bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB349: Cysteine restriction enhances antitumor immunity in colorectal cancer
Authors: Li Jichang , Xia Kang , Yang Zeruo , Pan Xiaoxue , Yang Xiaojing , Wang Pengyuan , Chen Shanwen 
Published: April 2024

Abstract
Background: Colon cancer is the second leading cause of cancer mortality worldwide, however, there are still issues with multidrug resistance and severe adverse reactions. Previous studies have shown that sulfur-containing amino acids are involved in cancer development, drug resistance, and immune evasion. Here, Our experimental findings suggested that restricting the intake of sulfur-containing amino acids may present a novel strategy for treating colorectal cancer.
Methods: We assessed the impact of sulfur-containing amino acid restriction (SAR) on distinct cellular subpopulations within the tumor microenvironment through single-cell sequencing on colon carcinogenesis induced by azoxymethane/dextran sodium sulfate (AOM/DSS). Employing our custom-produced neutralizing antibodies against SLC7A11 to restrict cysteine intake, we examined the therapeutic implications and underlying molecular mechanisms by RNA-seq, Multiplexed immunofluorescence staining and Western blotting.
Results: In the AOM/DSS model, SAR led to a slight reduction in mouse body weight compared to the normal diet. However, this dietary restriction significantly enhanced the survival rate of mice and effectively suppressed tumor growth. The single-cell sequencing results indicated a significant increase in the proportion of T cells within the tumor microenvironment in response to SAR. This suggested that restricting the intake of sulfur-containing amino acids may be a promising anti-tumor strategy. Previous studies have indicated high expression of the SLC7A11, a cysteine transporter protein, in various cancers, including colorectal cancer. To further investigate the role of cysteine in colorectal cancer, we developed the neutralizing antibody 1A4 against SLC7A11. Our results indicated that 1A4 markedly inhibited colorectal cancer development in mice. As known, 85% of colorectal cancers are microsatellite stable, which hardly benefit from treatment with immune checkpoint inhibitors (ICIs). Compared to anti-PD-1 and anti-CTLA4, 1A4 significantly inhibited the growth of CT26 in vivo. Multiplexed immunofluorescence staining results demonstrated that 1A4 significantly increased the proportion of CD8+ T cells in colorectal cancer tissues.
Conclusion: Limiting cysteine intake significantly inhibits the growth of colorectal cancer, increases the proportion of CD8+ T cells, and enhances anti-tumor immunity.
Citation Format: Jichang Li, Kang Xia, Zeruo Yang, Xiaoxue Pan, Xiaojing Yang, Pengyuan Wang, Shanwen Chen. Cysteine restriction enhances antitumor immunity in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB349.
Abstract LB405: CTP synthase 1 is a synthetic vulnerability in prostate cancer treated with supraphysiological androgen
Authors: Jonnatan Sheila , Kumar Rajendra , Vakkala Varsha , Vasan Karthik , Chalmers Zachary R. , Schmidt Daniel R. , Beer Philip A. , Heiden Matthew G. Vander , Denmeade Samuel R. , Chandel Navdeep S. , Sena Laura A. 
Published: April 2024

