bluuebunny/crossref_metadata_2025 huggingface dataset:
Accelerating universe in f(T) teleparallel gravity
Authors: Shukla Bhupendra Kumar , Sofuoğlu Değer , Khare Sandeep , Alfedeel Alnadhief H.A.
Published: July 2024

In recent decades, there has been significant research on the role of torsion in gravity, with a focus on aligning gravity with its gauge formulation and including spin into a geometric description. In order to account for the present phenomenon of the universe’s accelerated expansion, recent developments have introduced [Formula: see text] theories that rely on the disparities found in teleparallel gravity. Torsion, rather than curvature, is the fundamental geometric property that describes gravity in these theories. When compared to theories involving [Formula: see text] functions, the field equations are consistently of second order and surprisingly simple. We consider a specific type of function called torsion, which is defined as [Formula: see text]. The expression consists of two free parameters, [Formula: see text] and [Formula: see text], and the current value of the torsion scalar, [Formula: see text]. In order to solve the modified torsion field equations (MTFEs), we can utilize the parametrization of the deceleration parameter (DP) in terms of redshift, denoted as [Formula: see text]. Here, [Formula: see text] and [Formula: see text] represent the model parameters. The model parameters are determined by utilizing observable constraints, including as 57 Hubble data points, 1048 Pantheon supernovae type Ia data, and Baryon Acoustic Oscillations (BAO) datasets. In addition, we utilize Markov Chain Monte Carlo (MCMC) methods for statistical analysis.
Thermodynamic geometry of charged rotating black holes in Einsteinian cubic gravity
Authors: Keshavarzi Aghil , Ebadi Zahra , Mohammadzadeh Hosein
Published: July 2024

We study the thermodynamic geometry of two types of asymptotically anti-de Sitter black holes in four-dimensional Einsteinian cubic gravity, including the uncharged rotating and charged non-rotating black holes, applying the Ruppeiner thermodynamic geometry method. The divergence of the scalar curvature of the Ruppeiner metric ([Formula: see text]) is found to be related to the vanishing of the heat capacity. The stability of the solutions is shown to be affected by the Einsteinian cubic gravity coupling constant [Formula: see text]. In the unstable phase of the rotating black hole, the [Formula: see text] appeared to possess additional diverging points, where the number of these points and the behavior of [Formula: see text] are controlled by the angular momentum parameter. Also, for the charged non-rotating black hole case, we show that depending on the values of [Formula: see text], the solution may enjoy two types of phase transition and [Formula: see text] behaviors. The characteristic behavior of [Formula: see text] of these two types of black holes enabled us to recognize the types of interactions between microscopic degrees of freedom.
FAMILY FIRM NARCISSISM: CONCEPTUALISATION, MEASUREMENT, AND RELATIONSHIP TO INNOVATION
Authors: BENDIG DAVID , KLEINE-STEGEMANN LUCAS , BARTELS FLORIAN , SCHÄPERS PHILIPP
Published: July 2024

Family firm behaviour can be a potential root of innovation in family firms. Building on the theoretical perspectives of socioemotional wealth and narcissistic organisational identification, we introduce a novel concept and new measure for family firm narcissism (FFN). We suggest that FFN influences family firms’ innovation orientation (i.e., strategic innovativeness) and realised innovation outcome (i.e., digital inventiveness). Additionally, we assume that industry IT intensity, as an indicator of environmental pressure regarding digital transformation, moderates these relationships. To test the hypotheses, we investigated a longitudinal cross-industry sample, comprising 1,302 firm-year observations of S&P 500 family firms and analysed it with regression models. The results indicate that FFN is positively related to strategic innovativeness and negatively related to digital inventiveness. We further find that industry IT spending intensity amplifies both linkages. Our study contributes to the discussion on the family innovation agenda by (1) introducing the new concept and measure for FFN and (2) underlining its controversial impact and effectiveness on two central manifestations of innovation under the boundary conditions of digital transformation.
Low Resource Summarization using Pre-trained Language Models
Authors: Munaf Mubashir , Afzal Hammad , Mahmood Khawir , Iltaf Naima
Published: July 2024

With the advent of Deep Learning-based Artificial Neural Network models, Natural Language Processing (NLP) has witnessed significant improvements in textual data processing in terms of its efficiency and accuracy. However, the research is mostly restricted to high-resource languages such as English, and low-resource languages still suffer from a lack of available resources in terms of training datasets as well as models with even baseline evaluation results. Considering the limited availability of resources for low-resource languages, we propose a methodology for adapting self-attentive transformer-based architecture models (mBERT, mT5) for low-resource summarization, supplemented by the construction of a new baseline dataset (76.5k article, summary pairs) in a low-resource language, Urdu. Choosing news (a publicly available source) as the application domain has the potential to make the proposed methodology useful for reproducing in other languages with limited resources. Our adapted summarization model
urT5
with up to 44.78% reduction in size as compared to
mT5
can capture contextual information of the low-resource language effectively with an evaluation score (up to 46.35 ROUGE-1, 77 BERTScore) on par with state-of-the-art models in the high-resource language of English
(PEGASUS: 47.21, BART: 45.14 on XSUM Dataset)
. The proposed method provided a baseline approach toward extractive as well as abstractive summarization with competitive evaluation results in a limited resource setup.
TinyCheXReport: Compressed deep neural network for Chest X-ray report generation
Authors: Alotaibi Fahd Saleh , Alyoubi Khaled Hamed , Mittal Ajay , Gupta Vishal , Kaur Navdeep
Published: July 2024

