bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of the free boundary problem of vascular tumor growth with periodic nutrient supply and time delay terms
Authors: Xu Shihe
Published: May 2024

In this paper, a mathematical model for a solid spherically symmetric vascular tumor growth with nutrient periodic supply and time delays is studied. Compared to the apoptosis process of tumor cells, there is a time delay in the process of tumor cell division. The cells inside the tumor obtain nutrient [Formula: see text] through blood vessels, and the tumor attracts blood vessels at a rate proportional to [Formula: see text]. So, the boundary value condition [Formula: see text] holds on the boundary, where the function [Formula: see text] is the concentration of nutrient externally supplied to the tumor. Considering that the nutrients provided by the outside world are often periodic, the research in this paper assumes that [Formula: see text] is a periodic function. Sufficient conditions for the global stability of zero steady state are presented. Under certain conditions, we prove that there exists at least one periodic solution to the model. The results are illustrated by computer simulations.
Dielectric relaxation in BaTiO3–Bi(Zn1∕2Zr1∕2)O3
Authors: Wang Qian , Hu Jian-Hong , Liu Jun-Yi , Wang Chun-Ming , Wang Chun-Lei
Published: May 2024

Dielectric relaxation behaviors of (1–x)BaTiO3–xBi(Zn[Formula: see text]Zr[Formula: see text]O3 (BT–BZZ, [Formula: see text]) have been analyzed at various temperatures. Both Havriliak–Negami (H–N) and Jurlewicz–Weron–Stanislavsky (J–W–S) relaxations are identified in these ceramic compositions. H–N relaxation happens in compositions with a small mole ratio of Bi(Zn[Formula: see text]Zr[Formula: see text]O3 (BZZ), while J–W–S type relaxation appears in compositions with a large mole ratio. Static dielectric constant, relaxation time and Jonscher indices are also obtained. The general trend of static dielectric constants decreases with increasing mole ratio of BZZ, while the relaxation time increases dramatically correspondingly. The low Jonscher index m is about 0.45 at low temperature for compositions with high mole ratio and increases with increasing of temperature. The high Jonscher index 1–n is around 0.1 at low temperature for compositions with high mole ratio and slightly decreases with increasing of temperature. Jonscher indices diagram with compositions of different mole ratios is plotted for easy identification of the relaxation types. Our results indicate that the relaxation behaviors in this BT–BZZ system show a strong deviation from the standard Debye model.
The Establishment of an Emergency Management and Epidemiological Surveillance System in Hospital to Combat Pertussis
Authors: Koh Wen Wen , Shen Jian , Law Michelle Xiao Ying , Yuan Ying , Zhang Xinlin
Published: May 2024

The pertussis resurgence has currently become a global public health concern. The widespread vaccination of pertussis vaccine will inevitably lead to changes in the transmission pattern, epidemiological characteristics, and clinical manifestations of pertussis while reducing the overall incidence level. At present, there is no unified pertussis surveillance program across countries, and different surveillance and monitoring approaches are used in different regions, and the reported incidence levels and epidemiological characteristics vary greatly. The integration of emergency management and epidemiological research is essential in the combating of pertussis. Emergency management provides the rapid response necessary to mitigate the impact of an outbreak, while epidemiological research provides the knowledge and understanding to guide effective control strategies. Researchers should take a consideration and discussion about the role of traditional Chinese medicine in this epidemic, as well as the treatment and prevention in the whole course of the disease. Besides, a model of emergency management and epidemiological surveillance system should be established and continuously improved in clinical to combat the pertussis outbreak. This paper aims to provide an epidemic control model of the emergency management procedure in hospital for references, so that the clinical practitioners and healthcare workers may be better prepared and well-respond to a next epidemic.
Self-tuning Database Systems: A Systematic Literature Review of Automatic Database Schema Design and Tuning
Authors: Mozaffari Maryam , Dignös Anton , Gamper Johann , Störl Uta
Published: May 2024

Self-tuning is a feature of autonomic databases that includes the problem of automatic schema design. It aims at providing an optimized schema that increases the overall database performance. While in relational databases automatic schema design focuses on the automated design of the physical schema, in NoSQL databases all levels of representation are considered: conceptual, logical, and physical. This is mainly because the latter are mostly schema-less and lack a standard schema design procedure as is the case for SQL databases. In this work, we carry out a systematic literature survey on automatic schema design in both SQL
and
NoSQL databases. We identify the levels of representation and the methods that are used for the schema design problem, and we present a novel taxonomy to classify and compare different schema design solutions. Our comprehensive analysis demonstrates that, despite substantial progress that has been made, schema design is still a developing field and considerable challenges need to be addressed, notably for NoSQL databases. We highlight the most important findings from the results of our analysis and identify areas for future research work.
Nutrition, Other Environmental Influences, and Genetics in the Determination of Human Stature
Authors: Lui Julian C. , Palmer Amanda C. , Christian Parul
Published: May 2024

