bluuebunny/crossref_metadata_2025_split huggingface dataset:
Geodesics of Finsler Hayward black hole surrounded by quintessence
Authors: Yashwanth B. R. , Narasimhamurthy S. K. , Nekouee Z. , Malligawad Manjunath 
Published: December 2024

Abstract
This research paper delves into examining the Hayward black hole structure surrounded by quintessence within the framework of Finsler geometry. Our focus centers on the Finsler metric tensor development for black holes. This newly derived metric introduces significant deviations from regular black hole metrics found in general relativity due to the Finslerian term

$$\gamma $$

γ

presence, thus shedding fresh insights into the geometry and nature of black holes. Our findings reveal that the metric structure aligns closely with known Riemannian limits, affirming the congeniality of our model with existing theories. Furthermore, we extended our analysis to derive critical mass values and determine the normalization factor for the Hayward black hole within the Finlserian framework. The study encompasses a detailed description of the horizons and extremal conditions of the Hayward black hole surrounded by quintessence and the impact of the Finsler parameter

$$\gamma $$

γ

on them. Specifically, we explore the case where the quintessence state parameter is set to

$$\omega = -2/3$$

ω
=
-
2
/
3

. Our analysis delves into the effective potential, providing insights into null geodesics for various energy levels and examining the behavior of horizons by utilizing the definition of the effective potential. We also discuss the impact of

$$\gamma $$

γ

for the same. We compute and analyze the radius of circular orbits, the period, the instability characteristics of circular orbits, and the force acting on photons with the newly introduced parameter

$$\gamma $$

γ

within the quintessence field. We have thoroughly looked over the obtained results and discussed them. Additionally, we explore the shadow of the black hole in this context. Thereby, the validity and consistency of our Finslerian model are strengthened. In addition to increasing our understanding of black hole physics, this study paves the way for further research in the Finsler geometry domain and its applications in astrophysics.
Effect of Annealing Temperatures on Structural and Electrochemical Properties of Li[Ni0.5Co0.25Mn0.25]O2 Film Cathodes
Authors: G Prathibha , Mettu Maheshwar Reddy , Ravindar Reddy M. , Kuntigorla Manjula , Obili Mahammad Hussain 
Published: December 2024

Thin films of Li[Ni0.5Co0.25Mn0.25]O2 were prepared by RF-sputtering technique post-annealed the deposited films at various temperatures in a controlled oxygen atmosphere. The annealing temperature played an important role in the crystallinity of the films. The films post-annealed at optimized temperature displayed an X-ray diffraction peak at 18.29°, which can be ascribed to the Braggs reflection (003) of hexagonal Li[Ni0.5Co0.25Mn0.25]O2. The lattice parameters of the optimized films were a = 2.85 Å and c = 14.45 Å with c/a ratio equal to 5.070. The electrochemical activity of the post-annealed films was methodically investigated. The discharge capacity offered by the films is 40 μAh/cm2μm at 300 °C however this was further improved to 57.5 μAh/cm2.μm by post-annealing at 700 °C. Due to structural integrity of Li[Ni0.5Co0.25Mn0.25]O2 film may be used as cathode material for energy storage devices.
Targeting Arachidonic Acid Metabolism Enhances Immunotherapy Efficacy in ARID1A-Deficient Colorectal Cancer
Authors: Cui Luying , Liu Ruiqi , Han Shuling , Zhang Chunhui , Wang Bojun , Ruan Yuli , Yu Xuefan , Li Yien , Yao Yuanfei , Guan Xin , Liao Yuanyu , Su Dan , Ma Yue , Li Shuijie , Liu Chao , Zhang Yanqiao 
Published: December 2024

