bluuebunny/crossref_metadata_2025 huggingface dataset:
TRIM37 is a primate-specific E3 ligase for Huntingtin and accounts for the striatal degeneration in Huntington’s disease
Authors: Qin Yiyang , Chen Laiqiang , Zhu Wenzhen , Song Jiahong , Lin Jingpan , Li Yuwei , Zhang Jiawei , Song Xichen , Xing Tingting , Guo Tingting , Duan Xuezhi , Zhang Yiran , Ruan Eshu , Wang Qi , Li Bang , Yang Weili , Yin Peng , Yan Xiao-Xin , Li Shihua , Li Xiao-Jiang , Yang Su
Published: May 2024

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease characterized by preferential neuronal loss in the striatum. The mechanism underlying striatal selective neurodegeneration remains unclear, making it difficult to develop effective treatments for HD. In the brains of nonhuman primates, we examined the expression of Huntingtin (
HTT
), the gene responsible for HD. We found that HTT protein is highly expressed in striatal neurons due to its slow degradation in the striatum. We also identified tripartite motif-containing 37 (TRIM37) as a primate-specific protein that interacts with HTT and is selectively reduced in the primate striatum. TRIM37 promotes the ubiquitination and degradation of mutant HTT (mHTT) in vitro and modulates mHTT aggregation in mouse and monkey brains. Our findings suggest that nonhuman primates are crucial for understanding the mechanisms of human diseases such as HD and support TRIM37 as a potential therapeutic target for treating HD.
Harnessing the duality of bases toward controlled color and fluorescence
Authors: Wang Dingbowen , Wang Yi , Zimudzi Tawanda J. , Chen Long-Qing , Yang Jian
Published: May 2024

Bases can promote keto-enol tautomerism, a prevalent form of prototropic tautomerism, and facilitate the ring opening of anhydride ring structures. The intrinsic chemical distinctions between these processes provide an opportunity to modulate these seemingly parallel reactions. However, this potential remains largely unexplored. In this work, we report homophthalic anhydride, the first molecule exhibiting simultaneous halochromism, turn-on fluorescence (halofluorochromism), and subsequent self-destruction. Through comprehensive spectroscopic analysis and theoretical calculations, we unravel the mechanisms underlying these phenomena, revealing that the pivotal roles of the base’s basicity and nucleophilicity specifically allow us to achieve controlled durations of color change and turn-on fluorescence. Capitalizing on these intriguing properties, we develop a highly dynamic CMY (cyan-magenta-yellow) palette ideal for entity encryption and anti-counterfeiting applications. Our work reshapes the understanding of the relationship between the basicity and nucleophilicity of bases, enriching the comprehension of keto-enol tautomerism and homophthalic anhydride chemistry, and unveils a spectrum of potential applications.
Long-term early development research in congenital heart disease (LEADER-CHD): a study protocol for a prospective cohort observational study investigating the development of children after surgical correction for congenital heart defects during the first 3 years of life
Authors: Ferentzi Hannah , Pfitzer Constanze , Rosenthal Lisa-Maria , Berger Felix , Schmitt Katharina R L
Published: May 2024

Introduction

Congenital heart disease (CHD) is the most common birth defect. Studies on the development of children with CHD point towards deficits in motoric, cognitive and language development. However, most studies are cross-sectional and there is a gap in the knowledge concerning developmental trajectories, risk and protective factors and a lack of research concerning environmental predictors. Specifically, no studies have so far considered the importance of early caregiving experiences and child temperament for the development of children with CHD.

Methods

In a single-centre prospective cohort study, cognitive, motoric and language development of 180 children after corrective surgery for a simple transposition of the great arteries (TGA), tetralogy of Fallot (TOF) or ventricular septal defect (VSD) will be assessed at ages 12, 24 and 36 months with the Bayley Scales of Infant Development 3rd Edition (BSID-III). At age 12 months, a free-play video observation will be conducted to investigate the relationship between primary caregiver and child, and child temperament will be assessed with the Infant Behavior Questionnaire—Revised Short Version. Medical information will be obtained from patient records and demographic information via questionnaires.

Analysis

Frequency and severity of developmental delays will be reported descriptively. Differences between groups (TGA, TOF, VSD) will be subjected to repeated-measures analysis across time points. Multiple regressions will be applied for the analysis of predictors at each time point. For the analysis of differential developmental trajectories, mixed-model analysis will be applied.