Abstract
Bipolar androgen therapy (BAT) is the cyclical administration of supraphysiological androgen (SPA), which can be an effective treatment for 30-40% of patients with castration-resistant prostate cancer. We sought to improve the efficacy of BAT by better understanding its molecular consequences in prostate cancer. Given that the androgen receptor (AR) regulates cellular metabolism, we hypothesized that SPA induces dependencies on specific metabolic pathways that might be exploited therapeutically. A negative selection metabolism-focused CRISPR-KO screen in LNCaP cells treated with SPA suggested that the deletion of several enzymes involved in de novo nucleotide synthesis enhances growth suppression by SPA. A top hit was cytidine triphosphate synthase 1 (CTPS1). CTPS1 converts UTP to CTP in the final step of de novo pyrimidine synthesis. Exposure of SPA-treated prostate cancer cell lines to STP-B, a potent and highly selective inhibitor of CTPS1 (PMID 37008165), increased cell death in vitro and in vivo, indicating that CTPS1 constitutes a metabolic vulnerability in this context. Inhibition of CTPS1 with STP-B induced S phase cell cycle arrest and replication stress, as indicated by phosphorylation of RPA and CHEK proteins, which was augmented by treatment with SPA. CTPS1 likely becomes a vulnerability in SPA-treated prostate cancer due to the downregulation of MYC by SPA, which we found leads to a reduced abundance of enzymes required for nucleotide synthesis and nucleotides, particularly CTP. This rewires nucleotide synthesis and salvage pathway such that de novo synthesis of CTP is required to avoid replication stress and cell death. Altogether, this work suggests that inhibition of CTPS1 may enhance the efficacy of BAT through the induction of replication stress. Selective inhibitors of CTPS1 have entered clinical development (NCT05463263), increasing the feasibility of a combination therapy clinical trial design for patients with prostate cancer.
Citation Format: Sheila Jonnatan, Rajendra Kumar, Varsha Vakkala, Karthik Vasan, Zachary R. Chalmers, Daniel R. Schmidt, Philip A. Beer, Matthew G. Vander Heiden, Samuel R. Denmeade, Navdeep S. Chandel, Laura A. Sena. CTP synthase 1 is a synthetic vulnerability in prostate cancer treated with supraphysiological androgen [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB405.
Abstract SY41-01: Selection of targeted neoantigens for personalized cancer vaccines
Authors: Keskin Derin 
Published: April 2024

Abstract
Neoantigen targeting personalized cancer vaccines (PCV) have the potential to revolutionize cancer treatment. These personalized vaccines rely on accurate epitope prediction and selection. We previously reported phase I trials of neoantigen targeting PCV in melanoma and glioblastoma multiforme (GBM). Recently we concluded a trial in renal cell carcinoma (RCC) where the neoantigen targeting PCV was immunogenic in all patients, targeted cancer drivers, and demonstrated in vitro reactivity to primary patient tumors. The neoantigen selection pipeline at DFCI supporting clinical trials utilizes immunopeptidome-trained epitope prediction algorithms to design synthetic long peptides as vaccine antigens containing predicted HLA Class I neoantigens. We also prioritize highly expressed neoantigens and neoantigens originating from cancer drivers as vaccine epitopes. For future iterations of this pipeline, we aspire to include novel classes of neoantigens originating from endogenous human retroviruses (ERV), fusion epitopes, novel or unannotated open reading frames (nuORFs), and immunopeptidome-identified neoantigens. The neoantigen selection pipeline is currently supporting multiple cancer vaccine trials at DFCI targeting melanoma, GBM, RCC, ovarian cancer, and chronic lymphocytic leukemia (CLL).
Citation Format: Derin Keskin. Selection of targeted neoantigens for personalized cancer vaccines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr SY41-01.
Ventromedial frontoinsular connectivity is associated with long-term smoking behavior change in aging
Authors: Thovinakere Nagashree , Ai Meishan , Colina Adrián Noriega de la , Walker Caitlin , Baracchini Giulia , Tremblay-Mercier Jennifer , Villeneuve Sylvia , Spreng Nathan , Geddes Maiya R. 
Published: April 2024

