bluuebunny/crossref_metadata_2025 huggingface dataset:
A mean field problem approach for the double curvature prescription problem
Authors: Battaglia Luca , López–Soriano Rafael
Published: November 2024

In this paper we establish a new mean field-type formulation to study the problem of prescribing Gaussian and geodesic curvatures on compact surfaces with boundary, which is equivalent to the following Liouville-type PDE with nonlinear Neumann conditions: [Formula: see text] The underlying problem allows the application of straightforward variational techniques. Consequently, we provide three different existence results in the cases of positive, zero and negative Euler characteristics by means of variational techniques.
Solvable groups with four supercharacter theories
Authors: Armioun E.
Published: November 2024

The aim of this paper is to identify the solvable groups with four supercharacter theories. To achieve this, the research will first identify abelian groups with four supercharacter theories. Then it is proved that the only non-abelian group with four supercharacter theories is dihedral group of order 38.
Numerical Prediction and Experimental Verification of Dynamic Deflection Responses of Damaged Hybrid (Luffa- and Carbon-Nanotube-Reinforced) Polymeric Composite Panel Structure
Authors: Pattanayak Pritam , Giri Jayant , La-Lohedan Hamad A. , Akkasali Naveen Kumar , Meher Ashish Kumar , Bohidar Shailendra Kumar , Rana Yogesh , Kumar Vikash , Panda Subrata Kumar
Published: November 2024

The deflection responses of the nanotube- and Luffa-reinforced hybrid polymeric composite have been investigated in this paper with and without damage effect. The mathematical model is derived using higher-order kinematics and solved numerically with the help of isoparametric finite element steps. In addition, the influences of crack type of damage have also been introduced mathematically and solved to obtain the desired responses. The numerical model’s consistency and validity are established initially by solving a few numerical examples that consider the material and geometrical properties to be the same as the references. Further, the correctness of the model is revisited by comparing the results with in-house experimental data. The reference and numerical data have a maximum deviation of 5.19%, which falls within the acceptable range. The current numerical model efficacy can be seen from the comparison of the results. Finally, a few numerical examples are solved considering the variable geometry parameters and nanotube volume fractions. The influences of material and geometrical parameters on the structural final strength and the deflection parameters due to transient loadings are enumerated in detail.
Optimization Design of Pt/C Multilayer Supermirrorsfor Hard X-rays
Authors: Zheng Renzhou , Qiang Pengfei , Yan Yongqing , Li Yue , Zhou Qingyong , Sheng Lizhi
Published: November 2024

Aperiodic multilayers have important applications in hard X-rays astronomical observations due to their broadband responses. This paper presents an optimization model of Pt/C power-law graded stack multilayers using the IMD software. The reflectivity expression of multilayers was derived from the reflection theory of X-ray multilayers and Fresnel recursion formulas. Then, the effects of maximum bi-layer thickness ([Formula: see text]), ratio of high-density material thickness to bi-layer thickness ([Formula: see text]), power-law index ([Formula: see text]), number of bi-layers ([Formula: see text]), grazing incidence angle ([Formula: see text]), interfacial roughness ([Formula: see text]), and photon energy ([Formula: see text]) on the reflectivity were analyzed. The calculation results showed that the [Formula: see text], [Formula: see text] and [Formula: see text] control the shift of response range, absorption peak and Bragg peaks, respectively. And the decrease of [Formula: see text] and increase of [Formula: see text] and [Formula: see text] can result in the reduction of reflectivity at different energies. Additionally, an optimized multilayer structure was proposed according to the extremum of merit function, which can achieve a broadband reflectivity of no less than 0.6 from 1[Formula: see text]keV up to 80[Formula: see text]keV. These results can provide important references for the response characteristic analysis and optimization design of multilayers.
Hyper-viscoelastic modeling of brain tissues based on the Ogden model
Authors: Sun Peng , Zhu Lingrui , Xiao Rui
Published: November 2024

Constitutive modeling serves as a crucial tool for understanding and predicting the behavior of human brain tissue in both healthy and diseased states. This process necessitates the formulation of precise constitutive laws and the integration of ample experimental data to accurately correlate tissue deformation with stress. In this work, we present a phenomenological hyper-viscoelastic model based on the Ogden model that effectively differentiates between elastic and viscous stress responses, enhancing the precision in capturing the mechanical behavior of brain tissue. This includes aspects such as nonlinear response, rate dependence, and tensile–compressive asymmetry. We have validated our model using experimental data from porcine, monkey, and human brain tissues under a variety of loading conditions, thereby confirming its accuracy and reliability. Furthermore, we have undertaken comprehensive review and analysis of experimental conditions in the existing studies on porcine brain tissue, aiming to standardize data selection. The model demonstrates its ability to accurately predict the mechanical behavior across different human brain regions under varied loading scenarios with minimal adjustments. This significant progress promises to aid in the development of medical diagnostic tools and enhance research into brain functionality and injury mechanisms.
Synthesis, Characterization, Molecular Modeling Studies and Bioactivity of a Novel Bicyclic Compound of δ-lactam with Oxazepine Ring Containing Sulphur Substitute using an Economic Method
Authors: Muslim Rasim Farraj , Guma Manaf A. , Razzak Mahmood Ammar A. , Ahmad Iqrar , Hirad Abdurahman Hajinur , Patel Harun
Published: November 2024

