bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract C099: Mutant-selective, covalent inhibitors of K-Ras(G12D)
Authors: Zheng Qinheng , Zhang Ziyang , Guiley Keelan , Shokat Kevan 
Published: January 2024

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the most lethal common cancer. A high percentage (&gt;90%) of PDAC patients harbor KRAS mutations, with the majority expressing the K-Ras(G12D) missense mutation protein. Despite extensive drug discovery efforts across academia and industry, there are no approved drugs directly targeting oncogenic K-Ras(G12D) in a mutant-selective manner. We have developed a series of small molecules that form covalent bonds with the mutant protein at its missense site. The lead molecule inhibits the interaction of K-Ras with effector proteins, and therefore inhibits growth of KRASG12D-driven cancer cell lines but not non-G12D cells.
Citation Format: Qinheng Zheng, Ziyang Zhang, Keelan Guiley, Kevan Shokat. Mutant-selective, covalent inhibitors of K-Ras(G12D) [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C099.
Abstract PR10: Uridine-to-ribose axis supports glucose-restricted pancreatic cancer
Authors: Nwosu Zeribe C. , Ward Matthew H. , Sajjakulnukit Peter , Poudel Pawan , Ragulan Chanthirika , Kasperek Steven , Radyk Megan , Sutton Damien , Menjivar Rosa E. , Andren Anthony , Apiz-Saab Juan J. , Tolstyka Zachary , Brown Kristee , Lee Ho-Joon , Dzierozynski Lindsey , He Xi , Ps Hari , Ugras Julia , Nyamundanda Gift , Zhang Li , Halbrook Christopher J. , Carpenter Eileen , Shi Jiaqi , Shriver Leah P. , Patti Gary J. , Muir Alexander , di Magliano Marina Pasca , Sadanandam Anguraj , Lyssiotis Costas A. 
Published: January 2024

Abstract
Pancreatic ductal adenocarcinoma (PDA) is a lethal disease with a 5-year survival rate of 12% in the USA. PDA highly rely on glucose but is surrounded by a nutrient-limited microenvironment. How PDA survive such condition, and the metabolites enabling that process, is unclear. To determine how PDA adapt to starvation, we profiled the utility of &gt;175 metabolites by 21 pancreatic cell lines cultured in glucose limited condition. This nutrient profiling assay revealed that PDA use uridine when glucose is depleted. Uridine utilization strongly correlated with uridine phosphorylase 1 (UPP1) – the enzyme that breaks down uridine to uracil and ribose-1-phosphate. Metabolomics, including stable isotope tracing, revealed that when glucose is limited, PDA cells use the ribose from uridine to sustain central carbon metabolism and that this process is blocked upon the knockout of UPP1. We found that UPP1 is regulated by KRAS, is high in PDA, and correlates with poor survival in patients. Moreover, deletion of UPP1 blunted tumor growth in mice. Our data identify the uridine-ribose axis as a crucial compensatory pathway in nutrient-deprived PDA, suggesting a potential therapeutic target.
Citation Format: Zeribe C. Nwosu, Matthew H. Ward, Peter Sajjakulnukit, Pawan Poudel, Chanthirika Ragulan, Steven Kasperek, Megan Radyk, Damien Sutton, Rosa E. Menjivar, Anthony Andren, Juan J. Apiz-Saab, Zachary Tolstyka, Kristee Brown, Ho-Joon Lee, Lindsey Dzierozynski, Xi He, Hari Ps, Julia Ugras, Gift Nyamundanda, Li Zhang, Christopher J. Halbrook, Eileen Carpenter, Jiaqi Shi, Leah P. Shriver, Gary J. Patti, Alexander Muir, Marina Pasca di Magliano, Anguraj Sadanandam, Costas A. Lyssiotis. Uridine-to-ribose axis supports glucose-restricted pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr PR10.
TREX1 Inactivation Unleashes Cancer Cell STING–Interferon Signaling and Promotes Antitumor Immunity
Authors: Tani Tetsuo , Mathsyaraja Haritha , Campisi Marco , Li Ze-Hua , Haratani Koji , Fahey Caroline G. , Ota Keiichi , Mahadevan Navin R. , Shi Yingxiao , Saito Shin , Mizuno Kei , Thai Tran C. , Sasaki Nobunari , Homme Mizuki , Yusuf Choudhury Fabliha B. , Kashishian Adam , Panchal Jipsa , Wang Min , Wolf Benjamin J. , Barbie Thanh U. , Paweletz Cloud P. , Gokhale Prafulla C. , Liu David , Uppaluri Ravindra , Kitajima Shunsuke , Cain Jennifer , Barbie David A. 
Published: January 2024