Linear growth during three distinct stages of life determines attained stature in adulthood: namely, in utero, early postnatal life, and puberty and the adolescent period. Individual host factors, genetics, and the environment, including nutrition, influence attained human stature. Each period of physical growth has its specific biological and environmental considerations. Recent epidemiologic investigations reveal a strong influence of prenatal factors on linear size at birth that in turn influence the postnatal growth trajectory. Although average population height changes have been documented in high-income regions, stature as a complex human trait is not well understood or easily modified. This review summarizes the biology of linear growth and its major drivers, including nutrition from a life-course perspective, the genetics of programmed growth patterns or height, and gene–environment interactions that determine human stature in toto over the life span. Implications for public health interventions and knowledge gaps are discussed.
Guidelines for assessing maternal cardiovascular physiology during pregnancy and postpartum
Authors: Collins Helen E. , Alexander Barbara T. , Care Alison S. , Davenport Margie H. , Davidge Sandra T. , Eghbali Mansoureh , Giussani Dino A. , Hoes Martijn F. , Julian Colleen G. , LaVoie Holly A. , Olfert I. Mark , Ozanne Susan E. , Bytautiene Prewit Egle , Warrington Junie P. , Zhang Lubo , Goulopoulou Styliani
Published: May 2024

Maternal mortality rates are at an all-time high across the world and are set to increase in subsequent years. Cardiovascular disease is the leading cause of death during pregnancy and postpartum, especially in the United States. Therefore, understanding the physiological changes in the cardiovascular system during normal pregnancy is necessary to understand disease-related pathology. Significant systemic and cardiovascular physiological changes occur during pregnancy that are essential for supporting the maternal-fetal dyad. The physiological impact of pregnancy on the cardiovascular system has been examined in both experimental animal models and in humans. However, there is a continued need in this field of study to provide increased rigor and reproducibility. Therefore, these guidelines aim to provide information regarding best practices and recommendations to accurately and rigorously measure cardiovascular physiology during normal and cardiovascular disease-complicated pregnancies in human and animal models.
Improved Variable Structure Interacting Multimodels for Target Trajectory Tracking and Extrapolation
Authors: Ren Xuanming , Tang Xinmin , Zhou Yang , Guan Xiangmin
Published: May 2024

To improve the lengthy computation time of conventional variable structure interacting multiple model (VSIMM) algorithm and increase the precision of target prediction and extrapolation, the target state and flight intent information captured by the Automatic Dependent Surveillance-Broadcast (ADS-B) are used as the model’s prior information; combining this information with VSIMM theoretical framework, we purpose an intent variable structure interacting multiple model (INT-VSIMM) algorithm. Firstly, the motion pattern of the target in the flight phase of the flight path is decomposed, and complete sets of motion models are established. Secondly, according to the principle of directed graph switching, a model set switching method is designed, which is mainly based on “hard” switching and supplemented by “soft” switching. Finally, the INT-VSIMM algorithm is used to track the trajectory of the target aircraft, and short-term trajectory extrapolation is performed based on the target state estimation. The simulation results show that the target tracking performance computational time based on the INT-VSIMM algorithm is superior to the comparative existing methods, and the extrapolated trajectory has less error in the short term, which can satisfy the needs of conflict detection.
Inclusive Human Resource Management and Nurses’ Innovative Behavior during Crisis Events: The Roles of Job Crafting and Shared Leadership
Authors: Wu Yan , Zhu Hanqiu , Tan Wei , Liu Yifeng , Huang Wenjuan
Published: May 2024

Aims. Building on conservation of resources theory, our study investigates how inclusive human resource management (IHRM) promotes nurses’ innovative behavior through job crafting and further examines the moderating role of shared leadership. Background. Nurses’ involvement in innovation is essential to improve nursing care delivery and accommodate changing medical environments, especially in the face of crisis events like the COVID-19 outbreak. However, knowledge about the relationship between human resource management and nurses’ innovative behavior remains scarce. Methods. We collected three-wave data from 338 on-duty registered nurses at four public hospitals in China from November 2022 to January 2023. We used SPSS 22 to conduct hierarchical regressions to test our hypotheses. Results. IHRM positively predicted innovative behavior of nurses with the mediating role of job crafting. In addition, we found that IHRM was more effective in promoting job crafting and subsequent innovative behavior when nurses perceived high levels of shared leadership. Conclusion. IHRM initiated by the organization and shared leadership style are two collaborative approaches to facilitating nurses’ job crafting, thereby responding to the imperative need to foster nurses’ innovative behavior. Implications for Nursing Management. The present study emphasizes the important roles of IHRM and shared leadership in promoting nurses’ job crafting and subsequent innovative behavior, providing theoretical and practical implications for nursing management in the current dynamic and challenging environment.
Analysis of VOCs in Lueyang Black Chicken Breast Meat during the Steaming Process with GC-IMS and Stoichiometry
Authors: He Linlin , Chen Rui , Lan Fei , Yang Hui , Gao Ruichang , Jin Wengang
Published: May 2024

Steamed chicken breast meat attracts people for its unique flavor and nutritional benefits. In this study, the sensory evaluation of Lueyang black chicken breast meat during steaming was first performed, and their volatile organic compounds (VOCs) were further analyzed by gas chromatography-ion mobility spectroscopy (GC-IMS) combined with stoichiometry. The sensory results demonstrated that the Lueyang black chicken breast meat steamed for 15–30 min was more acceptable in taste, flavor, and chewiness. A total of 60 volatile flavor signal peaks were obtained, and 46 VOCs were recognized from qualitative analysis, containing 24 aldehydes (51.19–72.57%), 8 ketones (10.15–16.97%), 9 alcohols (7.98-13.16%), 2 furans (2.24–10.85%), 2 esters (0.54–1.56%), and 1 ether (0.05–2.47%). A stable and reliable prediction model was set up by orthogonal partial least squares-discriminant analysis (OPLS-DA), and 18 characteristic VOCs (including 10 aldehydes, 3 alcohols, 3 ketones, 1 furan, and 1 ether) were picked out through variable importance in the projection (VIP>1.0 and p<0.05). Principal component analysis (PCA) results indicated that the cumulative contribution ratio was 92% with PC1 68.7% and PC2 23.3%, respectively, indicating that these characteristic VOCs could well discriminate the steaming time of Lueyang black chicken breast meat. Heatmap clustering analysis also demonstrated a similar distinguishing effect. These results could provide references for the research, development, and quality control of ready-to-eat steamed products for Lueyang black chicken breast meat in the future.
Development of Anisogrid Lattice Composite Structures for Fighter Wing Applications
Authors: Kusni Muhammad , Hadi Bambang Kismono , Gunawan Leonardo , Syamsudin Hendri
Published: May 2024