Penicillin resistance is a commonly present and controversial matter due to the misuse by people for various reasons. However, few studies have examined the bioactivity of 5- and 6- membered rings. In this study, we aimed to synthesize a new compound containing a 5-membered ring following a short and low-cost method and combined it with oxazepine ring via Schiff bases to produce a bicyclic molecule (Lactozepine). In vitro examinations were conducted to assess the bioactivity of the prepared compound, including anti-bacterial, anti-fungal and antioxidant activities, which showed a wide zone of inhibition of lactozepine against Streptococcus pneumoniae but no inhibition was shown against Klebsiella pneumoniae and Staphylococcus aureus except at a high concentration similar to the result of the anti-fungal assessment. Furthermore, lactozepine showed significant antioxidant activity against free radical formation. The molecular modeling and docking assessment showed the ability of lactozepine to bind to bacterial proteins and inhibit their growth with the lowest free energy for the greatest and strongest binding affinity with the PDB crystal structures 1VQQ, 2WAE, 1PYY and 1IYS ranging from −6.5 and −7.9 kcal/mol. Moreover, the molecular dynamics (MD) simulation showed that RMSF for the assessed protein’s amino acids remained consistent and tightly bound to lactozepine in the dynamic state. The novel compound lactozepine, with [Formula: see text]-lactam rings attached to oxazepine showed bioactivity promising for in vivo studies in the future.
Patients’ Perceptions and Knowledge of Diabetes and Medications: Implications for Medication Adherence and Glycemic Control in Type 2 Diabetes Patients, Northern Ethiopia
Authors: Hadush Fikadu , Beedemariam Gebremedhin , Kahissay Mesfin Haile , Patel Shivani A. , Habte Bruck Messele
Published: November 2024

Globally, adherence to Type 2 diabetes mellitus (T2DM) medications remains suboptimal. There are limited insights, however, on this issue in the northern region of Ethiopia. This cross‐sectional study at Alamata General Hospital investigated the interplay between patients’ medication beliefs, diabetes knowledge, adherence, and glycemic control. Data collection was done using structured questionnaires and chart reviews, while descriptive and inferential statistics were for the analysis. Among 305 T2DM patients, poor medication adherence was prevalent (44.6%), alongside suboptimal glycemic control (75.7%). Patients diagnosed for over a decade had an adjusted odds ratio (AOR) of 3.87 for nonadherence, while high concern about medication side effects was associated with a 20.63‐fold higher nonadherence risk (AOR = 20.63). Low disease awareness increased nonadherence risk by 4.54 times (AOR = 4.54), while a strong belief in medication necessity was protective (AOR = 0.21). Poor glycemic control was associated with educational background, diabetes awareness, monthly income, and treatment modality. Urgently needed are tailored diabetes education programs in Northern Ethiopia to counteract high rates of poor medication adherence (AOR = 3.87) and glycemic control among T2DM patients. Targeted interventions, emphasizing knowledge enhancement and reinforcing positive beliefs, are essential for improving outcomes in this population.
GPR30 Selective Agonist G1 Exhibits Antiobesity Effects and Promotes Insulin Resistance and Gluconeogenesis in Postmenopausal Mice Fed a High‐Fat Diet
Authors: Liu Da , Zheng Mingqi , Lu Congcong , Miao Mengdan , Zhan Yinge , Ma Fangfang , Yin Yajuan , Wei Mei , Wang Wei , Wang Wenyao , Meng Xiangbin , Li Jing , Zhang Yaohua , Liu Gang , Tang Yi-Da
Published: November 2024

Background: G1, a specific agonist targeting the G protein–coupled receptor 30 (GPR30), has demonstrated significant involvement in combating obesity and regulating glucose homeostasis. Nevertheless, the beneficial effects of G1 treatment have solely been investigated in animal models under normal feeding conditions, leaving its therapeutic potential in high‐fat feeding scenarios unexplored.

Material and Methods: To address this gap, our study employed an ovariectomized high‐fat diet mouse model to assess the therapeutic effects of G1 in combating obesity and metabolic dysfunction.

Results: The findings revealed that G1 treatment resulted in weight loss, but concurrently led to increased blood glucose levels and insulin resistance. Treatment with G1 resulted in an amplification of fat mobilization and an enhancement of pyruvate carboxylase activity in mice fed a high‐fat diet. Moreover, the combined impact of G1 treatment and a high‐fat diet on pyruvate metabolism, as well as the regulation of crucial gluconeogenesis enzymes such as pyruvate dehydrogenase kinase 4 (PDK4), phosphoenolpyruvate carboxykinase (PEPCK), and glucose transporter 2 (GLUT2), expedites the elevation of blood glucose and the progression of insulin resistance.

Conclusions: These findings indicate that G1 treatment is influenced by a high‐fat diet, potentially disrupting glucolipid metabolism and promoting insulin resistance alongside its antiobesity effects. Consequently, further investigation is imperative to thoroughly explore this potential toxic side effect of G1 therapy.
Surveillance of Vector‐Borne Zoonotic Diseases in South Korea: Uncovering Novel Pathogen Carriers Among Rodents and Mites Nationwide
Authors: Kim Beoul , Lee You-Jeong , Lee Hee Il , Kwak Dongmi , Seo Min-Goo
Published: November 2024

Wild rodents and their ectoparasites are known reservoirs for various zoonotic pathogens, highlighting the need for detailed studies into their roles in disease transmission. Our research investigated the spatial distribution of rodents and their ectoparasites to better understand the epidemiology of vector‐borne zoonotic diseases (VBZDs), including severe fever with thrombocytopenia syndrome (SFTS), Lyme disease, Q fever, and scrub typhus. We analyzed samples from 540 rodents and 6785 mites, detecting the presence of Borrelia spp., the causative agent of Lyme disease, in 0.9% of rodents and SFTS virus (SFTSV) in 1.0%. In mites, Borrelia spp. and Orientia tsutsugamushi, the bacteria causing scrub typhus, were detected in 0.3% of samples each. Phylogenetic analysis identified the SFTSV sequence as type B3, the Borrelia spp. sequence as B. afzelii, and the O. tsutsugamushi sequence as Karp‐related. Notably, SFTSV was detected for the first time in mites in South Korea, and B. afzelii was found in mites for the first time globally. These findings emphasize the critical need for continuous analysis of VBZDs to anticipate future trends and develop a comprehensive monitoring system. Further research into the rodent and mite populations in South Korea is essential to fully assess the potential risks of VBZDs.
Reconfigurable Neuromorphic Neural Network Architecture
Authors: Sharma Kapil , Sarangi Pradeepta Kumar , Sharma Parth , Nayak Soumya Ranjan , Aluvala Srinivas , Swain Santosh Kumar
Published: November 2024