Ethics and dissemination

The study has been approved by the local medical ethics committee. Written informed consent will be obtained from all participants. Parents have the option to be debriefed about BSID-III results after each assessment and about the study results after project completion. Results will be disseminated in peer-reviewed journals and presented at conferences.

Trial registration number

DRKS00011006; Pre-results.
Impact of global monopole on heavy mesons in hot-dense medium
Authors: Abu-Shady M. , Ahmed Faizuddin
Published: May 2024

This research study primarily will focus on investigating how the topological effects influence the eigenvalue solutions in the presence of a hot-dense medium. To accomplish this, we employ the non-relativistic Schrödinger wave equation by taking into consideration both the quantum flux field and interaction potential. Through this approach, we determine the energy eigenvalues and their corresponding wave functions using the Nikiforov–Uvarov method. Our findings indicate that when we consider both the topological effects and the magnetic flux, [Formula: see text], there is a noticeable reduction in the binding energy within the hot-dense medium. Additionally, we analyze the role of the baryonic potential in shaping the binding energy within the [Formula: see text] plane. Interestingly, it is evident that the influence of the baryonic potential becomes more pronounced as its values decrease.
The 3D structure of the nucleons in perspective of the GPDs
Authors: Arami Niloufar , Taghavi-Shahri Fatemeh , Yazdi Zahra Alizadeh , Shoeibi S. , Arash Firooz
Published: May 2024

In this paper, we present our QCD analysis of the Nucleon Form Factors presented by JLab to extract a new parameterization for the valence Generalized Parton Distributions (GPDs), [Formula: see text] and [Formula: see text]. We choose simple parameterizations for [Formula: see text] and [Formula: see text] dependence of GPDs at zero skewness. These free parameters of the model are then obtained using old and new data of nucleon’s elastic electromagnetic form factors (FFs) from JLAB. We have also used the “Hessian method” to perform a careful estimation of the uncertainties for the nucleon GPDs and corresponding observables originate from experimental errors. We also calculate the parton distribution functions (PDFs) in Impact parameter space to show the 3D structure of the Nucleon. We also calculated the proton and the neutron charge densities [Formula: see text]. We show that there is a highly localized negative charge near the center of the neutron and it is because of the negatively charged down quarks dominating the high momentum quarks in the neutron. Finally using the obtained Dirac’s FF, we had an estimation for the proton charge radius. The predictions based on the obtained nucleon GPDs are in good agreement with all available experimental data and other phenomenological models.
A Low-Frequency Vibration Isolator Using Permanent Magnets and Kresling Origami Structure
Authors: Chen Tianyu , Tang Bo , Xu Ming , Zhang Kai
Published: May 2024

The performance deterioration behavior resulting from vibrations in various mechanical systems, such as precision instruments, has long plagued engineers. One efficient approach for vibration protection is to use a quasi-zero stiffness (QZS) structure, which has high static and low dynamic characteristics. In this study, a low-frequency vibration isolator using permanent magnets and a Kresling origami structure is proposed that works for both torsional and/or axial excitations. The responses to both deterministic and random excitations were studied by establishing dynamic equations. The results show that the coupling of the axial and torsional motions results in an additional mass, which reduces the frequency and improves the low-frequency performance of the QZS structure. Force transmissibility was used to demonstrate the effects of the QZS structure. Compared with the degenerated linear system, the force transmissibility was lower over a wider frequency range. The ratio of the mean–square force of the QZS structure to that of a degenerate linear system under random excitation was also investigated. For weak Gaussian white noise, the QZS structure is effective and suitable for varying frequencies. However, it does not work for strong excitations. The results also show that the system damping aids in vibration isolation. We believe that our work provides a new method for designing a QZS structure using origami structures for multidirectional excitations.
Stability and bifurcations of a host–parasitoid model with general host escape function and general stocking upon parasitoids
Authors: Bešo Emin , Drino Džana , Kalabušić Senada , Kovačević D. , Pilav Esmir
Published: May 2024