Abstract

A substantial fraction of cancers evade immune detection by silencing Stimulator of Interferon Genes (STING)-Interferon (IFN) signaling. Therapeutic reactivation of this program via STING agonists, epigenetic, or DNA-damaging therapies can restore antitumor immunity in multiple preclinical models. Here we show that adaptive induction of three prime exonuclease 1 (TREX1) restrains STING-dependent nucleic acid sensing in cancer cells via its catalytic function in degrading cytosolic DNA. Cancer cell TREX1 expression is coordinately induced with STING by autocrine IFN and downstream STAT1, preventing signal amplification. TREX1 inactivation in cancer cells thus unleashes STING–IFN signaling, recruiting T and natural killer (NK) cells, sensitizing to NK cell–derived IFNγ, and cooperating with programmed cell death protein 1 blockade in multiple mouse tumor models to enhance immunogenicity. Targeting TREX1 may represent a complementary strategy to induce cytosolic DNA and amplify cancer cell STING–IFN signaling as a means to sensitize tumors to immune checkpoint blockade (ICB) and/or cell therapies.

Significance:
STING–IFN signaling in cancer cells promotes tumor cell immunogenicity. Inactivation of the DNA exonuclease TREX1, which is adaptively upregulated to limit pathway activation in cancer cells, recruits immune effector cells and primes NK cell–mediated killing. Targeting TREX1 has substantial therapeutic potential to amplify cancer cell immunogenicity and overcome ICB resistance.
This article is featured in Selected Articles from This Issue, p. 695
Tierra de imbunches y ch’uqtas: la dis-capacidad como dispositivo colonial en América Latina y el Caribe
Authors: Vallejo Ortega Diana Carolina 
Published: January 2024

Este ensayo analiza la dis-capacidad como un dispositivo colonial en América Latina, destacando las implicaciones ontológicas y ético-políticas que esto tiene especialmente para los cuerpos que han sido etiquetados como discapacitados. Asimismo, en este ensayo se propone una respuesta alternativa a esta ontología colonial, reconociendo la existencia de cuerpos no normativos, imbunches y ch'uqtas —términos estos que hacen referencia a las identidades y experiencias de las personas que desafían la normatividad impostada/importada, como formas singulares de resistencia desde la diáspora al discurso y las prácticas hegemónicas. La noción de dis-capacidad se examina, entonces, desde una mirada crítica y en una perspectiva decolonial del pensamiento latinoamericano, que la entiende como un constructo sociocultural que se utiliza en calidad de herramienta de dominación y opresión. Se sostiene, así, que la dis-capacidad es impuesta sobre los cuerpos para mantener y reproducir las estructuras de poder y control. Mientras que la diáspora se plantea como un espacio de apertura y posibilidad para la resistencia contra la ontología colonial de la dis-capacidad. Desde este lugar, se invita a repensar y cuestionar las categorías impuestas, promoviendo una concepción más inclusiva y respetuosa de la diversidad de los cuerpos.

[1] Palabra que en mapuzugun, la lengua del pueblo mapuche que habita el territorio sur de Chile y Argentina, quiere decir ‘persona deforme o desproporcionada’.
[2] Palabra que en Quechua, lengua que se habla en territorio peruano y boliviano, propia de nacionalidad Quechua, quiere decir ‘torcido o feo’.
Asymmetric Dimethylarginine Enables Depolarizing Spikes and Vasospasm in Mesenteric and Coronary Resistance Arteries
Authors: Ng Yu Y. Hanson , Dora Kim A. , Lemmey Hamish A.L. , Lin JinHeng , Alden James , Wallis Lillian , Donovan Lucy , Shorthose Oliver , Leiper Fiona C. , Leiper James , Garland Christopher J. 
Published: January 2024