This paper presents research on the use of anisogrid lattice structures in fighter wing applications. While the anisogrid lattice structure has been widely used in spacecraft structures, its implementation in main aircraft structures is still limited. The study is aimed at investigating the feasibility of utilizing an anisogrid lattice structure in fighter wing design. The analysis and optimization focus on determining the optimal weight of the composite wing structure, considering static, buckling, and flutter failure constraints. Various lift distributions, including triangular, Schrenk, and constant, are applied to evaluate the structure’s response to static failure caused by aerodynamic loads. The anisogrid structure design incorporates inclined lattice elements between ribs and spars, with spar arrangement in the wing box featuring an anisogrid configuration. The anisogrid lattice structure is expected to produce higher bending and torsional stiffness compared to conventional orthogonal structures, producing better flutter and buckling characteristics. The optimized wing structure successfully meets static, buckling, and flutter load requirements at speeds below 500 m/s. The study showcases triangular, Schrenk, and constant load distributions resulting in half-wing masses of 504, 571, and 707 kg, respectively. The results show that flutter and buckling loads are no longer the critical loads in wing structural design but static load.
Interoperability Structure of Smart Water Conservancy Based on Internet of Things
Authors: Wang SongSong , Xu Ouguan
Published: May 2024

Massive smart water conservancy object (WCO) need to be connected for real-time monitoring and control, which produces massive data. Unfortunately, heterogeneous data structures and semantics lead to low interoperability between WCO and management systems. To address this challenge, we propose a novel interoperability structure for a smart water conservancy system based on the Internet of Things (IoT), and the key design includes a smart WCO terminal, interoperability network, special interoperability protocol, WCO information model, and cloud platform. Universal terminal and network are the base of interoperability hardware, and special interoperability protocol and information model for interconnection of WCO are designed for smart water conservancy management system. WCO can be connected to a water conservancy Big Data processing cloud platform for interoperability applications. The application results demonstrate that our proposed WCO’s interoperability structure has obvious advantages than the general IoT at WCO interoperability. The interoperability protocol is reliable, the information model can ease interoperability and security, and the semantic dictionary is very rich and covers all semantic services of WCO.
A Novel Strategy for Hypersonic Vehicle With Complex Distributed No-Fly Zone Constraints
Authors: Zhengxin Tao , Shifeng Zhang
Published: May 2024

Aiming at solving trajectory planning problem with complex distributed no-fly zone constraints, this paper proposed a novel obstacle avoidance strategy. For longitudinal motion, an angle of attack adjustment method is employed to adjust lift and design the angle of attack profile, while adjusting the bank angle for range and altitude correction to meet terminal constraints. For lateral motion, this paper developed enhanced attractive, repulsive, and velocity potential fields. Combined with the proposed repulsive force reconstruction method, this effectively resolves the overmaneuvering problem of traditional artificial potential field methods (APFMs) for vehicle. In order to avoid mismatched magnitudes of attractive and repulsive forces, a complementary no-fly zone avoidance strategy based on minimum turn radius is introduced, updating the bank angle command during no-fly zone avoidance. Simulation results indicate that the proposed strategy can address the avoidance of sudden threat, proving to be feasible and effective for handling complex distributed no-fly zone avoidance problems.
Supplementary Table 3 from Low-Carbohydrate Diet Score and the Risk of Colorectal Cancer: Findings from the Singapore Chinese Health Study
Authors: Yu Yi-Chuan , Paragomi Pedram , Jin Aizhen , Wang Renwei , Schoen Robert E. , Koh Woon-Puay , Yuan Jian-Min , Luu Hung N.
Published: May 2024

Supplementary Table S3 describes results from models without BMI variable adjustment (overall)
Table S6 from Exploring the Complex Relationship between Gut Microbiota and Risk of Colorectal Neoplasia Using Bidirectional Mendelian Randomization Analysis
Authors: Li Wanxin , Zhou Xuan , Yuan Shuai , Wang Lijuan , Yu Lili , Sun Jing , Chen Jie , Xiao Qian , Wan Zhongxiao , Zheng Ju-Sheng , Zhang Cai-Xia , Larsson Susanna C. , Farrington Susan M. , Law Philip , Houlston Richard S. , Tomlinson Ian , Ding Ke-Feng , Dunlop Malcolm G. , Theodoratou Evropi , Li Xue
Published: May 2024

Table S6 shows the forward MR analyses of 24 gut microbiota with the risk of colorectal cancer.
Supplemental Table 1 from Nitrated Polycyclic Aromatic Hydrocarbon (Nitro-PAH) Signatures and Somatic Mutations in Diesel Exhaust-Exposed Bladder Tumors
Authors: Gonzalez Nicole , Rao Nina , Dean Michael , Lee Donghyuk , Hurson Amber N. , Baris Dalsu , Schwenn Molly , Johnson Alison , Prokunina-Olsson Ludmila , Friesen Melissa C. , Zhu Bin , Rothman Nathaniel , Silverman Debra T. , Koutros Stella
Published: May 2024