Abstract
ARID1A, a core constituent of SWI/SNF complex, is mutated in approximately 10% of colorectal cancers (CRC). While ARID1A deficiency corresponds to heightened immune activity in CRC, immune checkpoint inhibitors (ICIs) have shown limited efficacy in these tumors. The discovery of targetable vulnerabilities associated with ARID1A deficiency in CRC could expand treatment options for patients. In this study, we demonstrated that arachidonic acid metabolism inhibitors synergize with ICIs in ARID1A-deficient CRC by enhancing the activity of CD8+ T cells and inhibiting vasculogenic mimicry (VM). Epigenetic analysis using ATAC-seq and ChIP-qPCR revealed that the lack of ARID1A results in reduced levels of PTGS1 and PTGS2, the key enzymes that control the arachidonic acid pathway. Low PTGS1 and PTGS2 expression generated a reliance on the remaining functionality of the arachidonic acid pathway in ARID1A-deficient cells. The arachidonic acid pathway inhibitor aspirin selectively inhibited the growth of ARID1A-deficient CRC, and aspirin sensitized tumors lacking ARID1A to immunotherapy. Together, these findings suggest that blocking arachidonic acid metabolism can enhance immune responses against tumors by activating CD8+ T cells and inhibiting VM, which synergizes with ICIs to improve treatment of ARID1A-deficient CRC.
Multiomics Reveals the Immunologic Features and the Immune Checkpoint Blockade Potential of Colorectal Medullary Carcinoma
Authors: Liu Chao , Zou Haoyi , Ruan Yuli , Fang Lin , Wang Bojun , Cui Luying , Wu Tong , Chen Zhuo , Dang Tianjiao , Lan Ya , Zhao Wenyuan , Zhang Chunhui , Meng Hongxue , Zhang Yanqiao 
Published: December 2024

Abstract

Purpose:
Colorectal medullary carcinoma (MeC) is extensive lymphocyte infiltration and is associated with an active immune response. However, studies to comprehensively explore the immune landscape and efficacy of immune checkpoint blockade (ICB) therapy in MeC are limited.

Experimental Design:
We screened 47 cases of MeC from the Harbin Medical University Cancer Hospital cohort. The immunologic characteristics of MeC were analyzed by targeted exon sequencing, NanoString nCounter gene expression sequencing, IHC, multiplexed immunofluorescence, and T-cell antigen receptor sequencing. An additional 47 patients with MeC who received ICB therapy were included in the retrospective analysis to verify the efficacy of immunotherapy.

Results:
Genomically, MeC tends to have a higher proportion of mismatch repair protein deficiency/microsatellite instability (MSI), ARID1A mutation, and ASCL2 amplification. Gene expression shows enriched immune response–related pathways while downregulating oncogenic pathways, such as glycolysis, epithelial–mesenchymal transition, and Wnt/β-catenin signaling. Further immune characterization showed that MeC showed advantages in antigen presentation, co-stimulatory molecules, effector molecules, immune checkpoints, and immune cell abundance. More importantly, both MSI and microsatellite-stable type MeC showed a similar state of high infiltration of immune cells, even better than MSI non-MeC. MeC infiltrated massive highly clonal immune cells, especially intraepithelial CD8+ T cells. In the retrospective cohort, there were 30 patients with MeC who received ICB therapy and achieved complete or partial response with an objective response rate of 63.8%, especially including 16 patients with microsatellite-stable colorectal cancer.

Conclusions:
MeC is a pathologic subtype with an active immune response and is a promising group for ICB therapy. This heightened immune response was not limited to the patients' microsatellite status.
Abstract IA014: Mechanistic insights for the advancement of PPARG inverse agonists in muscle invasive urothelial cancer
Authors: Stuckey Jacob I. , Mertz Jennifer , Wilson Jonathan , Li Yong , Chenail Gregg , Kuljanin Miljan , Audia James , Sims Robert 
Published: December 2024

Abstract
In the last decade, genetic activation of PPARG in muscle invasive urothelial cancer (MIUC) has emerged as a potential therapeutic intervention point. More than two decades ago, the first PPARG covalent inverse agonist was described. While cellularly potent, subsequent drug discovery efforts to understand and improve the pharmacology of this initial inverse agonist were largely unsuccessful until quite recently. We have recently disclosed FX-909, a covalent inverse agonist of PPARG that shows durable tumor regressions in PPARG-activated xenograft models. Detailed structural, biochemical and medicinal chemistry studies were critical to both rational and rapid evolution from previously described covalent PPARG inverse agonists to FX-909, which exhibits both superior pharmacological and in vivo properties. Mechanistic understanding of the altered conformational landscape of PPARG in MIUC integrated with detailed insights into the covalent reaction coordinate of PPARG inverse agonists enabled the design of FX-909, specifically tailored to exhibit robust “conformational biasing” that counters the PPARG conformational “activation bias” observed in MIUC.
Citation Format: Jacob I. Stuckey, Jennifer Mertz, Jonathan Wilson, Yong Li, Gregg Chenail, Miljan Kuljanin, James Audia, Robert Sims. Mechanistic insights for the advancement of PPARG inverse agonists in muscle invasive urothelial cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Optimizing Therapeutic Efficacy and Tolerability through Cancer Chemistry; 2024 Dec 9-11; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(12_Suppl):Abstract nr IA014.
Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer
Authors: Chesner Lisa N. , Polesso Fanny , Graff Julie N. , Hawley Jessica E. , Smith Alexis K. , Lundberg Arian , Das Rajdeep , Shenoy Tanushree , Sjöström Martin , Zhao Faming , Hu Ya-Mei , Linder Simon , Chen William S. , Hawkins Reed M. , Shrestha Raunak , Zhu Xiaolin , Foye Adam , Li Haolong , Kim Lisa M. , Bhalla Megha , O’loughlin Thomas , Kuzuoglu-Ozturk Duygu , Hua Junjie T. , Badura Michelle L. , Wilkinson Scott , Trostel Shana Y. , Bergman Andries M. , Ruggero Davide , Drake Charles G. , Sowalsky Adam G. , Fong Lawrence , Cooperberg Matthew R. , Zwart Wilbert , Guan Xiangnan , Ashworth Alan , Xia Zheng , Quigley David A. , Gilbert Luke A. , Feng Felix Y. , Moran Amy E. 
Published: December 2024