BACKGROUND:

Increased vasoreactivity due to reduced endothelial NO bioavailability is an underlying feature of cardiovascular disease, including hypertension. In small resistance arteries, declining NO enhances vascular smooth muscle (VSM) reactivity partly by enabling rapid depolarizing Ca
2+
-based spikes that underlie vasospasm. The endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) is metabolized by DDAH1 (dimethylarginine dimethylaminohydrolase 1) and elevated in cardiovascular disease. We hypothesized ADMA might enable VSM spikes and vasospasm by reducing NO bioavailability, which is opposed by DDAH1 activity and L-arginine.

METHODS:

Rat isolated small mesenteric arteries and myogenic rat-isolated intraseptal coronary arteries (RCA) were studied using myography, VSM intracellular recording, Ca
2+
imaging, and DDAH1 immunolabeling. Exogenous ADMA was used to inhibit NO synthase and a selective DDAH1 inhibitor, N
G
-(2-methoxyethyl) arginine, to assess the functional impact of ADMA metabolism.

RESULTS:

ADMA enhanced rat-isolated small mesenteric arteries vasoreactivity to the α
1
-adrenoceptor agonist, phenylephrine by enabling T-type voltage-gated calcium channel-dependent depolarizing spikes. However, some endothelium-dependent NO-vasorelaxation remained, which was sensitive to DDAH1-inhibition with N
G
-(2-methoxyethyl) arginine. In myogenically active RCA, ADMA alone stimulated depolarizing Ca
2+
spikes and marked vasoconstriction, while NO vasorelaxation was abolished. DDAH1 expression was greater in rat-isolated small mesenteric arteries endothelium compared with RCA, but low in VSM of both arteries. L-arginine prevented depolarizing spikes and protected NO-vasorelaxation in rat-isolated small mesenteric artery and RCA.

CONCLUSIONS:
ADMA increases VSM electrical excitability enhancing vasoreactivity. Endothelial DDAH1 reduces this effect, and low levels of DDAH1 in RCAs may render them susceptible to endothelial dysfunction contributing to vasospasm, changes opposed by L-arginine.
Shifting From Active to Passive Monitoring of Alzheimer Disease: The State of the Research
Authors: Popp Zachary , Low Spencer , Igwe Akwaugo , Rahman Md Salman , Kim Minzae , Khan Raiyan , Oh Emily , Kumar Ankita , De Anda‐Duran Ileana , Ding Huitong , Hwang Phillip H. , Sunderaraman Preeti , Shih Ludy C. , Lin Honghuang , Kolachalama Vijaya B. , Au Rhoda 
Published: January 2024

ABSTRACT
Most research using digital technologies builds on existing methods for staff‐administered evaluation, requiring a large investment of time, effort, and resources. Widespread use of personal mobile devices provides opportunities for continuous health monitoring without active participant engagement. Home‐based sensors show promise in evaluating behavioral features in near real time. Digital technologies across these methodologies can detect precise measures of cognition, mood, sleep, gait, speech, motor activity, behavior patterns, and additional features relevant to health. As a neurodegenerative condition with insidious onset, Alzheimer disease and other dementias (AD/D) represent a key target for advances in monitoring disease symptoms. Studies to date evaluating the predictive power of digital measures use inconsistent approaches to characterize these measures. Comparison between different digital collection methods supports the use of passive collection methods in settings in which active participant engagement approaches are not feasible. Additional studies that analyze how digital measures across multiple data streams can together improve prediction of cognitive impairment and early‐stage AD are needed. Given the long timeline of progression from normal to diagnosis, digital monitoring will more easily make extended longitudinal follow‐up possible. Through the American Heart Association–funded Strategically Focused Research Network, the Boston University investigative team deployed a platform involving a wide range of technologies to address these gaps in research practice. Much more research is needed to thoroughly evaluate limitations of passive monitoring. Multidisciplinary collaborations are needed to establish legal and ethical frameworks for ensuring passive monitoring can be conducted at scale while protecting privacy and security, especially in vulnerable populations.
Processionary Caterpillars at the Edge of Complexity
Authors: Collard Philippe 
Published: January 2024