Genes on panel
Table S4 from Trend in Cervical Cancer Incidence and Mortality Rates in China, 2006–2030: A Bayesian Age-Period-Cohort Modeling Study
Authors: Yuan Meiwen , Zhao Xuelian , Wang Honghao , Hu Shangying , Zhao Fanghui
Published: May 2024

Table S4 shows average age and standardized average age at death for cervical cancer between 2006 to 2030.
Table S2 from Trend in Cervical Cancer Incidence and Mortality Rates in China, 2006–2030: A Bayesian Age-Period-Cohort Modeling Study
Authors: Yuan Meiwen , Zhao Xuelian , Wang Honghao , Hu Shangying , Zhao Fanghui
Published: May 2024

Table S2 shows trends for age-specific cervical cancer incidence and mortality rates by region in China between 2006 to 2016.
Figure S4 from Trend in Cervical Cancer Incidence and Mortality Rates in China, 2006–2030: A Bayesian Age-Period-Cohort Modeling Study
Authors: Yuan Meiwen , Zhao Xuelian , Wang Honghao , Hu Shangying , Zhao Fanghui
Published: May 2024

Figure S4 age-period-cohort effect on cervical cancer mortality rates in China between 2006 to 2016.
Figure S2 from Trend in Cervical Cancer Incidence and Mortality Rates in China, 2006–2030: A Bayesian Age-Period-Cohort Modeling Study
Authors: Yuan Meiwen , Zhao Xuelian , Wang Honghao , Hu Shangying , Zhao Fanghui
Published: May 2024

Figure S2 shows trends for deaths during 2006−2016 and predicted from 2017 to 2030 in China.
Figure S1 from Trend in Cervical Cancer Incidence and Mortality Rates in China, 2006–2030: A Bayesian Age-Period-Cohort Modeling Study
Authors: Yuan Meiwen , Zhao Xuelian , Wang Honghao , Hu Shangying , Zhao Fanghui
Published: May 2024

Figure S1 shows trends for incidence cases during 2006−2016 and predicted from 2017 to 2030 in China.
Supplementary Table 3 from Somatic Mosaic Chromosomal Alterations and Death of Cardiovascular Disease Causes among Cancer Survivors
Authors: Sun Maxine , Cyr Marie-Christyne , Sandoval Johanna , Lemieux Perreault Louis-Philippe , Busque Lambert , Tardif Jean-Claude , Dubé Marie-Pierre
Published: May 2024

Supplementary Table 3: Sensitivity analyses by Cox regression considering additional covariates
Supplementary Table 16 from Somatic Mosaic Chromosomal Alterations and Death of Cardiovascular Disease Causes among Cancer Survivors
Authors: Sun Maxine , Cyr Marie-Christyne , Sandoval Johanna , Lemieux Perreault Louis-Philippe , Busque Lambert , Tardif Jean-Claude , Dubé Marie-Pierre
Published: May 2024

Supplementary Table 16: Cox regression analyses for the effect of mosaic chromosomal alterations on the risk of incident cardiovascular endpoints aged ≥65 years old (n=15,273)
Table S1 from Exploring the Complex Relationship between Gut Microbiota and Risk of Colorectal Neoplasia Using Bidirectional Mendelian Randomization Analysis
Authors: Li Wanxin , Zhou Xuan , Yuan Shuai , Wang Lijuan , Yu Lili , Sun Jing , Chen Jie , Xiao Qian , Wan Zhongxiao , Zheng Ju-Sheng , Zhang Cai-Xia , Larsson Susanna C. , Farrington Susan M. , Law Philip , Houlston Richard S. , Tomlinson Ian , Ding Ke-Feng , Dunlop Malcolm G. , Theodoratou Evropi , Li Xue
Published: May 2024

Table S1 shows the SNPs that associated with 24 microbiota taxa in MiBioGen (P<5×10-8).
Supplemental Table 3 from Measurement of Ovarian Tumor Immune Profiles by Multiplex Immunohistochemistry: Implications for Epidemiologic Studies
Authors: Hathaway Cassandra A. , Conejo-Garcia Jose R. , Fridley Brooke L. , Rosner Bernard , Saeed-Vafa Daryoush , Moran Segura Carlos , Nguyen Jonathan V. , Hecht Jonathan L. , Sasamoto Naoko , Terry Kathryn L. , Tworoger Shelley S. , Townsend Mary K.
Published: May 2024

Supplemental Table 3 shows case characteristics included on tissue microarrays in NHS and NHSII
Supplemental Table 7 from Nitrated Polycyclic Aromatic Hydrocarbon (Nitro-PAH) Signatures and Somatic Mutations in Diesel Exhaust-Exposed Bladder Tumors
Authors: Gonzalez Nicole , Rao Nina , Dean Michael , Lee Donghyuk , Hurson Amber N. , Baris Dalsu , Schwenn Molly , Johnson Alison , Prokunina-Olsson Ludmila , Friesen Melissa C. , Zhu Bin , Rothman Nathaniel , Silverman Debra T. , Koutros Stella
Published: May 2024