Increase in Chest X-ray (CXR) imaging tests has burdened radiologists, thereby posing significant challenges in writing radiological reports on time. Although several deep learning-based automatic report generation methods have been developed, most are over-parameterized. For deployment on edge devices with constrained processing power or limited resources, over-parameterized models are often too large. This article presents a compressed deep learning-based model that is 30% space efficient compared to the non-compressed base model, while both have comparable performance. The model comprising VGG19 and hierarchical long short-term memory equipped with a contextual word embedding layer is used as the base model. The redundant weight parameters are removed from the base model using unstructured one-shot pruning. To overcome the performance degradation, the lightweight pruned model is fine-tuned over publicly available OpenI dataset. The quantitative evaluation metric scores demonstrate that proposed model surpasses the performance of state-of-the-art models. Additionally, the proposed model, being 30% space efficient, is easily deployable in resource-limited settings. Thus, this study serves as baseline for development of compressed models to generate radiological reports from CXR images.
Unveiling Cyber Threat Actors: A Hybrid Deep Learning Approach for Behavior-Based Attribution
Authors: Böge Emirhan , Ertan Murat Bilgehan , Alptekin Halit , Çetin Orçun
Published: July 2024

In this article, we leverage natural language processing and machine learning algorithms to profile threat actors based on their behavioral signatures to establish identification for soft attribution. Our unique dataset comprises various actors and the commands they have executed, with a significant proportion using the Cobalt Strike framework in August 2020–October 2022. We implemented a hybrid deep learning structure combining transformers and convolutional neural networks to benefit global and local contextual information within the sequence of commands, which provides a detailed view of the behavioral patterns of threat actors. We evaluated our hybrid architecture against pre-trained transformer-based models such as BERT, RoBERTa, SecureBERT, and DarkBERT with our high-count, medium-count, and low-count datasets. Hybrid architecture has achieved F1-score of 95.11% and an accuracy score of 95.13% on the high-count dataset, F1-score of 93.60% and accuracy score of 93.77% on the medium-count dataset, and F1-score of 88.95% and accuracy score of 89.25% on the low-count dataset. Our approach has the potential to substantially reduce the workload of incident response experts who are processing the collected cybersecurity data to identify patterns.
Microbial Metabolites and Gut Immunology
Authors: Takeuchi Tadashi , Nakanishi Yumiko , Ohno Hiroshi
Published: July 2024

The intestine is the largest peripheral lymphoid organ in animals, including humans, and interacts with a vast array of microorganisms called the gut microbiota. Comprehending the symbiotic relationship between the gut microbiota and our immune system is essential not only for the field of immunology but also for understanding the pathogenesis of various systemic diseases, including cancer, cardiometabolic disorders, and extraintestinal autoimmune conditions. Whereas microbe-derived antigens are crucial for activating the intestinal immune system, particularly T and B cells, as environmental cues, microbes and their metabolites play a critical role in directing the differentiation of these immune cells. Microbial metabolites are regarded as messengers from the gut microbiota, since bacteria have the ability to produce unique molecules that humans cannot, and many immune cells in the intestine express receptors for these molecules. This review highlights the distinct relationships between microbial metabolites and the differentiation and function of the immune system.
Full-, Half-, and Symmetrical Cell Analysis of Lithium-Ion Battery Using Impedance and Nonlinear Frequency Response
Authors: Lee Yan Ying , Chan Hoon Seng , Ulrich Julian , Weber André , Krewer Ulrike
Published: July 2024

This study presents an in-depth analysis of the cathode and anode of a commercial 18650 lithium-ion battery by comparing their dynamic behaviors systematically with that of two additional experimental cell setups: (i) full-cell in a three-electrode setup and (ii) symmetrical cathode and anode cells. The analysis involves subjecting the cells to electrochemical impedance spectroscopy, distribution of relaxation times, and nonlinear frequency response analysis at different state-of-charges. Our findings highlight the importance of analyzing the electrodes in all three setups. The impedance and nonlinear frequency response features of the full-cell are also observed in the electrode-resolved cells. Symmetrical cells exhibit stronger impedance and nonlinear responses compared to the commercial cell and the cell with reference electrode, yet they allow identifying contributions of the single cells without artifacts from inductive loops caused by the reference electrode. By correlating nonlinear signals and characteristic peaks across different cell setups, cathode and anode processes and their respective characteristic frequencies can be clearly identified.
Electrochemical Oxidation of Ethanol and Methanol at Rh@Pt Catalysts at 80 °C in Proton Exchange Membrane (PEM) Cells
Authors: Ali Ahmed H. , Pickup Peter G.
Published: July 2024