Abstract
Tumors escape immune detection and elimination through a variety of mechanisms. Here, we used prostate cancer as a model to examine how androgen-dependent tumors undergo immune evasion through downregulation of the major histocompatibility complex class I (MHCI). We report that response to immunotherapy in late-stage prostate cancer is associated with elevated MHC expression. To uncover the mechanism, we performed a genome-wide CRISPR interference (CRISPRi) screen and identified androgen receptor (AR) as a repressor of the MHCI pathway. Syngeneic mouse models of aggressive prostate cancer deficient in Ar also demonstrated increased tumor immunogenicity and promoted T cell–mediated tumor control. Notably, the increase in MHCI expression upon AR blockade is transient and correlates with resistance to AR inhibition. Mechanistic studies identified androgen response elements upstream of MHCI transcription start sites which increased MHCI expression when deleted. Together, this body of work highlights another mechanism by which hormones can promote immune escape.

Significance:
Immunotherapy options for immune cold tumors, like prostate cancer, are limited. We show that AR downregulates MHCI expression/antigen presentation and that AR inhibition improves T-cell responses and tumor control. This suggests that treatments combining AR inhibitors and checkpoint blockade may improve tumor immune surveillance and antitumor immunity in patients.
First-in-Human Study of 23ME-00610, an Antagonistic Antibody for Genetically Validated CD200R1 Immune Checkpoint, in Participants with Advanced Solid Malignancies
Authors: Kummar Shivaani , Razak Albiruni Abdul , Laurie Scott , Glatt Dylan M. , Kell Sariah , Diep Anh N. , Schmidt Maike , Hom Clifford , German Chris , Shringarpure Suyash S. , Majeed Sophia R. , Rasco Drew 
Published: December 2024

Abstract

Purpose:
In this phase 1 portion of a first-in-human phase 1/2a study (NCT05199272), 23ME-00610 was evaluated in participants with advanced solid malignancies to determine its safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD). Exploratory biomarkers were evaluated to examine potential correlates of efficacy and safety.

Patients and Methods:
Eligible participants (≥18 years) were administered 23ME-00610 intravenously every 3 weeks (Q3W) using an accelerated titration design followed by a traditional 3 + 3 design, with an initial dose level of 2 mg.

Results:
Twenty-eight participants were enrolled across seven cohorts and received a median of four cycles of 23ME-00610. No treatment-related serious adverse events (AE) were observed, and the maximum tolerated dose was not reached. Overall, the PK of 23ME-00610 was linear and dose proportional for doses ≥60 mg, with a median terminal half-life of 13 days at 1,400 mg. Peripheral saturation of CD200R1 was observed for doses ≥60 mg. Immune-related AEs, including rash, pruritus, and hypothyroidism, were predicted by phenome-wide association studies and observed for doses ≥60 mg. A confirmed partial response was observed in a participant with well-differentiated pancreatic neuroendocrine cancer whose tumor was among those with the highest tumor CD200 expression.

Conclusions:
23ME-00610 has mild-to-moderate on-target AEs and PK/PD consistent with tumor target saturation and dosing every 3 weeks. The trend for clinical benefit in participants with tumor CD200 expression suggests that 23ME-00610 inhibits CD200R1 signaling and may reverse CD200-mediated immune evasion. Based on PK/PD, safety, and preliminary antitumor activity, 1,400 mg Q3W was selected as the dose for further study.

