified under hypoxic conditions. We have identified CAF-specific antigens that require evaluation for their immunogenicity, indicating the potential of CAFs as targets for antigen-based therapies.

Citation Format: Eralda Kina, Caroline Côté, Jean-David Larouche, Chantal Durette, Joel Lanoix, Eric Bonneil, Jean-Philippe Laverdure, Gabriel Ouellet Lavallée, Margaret Buchanan, Adriana , Fatima Mechta-Grigoriou, Pierre Thibault, Mark Basik, Claude Perreault. Antigen Presentation By Cancer-Associated Fibroblasts [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr A038.
Abstract A042: Common gamma-chain signaling in NK cells promotes their Flt3L-dependent support of cDC1s in melanoma
Authors: Avanessian Shayan C , van den Bijgaart Renske J.E. , Chew Nayvin W , Tang Thao T , Barry Kevin C
Published: October 2024

Natural killer (NK) cells are an innate lymphocyte population that have an inherent ability to recognize and eliminate malignant cells without requiring prior sensitization. However, NK cells are more than just a population of killers—they are prominent producers of cytokines and chemokines, lending them a pivotal ability to orchestrate robust immune responses involving other immune cell types. We have previously shown that NK cells in the tumor microenvironment (TME) are critical regulators of type one conventional dendritic cells (cDC1s), which are required for protective immune responses against cancer and for the success of checkpoint blockade immunotherapies. Through the production of the cDC1-formative cytokine FMS-like tyrosine kinase 3 ligand (Flt3l/Flt3L in mice or FLT3LG/FLT3LG in humans), NK cells support cDC1 abundance in the melanoma TME. Indeed, the abundance of this innate immune axis of NK cells-FLT3LG-cDC1s defines checkpoint blockade-responsiveness in melanoma patients. Despite this clear clinical relevance, the molecular and cellular mechanisms underlying NK cell regulation of FLT3LG are not understood. Here, we investigated signals that modulate NK cell activity and found that the common gamma- chain cytokines IL-2 and IL-15 are uniquely able to upregulate Flt3L production by NK cells, and that treatment of NK cells with IL-2 and IL-15 led to increased support of cDC1s both in-vitro and in-vivo. This local NK cell support of cDC1s in the TME, in combination with checkpoint blockade, potentiates tumor control in the non-responsive B16F10 melanoma model. Furthermore, we demonstrated that a particular subset of immunomodulatory NK cells that excels in cytokine production is primarily responsible for the production of Flt3L in response to common gamma-chain signaling. By analyzing human melanoma patient datasets, we found that the abundance of immunomodulatory NK cells within the TME correlates both with FLT3LG and cDC1 abundance. These findings define the features of the TME and of NK cells that promote successful cancer responses and will inform future NK cell-based therapy approaches.

Citation Format: Shayan C Avanessian, Renske J.E. van den Bijgaart, Nayvin W Chew, Thao T Tang, Kevin C Barry. Common gamma-chain signaling in NK cells promotes their Flt3L-dependent support of cDC1s in melanoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr A042.
Abstract A055: CD47 predominates over CD24 as a macrophage immune checkpoint in cancer
Authors: Meglan Anna , Allen Juliet , Vaccaro Kyle , Velarde José , Chen Victor , Ribeiro Juliano , Blandin Jasmine , Mishra Ranjan , Ho Raymond , Love Jennifer , Reinhardt Ferenc , Bell George W , Chen Jin , Weinberg Robert , Yang Dian , Weissman Jonathan , Weiskopf Kipp
Published: October 2024

Macrophages hold tremendous promise as effectors of cancer immunotherapy, but the best strategies to provoke these cells to attack tumors remain unknown. Here, we evaluated the therapeutic potential of targeting two distinct macrophage immune checkpoints: CD47 and CD24. We found that antibodies targeting these antigens could elicit maximal levels of phagocytosis when combined together in vitro. However, to our surprise, via unbiased genome-wide CRISPR screens, we found that CD24 primarily acts as a target of opsonization rather than an immune checkpoint. In a series of in vitro and in vivo genetic validation studies, we found that CD24 was neither necessary nor sufficient to protect cancer cells from macrophage phagocytosis in most mouse and human tumor models. Instead, anti-CD24 antibodies exhibit robust Fc-dependent activity, and as a consequence, they cause significant on-target hematologic toxicity that was life-threatening in syngeneic mice. To overcome these challenges and leverage our findings for therapeutic purposes, we engineered a collection of 77 novel bispecific antibodies that bind to a tumor antigen with one arm and engage macrophages with the second arm. We discovered multiple novel bispecifics that maximally activate macrophage-mediated cytotoxicity and reduce binding to healthy blood cells, including bispecifics targeting macrophage immune checkpoint molecules in combination with EGFR, TROP2, and CD71. Overall, our findings indicate that CD47 predominates over CD24 as a macrophage immune checkpoint in cancer, and that the novel bispecifics we created may be optimal immunotherapies to direct myeloid cells to eradicate solid tumors.

Citation Format: Anna Meglan, Juliet Allen, Kyle Vaccaro, José Velarde, Victor Chen, Juliano Ribeiro, Jasmine Blandin, Ranjan Mishra, Raymond Ho, Jennifer Love, Ferenc Reinhardt, George W Bell, Jin Chen, Robert Weinberg, Dian Yang, Jonathan Weissman, Kipp Weiskopf. CD47 predominates over CD24 as a macrophage immune checkpoint in cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr A055.