Efficient oxidation of ethanol to carbon dioxide is crucial for the development of sustainable electrochemical generation of power and hydrogen from bioethanol. However, high anode overpotentials and partial oxidation to acetaldehyde and acetic acid result in low efficiencies and waste management issues. Bimetallic Rh-Pt catalysts have shown enhanced activities and CO2 production in aqueous electrolytes, but not in proton exchange membrane (PEM) cells. In this work Rh@Pt core–shell catalysts, prepared from commercial carbon-supported Rh, have been evaluated in both aqueous H2SO4 and PEM cells. Cyclic voltammetry of aqueous methanol and ethanol has shown that the catalytic activity of the Pt shell is increased by the compressive strain induced by the Rh core, and that there is also a significant bifunctional effect at low Pt coverages. In PEM cells, these effects also increase selectivity for cleavage of the C–C bond of ethanol to produce CO2, which will enhance the efficiencies of ethanol fuel and electrolysis cells for producing power and hydrogen, respectively. Deposition of 0.5 monolayers of Pt onto the Rh core produced the highest CO2 yields at the lowest anode overpotentials, while higher coverages of Pt increased performances and CO2 yields at higher potentials.
Velocity dependence of sensory reweighting in human balance control
Authors: Missen Kyle J. , Carpenter Mark G. , Assländer Lorenz
Published: July 2024

This novel study examined the velocity dependence of sensory reweighting for human balance control using support surface tilt stimuli with independently varied amplitude and velocity. Estimates of the proprioceptive contribution to standing balance, derived from model-based interpretations of sway characteristics, showed greater sensitivity to changes in surface tilt velocity than surface tilt amplitude. These results support a velocity-based mechanism underlying sensory reweighting for human balance control.
Comprehensive Design Analysis of Economical E‐Bike Charger with IoT‐Empowered System for Real‐Time Parameter Monitoring
Authors: Ilahi Tehseen , Izhar Tahir , Ali Majid , Noor Usama , Siddique Mudassar , Khan Ehtisham Muhammad , Yousaf Roomana , Ali Ahmed , Khan Baseem
Published: July 2024

The demand for electrically powered transportation is increasing exponentially due to high fuel prices and global environmental issues. The use of electric bikes is increasing rapidly within urban mobility. The current E‐bike chargers are expensive and fail to provide proper authentication, real‐time monitoring, parameter analysis, health maintenance alerts, etc. To meet future demand, the paper presents detailed design procedures and experimental analysis of smart, user‐friendly, economical, and green charging solutions for electric bikes. The research provides an IoT‐based cheap charging facility for different workplaces, organizations, and highway rest areas. Real‐time pricing and parameters are sensed using an IoT module and observed online with a monitoring interface via the ThingSpeak platform. The parameters are visualized using both simulation and hardware analysis. The detailed power converter and high‐frequency transformer design procedure with mathematical equations are presented in the article. The proposed design improves reliability, security, timely maintenance, and system health conditions. The research provides economical off‐board charging stations with smart interfaces that can be accessed by users or service providers through the data cloud. The low‐cost smart charging stations promote the use of electric vehicles and decrease the charging anxiety of users. The proposed scheme reduces emissions problems, improves the air quality index, and facilitates people with affordable and reliable transportation.
Identification of Endoplasmic Reticulum Stress‐Related Biomarkers in Coronary Artery Disease
Authors: Lin Yuanyuan , Ni Lin , Yang Luqun , Li Hao , Chen Zelin , Gao Yuping , Zhu Kaiyi , Jia Yanni , Wu Zhifang , Li Sijin
Published: July 2024

Coronary artery disease (CAD) is caused by atherosclerotic lesions in the coronary vessels. Endoplasmic reticulum stress (ERS) acts in cardiovascular disease, and its role in CAD is not clear. A total of 13 differentially expressed ERS‐related genes (DEERSRGs) in CAD were identified. Functional enrichment analysis demonstrated the DEERSRGs were mainly enriched in endoplasmic reticulum (ER)‐related pathways. Then, eight genes (RCN2, HRC, DERL2, RNF183, CRH, TMED2, PPP1R15A, and IL1A) were authenticated as ERS‐related biomarkers in CAD by least absolute shrinkage and selection operator (LASSO). The receiver operating characteristic (ROC) analysis showed that the LASSO logistic model constructed based on biomarkers had a better diagnostic effect, which was confirmed by the ANN and GSE23561 datasets. Also, ROC results showed that seven of the eight biomarkers had better diagnostic effects. The nomogram model had good predictive power, and biomarkers were mostly enriched in pathways associated with CAD. The biomarkers were significantly associated with 10 immune cells, and RCN2, DERL2, TMED2, and RNF183 were negatively correlated with most chemokines. Eight biomarkers had significant correlations with both immunoinhibitors and immunostimulators. In addition, eight biomarkers were significantly different in both CAD and control samples, CRH and HRC were upregulated in CAD. The quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) showed that RCN2, HRC, DERL2, CRH, and IL1A were consistent with the bioinformatics analysis. RCN2, HRC, DERL2, RNF183, CRH, TMED2, PPP1R15A, and IL1A were identified as biomarkers of CAD. Functional enrichment analysis and immunoassays for biomarkers provide new ideas for the treatment of CAD.
Benzoylaconine: Potential Therapeutic Agent for Cardiovascular Diseases From Fuzi
Authors: Xu Chenggang , Tang Le , Hu Lixin , Huang Yunzhe , Tang Jin , Wang Xiaohu , Wang Feng
Published: July 2024