Significance:
Genome-wide association studies (GWAS) of the 23andMe genetic database identified CD200R1 as a promising therapeutic target for cancer. This phase 1 study of 23ME-00610, a CD200R1 antagonist IgG1, showed acceptable safety and tolerability, PK supporting Q3W dosing, and PD and preliminary clinical activity supporting an initial recommended phase 2 dose of 1,400 mg.
Burden of Cardio-Cerebrovascular and Renal Diseases Attributable to Systolic Hypertension in France in 2021
Authors: Grave Clémence , Bonaldi Christophe , Carcaillon-Bentata Laure , Gabet Amélie , Halimi Jean-Michel , Tzourio Christophe , Béjot Yannick , Torres Marion J. , Steg Philippe Gabriel , Durand Zaleski Isabelle , Blacher Jacques , Olié Valérie 
Published: December 2024

BACKGROUND:
Hypertension is the most common chronic disease and a major modifiable risk factor for cardio-cerebrovascular and renal diseases. This study estimated the national burden of hypertension, defined as systolic blood pressure ≥140 mm Hg, on morbidity and mortality in 2021 in France.

METHODS:
For all diseases causally associated with hypertension (cardiovascular diseases, chronic kidney diseases, and dementia), the number and proportion of cases attributable to hypertension in adults aged ≥35 years were estimated using population attributable fractions. Age- and sex-specific population attributable fractions were computed using the distribution of hypertension in the French population. These population attributable fractions were applied to nationwide statistics for mortality, hospitalizations, disease prevalence, years of life lost, years of life lived with disability, and disability-adjusted years of life.

RESULTS:
The largest population attributable fractions were for ischemic heart disease and hemorrhagic stroke, with over 40% of cases attributable to hypertension. Overall, more than 385 000 patients were hospitalized due to hypertension, with 3.7 million hospitalizations and 6.2 million hospital days (all hospitalizations, including 3.4 million for chronic kidney disease) and including 390 000 overnight hospitalization. In 2021, more than 1.15 million individuals lived with ischemic heart disease attributable to hypertension, 1.26 million with chronic kidney diseases, and 358 033 with heart failure. Among 184 059 annual deaths from cardiovascular diseases, dementia, and chronic kidney diseases, 30% (55 280 deaths) were attributable to hypertension. Hypertension accounted for 8.5% of all deaths and 498 052 years of life lost.

CONCLUSIONS:
In France, despite near-universal health coverage and free health care access, the burden attributable to hypertension remains high.
Real-time computation of brain E-field for enhanced transcranial magnetic stimulation neuronavigation and optimization
Authors: Hasan Nahian I. , Dannhauer Moritz , Wang Dezhi , Deng Zhi-De , Gomez Luis J. 
Published: December 2024

Abstract
Transcranial Magnetic Stimulation (TMS) coil placement and pulse waveform current are often chosen to achieve a specified E-field dose on targeted brain regions. TMS neuronavigation could be improved by including real-time accurate distributions of the E-field dose on the cortex. We introduce a method and develop software for computing brain E-field distributions in real-time enabling easy integration into neuronavigation and with the same accuracy as 1st-order finite element method (FEM) solvers. Initially, a spanning basis set (&lt;400) of E-fields generated by white noise magnetic currents on a surface separating the head and permissible coil placements are orthogonalized to generate the modes. Subsequently, Reciprocity and Huygens’ principles are utilized to compute fields induced by the modes on a surface separating the head and coil by FEM, which are used in conjunction with online (real-time) computed primary fields on the separating surface to evaluate the mode expansion. We conducted a comparative analysis of E-fields computed by FEM and in real-time for eight subjects, utilizing two head model types (SimNIBS’s ‘headreco’ and ‘mri2mesh’ pipeline), three coil types (circular, double-cone, and Figure-8), and 1000 coil placements (48,000 simulations). The real-time computation for any coil placement is within 4 milliseconds (ms), for 400 modes, and requires less than 4 GB of memory on a GPU. Our solver is capable of computing E-fields within 4 ms, making it a practical approach for integrating E-field information into the neuronavigation systems without imposing a significant overhead on frame generation. The software is available at https://github.com/NahianHasan/Real-Time-TMS.
Mapping multi-modal dynamic network activity during naturalistic music listening
Authors: Faber Sarah , Brown Tanya , Carpentier Sarah , McIntosh A.R. 
Published: December 2024