This paper analyzes the generalization of a model presented in J. Bektešević, V. Hadžiabdić, S. Kalabušić, M. Mehuljić and E. Pilav [Dynamics of a class of host–parasitoid models with external stocking upon parasitoids, Adv. Differ. Equ. 2021(31) (2021)]. The study explores the behavior of the solution near equilibrium points when the system has different outcomes, such as extinction, infinitely many exclusion points or unique exclusion and coexistence. We prove global stability for the extinction and host-exclusion equilibrium. We also investigate the non-hyperbolic case of parasitoid-exclusion equilibrium and delve deeper into the 1:1 resonance. The transcritical bifurcation occurs at the host-exclusion equilibrium, indicating a threshold for host population invasion through transcritical bifurcation. Moreover, the local dynamics around the coexisting equilibrium can be highly complex due to the appearance of the Neimark–Sacker and period-doubling bifurcations. We provide the explicit form of the first Lyapunov exponent for the Neimark–Sacker bifurcation. Through numerical examples, we illustrate the theoretical findings.
AI in Emergency Management: Ethical Considerations and Challenges
Authors: Visave Jaideep
Published: May 2024

The integration of Artificial Intelligence (AI) in emergency management presents opportunities to improve crisis response and recovery efforts. However, it also brings forth a range of issues and hurdles that require navigation. This study delves into the implications of implementing AI in emergency management focusing on aspects like bias and discrimination, transparency and clarity, privacy and security data accuracy and accessibility ethical decision-making processes, public trust and acceptance safety measures and regulations among others. By examining real-world instances and potential future scenarios, we shed light on the impacts and moral dilemmas arising from the use of AI during emergencies. The study advocates for crafting frameworks and guidelines while actively engaging the public in governing AI to ensure responsible and efficient utilization of this technology in such a crucial domain. By tackling these challenges head on, we seek to contribute to the conversation about harnessing AI’s capabilities, in emergency management while upholding ethical standards and safeguarding the rights and dignity of affected communities.
Using Multi-dimensional Quorums for Optimal Resilience in Multi-resource Blockchains
Authors: Sun Yucheng , Hou Ruomu , Yu Haifeng
Published: May 2024

Permissionless blockchains commonly use resource challenges to defend against sybil attacks. For example, popular resource challenge designs include Proof-of-Work and Proof-of-Stake. It is well-known that simultaneously exploiting multiple resources can help make a permissionless blockchain more robust. For example, combining PoW and PoS can help to keep a blockchain secure, even when the attacker controls more than 50% of the computational power in the system.

While there have been existing efforts for combining multiple resources in blockchains, they only provide partial solutions. Specifically, it is currently still unclear
how to combine PoW and PoS, or multiple resources in general, to achieve optimal resilience
. Here, by
optimal resilience
, we mean that the blockchain can tolerate every
security region
, unless that security region is proven to be impossible to tolerate. Existing designs are not able to achieve such optimal resilience.

As our central contribution, this work proposes the novel design and formal security analysis of a blockchain protocol that combines PoS and PoW, which can be further generalized to multiple resources. Our blockchain is the
very first
blockchain that can achieve
optimal resilience
. Our design also overcomes a common tricky issue of PoW difficulty adjustment in previous designs. We have further implemented a research prototype of our blockchain design and experimentally demonstrated its good end-to-end performance.
(Invited) Near-Field Optics and Its Applications in Nanoscale Materials: A Review
Authors: Fanchini Giovanni , Stocek Noah B. , Wong Victor
Published: May 2024

In this paper, we first offer an overview of aperture-type scanning near field optical microscopy –a family of super-resolution imaging techniques based on evanescent waves, which can be combined with atomic force microscopy and are capable of subwavelength resolution nano-optical imaging. In the second part of this review, we will discuss a few applications in which our group capitalized on the super-resolution resolving power of SNOM to design specific nano-optical and nano-photonic systems for light harvesting, resistive memory device applications and nanoscale thermo-optical management. Specific case studies that will be presented include the characterization of weakly photoluminescent and curved carbon dots for memory device applications, the three-dimensional characterization of plasmon-enhanced nanophotonic devices, as well as the development of near-field thermoreflectance imaging for nanophotonic-based thermal management applications. Collectively, our study well represents the versability of SNOM as a unique super-resolution nanophotonic tool for the investigation of light-matter interaction at the nanoscale.
High Temperature and FORC Investigations of Semiconducting/Ferromagnetic Nanocomposites
Authors: Granitzer Petra , Rumpf Klemens , Gonzalez-Rodriguez Roberto , Coffer Jeffery , Nachtnebel Manfred
Published: May 2024