Neural network (NN), also known as artificial neural network (ANN), provides efficient results in every computation, whether it is pattern recognition, forecasting, customer research, data validation, risk management, data mining, etc. In each computation, NN requires a specific dataset, and according to the datasets, a new NN structure is used to compute the results. Thus, these NN structures mostly depend upon the type of datasets. The current study presents a method that comprises a dedicated architecture known as neuromorphic neural network (NNN), which is made up of optical waveguides that enable high communication and data processing speed at the same time. We have also proposed three algorithms for configuring and building distinct ANN structures from the same architecture. These dedicated structures are not dependent on the datasets and employ the necessary processing element (PE) nodes to function as neurons in the hidden layer. Because specialized resources will be employed to perform operations in the hidden layer, these designs may produce more efficient outcomes than the present logical NN. Furthermore, we assessed our proposed architecture in terms of communication latency, deadlock prevention, energy consumption, and power usage. The simulation results show that deadlocks are avoided to the greatest extent possible, power consumption is reduced by up to 95%, and communicational latency is accomplished in the order of femtoseconds while conversing among PE nodes. The proposed architecture and simulation results promise an alternative for logical NN as well as improved results in terms of speed and efficiency.
New Hybrid Feature Selection Approaches Based on ANN and Novel Sparsity Norm
Authors: Nemati Khadijeh , Refahi Sheikhani Amir Hosein , Kordrostami Sohrab , Khoshhal Roudposhti Kamrad
Published: November 2024

Feature selection is crucial for minimizing redundancy in information and addressing the limitations of traditional classification methods when dealing with large datasets and numerous features in many machine learning applications. To improve the classification, this article introduced two hybrid methods utilizing a genetic algorithm and a gray wolf algorithm with structured dispersion norms for feature selection. These techniques involved the utilization of a genetic algorithm and a gray wolf algorithm for feature selection. The features selected by these algorithms were used in the classification process by employing a two‐layer perceptron as a classifier. The novel sparse norm is employed to assess and compute classification errors in these methodologies. To assess the effectiveness of the suggested techniques, they were compared with the existing feature selection methods using various publicly accessible datasets. The results of the experiments consistently demonstrate that the proposed methods outperform other approaches.
A Novel Thermoelectric Generation Array Reconfiguration to Reduce Mismatch Power Loss Under Nonuniform Temperature Distribution
Authors: Tang Mingfeng , Wang Jun , Ou Yangqi , Tang Ziqiao
Published: November 2024

In practice, industrial exhaust emissions as well as emissions from automobiles, ships, biomass combustion, etc., can be potential application areas for thermoelectric generation (TEG). However, the structural design of heat exchange equipment is usually limited by the internal flow field, resulting in uneven temperature distribution on the heat exchange equipment’s surface. The resulting mismatch power loss is a major challenge for thermoelectric power generation. In this study, based on the characteristics of the surface temperature distribution of heat exchange equipment in the context of gas emissions, a static reconfiguration scheme is proposed for reconfiguring honeycomb (HC) arrays using the symmetric interval crossing (SIC) method. Based on a fixed interconnect array configuration, the solution requires only a change in the location of the modules and no change in the electrical connections, thus reducing mismatch losses while lowering manufacturing costs. Test experiments are conducted for 6 × 6 TEG arrays, mismatch losses are evaluated for four nonuniform temperature distribution cases, and the performance of seven different TEG array configurations is compared. The findings demonstrate that, in nonuniform temperature distribution scenarios, the SIC method can effectively reduce mismatch losses and has a greater output power than alternative array configurations.
Evaluating the Toxicity Induced by Bisphenol F in Labeo rohita Fish Using Multiple Biomarker Approach
Authors: Ahmad Shabbir , Akmal Hasnain , Shahzad Khurram , Ahmad Khan Muhammad Khalil , Jabeen Farhat
Published: November 2024

Bisphenol F (BPF) is an emerging contaminant extensively used in the pharmaceutical, chemical, and food industries, exerting deleterious effects on human and wildlife health. Therefore, the current study was conducted to assess the toxicity induced by BPF in rohu Labeo rohita using multiple biomarkers such as oxidative stress, activity of antioxidant enzymes, biochemical parameters, histology, and genotoxicity. Fish were separated into four groups (T1–T4). Group T1 served as a control (0 μg/L), while Groups T2, T3, and T4 were exposed to BPF concentrations of 600 μg/L, 1200 μg/L, and 1800 μg/L, respectively, for 21 days. Results showed a significant (p < 0.05) increase in oxidative biomarkers (thiobarbituric acid reactive substance [TBARS] and reactive oxygen species [ROS]), while the concentration of antioxidant biomarkers (peroxidase [POD], superoxide dismutase [SOD], reduced glutathione [GSH], and catalase) was significantly (p < 0.05) decreased with the rising concentration of BPF in the liver, gills, and kidney of fish. Significant reduction (p < 0.05) in biochemical parameters was measured from collected whole blood, including red blood cells (RBCs), hemoglobin (HGB), mean corpuscular HGB (MCH), MC volume (MCV), hematocrit (HCT), MC HGB concentration (MCHC), platelets, low‐density lipoprotein (LDL), cholesterol, high‐density lipoprotein (HDL), total proteins, very LDL (VLDL), albumin and globulin, while white blood cells (WBCs), neutrophils, triglycerides, aspartate aminotransferase (AST), blood glucose, and alanine transaminase (ALT) levels were increased significantly (p < 0.05). Comet assay showed the DNA damage potential of BPF in erythrocytes. Histological examination showed that exposure to BPF causes several degenerative effects in the soft tissues (gills, liver, and kidney) of treated fish. It is concluded that BPF induces deleterious effects via disruptions in histological, genotoxic, and biochemical alterations in several organs of exposed fish.
Energy and Exergy Analyses of Supercritical Coal‐Fired Power Plant With Single Reheat and Regenerative
Authors: Khawaja Aaqib Hussain , Shaikh Nasir Uddin , Kumar Laveet , Sleiti Ahmad K.
Published: November 2024