Cosine similarities for all signatures
Supplemental Table 1 from Measurement of Ovarian Tumor Immune Profiles by Multiplex Immunohistochemistry: Implications for Epidemiologic Studies
Authors: Hathaway Cassandra A. , Conejo-Garcia Jose R. , Fridley Brooke L. , Rosner Bernard , Saeed-Vafa Daryoush , Moran Segura Carlos , Nguyen Jonathan V. , Hecht Jonathan L. , Sasamoto Naoko , Terry Kathryn L. , Tworoger Shelley S. , Townsend Mary K.
Published: May 2024

Supplemental Table 1 shows the correlations of percentages of the markers in the tumor.
Supplementary Table S4 from COVID-19 Outcomes by Cancer Status, Site, Treatment, and Vaccination
Authors: Salvatore Maxwell , Hu Miriam M. , Beesley Lauren J. , Mondul Alison M. , Pearce Celeste Leigh , Friese Christopher R. , Fritsche Lars G. , Mukherjee Bhramar
Published: May 2024

Logistic regression odds ratios (95% CI) for COVID-19 outcomes by chemotherapy treatment (without hematologic malignancy patients).
Supplementary Table 7 from Associations between MICA and MICB Genetic Variants, Protein Levels, and Colorectal Cancer: Atherosclerosis Risk in Communities (ARIC)
Authors: Wang Shuo , Onyeaghala Guillaume C. , Pankratz Nathan , Nelson Heather H. , Thyagarajan Bharat , Tang Weihong , Norby Faye L. , Ugoji Chinenye , Joshu Corinne E. , Gomez Christian R. , Couper David J. , Coresh Josef , Platz Elizabeth A. , Prizment Anna E.
Published: May 2024

Supplemental Table 7 shows the association of sMICA and sMICB levels (continuous variables) and pre-selected SNPsa with risk of CRC stratified by family history of CRC.
Supplementary Table 3 from Associations between MICA and MICB Genetic Variants, Protein Levels, and Colorectal Cancer: Atherosclerosis Risk in Communities (ARIC)
Authors: Wang Shuo , Onyeaghala Guillaume C. , Pankratz Nathan , Nelson Heather H. , Thyagarajan Bharat , Tang Weihong , Norby Faye L. , Ugoji Chinenye , Joshu Corinne E. , Gomez Christian R. , Couper David J. , Coresh Josef , Platz Elizabeth A. , Prizment Anna E.
Published: May 2024

Supplemental Table 3 shows the associations between pre-selected SNPs and CRC risk stratified by sex, race, or diabetes status.
Supplementary Table 2 from Associations between MICA and MICB Genetic Variants, Protein Levels, and Colorectal Cancer: Atherosclerosis Risk in Communities (ARIC)
Authors: Wang Shuo , Onyeaghala Guillaume C. , Pankratz Nathan , Nelson Heather H. , Thyagarajan Bharat , Tang Weihong , Norby Faye L. , Ugoji Chinenye , Joshu Corinne E. , Gomez Christian R. , Couper David J. , Coresh Josef , Platz Elizabeth A. , Prizment Anna E.
Published: May 2024

Supplemental Table 2 shows the associations between pre-selected SNPs and Visit 2 sMICA and sMICB levels (continuous variables) stratified by sex, race, or diabetes status.
Assessing Helicobacter Pylori Infections Among Adults From the Navajo Nation
Authors: Pete D , Phipps AI , Salama NR , Lampe JW , Wu MC
Published: May 2024

A substantial burden of stomach cancer continues to be observed in American Indians in the United States (US). The Navajo Nation, the largest American Indian tribe in the Southwestern US, is experiencing a higher incidence of stomach cancer compared to the general population in the region, possibly due to the high prevalence of Helicobacter pylori (H. pylori) infection, an infectious pathogen that colonizes the stomach and is a major risk factor for stomach cancer. To assess the prevalence, virulence, and risk factors for H. pylori infection in Navajo adults, we initiated a cross-sectional study in two geographic areas of the Navajo Nation. Study recruitment occurred from January to October 2021 during the COVID-19 pandemic. Participants were recruited using online and offline platforms, including social media, a study website, newspaper advertisements, flyers, word of mouth, and community outreach. Demographic, health, behavioral, environmental, and diet factors were assessed from health and food frequency questionnaires. H. pylori infection and cagA virulence were detected from stool samples by droplet digital PCR. Of 99 participants recruited, 56.6% (95% CI: 46.2–66.5) of participants were infected with H. pylori and, among H. pylori-infected participants, 78.6% (95% CI: 65.6–88.4) were infected with a cagA-positive H. pylori strain. Having a history of H. pylori infection was inversely associated with H. pylori infection (OR = 0.05, 95% CI: 0.01–0.34, P = 0.005), and using Navajo herbal medicine once a month was positively associated with H. pylori infection (OR = 7.28, 95% CI: 1.40–61.12, P = 0.03). No significant associations were observed with other risk factors (e.g., older age, males, lower education levels, smoking, alcohol use, and high sodium intake). The prevalence of H. pylori infection was two times higher in adults in the Navajo ABID study compared to the US population (27% seroprevalence), and the prevalence of the cagA gene in H. pylori-infected participants was four times higher than the US population cagA gene prevalence in White people (19% seroprevalence). These findings provide a greater understanding of the burden of H. pylori and cagA-positive infections and can inform prevention strategies to reduce H. pylori infections in the Navajo Nat.
Incident Diabetes By Obesity-Related Cancer Status and Cancer Treatment Type: A Prospective Study Using Electronic Medical Records Data
Authors: Winn M , Pauleck S , Viskochil R , Ulrich CM , Post A , Richardson S , Colman H , Hu-Lieskovan S , Litchman M , Playdon MC , Hardikar S.
Published: May 2024