In the frame of this work the temperature-dependency of the magnetization of various composite systems consisting of porous silicon (PSi) and silicon nanotubes (SiNTs) with embedded Ni, NiCo, FePt, and Fe3O4 structures is discussed. The temperature is varied between 80 and 1273 K which allows to determine the Curie Temperature of the composites which is higher than for the corresponding bulk materials. Magnetic cross-talk between metal deposits can be controlled by the morphology of the porous silicon (pore diameter and distance between the pores) or silicon nanotubes (inner diameter and wall thickness) and also by the distribution and size of the deposits within the pores. To get a clear knowledge about the magnetic interactions single hysteresis curves are not sufficient and thus first order reversal curves (FORC) are performed. Magnetic coupling is present for Ni, Co and NiCo deposits, whereas in the case of Fe3O4 and FePt nanoparticle loading no magnetic cross-talk between the particles is observed.
Eliminating the Bias from Liquid-Junction Potential for Charge-Transfer Analysis
Authors: Vullev Valentine I. , O`Mari Jaime O.
Published: May 2024

Liquid junctions in electrochemical cells introduce potentials that can strongly affect measurements. Such liquid-junction potential errors can exceed 100 mV. In the analysis of charge-transfer thermodynamics, error differences of 100 mV can have substantial impact on the interpretations. Discussion herein outlines an approach for eliminating the effects of liquid-junction potentials from charge-transfer analysis.
A WS2/CNF Nanocomposite for Electrochemical Sensing Applications
Authors: Barwa Tara N , Alves Daniele , Luo Yiran , Dempsey Eithne , Breslin Carmel B
Published: May 2024

It is well recognized that antimicrobials are central to society, but they have also entered the aquatic environment posing risks to public health and our essential ecosystems. Therefore, the detection of antimicrobial drugs at low concentration levels in aquatic environments is essential. In this study, a new composite comprising tannic acid modified carbon nanofibers (CNFs) and WS2 was formed to give CNF/WS2 and used in the electrochemical detection of ornidazole, an antimicrobial drug. Ornidazole is a well-known nitroimidazole and it has been detected in various water bodies. Using the CNF/WS2 composite, a linear concentration range extending from 10 nM to 260 mM ornidazole, with a sensitivity of 1.37 mA mM–1 cm–2 was obtained. Very good selectivity was achieved, and the sensor performed well in the analysis of ornidazole in river water, with recoveries ranging from 88.3 to 107.3%.
Printable MXene Ink Hybridized with ZSM-5 for Gas Sensing and CO2 Capturing
Authors: 夏 胜辉 , Chen Chen , Liu Jinhong , Leatt Kyle , Thundat Thomas , Khosla Ajit
Published: May 2024

MXene has garnered significant attention as a two-dimensional material with exceptional physicochemical properties for gas sensing development. This study utilized ZSM-5 nanoparticles loaded with MXene to prepare printable inks, aiming to explore novel applications of MXene in the gas sensing field. The morphology of MXene/ZSM-5 was characterized using scanning electron microscopy (SEM) and transmission electron microscopy (TEM), demonstrating the typical layered structure of MXene and particle morphology of composite ZSM-5. X-ray photoelectron spectroscopy (XPS) confirmed no production of TiO2 by providing valence information on elements. Thermogravimetric analysis (TG) revealed excellent thermal stability. To verify functional gas sensing feasibility, various hydrocarbons and common gases underwent adsorption and desorption tests (BET). Results showed that MXene loaded with ZSM-5 exhibited good adsorbability for C4H10, C7H8, SF6, H2O and O2 while having a certain trapping effect on CO2. Through testing and analyzing printing results, it was found that the MXene/ZSM-5 ink overcame dispersion issues present in pure MXene ink.
Infection with COVID-19 Complicated by Sinus Arrest
Authors: Zhang Guojun , He Shuai , Lin Lu , Gan Pengcheng
Published: May 2024