This paper investigates energy and exergy analyses of 660 MW capacity supercritical coal power plant with single reheat and regenerative. The fuel utilized in the plant is a combination of sub‐bituminous and lignite coal. It is found that the turbine section of the system exhibits the highest energy efficiency (around 94.17%) and exergy efficiency (around 90.73%). Also, 82.07% of the total exergy destruction is found for the boiler, and the remaining 17.93% of the irreversibility is determined for the turbine, condenser, and other components. The overall cycle energy efficiency at maximum load is computed as 40.77%, while the overall cycle exergy efficiency at maximum load is found to be 39.69%. These findings provide valuable insights into the performance of the power plant and suggest the improvements needed in performance enhancement of the boiler.
Convex Optimization Algorithm for Maximizing Directivity of Conformal Array With DRR Constraint
Authors: Liu Chao , Zhu Tongtao , Qian Junjie , Zhang Lei , Zhang Xiaoyuan
Published: November 2024

The inconsistency of conformal array elements poses a huge challenge to pattern synthesis. Based on convex optimization theory, this paper proposes a novel directivity pattern synthesis method. It can maximize the directivity of dual‐polarized conformal arrays with a low dynamic range ratio (DRR). Firstly, the directivity function is presented under a dual‐polarized conformal array. Then the pattern synthesis based on maximizing directivity is summarized as a multiconstraint optimization problem. In addition, the DRR constraint is introduced to control the weight range. By using Taylor expansion, the problem is transformed into a convex optimization problem and solved iteratively. Finally, simulation results demonstrate that the proposed method can effectively achieve a good directivity pattern with low sidelobe level (SLL) and low DRR.
Fluorescence Lifetime Imaging Enables In Vivo Quantification of PD-L1 Expression and Intertumoral Heterogeneity
Authors: Pal Rahul , Krishnamoorthy Murali , Matsui Aya , Kang Homan , Morita Satoru , Taniguchi Hajime , Kobayashi Tatsuya , Morita Atsuyo , Choi Hak Soo , Duda Dan G. , Kumar Anand T. N.
Published: November 2024

Patient selection for cancer immunotherapy requires precise, quantitative readouts of biomarker expression in intact tumors that can be reliably compared across multiple subjects over time. The current clinical standard biomarker for assessing immunotherapy response is PD-L1 expression, typically quantified using IHC. This method, however, only provides snapshots of PD-L1 expression status in microscopic regions of ex vivo specimens. Although various targeted probes have been investigated for in vivo imaging of PD-L1, nonspecific probe accumulation within the tumor microenvironment has hindered accurate quantification, limiting the utility for preclinical and clinical studies. Here, we demonstrated that in vivo time-domain fluorescence imaging of an anti–PD-L1 antibody tagged with the near-infrared fluorophore IRDye 800CW (αPDL1-800) can yield quantitative estimates of baseline tumor PD-L1 heterogeneity across untreated mice, as well as variations in PD-L1 expression in mice undergoing clinically relevant anti–PD-1 treatment. The fluorescence lifetime (FLT) of PD-L1–bound αPDL1-800 was significantly longer than the FLT of nonspecifically accumulated αPDL1-800 in the tumor microenvironment. This FLT contrast allowed quantification of PD-L1 expression across mice both in superficial breast tumors using planar FLT imaging and in deep-seated liver tumors (>5 mm depth) using the asymptotic time-domain algorithm for fluorescence tomography. These findings suggest that FLT imaging can accelerate the preclinical investigation and clinical translation of new immunotherapy treatments by enabling robust quantification of receptor expression across subjects.

Significance: Fluorescence lifetime imaging can quantify PD-L1 expression across multiple mice undergoing anti–PD-1 treatment, providing a critically needed noninvasive imaging method to quantify immunotherapy targets in vivo.
Modeling Drug Responses and Evolutionary Dynamics Using Patient-Derived Xenografts Reveals Precision Medicine Strategies for Triple-Negative Breast Cancer
Authors: Shea Abigail , Eyal-Lubling Yaniv , Guerrero-Romero Daniel , Manzano Garcia Raquel , Greenwood Wendy , O’Reilly Martin , Georgopoulou Dimitra , Callari Maurizio , Lerda Giulia , Wix Sophia , Giovannetti Agnese , Masina Riccardo , Esmaeilishirazifard Elham , Cope Wei , Martin Alistair G. , Nagano Ai , Young Lisa , Kupczak Steven , Cheng Yi , Bardwell Helen , Provenzano Elena , Kane Justine , Lay Jonny , Grybowicz Louise , McAdam Karen , Caldas Carlos , Abraham Jean , Rueda Oscar M. , Bruna Alejandra
Published: November 2024

The intertumor and intratumor heterogeneity of triple-negative breast cancers, which is reflected in diverse drug responses, interplays with tumor evolution. In this study, we developed a preclinical experimental and analytical framework using patient-derived tumor xenografts (PDTX) from patients with treatment-naïve triple-negative breast cancers to test their predictive value in personalized cancer treatment approaches. Patients and their matched PDTXs exhibited concordant drug responses to neoadjuvant therapy using two trial designs and dosing schedules. This platform enabled analysis of nongenetic mechanisms involved in relapse dynamics. Treatment resulted in permanent phenotypic changes, with functional and therapeutic consequences. High-throughput drug screening methods in ex vivo PDTX cells revealed patient-specific drug response changes dependent on first-line therapy. This was validated in vivo, as exemplified by a change in olaparib sensitivity in tumors previously treated with clinically relevant cycles of standard-of-care chemotherapy. In summary, PDTXs provide a robust tool to test patient drug responses and therapeutic regimens and to model evolutionary trajectories. However, high intermodel variability and permanent nongenomic transcriptional changes constrain their use for personalized cancer therapy. This work highlights important considerations associated with preclinical drug response modeling and potential uses of the platform to identify efficacious and preferential sequential therapeutic regimens.