Abstract
This article deals with individuals moving in procession in real and artificial societies. A procession is a minimal form of society in which individual behavior is to go in a given direction and the organization is structured by the knowledge of the one ahead. This simple form of grouping is common in the living world, and, among humans, procession is a very circumscribed social activity whose origins are certainly very remote. This type of organization falls under microsociology, where the focus is on the study of direct interactions between individuals within small groups. In this article, we focus on the particular case of pine tree processionary caterpillars (Thaumetopoea pityocampa). In the first part, we propose a formal definition of the concept of procession and compare field experiments conducted by entomologists with agent-based simulations to study real caterpillars’ processionaries as they are. In the second part, we explore the life of caterpillars as they could be. First, by extending the model beyond reality, we can explain why real processionary caterpillars behave as they do. Then we report on field experiments on the behavior of real caterpillars artificially forced to follow a circular procession; these experiments confirm that each caterpillar can either be the leader of the procession or follow the one in front of it. In the third part, by allowing variations in the speed of movement on an artificial circular procession, computational simulations allow us to observe the emergence of unexpected mobile spatial structures built from regular polygonal shapes where chaotic movements and well-ordered forms are intimately linked. This confirms once again that simple rules can have complex consequences.
Live Coding Machine Learning: Finding the Moments of Intervention in Autonomous Processes
Authors: Paz Iván , Knotts Shelly 
Published: January 2024

Abstract
Machine learning (ML) deals with algorithms able to learn from data, with the primary aim of finding optimum solutions to perform tasks autonomously. In recent years there has been development in integrating ML algorithms with live coding practices, raising questions about what to optimize or automate, the agency of the algorithms, and in which parts of the ML processes one might intervene midperformance. Live coding performance practices typically involve conversational interaction with algorithmic processes in real time. In analyzing systems integrating live coding and ML, we consider the musical and performative implications of the “moment of intervention” in the ML model and workflow, and the channels for real-time intervention. We propose a framework for analysis, through which we reflect on the domain-specific algorithms and practices being developed that combine these two practices.
Individual and gender inequality in computer science: A career study of cohorts from 1970 to 2000
Authors: Lietz Haiko , Jadidi Mohsen , Kostic Daniel , Tsvetkova Milena , Wagner Claudia 
Published: January 2024

Abstract
Inequality prevails in science. Individual inequality means that most perish quickly and only a few are successful, and gender inequality implies that there are differences in achievements for women and men. Using large-scale bibliographic data and following a computational approach, we study the evolution of individual and gender inequality for cohorts from 1970 to 2000 in the whole field of computer science as it grows and becomes a team-based science. We find that individual inequality in productivity (publications) increases over a scholar’s career but is historically invariant, whereas individual inequality in impact (citations), albeit larger, is stable across cohorts and careers. Gender inequality prevails regarding productivity, but there is no evidence for differences in impact. The Matthew Effect is shown to accumulate advantages to early achievements and to become stronger over the decades, indicating the rise of a “publish or perish” imperative. Only some authors manage to reap the benefits that publishing in teams promises. The Matthew Effect then amplifies initial differences and propagates the gender gap. Women continue to fall behind because they continue to be at a higher risk of dropping out for reasons that have nothing to do with early-career achievements or social support.
Harvesting the Rain: The Adoption of Environmental Technologies in the Sahel
Authors: Aker Jenny C. , Jack B. Kelsey 
Published: January 2024

Abstract
Many agricultural and environmental technologies require upfront investments. This may deter adoption, particularly in settings characterized by information liquidity and credit constraints. We test for these barriers to the adoption of an agricultural technique that helps address land degradation in Niger. We find little evidence that liquidity or credit constraints deter adoption: instead, providing farmers with training increases the share of adopters by over 90 percentage points. Conditional or unconditional cash transfers have no additional effect. Adoption increases agricultural output and reduces land turnover in the longerterm. In our setting, training provides both specific technical knowledge and addresses behavioral constraints.
Adaptation to the Fourth Industrial Revolution among Generation Y in Rural Africa
Authors: Oki Olukayode Ayodele , Uleanya Chinaza , Fikisi Sesona 
Published: January 2024