Modern pharmacological studies have elucidated the presence of aconitine (AC) alkaloids, polysaccharides, and saponins as the primary bioactive constituents of Fuzi. Among these, benzoylaconine, a pivotal active compound, demonstrates notable pharmacological properties including antitumor, anti‐inflammatory, and cardiovascular protective effects. In recent years, benzoylaconine has garnered significant attention in basic research on heart diseases, emerging as a focal point of investigation. This paper presents a comprehensive review of the pharmacological effects of benzoylaconine, alongside an overview of advancements in metabolic characterization. The objective is to furnish valuable insights that can serve as a cornerstone for further exploration, utilization, and advancement of benzoylaconine in pharmacological research.
Perovskite Solar Cells With Modified Carbon Electrode and CuSCN Interlayer Processed Under Ambient Conditions
Authors: Sulistianto Junivan , Konno Akinori , Abuzairi Tomy , Poespawati Nji Raden
Published: July 2024

Carbon‐based perovskite solar cells (PSCs) have the advantages of a long lifetime and are compatible with highly scalable manufacturing processes. The use of carbon electrodes and the absence of a hole selective layer (HSL) promote a simplified fabrication process. However, the efficiency of HSL‐free carbon‐based PSCs is inferior to PSCs that utilize metal electrodes and HSL due to poor hole extraction at the perovskite/carbon interface. To overcome those issues, researchers added an interlayer on the perovskite/carbon interface or incorporated additive material into the carbon layer. However, there is limited research on utilizing both strategies to improve carbon‐based PSC performance. Here, we use CuSCN as an interlayer between the perovskite/carbon interface and a carbon additive in carbon‐based PSCs. By utilizing both strategies, the charge transfer of carbon‐based PSC was significantly improved compared to carbon‐based PSC utilizing only one improvement strategy. Confirmed by photoluminescence (PL) and electrochemical impedance spectroscopy (EIS) characterizations, the CuSCN interlayer and CuSCN‐incorporated carbon electrode enable more efficient hole transfer, resulting in an increased power conversion efficiency from 0.58% to 5.06%. The proposed PSC structure shows promising results for further improving carbon‐based PSC performance.
Methylxanthine and Flavonoid Contents from Guarana Seeds (Paullinia cupana): Comparison of Different Drying Techniques and Effects of UV Radiation
Authors: da Silva Junior André Luiz Sampaio , Nascimento Madson Moreira , Santos Herick Macedo , Lôbo Ivon Pinheiro , de Oliveira Rosilene Aparecida , de Jesus Raildo Mota
Published: July 2024

Guarana seeds are typically processed using one of three drying methods: traditional sun exposure, greenhouse drying, or the alguidar oven technique. In our research, we evaluated the contents of methylxanthines and flavan‐3‐ols in sun‐ and alguidar‐dried guarana seeds from Bahia State’s Low Sul Identity Territory. Caffeine, theobromine, catechin, and epicatechin were determined by high‐performance liquid chromatography with UV‐visible detection (HPLC/UV‐vis). Statistical tools, including analysis of variance (ANOVA), Tukey’s test, and exploratory analysis, were employed to analyze the obtained data. Our findings indicated that the flavan‐3‐ols content in sun‐dried guarana samples was lower compared to those dried using the alguidar oven, possibly due to exposure to ultraviolet radiation from solar energy. Conversely, we observed no significant differences (p > 0.05) in the average contents of methylxanthines between the two drying methods. Our supplementary experiments involving UV‐A and UV‐C radiation lamps revealed a decreasing trend in methylxanthines and flavan‐3‐ols contents with increasing duration of UV radiation exposure.
Dynamic Analysis of the Guiding Shoe considering Contact Gap and Pose Disturbance
Authors: Wan Lirong , Wang Jinwei , Ma Dejian , Zeng Qingliang
Published: July 2024

The pose disturbance of the guide shoe under complex working conditions can lead to collision, impact, and wear failure between the guide shoe and the pin row. To explore the damage law of pose disturbance on the guiding shoe, a rigid‐flexible coupling dynamic model of the walking mechanism considering the contact gap between the guiding shoe and the pin row was constructed. The contact characteristics of the guiding shoe under different poses were analyzed. The results indicate that the swing around the x‐axis has the most significant impact on the guiding shoe, with stress concentration primarily occurring near the corner of the trench. The posture of swinging solely around the y‐axis weakens the supporting effect of the guide shoe, resulting in stress concentration on the end face of the left side face. Swinging around the z‐axis results in stress concentrations on the upper faces of the shoe. Research shows that the angular velocity of the guiding shoe around the x‐axis and z‐axis is highly sensitive to variations in traction speed. In addition, an increase in lateral force weakens the support effect of the guiding shoe, resulting in elevated contact force on the lower side of the guiding shoe and increased y‐direction load on the walking wheel. The research results provide a reference for exploring the influence of walking unit postures on the failure of the guiding shoe and for improving shearer traction reliability.
Supplementary Data from A Pan-Cancer Patient-Derived Xenograft Histology Image Repository with Genomic and Pathologic Annotations Enables Deep Learning Analysis
Authors: White Brian S. , Woo Xing Yi , Koc Soner , Sheridan Todd , Neuhauser Steven B. , Wang Shidan , Evrard Yvonne A. , Chen Li , Foroughi pour Ali , Landua John D. , Mashl R. Jay , Davies Sherri R. , Fang Bingliang , Rosa Maria Gabriela , Evans Kurt W. , Bailey Matthew H. , Chen Yeqing , Xiao Min , Rubinstein Jill C. , Sanderson Brian J. , Lloyd Michael W. , Domanskyi Sergii , Dobrolecki Lacey E. , Fujita Maihi , Fujimoto Junya , Xiao Guanghua , Fields Ryan C. , Mudd Jacqueline L. , Xu Xiaowei , Hollingshead Melinda G. , Jiwani Shahanawaz , Acevedo Saul , Davis-Dusenbery Brandi N. , Robinson Peter N. , Moscow Jeffrey A. , Doroshow James H. , Mitsiades Nicholas , Kaochar Salma , Pan Chong-xian , Carvajal-Carmona Luis G. , Welm Alana L. , Welm Bryan E. , Govindan Ramaswamy , Li Shunqiang , Davies Michael A. , Roth Jack A. , Meric-Bernstam Funda , Xie Yang , Herlyn Meenhard , Ding Li , Lewis Michael T. , Bult Carol J. , Dean Dennis A. , Chuang Jeffrey H.
Published: July 2024