Significance: Patient-derived tumor xenografts from treatment-naïve breast cancer samples can predict patient drug responses and model treatment-induced phenotypic and functional evolution, making them valuable preclinical tools.
Small Area Estimation of PSA Testing in US States and Counties
Authors: Liu Benmei , Pleis John R. , Khan Diba , Parsons Van L. , Lee Richard , Cai Bill , Town Machell , Feuer Eric J. , He Yulei
Published: November 2024

Background:

In 2012, the US Preventive Services Task Force recommended against prostate cancer screening using the PSA test for all age groups. In 2018, the US Preventive Services Task Force’s recommendation shifted from a “D” (not recommended) to a “C” (selectively offering PSA-based screening based on professional judgment and patient preferences) in men ages 55 to 69. Limited reliable county-level prostate cancer screening data are available for cancer surveillance purposes.

Methods:

Utilizing data from the National Health Interview Survey (NHIS) and Behavioral Risk Factor Surveillance System (BRFSS) collected in 2012 to 2019, state- and county-level small area models were developed for estimating PSA testing. Model diagnosis, internal validation, and external validation examining associations of PSA testing and prostate cancer incidence were conducted.

Results:

Model-based estimates of PSA testing rates were produced for all US states and 3,142 counties for two data periods: 2012 to 2016 and 2018 to 2019. Geographic variations across counties were demonstrated through maps. Moderate positive correlations between PSA-based screening and prostate cancer incidence were observed, e.g., the state-level weighted Pearson’s correlation coefficients were 0.5025 (P value = 0.0002) and 0.3691 (P value = 0.0077) for 2012 to 2016 and 2018 to 2019, respectively.

Conclusions:

These modeled estimates showed improved precision and adjusted for the differences between the BRFSS and NHIS. The approach of combining the NHIS and BRFSS utilized strengths of the larger sample size of the BRFSS and generally higher response rates and better household coverage from the NHIS.

Impact:

The resulting small area estimates offer a valuable resource for the cancer surveillance community, aiding in targeted interventions, decision making, and further research endeavors.
Supplementary Table 3 from Upregulation of C/EBPα Inhibits Suppressive Activity of Myeloid Cells and Potentiates Antitumor Response in Mice and Patients with Cancer
Authors: Hashimoto Ayumi , Sarker Debashis , Reebye Vikash , Jarvis Sheba , Sodergren Mikael H. , Kossenkov Andrew , Sanseviero Emilio , Raulf Nina , Vasara Jenni , Andrikakou Pinelopi , Meyer Tim , Huang Kai-Wen , Plummer Ruth , Chee Cheng E. , Spalding Duncan , Pai Madhava , Khan Shahid , Pinato David J. , Sharma Rohini , Basu Bristi , Palmer Daniel , Ma Yuk-Ting , Evans Jeff , Habib Robert , Martirosyan Anna , Elasri Naouel , Reynaud Adeline , Rossi John J. , Cobbold Mark , Habib Nagy A. , Gabrilovich Dmitry I.
Published: November 2024

Phenotype of cells used for the analysis of tumour tissues
Supplementary table S5 from Pretreatment Tissue TCR Repertoire Evenness Is Associated with Complete Pathologic Response in Patients with NSCLC Receiving Neoadjuvant Chemoimmunotherapy
Authors: Casarrubios Marta , Cruz-Bermúdez Alberto , Nadal Ernest , Insa Amelia , García Campelo María del Rosario , Lázaro Martín , Dómine Manuel , Majem Margarita , Rodríguez-Abreu Delvys , Martínez-Martí Alex , de Castro-Carpeño Javier , Cobo Manuel , López-Vivanco Guillermo , Del Barco Edel , Bernabé Caro Reyes , Viñolas Nuria , Barneto Aranda Isidoro , Viteri Santiago , Massuti Bartomeu , Barquín Miguel , Laza-Briviesca Raquel , Sierra-Rodero Belén , Parra Edwin R. , Sanchez-Espiridion Beatriz , Rocha Pedro , Kadara Humam , Wistuba Ignacio I. , Romero Atocha , Calvo Virginia , Provencio Mariano
Published: November 2024

Table S5: Gene Ontology enrichment analysis of differentially expressed genes between High and Low Top 1% clonal space tumors.
Supplementary table S4 from Pretreatment Tissue TCR Repertoire Evenness Is Associated with Complete Pathologic Response in Patients with NSCLC Receiving Neoadjuvant Chemoimmunotherapy
Authors: Casarrubios Marta , Cruz-Bermúdez Alberto , Nadal Ernest , Insa Amelia , García Campelo María del Rosario , Lázaro Martín , Dómine Manuel , Majem Margarita , Rodríguez-Abreu Delvys , Martínez-Martí Alex , de Castro-Carpeño Javier , Cobo Manuel , López-Vivanco Guillermo , Del Barco Edel , Bernabé Caro Reyes , Viñolas Nuria , Barneto Aranda Isidoro , Viteri Santiago , Massuti Bartomeu , Barquín Miguel , Laza-Briviesca Raquel , Sierra-Rodero Belén , Parra Edwin R. , Sanchez-Espiridion Beatriz , Rocha Pedro , Kadara Humam , Wistuba Ignacio I. , Romero Atocha , Calvo Virginia , Provencio Mariano
Published: November 2024

Table S4: Differentially expressed genes between High and Low Top 1% clonal space tumors.
Figure S4 from Pretreatment Tissue TCR Repertoire Evenness Is Associated with Complete Pathologic Response in Patients with NSCLC Receiving Neoadjuvant Chemoimmunotherapy
Authors: Casarrubios Marta , Cruz-Bermúdez Alberto , Nadal Ernest , Insa Amelia , García Campelo María del Rosario , Lázaro Martín , Dómine Manuel , Majem Margarita , Rodríguez-Abreu Delvys , Martínez-Martí Alex , de Castro-Carpeño Javier , Cobo Manuel , López-Vivanco Guillermo , Del Barco Edel , Bernabé Caro Reyes , Viñolas Nuria , Barneto Aranda Isidoro , Viteri Santiago , Massuti Bartomeu , Barquín Miguel , Laza-Briviesca Raquel , Sierra-Rodero Belén , Parra Edwin R. , Sanchez-Espiridion Beatriz , Rocha Pedro , Kadara Humam , Wistuba Ignacio I. , Romero Atocha , Calvo Virginia , Provencio Mariano
Published: November 2024