Abstract
A central question in the field of cognitive aging and behavioral neuroscience is what enables some individuals to successfully change their behavior more than others? Smoking is a significant risk factor for cognitive decline, particularly in vulnerable populations, including those who are at an elevated risk for Alzheimer’s disease (AD). Developing effective smoking reduction strategies is therefore a public health priority. The goal of the current study is to better understand the brain mechanisms underlying long-term smoking behavior change in cognitively normal, but at-risk, older adults. Neuroimaging and human lesion studies have implicated the insula and its functional network in subjective interoceptive awareness of cigarette craving and smoking-cue reactivity. We sought to characterize the extent to which anterior insular resting-state functional connectivity (RSFC) MRI predicted long-term smoking reduction (mean: 2.7 years, range 8 months–4 years) using a seed-to-voxel approach. Twenty-three (18 women; 26% APOE4 carriers; 61.5 years, SD = 3.7) cognitively unimpaired older individuals who smoked cigarettes at their baseline visit and have a first-degree family history of AD (at least one parent or multiple siblings affected) were included from a prospective longitudinal cohort, Pre-symptomatic Evaluation of Experimental or Novel Treatments for Alzheimer Disease (PREVENT-AD) in the current study. We found that reduced long-term smoking behavior was associated with enhanced antagonistic RSFC between bilateral anterior insula (aINS) and ventromedial prefrontal cortex (vmPFC). In a second pre-registered replication study within a larger, independent sample of 118 cognitively normal older adults who smoked cigarettes at baseline from the UK Biobank (73 women; 27.9% APOE4 carriers; 60.3 years, SD = 2.7), we found that baseline enhanced antagonistic RSFC between anterior insula and vmPFC predicted long-term smoking reduction (mean 5.2 years; ranging from 3 years to 7 years). To our knowledge, this is the largest study to examine the neural substrates of long-term smoking cessation in human aging. Our results suggest that antagonistic RSFC between aINS and vmPFC is a brain marker of future smoking reduction and disease prevention in older adults at risk for AD.
Men of Letters: Perspectives on Multisensory Environments in the Hall-McLuhan Correspondence, 1961–1977
Authors: Muench Wolfgang 
Published: April 2024

Abstract
This paper introduces critical elements in the substantial, albeit mostly unpublished, correspondence between cultural anthropologist Edward T. Hall and media theorist Marshall McLuhan related to artistic practice with emerging media technologies in the 1960s. It contextualizes their exchange within the broader theoretical discourses and artistic practices surrounding systems theory and media technology and highlights intersections between Hall and McLuhan’s theoretical frameworks related to concepts of indeterminism, systems theory, and cybernetics in technology-based, kinesthetic, multisensory mediated environments in the 1960s. It particularly focuses on overlapping conceptual approaches toward the interrelation between the individual, the socio-cultural environment, and the emerging media-technological ecosystem.
Genetic basis for Rapana venosa with different peristome color based on microsatellite, DNA methylation, and transcriptome analysis
Authors: Zou Shanmei , Gao Zhan , Wu Xuemin , Yu Xinke , Sun Tiantian , Wang Changhai 
Published: April 2024

Abstract
Rapana venosa, a well-known and economic species mainly distributed in the Asian region, has three distinct color patterns in the peristome: pure orange, pure dark stripes, and part stripes. The present study combined microsatellite, DNA methylation, and transcriptome to assess the genetic basis of three color patterns of R. venosa in the peristome. The different color patterns of R. venosa showed no significant genetic differentiation, and each color group was relatively independent with respect to gene flow. Each color pattern showed a high methylation rate of more than 60%. The full-methylation rates for the three color patterns were 34.47%, 35.67%, and 32.54%, respectively. The Gene Ontology (GO) classification and functional enrichment revealed three ontologies: molecular function, cellular components, and biological processes. The function of translation, ribosomal structure, and biogenesis accounted for the top classification, followed by general function prediction. This study also revealed some functional genes related to color and shell formation, including Scavenger receptor cysteine-rich protein (SRCR), beta-carotene ketolase, tyrosinase proteins, and Lustrin A. These findings suggest that the color polymorphism of R. venosa is possibly attributed to environmental effects. The research is also essential for selecting better germplasm for the breeding of Rapana venosa.
Zonal Wavenumber 3 Forces Extreme Precipitation in South America
Authors: Ortiz-Guzmán Valentina , Jucker Martin , Sherwood Steven C. 
Published: April 2024