Supplementary methods
Table S1 from Single-Cell and Spatial Transcriptome Profiling Identifies the Transcription Factor BHLHE40 as a Driver of EMT in Metastatic Colorectal Cancer
Authors: Yang Sheng , Zhang Dongsheng , Sun Qingyang , Nie Hongxu , Zhang Yue , Wang Xiaowei , Huang Yuanjian , Sun Yueming
Published: July 2024

Supplementary Table S1: Detailed sources and clinical information for each 22 single-cell RNA-seq sample.
Figure S2 from Single-Cell and Spatial Transcriptome Profiling Identifies the Transcription Factor BHLHE40 as a Driver of EMT in Metastatic Colorectal Cancer
Authors: Yang Sheng , Zhang Dongsheng , Sun Qingyang , Nie Hongxu , Zhang Yue , Wang Xiaowei , Huang Yuanjian , Sun Yueming
Published: July 2024

Figure S2. Heatmap of top 10 differentially expressed genes in 6 CAF subtypes.
Supplementary Figure 8 from GPR1 and CMKLR1 Control Lipid Metabolism to Support the Development of Clear Cell Renal Cell Carcinoma
Authors: Wang Dazhi , Mahmud Iqbal , Thakur Vijay S. , Tan Sze Kiat , Isom Daniel G. , Lombard David B. , Gonzalgo Mark L. , Kryvenko Oleksandr N. , Lorenzi Philip L. , Tcheuyap Vanina T. , Brugarolas James , Welford Scott M.
Published: July 2024

Supplementary Figure 8
Supplementary Figure 12 from GPR1 and CMKLR1 Control Lipid Metabolism to Support the Development of Clear Cell Renal Cell Carcinoma
Authors: Wang Dazhi , Mahmud Iqbal , Thakur Vijay S. , Tan Sze Kiat , Isom Daniel G. , Lombard David B. , Gonzalgo Mark L. , Kryvenko Oleksandr N. , Lorenzi Philip L. , Tcheuyap Vanina T. , Brugarolas James , Welford Scott M.
Published: July 2024

Supplementary Figure 12
Supplementary Fig S6 from A Tetravalent Bispecific Antibody Selectively Inhibits Diverse FGFR3 Oncogenic Variants
Authors: Yang Yan , Suhasini Avvaru N. , Jiang Zaoli , Liu Nina , Rosconi Michael , Zhang Bojie , Li Yinyin , Dudgeon Drew , Seong Changhyun , Kim Steven , Rafique Ashique , Huang Tammy , Bhosle Sangram , Krueger Pamela , Ullman Erica , Olson William , Lin John C. , Shen Yang , Daly Christopher
Published: July 2024

Supplementary Fig S6
Supplementary Data from Comprehensive Genetic Profiling Reveals Frequent Alterations of Driver Genes on the X Chromosome in Extranodal NK/T-cell Lymphoma
Authors: Ito Yuta , Marouf Amira , Kogure Yasunori , Koya Junji , Liévin Raphaël , Bruneau Julie , Tabata Mariko , Saito Yuki , Shingaki Sumito , Yuasa Mitsuhiro , Yamaguchi Kentaro , Murakami Koichi , Weil Robert , Vavasseur Manon , Andrieu Guillaume P. , Latiri Mehdi , Veleanu Layla , Dussiot Michaël , André Isabelle , Joshi Akshay , Lagresle-Peyrou Chantal , Magerus Aude , Chaubard Sammara , Lavergne David , Bachy Emmanuel , Brunet Erika , Fataccioli Virginie , Brouzes Chantal , Laurent Camille , de Leval Laurence , Traverse-Glehen Alexandra , Bossard Céline , Parrens Marie , Meignin Véronique , Philippe Laure , Rossignol Julien , Suarez Felipe , Michot Jean-Marie , Tournilhac Olivier , Damaj Gandhi , Lemonnier François , Bôle-Feysot Christine , Nitschké Patrick , Tesson Bruno , Laurent Cécile , Molina Thierry , Asnafi Vahid , Watatani Yosaku , Chiba Kenichi , Okada Ai , Shiraishi Yuichi , Tsukita Sachiko , Izutsu Koji , Miyoshi Hiroaki , Ohshima Koichi , Sakata Seiji , Dobashi Akito , Takeuchi Kengo , Sanada Masashi , Gaulard Philippe , Jaccard Arnaud , Ogawa Seishi , Hermine Olivier , Kataoka Keisuke , Couronné Lucile
Published: July 2024