Clonal space occupied by shared or newly emergent clones top 1% post-T clones in PBMCs at pre- and post-treatment timepoints.
Figure S1 from Pretreatment Tissue TCR Repertoire Evenness Is Associated with Complete Pathologic Response in Patients with NSCLC Receiving Neoadjuvant Chemoimmunotherapy
Authors: Casarrubios Marta , Cruz-Bermúdez Alberto , Nadal Ernest , Insa Amelia , García Campelo María del Rosario , Lázaro Martín , Dómine Manuel , Majem Margarita , Rodríguez-Abreu Delvys , Martínez-Martí Alex , de Castro-Carpeño Javier , Cobo Manuel , López-Vivanco Guillermo , Del Barco Edel , Bernabé Caro Reyes , Viñolas Nuria , Barneto Aranda Isidoro , Viteri Santiago , Massuti Bartomeu , Barquín Miguel , Laza-Briviesca Raquel , Sierra-Rodero Belén , Parra Edwin R. , Sanchez-Espiridion Beatriz , Rocha Pedro , Kadara Humam , Wistuba Ignacio I. , Romero Atocha , Calvo Virginia , Provencio Mariano
Published: November 2024

PFS and OS survival stratified by pre-treatment evenness, TMB, and PD-L1. Correlation between tissue evenness and TMB or PD-L1. Mutations and pre-treatment tissue top 1% clonal space.
Supplementary Data from Early Use of High-Dose Glucocorticoid for the Management of irAE Is Associated with Poorer Survival in Patients with Advanced Melanoma Treated with Anti–PD-1 Monotherapy
Authors: Bai Xue , Hu Jiani , Betof Warner Allison , Quach Henry T. , Cann Christopher G. , Zhang Michael Z. , Si Lu , Tang Bixia , Cui Chuanliang , Yang Xiaoling , Wei Xiaoting , Pallan Lalit , Harvey Catriona , Manos Michael P. , Ouyang Olivia , Kim Michelle S. , Kasumova Gyulnara , Cohen Justine V. , Lawrence Donald P. , Freedman Christine , Fadden Riley M. , Rubin Krista M. , Sharova Tatyana , Frederick Dennie T. , Flaherty Keith T. , Rahma Osama E. , Long Georgina V. , Menzies Alexander M. , Guo Jun , Shoushtari Alexander N. , Johnson Douglas B. , Sullivan Ryan J. , Boland Genevieve M.
Published: November 2024

Supplementary tables and figures Fig S1. Week 26 landmark analysis for high-dose GCC associated irAE and its association with post-irAE PFS and post-irAE OS.
Data from Circulating HPV DNA as a Marker for Early Detection of Relapse in Patients with Cervical Cancer
Authors: Jeannot Emmanuelle , Latouche Aurélien , Bonneau Claire , Calméjane Marie-Ange , Beaufort Corine , Ruigrok-Ritstier Kirsten , Bataillon Guillaume , Larbi Chérif Linda , Dupain Célia , Lecerf Charlotte , Popovic Marina , de la Rochefordière Anne , Lecuru Fabrice , Fourchotte Virginie , Jordanova Ekaterina S. , von der Leyen Heiko , Tran-Perennou Carine , Legrier Marie-Emmanuelle , Dureau Sylvain , Raizonville Laurence , Bello Roufai Diana , Le Tourneau Christophe , Bièche Ivan , Rouzier Roman , Berns Els M.J.J. , Kamal Maud , Scholl Suzy
Published: November 2024

AbstractPurpose:
Almost all cervical cancers are caused by human papillomavirus (HPV) and patients with advanced stage are at high risk for relapse. Circulating HPV DNA (HPV ctDNA) may serve as a residual tumor marker at the end of chemoradiation or to predict relapse during the follow-up period.
Experimental Design:
We analyzed serum samples from 94 HPV16- or HPV18-related CCs from the BioRAIDs prospective cohort. Samples were collected before and after treatment and during an 18-month follow-up period. Using digital droplet PCR (ddPCR), we assessed the relevance of circulating HPV E7 gene as a marker for residual disease compared to HPV integration site and PIK3CA mutations. Finally, the prognostic impact of circulating HPV E7 gene was assessed with its prediction value of relapse.
Results:
HPV E7 gene was the most sensitive tumor marker, superior to both HPV integration sites and PIK3CA mutations in serum. Circulating HPV DNA (HPV ctDNA) was detected in 63% (59/94) of patients, before treatment. HPV ctDNA detection in serum sample was associated with high FIGO stage (P = 0.02) and para-aortic lymph node involvement (P = 0.01). The level of HPV ctDNA was positively correlated with HPV copy number in the tumor (R = 0.39, P < 0.001). Complete clearance of HPV ctDNA by the end of treatment was significantly associated with a longer PFS (P < 0.0001). Patients with persistent HPV ctDNA in serum relapsed with a median time of 10 months (range, 2–15) from HPV ctDNA detection.
Conclusions:
HPV ctDNA detection is a useful marker to predict relapse in cervical cancer.

See related commentary by Wentzensen and Clarke, p. 5733
Data from Upregulation of C/EBPα Inhibits Suppressive Activity of Myeloid Cells and Potentiates Antitumor Response in Mice and Patients with Cancer
Authors: Hashimoto Ayumi , Sarker Debashis , Reebye Vikash , Jarvis Sheba , Sodergren Mikael H. , Kossenkov Andrew , Sanseviero Emilio , Raulf Nina , Vasara Jenni , Andrikakou Pinelopi , Meyer Tim , Huang Kai-Wen , Plummer Ruth , Chee Cheng E. , Spalding Duncan , Pai Madhava , Khan Shahid , Pinato David J. , Sharma Rohini , Basu Bristi , Palmer Daniel , Ma Yuk-Ting , Evans Jeff , Habib Robert , Martirosyan Anna , Elasri Naouel , Reynaud Adeline , Rossi John J. , Cobbold Mark , Habib Nagy A. , Gabrilovich Dmitry I.
Published: November 2024