As a respiratory tract-transmitted disease, coronavirus disease 2019 (COVID-19) exerts a profound immune injury effect, leading not only to pulmonary impairment but also to cardiac complications. We present a case of a 79-year-old woman, who had previously contracted COVID-19 and subsequently developed sinus arrest (SA) following her second infection. The longest asystole time detected by Holter monitoring was 7.2 seconds. Although the patient met criteria for permanent pacemaker implantation, her family declined this intervention and conservative management was pursued instead. However, after a period of observation, the patient’s SA resolved. The present case study describes a patient who experienced SA upon reinfection with COVID-19, which was not present during the initial infection. It emphasizes the impact of COVID-19 on cardiac health, particularly its potential to induce arrhythmias. In addition, it is worth noting that the arrhythmia induced by a COVID-19 infection may show reversibility, suggesting that a permanent pacemaker might not be the priority option if further pacing therapy is being considered.
Table S9 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 S9 shows the reverse MR analyses of colorectal cancer, adenoma and polyps with the abundance of nine gut microbiota.
Table S7 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 S7 shows the forward MR analyses of nine gut microbiota with the risk of colorectal cancer.
Table S2 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 S2 shows the SNPs that associated with nine microbiota taxa (P<1×10-5).
Supplemental Table 3 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

Case-case associations between REC and TP53 mutation, NEBCS
Table S3 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 S3 shows proportion of incidence cases by age group between 2006 to 2016.
Table 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

Table S1 shows average age and standardized average age at diagnosis for cervical cancer between 2006 to 2030.
Supplementary Table 7 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 7: The effect of autosomal mosaic chromosomal alterations on death of cardiovascular disease causes, coronary artery disease causes, from cancer and any cause of death
Supplementary Table 6 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 6: Cox regression analyses evaluating the effect of mosaic chromosomal alterations on the risk of death of cardiovascular disease causes, coronary artery disease causes, from cancer, and any cause of death by chemotherapy status
Supplementary Table 4 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 4: Multivariable competing-risks regression model for the prediction of death of CVD causes and CAD causes
Supplementary Table 2 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 2: ICD-9 and ICD-10 diagnostic and procedure codes for inpatient cardiovascular-related endpoints and for the primary endpoints
Table S4 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 S4 shows the SNPs for colorectal cancer.
Supplementary Table 11 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 11: The effect of mosaic chromosomal alterations (mCA) on death of cardiovascular disease causes, coronary artery disease causes, from cancer, and any-cause death with a mCA-by-cancer status interaction term in all patients
Supplemental Table 2 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 2 shows the distribution of presence/absence of percentage of the marker in the tumor, by age of sample for type I and type II tumors
Supplemental Table 4 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

specific TP53 mutations and ever diesel
Supplemental Table 2 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

study characteristics
Supplementary Table S5 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 cancer treatment type using restricted electronic health record for cancer recency analysis.
Supplementary Table S1 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

Phecodes used to identify individuals with cancer, along with their phenotype description and the number of individuals in the tested positive cohort with the corresponding phecode.
Supplementary Figure S9 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

COVID-19 hospitalization among recent cancer (within three years of positive COVID-19 test; n = 6,143) and non-cancer patients (n = 41,545) who tested positive and have non-missing covariates. The results were from the model logit P(YHospitalization = 1|X, Cancer, Covariate) = β0 + βXX + βCancerCancer + βIntX × Cancer + βCovCovariate, where Covariate = Age + Race/Ethnicity + Sex + Disadvantage Index (quartile) + Comorbidity Score. Reference groups were age: 18 to 35, sex: female, BMI: 18.5 to 25, race: white/non-Hispanic, smoking status: never. A unit change in the continuous age variable is 10 years. The comorbidity score ranges from 0 to 6 and is the sum of indicators for presence of six categories of preexisting conditions in the electronic health record.
Supplementary Figure S7 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

COVID-19 ICU admission among cancer (n = 12,995) and non-cancer patients (n = 34,693) who tested positive and had non-missing covariates. The results were from the model logit P(YICU = 1|X, Cancer, Covariate) = β0 + βXX + βCancerCancerStatus + βIntX × CancerStatus + βCovCovariate, where Covariate = Age + Race/Ethnicity + Sex + Disadvantage Index (quartile) + Comorbidity Score. Reference groups were age: 18 to 35, sex: female, BMI: 18.5 to 25, race: white/non-Hispanic, smoking status: never. A unit change in the continuous age variable is 10 years. The comorbidity score ranges from 0 to 6 and is the sum of indicators for presence of six categories of preexisting conditions in the electronic health record.
Supplementary Table 8 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 8 shows the associations of pre-selected SNPs with Visit 2 sMICA and sMICB levels and CRC risk without adjustment for ancestry markers.
Supplementary Figure S1 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