Abstract
The Southern Hemisphere climate and weather are affected by several modes of variability and climate phenomena across different time and spatial scales. An additional key component of the atmosphere dynamics that greatly influences weather is quasi-stationary Rossby waves, which attract particular interest as they are often associated with synoptic-scale extreme events. In the Southern Hemisphere extratropical circulation, the most prominent quasi-stationary Rossby wave pattern is the zonal wavenumber 3 (ZW3), which has been shown to have impacts on meridional heat and momentum transport in mid- to high latitudes and on the Antarctic sea ice extent. However, little is known about its impacts outside of polar regions. In this work, we use ERA5 reanalysis data on monthly time scales to explore the influence of phase and amplitude of ZW3 on temperature and precipitation across the Southern Hemisphere midlatitudes. Our results show a significant impact in various regions for all seasons. One of the most substantial effects is observed in precipitation over southeastern Brazil during austral summer, where different phases of the ZW3 force opposite anomalies. When using the ZW3 phase and amplitude as prior information, the probability of occurrence of precipitation extremes in this region increases up to three times. Additionally, we find that this ZW3 weather signature is largely independent of the zonally symmetric Southern Annular Mode (SAM); neither does it seem to be linked to El Niño–Southern Oscillation (ENSO) or Indian Ocean dipole (IOD) signal.
Cross-Shelf Exchange in Prograde Antarctic Troughs Driven by Offshore-Propagating Dense Water Eddies
Authors: Gaul Alan , Zhang Weifeng (Gordon) , Cenedese Claudia 
Published: April 2024

Abstract
This study examines the link between near-bottom outflows of dense water formed in Antarctic coastal polynyas and onshore intrusions of Circumpolar Deep Water (CDW) through prograde troughs cutting across the continental shelf. Numerical simulations show that the dense water outflow is primarily in the form of cyclonic eddies. The trough serves as a topographic guide that organizes the offshore-moving dense water eddies into a chain pattern. The offshore migration speed of the dense water eddies is similar to the velocity of the dense water offshore flow in the trough, which scaling analysis finds to be proportional to the reduced gravity of the dense water and the slope of the trough sidewalls and to be inversely proportional to the Coriolis parameter. Our model simulations indicate that, as these cyclonic dense water eddies move across the trough mouth into the deep ocean, they entrain CDW from offshore and carry CDW clockwise along their periphery into the trough. Subsequent cyclonic dense water eddies then entrain the intruding CDW further toward the coast along the trough. This process of recurring onshore entrainment of CDW by a topographically constrained chain of offshore-flowing dense water eddies is consistent with topographic hotspots of onshore intrusion of CDW around Antarctica identified by other studies. It can bring CDW from offshore to close to the coast and thus impact the heat flux into Antarctic coastal regions, affecting interactions among ocean, sea ice, and ice shelves.

Significance Statement
Troughs cutting across the Antarctic continental shelf are a major conduit for the transport of dense shelf water from coastal formation regions to the shelf break. This study describes a process in which clockwise-spinning eddies moving offshore in prograde troughs successively entrain filaments of relatively warm Circumpolar Deep Water from offshore across the entire shelf and into the coastal region. This eddy-induced transport provides a new understanding of the shelf edge exchange process identified in previous studies and a mechanism for further onshore intrusion of the warm Circumpolar Deep Water over parts of the Antarctic shelf. The resultant onshore heat flux could potentially bring a substantial amount of heat from offshore into the coastal region and thus affect ice–ocean interactions through melting sea ice and ice shelves.
Structural improvement of 3D woven honeycomb composite liner for enhanced energy absorption and impact performance in aircrew helmet
Authors: Singh Omender , Behera BK 
Published: April 2024

This study aims to enhance the performance of aircrew helmet liners made of 3D woven honeycomb composites through structural improvements. To achieve this, an optimization of the honeycomb design was carried out using a statistical tool by varying its geometrical parameters. A Box Behnken design was employed, using three independent factors: cell height, cell size, and cell wall thickness to assess its impact and their interactions on responses. The performance was evaluated using a multiobjective response to maximize impact energy absorption, achieve the target cushion factor, and balance relative density for lightweight design. Since the liner materials were subjected to flatwise compression and dynamic impact tests to assess the performance. Their behavior. The results revealed that the honeycomb core with a cell height of 15 mm, a cell size of 10 mm, and a cell wall thickness of 0.6 mm exhibited good behavior. The response surface analysis and contour plots were used to analyze the interactions and combined effects of variables on each response. It was observed that lesser cell size shows significant improvement in impact energy with higher wall thickness. However, the cushion factor implies inadequate energy mitigation. The analysis comparing desirability and confirmatory experiments highlighted the potential for the aircrew helmet liner to achieve its maximum performance. This study provides valuable insights into the structural design of 3D woven honeycomb composite liners for aircrew helmets and its findings signify the potential for applications in the aerospace and defense industries.
Hierarchically porous surface of HA-sandblasted Ti implant screw using the plasma electrolytic oxidation: Physical characterization and biological responses
Authors: Choe YoungEun , Li Cheng Ji , Yeo Dong-Hyeon , Kim Yu-Jin , Lee Jung-Hwan , Lee Hae-Hyoung 
Published: April 2024