AbstractPurpose:
To evaluate the mechanisms of how therapeutic upregulation of the transcription factor, CCAAT/enhancer-binding protein alpha (C/EBPα), prevents tumor progression in patients with advanced hepatocellular carcinoma (HCC) and in different mouse tumor models.
Experimental Design:
We conducted a phase I trial in 36 patients with HCC (NCT02716012) who received sorafenib as part of their standard care, and were given therapeutic C/EBPα small activating RNA (saRNA; MTL-CEBPA) as either neoadjuvant or adjuvant treatment. In the preclinical setting, the effects of MTL-CEBPA were assessed in several mouse models, including BNL-1ME liver cancer, Lewis lung carcinoma (LLC), and colon adenocarcinoma (MC38).
Results:
MTL-CEBPA treatment caused radiologic regression of tumors in 26.7% of HCC patients with an underlying viral etiology with 3 complete responders. MTL-CEBPA treatment in those patients caused a marked decrease in peripheral blood monocytic myeloid-derived suppressor cell (M-MDSC) numbers and an overall reduction in the numbers of protumoral M2 tumor-associated macrophages (TAM). Gene and protein analysis of patient leukocytes following treatment showed CEBPA activation affected regulation of factors involved in immune-suppressive activity. To corroborate this observation, treatment of all the mouse tumor models with MTL-CEBPA led to a reversal in the suppressive activity of M-MDSCs and TAMs, but not polymorphonuclear MDSCs (PMN-MDSC). The antitumor effects of MTL-CEBPA in these tumor models showed dependency on T cells. This was accentuated when MTL-CEBPA was combined with checkpoint inhibitors or with PMN-MDSC–targeted immunotherapy.
Conclusions:
This report demonstrates that therapeutic upregulation of the transcription factor C/EBPα causes inactivation of immune-suppressive myeloid cells with potent antitumor responses across different tumor models and in cancer patients. MTL-CEBPA is currently being investigated in combination with pembrolizumab in a phase I/Ib multicenter clinical study (NCT04105335).
Data from Early Use of High-Dose Glucocorticoid for the Management of irAE Is Associated with Poorer Survival in Patients with Advanced Melanoma Treated with Anti–PD-1 Monotherapy
Authors: Bai Xue , Hu Jiani , Betof Warner Allison , Quach Henry T. , Cann Christopher G. , Zhang Michael Z. , Si Lu , Tang Bixia , Cui Chuanliang , Yang Xiaoling , Wei Xiaoting , Pallan Lalit , Harvey Catriona , Manos Michael P. , Ouyang Olivia , Kim Michelle S. , Kasumova Gyulnara , Cohen Justine V. , Lawrence Donald P. , Freedman Christine , Fadden Riley M. , Rubin Krista M. , Sharova Tatyana , Frederick Dennie T. , Flaherty Keith T. , Rahma Osama E. , Long Georgina V. , Menzies Alexander M. , Guo Jun , Shoushtari Alexander N. , Johnson Douglas B. , Sullivan Ryan J. , Boland Genevieve M.
Published: November 2024

AbstractPurpose:
Programmed cell death receptor-1 (PD-1) inhibitors are frontline therapy in advanced melanoma. Severe immune-related adverse effects (irAEs) often require immunosuppressive treatment with glucocorticoids (GCCs), but GCC use and its correlation with patient survival outcomes during anti–PD-1 monotherapy remains unclear.
Experimental Design:
In this multicenter retrospective analysis, patients treated with anti–PD-1 monotherapy between 2009 and 2019 and detailed GCC use, data were identified from five independent cohorts, with median follow-up time of 206 weeks. IrAEs were tracked from the initiation of anti–PD-1 until disease progression, initiation of a new therapy, or last follow-up. Correlations between irAEs, GCC use, and survival outcomes were analyzed.
Results:
Of the entire cohort of 947 patients, 509 (54%) developed irAEs. In the MGH cohort [irAE(+) n = 90], early-onset irAE (within 8 weeks of anti–PD-1 initiation) with high-dose GCC use (≥60-mg prednisone equivalent once a day) was independently associated with poorer post-irAE PFS/OS (progression-free survival/overall survival) [post-irAE PFS: HR, 5.37; 95% confidence interval (CI), 2.10–13.70; P < 0.001; post-irAE OS: HR, 5.95; 95% CI, 2.20–16.09; P < 0.001] compared with irAEs without early high-dose GCC use. These findings were validated in the combined validation cohort [irAE(+) n = 419, post-irAE PFS: HR, 1.69; 95% CI, 1.04–2.76; P = 0.04; post-irAE OS: HR, 1.97; 95% CI, 1.15–3.39; P = 0.01]. Similar findings were also observed in the 26-week landmark analysis for post–irAE-PFS but not for post–irAE-OS. A sensitivity analysis using accumulated GCC exposure as the measurement achieved similar results.
Conclusions:
Early high-dose GCC use was associated with poorer PFS and OS after irAE onset. Judicious use of GCC early during anti–PD-1 monotherapy should be considered. Further prospective randomized control clinical trials designed to explore alternative irAE management options are warranted.
Targeting c-MET for Endoscopic Detection of Dysplastic Lesions within Barrett’s Esophagus Using EMI-137 Fluorescence Imaging
Authors: Huang Yi-Jhih , Rieder Jonas , Tan Kel Vin , Tenditnaya Anna , Vojnovic Borivoj , Gorpas Dimitris , Quante Michael , Vallis Katherine A.
Published: November 2024

Purpose:

Esophageal cancer carries a poor prognosis with a 5-year overall survival of less than 20%. Barrett’s esophagus increases the risk of esophageal adenocarcinoma. The aim of this study was to investigate the ability of EMI-137, a mesenchymal–epithelial transition factor (c-MET)-targeting optical imaging tracer, to detect dysplasia in Barrett’s esophagus.