Supplementary Figures S1-S10, Supplementary Table Legends
Supplementary Fig S1 from A Tetravalent Bispecific Antibody Selectively Inhibits Diverse FGFR3 Oncogenic Variants
Authors: Yang Yan , Suhasini Avvaru N. , Jiang Zaoli , Liu Nina , Rosconi Michael , Zhang Bojie , Li Yinyin , Dudgeon Drew , Seong Changhyun , Kim Steven , Rafique Ashique , Huang Tammy , Bhosle Sangram , Krueger Pamela , Ullman Erica , Olson William , Lin John C. , Shen Yang , Daly Christopher
Published: July 2024

Supplementary Fig S1
Figure S9 from Omental Preadipocytes Stimulate Matrix Remodeling and IGF Signaling to Support Ovarian Cancer Metastasis
Authors: Waters Jennifer A. , Robinson Mikella , Lujano-Olazaba Omar , Lucht Cassidy , Gilbert Samuel F. , House Carrie D.
Published: July 2024

knockdown of COL1A2 and COL6A2
Figure S5 from Omental Preadipocytes Stimulate Matrix Remodeling and IGF Signaling to Support Ovarian Cancer Metastasis
Authors: Waters Jennifer A. , Robinson Mikella , Lujano-Olazaba Omar , Lucht Cassidy , Gilbert Samuel F. , House Carrie D.
Published: July 2024

Proliferation assay
Figure S3 from Omental Preadipocytes Stimulate Matrix Remodeling and IGF Signaling to Support Ovarian Cancer Metastasis
Authors: Waters Jennifer A. , Robinson Mikella , Lujano-Olazaba Omar , Lucht Cassidy , Gilbert Samuel F. , House Carrie D.
Published: July 2024

Analysis of resected tumors
Figure S2 from Omental Preadipocytes Stimulate Matrix Remodeling and IGF Signaling to Support Ovarian Cancer Metastasis
Authors: Waters Jennifer A. , Robinson Mikella , Lujano-Olazaba Omar , Lucht Cassidy , Gilbert Samuel F. , House Carrie D.
Published: July 2024

gene expression and tumor promoting properties of preadipocytes versus mature adipocytes
Data from CD106 in Tumor-Specific Exhausted CD8+ T Cells Mediates Immunosuppression by Inhibiting TCR Signaling
Authors: Naoi Yuto , Morinaga Takao , Nagasaki Joji , Ariyasu Ryo , Ueda Youki , Yamashita Kazuo , Zhou Wenhao , Kawashima Shusuke , Kawase Katsushige , Honobe-Tabuchi Akiko , Ohnuma Takehiro , Kawamura Tatsuyoshi , Umeda Yoshiyasu , Kawahara Yu , Nakamura Yasuhiro , Kiniwa Yukiko , Yamasaki Osamu , Fukushima Satoshi , Kawazu Masahito , Suzuki Yutaka , Nishikawa Hiroyoshi , Hanazawa Toyoyuki , Ando Mizuo , Inozume Takashi , Togashi Yosuke
Published: July 2024

Abstract
T-cell exhaustion is a major contributor to immunosuppression in the tumor microenvironment (TME). Blockade of key regulators of T-cell exhaustion, such as programmed death 1, can reinvigorate tumor-specific T cells and activate antitumor immunity in various types of cancer. In this study, we identified that CD106 was specifically expressed in exhausted CD8+ T cells in the TME using single-cell RNA sequencing. High CD106 expression in the TME in clinical samples corresponded to improved response to cancer immunotherapy. CD106 in tumor-specific T cells suppressed antitumor immunity both in vitro and in vivo, and loss of CD106 in CD8+ T cells suppressed tumor growth and improved response to programmed death 1 blockade. Mechanistically, CD106 inhibited T-cell receptor (TCR) signaling by interacting with the TCR/CD3 complex and reducing its surface expression. Together, these findings provide insights into the immunosuppressive role of CD106 expressed in tumor-specific exhausted CD8+ T cells, identifying it as a potential biomarker and therapeutic target for cancer immunotherapy.

Significance: CD106 is specifically expressed in tumor-specific exhausted CD8+ T cells and inhibits the TCR signaling pathway by reducing surface expression of the TCR/CD3 complex to suppress antitumor immunity.
A Pan-Cancer Patient-Derived Xenograft Histology Image Repository with Genomic and Pathologic Annotations Enables Deep Learning Analysis
Authors: White Brian S. , Woo Xing Yi , Koc Soner , Sheridan Todd , Neuhauser Steven B. , Wang Shidan , Evrard Yvonne A. , Chen Li , Foroughi pour Ali , Landua John D. , Mashl R. Jay , Davies Sherri R. , Fang Bingliang , Raso Maria Gabriela , Evans Kurt W. , Bailey Matthew H. , Chen Yeqing , Xiao Min , Rubinstein Jill C. , Sanderson Brian J. , Lloyd Michael W. , Domanskyi Sergii , Dobrolecki Lacey E. , Fujita Maihi , Fujimoto Junya , Xiao Guanghua , Fields Ryan C. , Mudd Jacqueline L. , Xu Xiaowei , Hollingshead Melinda G. , Jiwani Shahanawaz , Acevedo Saul ,   PDXNet Consortium, Davis-Dusenbery Brandi N. , Robinson Peter N. , Moscow Jeffrey A. , Doroshow James H. , Mitsiades Nicholas , Kaochar Salma , Pan Chong-xian , Carvajal-Carmona Luis G. , Welm Alana L. , Welm Bryan E. , Govindan Ramaswamy , Li Shunqiang , Davies Michael A. , Roth Jack A. , Meric-Bernstam Funda , Xie Yang , Herlyn Meenhard , Ding Li , Lewis Michael T. , Bult Carol J. , Dean Dennis A. , Chuang Jeffrey H.
Published: July 2024