Abstract
The study investigates adaptation to the Fourth Industrial Revolution (4IR) among the rural youth in Qunu, Eastern Cape, South Africa. The broad focus on 4IR in job creation is its impact on youth skills development, and an important question is how rural youth benefit from 4IR opportunities. With few studies conducted on the topic of youth skills development in the context of 4IR, an investigation of the problems faced by the rural youth in Qunu in accessing emerging technologies was deemed to be of value. Mixed-method research was employed with a sample of 44 young people living in Qunu. Data was analysed using themes. The findings of this study indicate that the respondents had inadequate knowledge about 4IR and the opportunities it offers. Also, little is being done to improve the skills of the youth, though they show interest in improving their IT skills.
Attribution of the August 2022 Extreme Heatwave in Southern China: Role of Dynamical and Thermodynamical Processes
Authors: Gong Hainan , Ma Kangjie , Hu Zhiyuan , Dong Zizhen , Ma Yuanyuan , Chen Wen , Wu Renguang , Wang Lin 
Published: January 2024

Abstract
We estimate that anthropogenic forcing caused half of the observed temperature anomaly during the August 2022 heatwave in southern China. Thermodynamical processes, especially soil moisture–SAT feedback, amplified the heatwave.
Association Between Preoperative Long-Term Poor Sleep Quality and Postoperative Delirium in Elderly Patients Undergoing Cardiac Surgery: A Multi-Center Observational Study
Authors: Huang Zhilian , Huang Chengfeng , Deng Yanfang , Lu Hao , Shi Lifang 
Published: January 2024

Background Delirium is a common complication in elderly patients after cardiac surgery, and sleep disorders have been suggested as a potential risk factor. However, few studies have explored the link between long-term preoperative poor sleep quality and postoperative delirium (POD) in this population. This study aimed to investigate the association between preoperative sleep quality and POD in elderly cardiac surgery patients. Methods The study enrolled 194 patients aged 60 years or older who underwent cardiac surgery. The Pittsburgh Sleep Quality Index (PSQI) objectively assessed preoperative sleep quality, while the Confusion Assessment Method screened for POD. The measurable outcomes encompassed the identification of risk factors associated with POD, while the secondary outcomes focused on factors influencing levels of consciousness. The statistical analysis is logistic regression analysis. Results Patients with POD had a higher prevalence of preoperative sleep disorders and higher PSQI scores than those without delirium (12.9 ± 5.1 vs 7.8 ± 3.4, P = .007). Logistic regression analysis demonstrated that the number of months with high PSQI scores and age were significantly associated with POD. The predictive ability of the number of months with high PSQI scores for POD was .762 (95% CI: .671-.854). Multivariate linear regression analysis revealed that preoperative sleep disorder was a significant predictor of exacerbation of POD ( P < .05). Conclusion This study suggests that long-term poor preoperative sleep quality, as assessed by the PSQI, is associated with an increased risk of POD in elderly patients undergoing cardiac surgery.
The biological role and future therapeutic uses of nitric oxide in extracorporeal membrane oxygenation, a narrative review
Authors: Brinkley Lindsey , Brock Michael A , Stinson Griffin , Bilgili Ahmet , Jacobs Jeffrey P , Bleiweis Mark , Peek Giles J 
Published: January 2024

Background Nitric oxide (NO) is a gas naturally produced by the human body that plays an important physiological role. Specifically, it binds guanylyl cyclase to induce smooth muscle relaxation. NO’s other protective functions have been well documented, particularly its protective endothelial functions, effects on decreasing pulmonary vascular resistance, antiplatelet, and anticoagulation properties. The use of nitric oxide donors as vasodilators has been known since 1876. Inhaled nitric oxide has been used as a pulmonary vasodilator and to improve ventilation perfusion matching since the 1990s. It is currently approved by the United States Food and Drug Administration for neonates with hypoxic respiratory failure, however, it is used off-label for acute respiratory distress syndrome, acute bronchiolitis, and COVID-19. Purpose In this article we review the currently understood biological action and therapeutic uses of NO through nitric oxide donors such as inhaled nitric oxide. We will then explore recent studies describing use of NO in cardiopulmonary bypass and extracorporeal membrane oxygenation and speculate on NO’s future uses.