Flowchart describing derivation of COVID-19 tested analytic cohort from raw COVID-19 tested data.
Supplementary Table 10 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 10 shows that associations between mean of Visit 2 and Visit 3 sMICA and sMICB levels (continuous variables) with CRC risk.
Data 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

AbstractBackground:
Despite the immunogenic nature of many ovarian tumors, treatment with immune checkpoint therapies has not led to substantial improvements in ovarian cancer survival. To advance population-level research on the ovarian tumor immune microenvironment, it is critical to understand methodologic issues related to measurement of immune cells on tissue microarrays (TMA) using multiplex immunofluorescence (mIF) assays.
Methods:
In two prospective cohorts, we collected formalin-fixed, paraffin-embedded ovarian tumors from 486 cases and created seven TMAs. We measured T cells, including several sub-populations, and immune checkpoint markers on the TMAs using two mIF panels. We used Spearman correlations, Fisher exact tests, and multivariable-adjusted beta-binomial models to evaluate factors related to immune cell measurements in TMA tumor cores.
Results:
Between-core correlations of intratumoral immune markers ranged from 0.52 to 0.72, with more common markers (e.g., CD3+, CD3+CD8+) having higher correlations. Correlations of immune cell markers between the whole core, tumor area, and stromal area were high (range 0.69–0.97). In multivariable-adjusted models, odds of T-cell positivity were lower in clear cell and mucinous versus type II tumors (ORs, 0.13–0.48) and, for several sub-populations, were lower in older tissue (sample age > 30 versus ≤ 10 years; OR, 0.11–0.32).
Conclusions:
Overall, high correlations between cores for immune markers measured via mIF support the use of TMAs in studying ovarian tumor immune infiltration, although very old samples may have reduced antigenicity.
Impact:
Future epidemiologic studies should evaluate differences in the tumor immune response by histotype and identify modifiable factors that may alter the tumor immune microenvironment.
Abstract A014: PIK3CA mutation might confer resistance to an FGFR inhibitor, erdafitinib, in urothelial cancer cells
Authors: Arai Seiji , Sawada Tatsuhiro , Ohtsu Akira , Onose Mai , Maeno Yuta , Sekine Yoshitaka , Suzuki Kazuhiro
Published: May 2024

Objective: Metastatic urothelial carcinoma (mUC) has a poor prognosis. In the United States, an FGFR inhibitor (erdafitinib) was approved for mUC patients with FGFR2/3 alterations. Significantly, FGFR3 mutations are associated with favorable outcomes in UC but might also be associated with less sensitivity to immune checkpoint inhibitors, especially in metastatic upper tract UC (mUTUC). Therefore, erdafitinib can be an optimal candidate for mUTUC with FGFR3 mutations before treatment with immune checkpoint inhibitors. However, the duration of response for erdafitinib is limited in many patients. Hence, this study aimed to elucidate the resistance mechanism of erdafitinib and develop a new treatment for mUC. Methods: UC cell lines with FGFR3 alterations were exposed to erdafitinib for an extended period to create resistant cell lines. We assessed genetic modifications in the resistant lines. We also investigated the susceptibility to specific therapeutic agents for cancer-associated gene mutations in vitro and in vivo. [Results] Whole exome sequencing demonstrated PIK3CA gene mutations in two resistant lines. Significantly, a PI3K inhibitor showed apoptosis in resistant cells in vitro. Moreover, alpelisib showed a statistically significant growth inhibitory effect on erdafitinib-resistant UC tumors in vivo compared to control or erdafitinib treatment. Conclusions: PIK3CA gene mutations may be one of the resistant mechanisms to erdafitinib and can also be targetable with a commercially available PI3K inhibitor in mUC.