Patient-derived xenografts (PDX) model human intra- and intertumoral heterogeneity in the context of the intact tissue of immunocompromised mice. Histologic imaging via hematoxylin and eosin (H&E) staining is routinely performed on PDX samples, which could be harnessed for computational analysis. Prior studies of large clinical H&E image repositories have shown that deep learning analysis can identify intercellular and morphologic signals correlated with disease phenotype and therapeutic response. In this study, we developed an extensive, pan-cancer repository of >1,000 PDX and paired parental tumor H&E images. These images, curated from the PDX Development and Trial Centers Research Network Consortium, had a range of associated genomic and transcriptomic data, clinical metadata, pathologic assessments of cell composition, and, in several cases, detailed pathologic annotations of neoplastic, stromal, and necrotic regions. The amenability of these images to deep learning was highlighted through three applications: (i) development of a classifier for neoplastic, stromal, and necrotic regions; (ii) development of a predictor of xenograft-transplant lymphoproliferative disorder; and (iii) application of a published predictor of microsatellite instability. Together, this PDX Development and Trial Centers Research Network image repository provides a valuable resource for controlled digital pathology analysis, both for the evaluation of technical issues and for the development of computational image–based methods that make clinical predictions based on PDX treatment studies.

Significance: A pan-cancer repository of >1,000 patient-derived xenograft hematoxylin and eosin–stained images will facilitate cancer biology investigations through histopathologic analysis and contributes important model system data that expand existing human histology repositories.
Contribution of Prediagnostic Host Factors to Shaping the Stromal Microenvironment of Breast Cancer among Sub-Saharan African Women
Authors: Abubakar Mustapha , Ahearn Thomas U. , Duggan Maire A. , Lawrence Scott , Adjei Ernest K. , Clegg-Lamptey Joe-Nat , Yarney Joel , Wiafe-Addai Beatrice , Awuah Baffour , Wiafe Seth , Nyarko Kofi , Aitpillah Francis S. , Ansong Daniel , Hewitt Stephen M. , Brinton Louise A. , Figueroa Jonine D. , Garcia-Closas Montserrat , Edusei Lawrence , Titiloye Nicolas ,   for the Ghana Breast Health Study Team
Published: July 2024

Background:

The stromal microenvironment (SME) is integral to breast cancer biology, impacting metastatic proclivity and treatment response. Emerging data indicate that host factors may impact the SME, but the relationship between prediagnostic host factors and SME phenotype remains poorly characterized, particularly among women of African ancestry.

Methods:

We conducted a case-only analysis involving 792 patients with breast cancer (17–84 years) from the Ghana Breast Health Study. High-accuracy machine-learning algorithms were applied to standard H&E-stained images to characterize SME phenotypes [including percent tumor-associated connective tissue stroma, Ta-CTS (%); tumor-associated stromal cellular density, Ta-SCD (%)]. Associations between prediagnostic host factors and SME phenotypes were assessed in multivariable linear regression models.

Results:

Decreasing Ta-CTS and increasing Ta-SCD were associated with aggressive, mostly high-grade tumors (P-value < 0.001). Several prediagnostic host factors were associated with Ta-SCD independently of tumor characteristics. Compared with nulliparous women, parous women had higher levels of Ta-SCD [mean (standard deviation, SD) = 31.3% (7.6%) vs. 28.9% (7.1%); P-value = 0.01]. Similarly, women with a positive family history of breast cancer had higher levels of Ta-SCD than those without family history [mean (SD) = 33.0% (7.5%)] vs. 30.9% (7.6%); P-value = 0.03]. Conversely, increasing body size was associated with decreasing Ta-SCD [mean (SD) = 31.6% (7.4%), 31.4% (7.3%), and 30.1% (8.0%) for slight, average, and large body sizes, respectively; P-value = 0.005].

Conclusions:

Epidemiological risk factors were associated with varying degrees of stromal cellularity in tumors, independently of clinicopathological characteristics.

Impact:

The findings raise the possibility that epidemiological risk factors may partly influence tumor biology via the stromal microenvironment.
Supplementary Data Tables from Near-infrared Photoimmunotherapy Targeting Cancer-Associated Fibroblasts in Patient-Derived Xenografts Using a Humanized Anti-Fibroblast Activation Protein Antibody
Authors: Kobayashi Teruki , Noma Kazuhiro , Nishimura Seitaro , Kato Takuya , Nishiwaki Noriyuki , Ohara Toshiaki , Kunitomo Tomoyoshi , Kawasaki Kento , Akai Masaaki , Komoto Satoshi , Kashima Hajime , Kikuchi Satoru , Tazawa Hiroshi , Shirakawa Yasuhiro , Choyke Peter L. , Kobayashi Hisataka , Fujiwara Toshiyoshi
Published: July 2024