The surface topological features of bioimplants are among the key indicators for bone tissue replacement because they directly affect cell morphology, adhesion, proliferation, and differentiation. In this study, we investigated the physical, electrochemical, and biological responses of sandblasted titanium (SB-Ti) surfaces with pore geometries fabricated using a plasma electrolytic oxidation (PEO) process. The PEO treatment was conducted at an applied voltage of 280 V in a solution bath consisting of 0.15 mol L−1 calcium acetate monohydrate and 0.02 mol L−1 calcium glycerophosphate for 3 min. The surface chemistry, wettability, mechanical properties and corrosion behavior of PEO-treated sandblasted Ti implants using hydroxyapatite particles (PEO-SB-Ti) were improved with the distribution of calcium phosphorous porous oxide layers, and showed a homogeneous and hierarchically porous surface with clusters of nanopores in a bath containing calcium acetate monohydrate and calcium glycerophosphate. To demonstrate the efficacy of PEO-SB-Ti, we investigated whether the implant affects biological responses. The proposed PEO-SB-Ti were evaluated with the aim of obtaining a multifunctional bone replacement model that could efficiently induce osteogenic differentiation as well as antibacterial activities. These physical and biological responses suggest that the PEO-SB-Ti may have a great potential for use an artificial bone replacement compared to that of the controls.
Lack of awareness of systemic lupus erythematosus and its consequences in a cohort of moderate and severe patients in Spain: The LupusVoice study
Authors: Galindo Izquierdo Maria , Borrás Blasco Joaquín , Pérez Ortega Silvia , Salman-Monte Tarek Carlos , Vela-Casasempere Paloma , Rodríguez Almaraz Esther , Calvo-Alen Jaime , Álvaro-Gracia Álvaro José María , Barbado Ajo Mͣ Julia , Rubio Renau Raül , Galvez-Fernandez Marta , Bahamontes-Rosa Noemí , Sánchez-Covisa Hernández Joaquín , Solà Marsiñach Carlota 
Published: April 2024

Background and objectives Systemic lupus erythematosus (SLE) is an autoimmune condition that can highly impact patients’ quality of life (QoL). However, there is a lack of knowledge about SLE, affecting the general population and health care professionals (HCPs) alike. This lack of knowledge has negative implications for patients and the healthcare system, worsening prognosis, negatively impacting QoL, and increasing healthcare utilization. The aim of this paper is to draw attention, according to the perspective of the participants of this study, to the lack of awareness of SLE and its consequences in Spain, and to suggest improvements. Patients and methods This qualitative, descriptive, observational, multicenter, and cross-sectional study included 40 patients with moderate or severe SLE, recruited during their routine visits in six university hospitals in Spain. The study also included 11 caregivers and 9 HCPs. All participants were individually interviewed. Data from the interviews were coded and analyzed thematically by two anthropologists following a phenomenological perspective. Results Our study identified a lack of disease awareness among primary care physicians, emergency medicine doctors, and other specialists treating SLE symptomatology. This led to diagnostic delays, which had a clinical and emotional impact on patients. Furthermore, symptom awareness was found to be context dependent. Differences in symptom awareness between HCPs and patients led to a mismatch between the severity evaluation made by doctors and patients. Some HCPs did not consider the limitations of the current severity evaluation of SLE, and therefore attributed symptoms potentially caused by SLE to the unfavorable socioeconomic conditions patients lived in. Finally, a lack of social awareness among friends, family members, and romantic partners led to lower social support, increased isolation, and negative physical and emotional impact for patients. Gender differences in the provision of support were identified. Conclusion This study highlights the need to increase SLE awareness among patients, HCPs, and the broader public in order to improve patient QoL. Being aware of the clinical and emotional impact of such lack of awareness, as well as the role played by context on the patient experience of SLE, is a crucial step towards achieving this goal.