Citation Format: Seiji Arai, Tatsuhiro Sawada, Akira Ohtsu, Mai Onose, Yuta Maeno, Yoshitaka Sekine, Kazuhiro Suzuki. PIK3CA mutation might confer resistance to an FGFR inhibitor, erdafitinib, in urothelial cancer cells [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 A014.
Abstract A027: The role of nuclear receptors as promoters of luminal tumors and suppressors of basal/squamous tumors
Authors: Mendelsohn Cathy L. , Plumber Sakina A. , Tate Tiffany
Published: May 2024

Bladder cancers (BCs) can be divided into 2 major subgroups, basal/squamous (BASQ) tumors that are muscle invasive and luminal tumors which are relatively benign. Pparg, has been suggested to act as a tumor suppressor in BASQ tumors, where its expression is low or undetectable. Here we tested the effects of rosiglitazone, Pparg agonist in a mouse model of BASQ BC. We find that rosiglitazone alone, reduced proliferation but did not decrease tumor volume, while treatment with rosiglitazone plus trametinib, a MEK inhibitor induced apoptosis and reduced tumor volume by 91% after 1 month. Rosiglitazone and trametinib also induced a shift from BASQ to luminal differentiation in tumors, which our analysis suggests is mediated by retinoid signaling, a pathway known to drive the luminal differentiation program. Our data suggest that rosiglitazone, trametinib, and retinoids, which are all FDA approved, may be clinically active in BASQ tumors in patients.

Citation Format: Cathy L. Mendelsohn, Sakina A. Plumber, Tiffany Tate. The role of nuclear receptors as promoters of luminal tumors and suppressors of basal/squamous tumors [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 A027.
Abstract B021: Targeting nucleotide excision repair in non-muscle invasive bladder cancer
Authors: Xu Dongbo , Wang Li , Wieczorekl Kyle , Tian Zhiyu , Li Qiang
Published: May 2024

Background: Previous studies demonstrated that nucleotide excision repair (NER) plays a critical role in cisplatin-based chemotherapy response in muscle-invasive bladder cancer (MIBC), and that spironolactone (SP) is a potent NER inhibitor. We sought to investigate the role of SP in enhancing the response to mitomycin chemotherapy in non-muscle invasive bladder cancer (NMIBC). Materials and Methods: KU1919 cells (NER proficient) were used for chemotherapy response to mitomycin. Cell viability was examined using CellTiter-Glo. IC50 concentrations were calculated using a four-parameter sigmoidal model and plots generated by GraphPad Prism 9. Drug combination indexes (CI) of chemotherapy and SP were calculated using Chou-Talalay method. Cell cycle and apoptosis analysis were measured by assay and Annexin V apoptosis detection kit. DNA damage response and apoptosis signaling were examined by Western blot of gamma-H2AX, cleaved Caspase-3, and cleaved PARP. Results: Combinations of mitomycin and SP (2 μM: 40 μM, CI = 0.09) resulted in strong synergies in KU1919 cells. Mitomycin combined with SP led to more cells with a sub-G1 phase DNA content (9.43% vs. 4.69%, P < 0.01) and apoptosis (55.85% vs. 13.11% P < 0.01) than treatment with mitomycin alone. Western blot analyses showed that the addition of SP to mitomycin treatment induced increased protein expression of DNA damage response genes (gamma-H2AX) and activation of apoptosis (cleaved Caspase-3 and cleaved PARP). Conclusion: Targeting the NER pathway with SP in NMIBC enhances mitomycin-induced DNA damage signaling and subsequent cell apoptosis. These findings offer proof of concept and rationale for combining NER inhibitors with intravesical chemotherapy in NMIBC.

Citation Format: Dongbo Xu, Li Wang, Kyle Wieczorekl, Zhiyu Tian, Qiang Li. Targeting nucleotide excision repair in non-muscle invasive bladder cancer [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 B021.
Abstract IA006: Towards ctDNA-guided treatment of muscle-invasive bladder cancer
Authors: Dyrskjøt Lars
Published: May 2024