Background: Diabetes has been associated with an increased risk of the development of multiple cancers, however evidence for development of diabetes after cancer diagnosis is limited. Methods: Using data on 7,702 cancer patients treated at the Huntsman Cancer Institute, a comprehensive cancer center in Utah, we examined the association of systemic cancer treatments (chemotherapy, immunotherapy, hormone therapy, and corticosteroids) and obesity-related cancer (ORC) status with the development of diabetes after cancer diagnosis. Cox proportional-hazards models adjusting for relevant covariates [age, sex, race, body mass index at cancer diagnosis, and ORC status (in treatment–related models only)] were used to calculate hazard ratios (HR) and 95% confidence intervals (CI). Diabetes, cancer treatments, and cancer sites were identified using ICD codes and tumor histology. Results: 975(12.7%) cancer patients had incident diabetes (723 type-2 diabetes), and the mean time to diabetes diagnosis was 4.4 years after cancer diagnosis. 35.1% cancer patients received chemotherapy, 11.8% received immunotherapy, 19.5% received hormone therapy, 38.8% received corticosteroids, and 40.8% were diagnosed with an ORC. ORC patients and corticosteroid users had a statistically significant elevated risk of new-onset diabetes [HR (95% CI) = 1.43 (1.24–1.65) and 1.29 (1.13–1.47), respectively] compared to patients with a non-ORC and non-users of corticosteroids. Interestingly, patients who received chemotherapy or hormone therapy had a statistically significant lower risk of new-onset diabetes [HR(95% CI) = 0.69 (0.60–0.79) and 0.68 (0.58–0.81), respectively] compared to patients who did not receive these treatments. Stratified analyses evaluating death as a competing risk factor are ongoing. Conclusion: We observed statistically significant 1.43-times and 1.29-times increased risk of incident diabetes after cancer diagnosis in ORC patients and corticosteroid users. These results suggest that certain cancer treatments may increase diabetes risk. As monitoring cancer patients for new onset diabetes is currently not a clinical standard, understanding diabetes risk in cancer patients can inform strategies for monitoring cancer patients to prevent diabetes development.
Abstract A001: Urine-based liquid biopsy test for the detection of residual bladder cancer in radical cystectomy patients
Authors: Abbosh Philip H. , Valentine Henkel , Arya Rhea
Published: May 2024

One commonly employed management strategy for muscle-invasive bladder cancer (MIBC) is neoadjuvant chemotherapy followed by radical cystectomy (RC) and urinary diversion. Approximately 35% of patients achieve a pathologic complete response (pCR) when evaluated from RC specimens. RC with urinary diversion is a life-altering operation with high complication rates and therefore determining who are complete responders would improve quality of life and could decrease costs and still achieve a high cure rate via RC avoidance. Unfortunately, current methods cannot accurately identify complete responders. Our lab has developed a urine-based liquid biopsy test in which DNA isolated from urine and germline is isolated and subjected to panel exome sequencing for enumeration of somatic variants. This occurs under the premise that tumor DNA identified (as mutant alleles) is a marker of residual disease while the absence of tumor DNA (meaning the absence of mutant alleles) can indicate a pCR. A 60 gene panel was designed to be used for exonic sequencing of urinary DNA (uDNA) to identify mutations indicative of bladder cancer or therapeutic targets. We have shown that most mutations in tumor tissue (Mt) are detectable as mutations in urine (Mu). We also showed that the presence or absence of residual Mu after completion of chemotherapy strongly associates with residual disease or pCR at the time of RC, respectively. Therefore, this test could be used after neoadjuvant therapy to better identify patients for RC avoidance. We optimized this test by studying pre-analytical factors affecting the yield, purity, and integrity of uDNA and the quality of sequencing data using prospectively collected samples from patients with MIBC. We are also in the process of testing commercial and novel preservatives to optimize DNA integrity, yield, and mutation detection accuracy to enable temporary ambient temperature storage without compromising mutation detection, permitting shipping/centralized testing. Lastly, we are comparing two library preparation approaches. Study of these preanalytical factors has increased the number of Mu that can be detected and were applied to a cohort of patients who underwent bladder sparing curative-intent treatment in a prospective clinical trial. Studies described herein will enable liquid biopsy tests to accurately identify patients with pCR after neoadjuvant therapy and might safely avoid radical cystectomy.

Citation Format: Philip H. Abbosh, Henkel Valentine, Rhea Arya. Urine-based liquid biopsy test for the detection of residual bladder cancer in radical cystectomy patients [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr A001.
Abstract A006: Bladder cancer risk stratification with the Oncuria 10 plex bead-based urinalysis assay using three different Luminex xMAP instrumentation platforms
Authors: Sakatani Toru , Tanaka Sunao , Murakami Kaoru , Waldron Richard , Hogrefe Wayne , Rosser Charles , Furuya Hideki
Published: May 2024