Experimental Design:

c-MET expression in human esophageal tissue was investigated using Gene Expression Omnibus datasets, tissue microarrays, and Barrett’s esophagus biopsies. EMI-137 was tested in a dual xenograft mouse model bearing OE33 (c-MET high expression) and FLO-1 (c-MET low expression) tumors. Fluorescence molecular endoscopy was performed in a mouse model of Barrett’s-like metaplasia and dysplasia (L2-IL1β). Tumors and organs of interest were evaluated through ex vivo fluorescence imaging.

Results:

MET mRNA expression analyses and c-MET immunostaining confirmed upregulation of c-MET in Barrett’s esophagus and esophageal adenocarcinoma compared with normal epithelium. There was strong accumulation of EMI-137 in OE33 xenografts 3 hours after injection, decreasing by more than 50% on coinjection of a 10-fold molar excess of unlabeled EMI-137. The target-to-background ratio at 3 hours after injection for OE33 and FLO-1 tumors was 10.08 and 1.42, respectively. Fluorescence molecular endoscopy of L2-IL1β mice showed uptake of EMI-137 in dysplastic lesions within Barrett’s esophagus with a target-to-background ratio of 1.9 in vivo and greater than 2 in ex vivo fluorescence imaging.

Conclusions:

EMI-137 accumulates in dysplastic lesions within Barrett’s esophagus and also in c-MET–positive esophageal adenocarcinoma. EMI-137 imaging has potential as a screening and surveillance tool for patients with Barrett’s esophagus and as a means to detecting dysplasia and esophageal adenocarcinoma.
Pathogenic Variants in Cancer Susceptibility Genes Predispose to Ductal Carcinoma In Situ of the Breast
Authors: Huang Huaizhi , Couch Ronan E. , Karam Rachid , Hu Chunling , Boddicker Nicholas , Polley Eric C. , Na Jie , Ambrosone Christine B. , Yao Song , Trentham-Dietz Amy , Eliassen A. Heather , Penney Kathryn , Brantley Kristen , Bodelon Clara , Teras Lauren R. , Hodge James , Patel Alpa , Haiman Christopher A. , John Esther M. , Neuhausen Susan L. , Martinez Elena , Lacey James V. , O’Brien Katie M. , Sandler Dale P. , Weinberg Clarice R. , Palmer Julie R. , Bertrand Kimberly A. , Vachon Celine M. , Olson Janet E. , Ruddy Kathryn E. , Anton-Culver Hoda , Ziogas Argyrios , Goldgar David E. , Nathanson Katherine L. , Domchek Susan M. , Weitzel Jeffrey N. , Kraft Peter , Dolinsky Jill S. , Pesaran Tina , Richardson Marcy E. , Yadav Siddhartha , Couch Fergus J.
Published: November 2024

Purpose:

To determine the relationship between germline pathogenic variants (PV) in cancer predisposition genes and the risk of ductal carcinoma in situ (DCIS).

Experimental Design:

Germline PV frequencies in breast cancer predisposition genes (ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, PALB2, RAD51C, and RAD51D) were compared between DCIS cases and unaffected controls and between DCIS and invasive ductal breast cancer (IDC) cases from a clinical testing cohort (n = 9,887), a population-based cohort (n = 3,876), and the UK Biobank (n = 2,421). The risk of contralateral breast cancer (CBC) for DCIS cases with PV was estimated in the population-based cohort.

Results:

Germline PV were observed in 6.5% and 4.6% of women with DCIS in the clinical testing and population-based cohorts, respectively. BRCA1, BRCA2, and PALB2 PV frequencies were significantly lower among women with DCIS than those with IDC (clinical cohort: 2.8% vs. 5.7%; population-based cohort: 1.7% vs. 3.7%), whereas the PV frequencies for ATM and CHEK2 were similar. ATM, BRCA1, BRCA2, CHEK2, and PALB2 PV were significantly associated with an increased risk of DCIS (OR > 2.0), but only BRCA2 PV were associated with high risk (OR > 4) in both cohorts. The cumulative incidence of CBC among carriers of PV in high-penetrance genes with DCIS was 23% over 15 years.

Conclusions:

The enrichment of PV in ATM, BRCA1, BRCA2, CHEK2, and PALB2 among women with DCIS suggests that multigene panel testing may be appropriate for women with DCIS. Elevated risks of CBC in carriers of PV in high-penetrance genes with DCIS confirmed the utility of testing for surgical decision-making.
Supplementary Figure 4 from Acetalax (Oxyphenisatin Acetate, NSC 59687) and Bisacodyl Cause Oncosis in Triple-Negative Breast Cancer Cell Lines by Poisoning the Ion Exchange Membrane Protein TRPM4
Authors: Mizunuma Makito , Redon Christophe E. , Saha Liton Kumar , Tran Andy D. , Dhall Anjali , Sebastian Robin , Taniyama Daiki , Kruhlak Michael J. , Reinhold William C. , Takebe Naoko , Pommier Yves
Published: November 2024

Scatter plot of Acetalax activity versus TRPM4 transcript expression.
Supplementary Figure 3 from Acetalax (Oxyphenisatin Acetate, NSC 59687) and Bisacodyl Cause Oncosis in Triple-Negative Breast Cancer Cell Lines by Poisoning the Ion Exchange Membrane Protein TRPM4
Authors: Mizunuma Makito , Redon Christophe E. , Saha Liton Kumar , Tran Andy D. , Dhall Anjali , Sebastian Robin , Taniyama Daiki , Kruhlak Michael J. , Reinhold William C. , Takebe Naoko , Pommier Yves
Published: November 2024

Mitochondrial morphological changes caused by Acetalax in BT549.
Supplementary Figure 2 from Acetalax (Oxyphenisatin Acetate, NSC 59687) and Bisacodyl Cause Oncosis in Triple-Negative Breast Cancer Cell Lines by Poisoning the Ion Exchange Membrane Protein TRPM4
Authors: Mizunuma Makito , Redon Christophe E. , Saha Liton Kumar , Tran Andy D. , Dhall Anjali , Sebastian Robin , Taniyama Daiki , Kruhlak Michael J. , Reinhold William C. , Takebe Naoko , Pommier Yves
Published: November 2024

Morphological changes in TRPM4-KO and chronic exposure (CE) cells.