Cancer cells release cell-free DNA with tumor-specific molecular alterations into circulation, known as circulating tumor DNA (ctDNA). Numerous studies have underscored the biomarker potential of ctDNA in detecting minimal residual disease across various cancer types, including bladder cancer. The rapid clearance of ctDNA from circulation, typically under two hours, makes it an ideal candidate for real-time monitoring of tumor burden following surgical interventions and throughout oncological treatments. For ctDNA measurements to be effectively incorporated into clinical decision-making, it is crucial to conduct ctDNA-guided intervention trials that demonstrate tangible clinical benefits. Current trials focusing on muscle-invasive bladder cancer (MIBC) are supported by recent exploratory sub-analyses of completed clinical trials, which have shown that ctDNA can effectively guide treatment decisions in this context. Beyond guiding adjuvant treatments, ctDNA holds potential for directing bladder preservation strategies, potentially in combination with urinary tumor-derived DNA (utDNA) measurements. The need for treatment de-escalation, such as in neoadjuvant chemotherapy (NAC), is underscored by the observation that a significant proportion of patients undergo treatments that result in considerable adverse effects without achieving pathologic response. Traditional decision-making in cancer treatment, largely reliant on imaging-based criteria like the Response Evaluation Criteria in Solid Tumors (RECIST), often does not adequately reflect the ultimate clinical endpoint of overall survival. A ctDNA-based measure that considers ctDNA dynamics during treatment could serve as a superior tool or complement to current strategies. In conclusion, ctDNA has demonstrated significant promise as a biomarker in both retrospective and prospective studies for risk assessment in MIBC. The clinical value of ctDNA-guided treatment will soon be determined by ongoing clinical trials (TOMBOLA, IMvigor011, MODERN). In my presentation I will address the potential clinical impact of ctDNA analyses, the technological aspects involved, how urine analyses may supplement these findings, and future directions in the field.

Citation Format: Lars Dyrskjøt. Towards ctDNA-guided treatment of muscle-invasive bladder cancer [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 IA006.
Abstract IA013: Current state of the art: Bladder-preserving trimodality therapy for muscle-invasive bladder cancer
Authors: Efstathiou Jason A.
Published: May 2024

Many muscle-invasive bladder cancer (MIBC) patients are not getting curative treatment, there remains an undertreated/underserved population and a huge unmet need. Some are not good surgical candidates and others decline a radical cystectomy given concerns regarding its morbidity. Trimodality therapy (TMT), comprising of a maximal transurethral resection of bladder tumor (TURBT) followed by chemoradiation (with salvage cystectomy reserved for those that incur a muscle-invasive recurrence), has emerged as a viable bladder-preserving alternative to radical cystectomy for selected patients. In clinically-matched cohorts, survival is comparable to radical cystectomy in the modern era. More than 85% of contemporary patients keep their own native bladder and long-term quality of life after bladder preservation is good. Salvage cystectomy is feasible and can be curative for those with MIBC recurrences. TMT is now supported by numerous clinical guidelines, including NCCN (category 1 recommendation for stage II and IIIA). There are opportunities to continue to optimize clinical staging of disease (e.g. MRI), delivery of RT (e.g. image guidance, adaptive delivery, dose escalation, hypofractionation, field design) and systemic therapies (e.g. concurrent, neoadjuvant and adjuvant, including possibly immunotherapy) to improve outcomes. Ongoing trials (such as SWOG/NRG 1806 which recently closed to accrual) will inform the addition of immunotherapy to TMT. Validation of biomarkers in independent cohorts and in prospective trials is necessary to further guide bladder preservation therapy for MIBC and for personalized treatment selection. Ultimately, MIBC patients should be seen in a multidisciplinary environment where informed decision making by the patient is key.

Citation Format: Jason A. Efstathiou. Current state of the art: Bladder-preserving trimodality therapy for muscle-invasive bladder cancer [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 IA013.
Abstract IA015: Optimizing cystectomy outcomes in MIBC: What's new in 2024?
Authors: Teoh Jeremy
Published: May 2024

Muscle-invasive bladder cancer often requires radical cystectomy, which is a major and complex surgery carrying significant morbidities. Optimizing the outcomes of radical cystectomy involves a multifaceted approach. There are three main aspects that we must focus on, namely the peri-operative, functional and oncological outcomes. Firstly, perioperative outcomes can be enhanced by leveraging robotic technology for the procedure, coupled with intracorporeal urinary diversion techniques. Recent evidence has shown benefits in terms of reducing blood loss, shortening hospital stay and improving quality of life. Secondly, to optimize functional outcomes, organ sparing surgery techniques can be considered when possible. Preserving organ function can improve the quality of life after surgery, especially in terms of urinary and sexual functioning. Thirdly, optimizing oncological outcomes can be achieved through the integration of neoadjuvant immunotherapy into treatment protocols. This innovative approach can potentially improve the long-term survival outcomes following radical cystectomy. By addressing these three key aspects, a more comprehensive and effective strategy can be developed to optimize the results of radical cystectomy for patients with muscle-invasive bladder cancer.

Citation Format: Jeremy Teoh. Optimizing cystectomy outcomes in MIBC: What's new in 2024? [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 IA015.