Introduction and Objectives Oncuria® is a bead-based multiplex fluorescence immunoassay that coordinately measures 10 protein biomarkers in urine samples. The current study compared assay performance and output when urine samples were evaluated with the Oncuria assay using three different fluorescence-analyzing instruments commonly used in diagnostic laboratories worldwide. Methods We compared the performance of the clinically validated Oncuria bladder cancer (BC) multiplex immunoassay when data output was generated on three different analyzer systems. Voided urine samples from 36 subjects (18 with BC and 18 Controls) were reacted with Oncuria test reagents in three 96 well microtiter plates, and consecutively evaluated on the LED/image based MagPix, and laser/flow based Luminex 200 and FlexMap 3D (all xMAP instruments from Luminex Corp., Austin, TX). The BC assay uses magnetic bead based fluorescence technology (xMAP, Multi-analyte profiling; Luminex) to simultaneously quantify 10 protein analytes in urine specimens [i.e., angiogenin (ANG), apolipoprotein E (ApoE), carbonic anhydrase IX (CA9), CXCL8/interleukin-8 (IL-8), matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-10 (MMP-10), serpin A1/alpha-1 anti-trypsin (A1AT), serpin E1/plasminogen activator inhibitor-1 (PAI-1), CD138/syndecan-1 (SDC1), and vascular endothelial growth factor-A (VEGF-A)]. Results All three platforms categorized all 10 analytes in identical samples at nearly identical concentrations, with variance across systems typically <5%. While the most contemporary instrument, the FlexMap 3D, output higher raw fluorescence values than the two comparator systems, standard curve slopes and analyte concentrations determined in urine samples were concordant across all three units. Forty-four percent of BC samples registered ≥1 analyte above the highest standard concentration, i.e., A1AT (n=7/18), IL-8 (n=5), and/or ANG (n=2). In Controls, A1AT was higher in one sample. Conclusions In conclusion, the Oncuria BC assay performed similarly well across three different flow analysis platforms for all 10 analytes simultaneously evaluated in urine samples. This agreement across instruments indicates that the test is amenable to standardized performance in laboratories using existing xMAP, without requiring costly outlays for new equipment.

Citation Format: Toru Sakatani, Sunao Tanaka, Kaoru Murakami, Richard Waldron, Wayne Hogrefe, Charles Rosser, Hideki Furuya. Bladder cancer risk stratification with the Oncuria 10 plex bead-based urinalysis assay using three different Luminex xMAP instrumentation platforms [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr A006.
Abstract A019: TRIM29 enhances the invasion of bladder cancer cells by modulating the intermediate filament network and focal adhesions
Authors: Wang Yin , Jerome Nicole A. , Kelleher Allan , Henderson Marian L. , Day Mark , Coulombe Pierre A. , Palmbos Phillip L.
Published: May 2024

Background: Bladder cancer patient treatment and outcomes are determined by the tumor’s ability to invade and metastasize. Our previous work has shown that TRIM29, also known as ATDC, is regulated by TP63 in basal bladder cancers, where it promotes cancer invasion and metastasis. We also observe that TRIM29 predominately localizes to intermediate filaments in invasive bladder cancer cells. Hypothesis: TRIM29 promotes the invasive progression of bladder cancer by regulating K14-containing intermediate filaments and focal adhesions. Methods: To test this hypothesis, we utilized cell culture models of bladder cancer, live cell imaging and 2D and 3D invasion assays to examine the role of TRIM29 in the regulation of K14, focal adhesions and the migration and invasion and bladder cancer cells. Results: We observed a physical interaction between TRIM29 and K14 filamentous structures in bladder cancer cells. We also found that TRIM29 and K14 regulate focal adhesion stability during bladder cancer invasion. Finally, we found that both K14 and the focal adhesion protein, zyxin (ZYX), are essential for bladder cancer migration and invasion, acting downstream of TRIM29. Conclusions: Our findings highlight a novel role for TRIM29 in regulating the cytoskeleton and focal adhesion dynamics during tumor cell invasion and suggest a potential therapeutic pathway for treating bladder cancer.

Citation Format: Yin Wang, Nicole A. Jerome, Allan Kelleher, Marian L. Henderson, Mark Day, Pierre A. Coulombe, Phillip L. Palmbos. TRIM29 enhances the invasion of bladder cancer cells by modulating the intermediate filament network and focal adhesions [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr A019.
Abstract IA005: Y chromosome loss in cancer drives growth by evasion of adaptive immunity
Authors: Theodorescu Dan
Published: May 2024

Loss of the Y chromosome (LOY) is observed in 10-40% of bladder cancers, but its clinical and biological significance is unknown. We will present genomic and transcriptomic studies that show LOY correlates with poor prognoses in patients. We performed studies of murine bladder cancer cells with LOY as well as those with deletion of Y chromosome by CRISPR/Cas9 and compared them to cells with and intact Y chromosome as controls. Y+ and Y- tumors grew similarly in vitro, while Y- tumors grew faster than Y+ tumors in immune competent hosts in a T cell-dependent manner. Flow cytometric analyses demonstrated that Y- tumors promote exhaustion of CD8+ T cells in the tumor microenvironment. These findings were supported by data obtained from single-nuclei RNA sequencing and spatial proteomic evaluation of human bladder cancers. Compared to Y+ tumors, Y- tumors exhibited a superior response to anti-PD-1 therapy in mice. In bladder cancer patients those with LOY tumors have better prognosis than those with Y+ tumors. This is the first evidence demonstrating that LOY in tumors alters T cell function by promoting T cell exhaustion and sensitizes them to PD-1-targeted immunotherapy. This work provides novel insights into basic LOY biology as well as the potential for the development of biomarkers for improved cancer immunotherapy.