Abstract
The human brain is a complex, adaptive system capable of parsing complex stimuli and generating complex behaviour. Understanding how to model and interpret the dynamic relationship between brain, behaviour, and the environment will provide vital information on how the brain responds to real-world stimuli, develops and ages, and adapts to pathology. Modelling together numerous streams of dynamic data, however, presents sizable methodological challenges. In this paper, we present a novel workflow and sample interpretation of a data set incorporating brain, behavioural, and stimulus data from a music listening study. We use hidden Markov modelling (HMM) to extract state time series from continuous high-dimensional EEG and stimulus data, estimate time series variables consistent with HMM from continuous low-dimensional behavioural data, and model the multi-modal data together using partial least squares (PLS). We offer a sample interpretation of the results, including a discussion on the limitations of the currently available tools, and discuss future directions for dynamic multi-modal analysis focusing on naturalistic behaviours.
Building Food Markets as a Method for Confronting the Rise of Authoritarian Populism: How the New Political Regime Has Forced Rural Movements to Create New Action Repertoires in Southern Brazil
Authors: Pizarro Muñoz Estevan Felipe , de Castro Camila Penna , Niederle Paulo André 
Published: December 2024

This article examines how the political construction of food markets acts as a strategy for collective action with regards to three rural movements in Brazil: CONTAG, the MST, and Rede Ecovida. Each used food markets to confront the effects of a regime change that occurred with the rise of a populist authoritarian government. The research for this article was conducted between October 2017 and December 2020 through documentary analysis, observation, and interviews with social leaders. The results show how, since Jair Bolsonaro’s election as president, building new markets became vital to movements that sought to resist the influence of authoritarian populism as well as those that sought to dismantle public policies. A comparative analysis between the three movements also demonstrates how their diverse forms of organization and different political projects led to variations in how markets became privileged within larger political campaigns. O artigo discute a construção política de mercados alimentares como estratégia de ação coletiva de três movimentos rurais brasileiros (CONTAG, MST e Rede Ecovida) em face da mudança de regime ocasionada pela ascensão de um governo populista autoritário. A pesquisa foi realizada entre outubro de 2017 e dezembro de 2020, por meio de análise documental, observação e entrevistas com lideranças sociais. Os resultados apontam que, a partir da chegada de Jair Bolsonaro à presidência, a construção de novos mercados tornou-se um componente essencial de resistência ao populismo autoritário e ao consequente desmantelamento das políticas públicas. A análise comparativa entre os três movimentos também demonstra que seus distintos formatos organizacionais e projetos políticos repercutem em diferenças com relação aos mercados privilegiados pela ação política.
Symptom Burden and Quality of Life in Long-Term Survivors with Head and Neck Cancer
Authors: Gostian Magdalena , Allner Moritz , Rak Atina , Balk Matthias , Rupp Robin , Ostgathe Christoph , Mantsopoulos Konstantinos , Sievert Matti , Iro Heinrich , Hecht Markus , Gostian Antoniu-Oreste 
Published: December 2024

Objectives: In this study, long-term survivors of head and neck cancer (HNC) were evaluated regarding their symptom burden and quality of life (QoL). Methods: This prospective study was performed during the regular follow-up consultations at one of Germany’s largest tertiary referral centers for HNC. The assessment included demographic, clinical, and oncological data, as well as the MIDOS(2) and the University of Washington Quality of Life Questionnaire (UW QoL) questionnaires. Patients were subdivided based on their disease stage, that is, early cancer stages (UICC I/II) and advanced cancer stages UICC (III/IV). Results: Between January 1, 2019 and December 31, 2019, 212 HNC patients with a mean follow-up of 46.36 ± 43.64 months were included (120 patients UICC stage I/II (22.5% female, mean age 61.93 ± 12.38 years) versus 92 patients UICC stage III/IV (25.0% female, mean age 63.73 ± 11.74 years)). For all patients evaluated (UICC I/II versus III/IV), the three most common symptoms were tiredness (47.5 vs 60.9%, P = .073, r = .123), anxiety (35.8 vs 32.6%, P = .624, phi = .034) and drowsiness (35.0 vs 44.6%, P = .157, phi = .097). Patients diagnosed with UICC III/IV stages reported loss of appetite significantly more frequently and with a high level of severity (15.0 vs 32.6%, P = .002, phi = .157; 0.23 ± 0.60 vs 0.47 ± 0.78, P = .003, r = .203). The overall symptom burden was low with a severity sum score (min 0-max 30) of 3.04 ± 3.29 versus 3.58 ± 3.38 ( P = .143, r = .100). All patients rated their QoL as good (65.67 ± 20.93 vs 59.56 ± 22.00, P = .043, r = .139). Conclusion: The overall symptom burden of long-term survivors of HNC is encouragingly low. Trial registration: The study was registered in the German Registry for Clinical Studies (application No.: 00017122). Date of registration: 15.08.2019. https://drks.de/search/de/trial/DRKS00017122 .