Citation Format: Dan Theodorescu. Y chromosome loss in cancer drives growth by evasion of adaptive immunity [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr IA005.
Abstract IA019: Lessons from glioblastoma diversity, heterogeneity, and beginnings
Authors: Parada Luis F.
Published: May 2024

Glioblastoma (GBM) is a dire disease with poor prognosis and survival outcomes have changed little over the past two decades. Various genomic studies have emphasized the heterogeneity of GBM yet a consensus on the causes and its role in tumor recurrence has not been reached. Multiple studies using genetic and patient-derived xenograft (PDX) mouse models have demonstrated an inverse relationship between differentiation state and tumor initiation efficiency with neural stem and progenitor cells as the most efficient. However, other studies have proposed that well differentiated cells like neurons and astrocytes can form tumors. In addition, bioinformatic analyses of human primary GBM have reported that plasticity allows for mobility among cell states exist. Regardless of transcriptional modulation in GBM cells, to achieve progress in understanding and addressing clinical recurrence, the outstanding goal remains to identify and isolate the GBM cell type(s) responsible for therapy resistance and recurrence. To achieve this, we have employer autochthonous GBM models as well as orthotopic patient derived xenografts to in parallel examine tumor heterogeneity, cell of origin, and functional consequences.

Citation Format: Luis F. Parada. Lessons from glioblastoma diversity, heterogeneity, and beginnings [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr IA019.
Dom João IV e o café (1808-1821)
Authors: Rabello David
Published: May 2024

This study aims at questioning the moment in which the coffee acquired economic importance in the Capitania of Rio de Janeiro. Pombal, Vandelli and Azeredo Coutinho, for example, did not seem to have realized the future importance that the coffee would have in the Portuguese economy. However, in Brazil, the Prince Regent João stimulated the culture of coffee. Had he realized the potential resources which this product would represent or was the coffee a happy reality already in his government in Brazil?
Left Atrial Mechanics Following Preeclamptic Pregnancy
Authors: O’Driscoll Jamie M. , McCarthy Fergus P. , Giorgione Veronica , Jalaludeen Navazh , Seed Paul T. , Gill Carolyn , Sparkes Jenie , Poston Lucilla , Marber Mike , Shennan Andrew H. , Chappell Lucy C. , Thilaganathan Basky , Leeson Paul
Published: May 2024

BACKGROUND:

Preterm preeclampsia is a pregnancy complication associated with myocardial dysfunction and premature cardiovascular disease morbidity and mortality. Left atrial (LA) strain is a noninvasive index of left ventricular end diastolic pressure and an early marker of heart failure risk. This study aimed to evaluate LA strain during the postpartum period in participants with and without preterm preeclampsia and to assess whether this varied in the presence of hypertension, cardiac dysfunction or both.

METHODS:

In this longitudinal cohort study, 321 women from 28 hospitals with preterm preeclampsia (cases) underwent cardiovascular assessment 6 months postpartum. This is a secondary analysis of the PHOEBE study (ISRCTN01879376). An uncomplicated pregnancy control group (n=30) was recruited from a single center for comparison. A full cross-sectional transthoracic echocardiogram was performed, and from these images, the myocardial strain of the left atrium, including reservoir, conduit, and contractile strain, as well as LA stiffness, were calculated.

RESULTS:

At 6 months postpartum, compared with controls, prior preeclampsia was associated with a significantly attenuated LA reservoir, conduit, and contractile strain, as well as increased LA stiffness (all
P
<0.001). LA strain was further reduced in preeclamptic women who had and had not developed hypertension, systolic, or diastolic dysfunction at 6 months postpartum (all
P
<0.05).

CONCLUSIONS:

LA mechanics were significantly attenuated at 6 months postpartum in participants with preterm preeclampsia, whether or not they remained hypertensive or had evidence of ventricular dysfunction. Further studies are needed to determine whether postnatal LA strain may identify women at greater risk for future cardiovascular disease.
Sex-Dependency of T Cell-Induced Salt-Sensitive Hypertension and Kidney Damage
Authors: Abais-Battad Justine M. , Dasinger John Henry , Lund Hayley , Burns-Ray Emily C. , Walton Samuel D. , Baldwin Kaitlyn E. , Fehrenbach Daniel J. , Cherian-Shaw Mary , Mattson David L.
Published: May 2024

BACKGROUND:

It is established that the immune system, namely T cells, plays a role in the development of hypertension and renal damage in male Dahl salt-sensitive (SS) rats, but far less is known about this relationship in females. Rats with genetically deleted T cells via
CD247
gene mutation on the Dahl SS background (SS
CD247−/−
) were utilized to interrogate the effect of sex and T cells on salt sensitivity.

METHODS:

We assessed the hypertensive and kidney injury phenotypes in male versus female SS and SS
CD247−/−
rats challenged with 3 weeks of high salt (4.0% NaCl). Differences in T cell activation genes were examined in renal T cells from male and female SS rats, and a sex-specific adoptive transfer was performed by injecting male or female splenocytes into either male or female SS
CD247−/−
recipients to determine the potential contribution of T cell sex.

RESULTS:

The lack of functional T cells in SS
CD247−/−
rats significantly reduced salt-induced hypertension and proteinuria in both sexes, although SS
CD247−/−
females exhibited greater protection from kidney damage. Adoptive transfer of either Dahl SS male or female splenocytes into SS
CD247−/−
male recipients exacerbated hypertension and proteinuria compared with controls, while in SS
CD247−/−
female recipients, exacerbation of disease occurred only upon transfer of male, but not female, SS splenocytes.

CONCLUSIONS:

The absence of T cells in the SS
CD247−/−
normalized sex differences in blood pressure, though sex differences in renal damage persisted. Splenocyte transfer experiments demonstrated that salt sensitivity is amplified if the sex of the T cell or the recipient is male.