Supplementary Tables
Supplementary Figure S7 from The Novel ATR Inhibitor M1774 Induces Replication Protein Overexpression and Broad Synergy with DNA-targeted Anticancer Drugs
Authors: Jo Ukhyun , Arakawa Yasuhiro , Zimmermann Astrid , Taniyama Daiki , Mizunuma Makito , Jenkins Lisa M. , Maity Tapan , Kumar Suresh , Zenke Frank T. , Takebe Naoko , Pommier Yves
Published: July 2024

This figure shows synergistic combination effects, representative images, and profiling of cell viability in colorectal cancer organoids.
Supplementary Figure S5 from The Novel ATR Inhibitor M1774 Induces Replication Protein Overexpression and Broad Synergy with DNA-targeted Anticancer Drugs
Authors: Jo Ukhyun , Arakawa Yasuhiro , Zimmermann Astrid , Taniyama Daiki , Mizunuma Makito , Jenkins Lisa M. , Maity Tapan , Kumar Suresh , Zenke Frank T. , Takebe Naoko , Pommier Yves
Published: July 2024

This figure shows profiling of cell viability after M1774 treatment in DMS114 and DU145 cells, and a correlation plot between topotecan and SLFN11 expression.
Movie S4 from Optimizing the Design and Geometry of T Cell–Engaging Bispecific Antibodies Targeting CEA in Colorectal Cancer
Authors: Elsayed Abdullah , Plüss Louis , Nideroest Larissa , Rotta Giulia , Thoma Marina , Zangger Nathan , Peissert Frederik , Pfister Stefanie K. , Pellegrino Christian , Dakhel Plaza Sheila , De Luca Roberto , Manz Markus G. , Oxenius Annette , Puca Emanuele , Halin Cornelia , Neri Dario
Published: July 2024

Supplementary Movie4
Movie S3 from Optimizing the Design and Geometry of T Cell–Engaging Bispecific Antibodies Targeting CEA in Colorectal Cancer
Authors: Elsayed Abdullah , Plüss Louis , Nideroest Larissa , Rotta Giulia , Thoma Marina , Zangger Nathan , Peissert Frederik , Pfister Stefanie K. , Pellegrino Christian , Dakhel Plaza Sheila , De Luca Roberto , Manz Markus G. , Oxenius Annette , Puca Emanuele , Halin Cornelia , Neri Dario
Published: July 2024

Supplementary Movie3
Figure S4 from Optimizing the Design and Geometry of T Cell–Engaging Bispecific Antibodies Targeting CEA in Colorectal Cancer
Authors: Elsayed Abdullah , Plüss Louis , Nideroest Larissa , Rotta Giulia , Thoma Marina , Zangger Nathan , Peissert Frederik , Pfister Stefanie K. , Pellegrino Christian , Dakhel Plaza Sheila , De Luca Roberto , Manz Markus G. , Oxenius Annette , Puca Emanuele , Halin Cornelia , Neri Dario
Published: July 2024

Supplementary Figure S4
Supplementary Figure 1 from Ultrasensitive Response Explains the Benefit of Combination Chemotherapy Despite Drug Antagonism
Authors: Patterson Sarah C. , Pomeroy Amy E. , Palmer Adam C.
Published: July 2024

Supplemental Figure 1. Reproducibility and dynamic range of in vitro experiments. A) Consistency of measured isobolograms among biological replicates (independently propagated cultures; left and right columns) and among technical replicates (different microtiter plates; top and bottom rows). Cell line = MTA, n = 1 per plot here, with each of 4 plots averaged to produce isobolograms in Supplemental Figure 2. B) Dynamic range of CLARIOstar microplate reader is linear over 5 orders of magnitude in cell density (10¹ to 10⁵ Ki-JK cells per well). Red shaded region represents 95% confidence interval of population mean (n = 16). C) Reproducibility of two replicate 15-day treatments conducted two weeks apart from one another. Untreated cells are compared to the two-halves dosing scheme where 12.5 nM doxorubicin was administered for 72 hours on Days 0 and 6 (as shown in Figure 1). Cell line = MTA, n=6, error bars represent 95% confidence interval.
Supplementary Data File 1 from Ultrasensitive Response Explains the Benefit of Combination Chemotherapy Despite Drug Antagonism
Authors: Patterson Sarah C. , Pomeroy Amy E. , Palmer Adam C.
Published: July 2024

Source data from all experiments, specifically Figures 1A, 1B, 1C, 1D, 2A, 2B, 3B, S2, S3, S4, S5, S6.
Data from Near-infrared Photoimmunotherapy Targeting Cancer-Associated Fibroblasts in Patient-Derived Xenografts Using a Humanized Anti-Fibroblast Activation Protein Antibody
Authors: Kobayashi Teruki , Noma Kazuhiro , Nishimura Seitaro , Kato Takuya , Nishiwaki Noriyuki , Ohara Toshiaki , Kunitomo Tomoyoshi , Kawasaki Kento , Akai Masaaki , Komoto Satoshi , Kashima Hajime , Kikuchi Satoru , Tazawa Hiroshi , Shirakawa Yasuhiro , Choyke Peter L. , Kobayashi Hisataka , Fujiwara Toshiyoshi
Published: July 2024

Abstract
Esophageal cancer remains a highly aggressive malignancy with a poor prognosis, despite ongoing advancements in treatments such as immunotherapy. The tumor microenvironment, particularly cancer-associated fibroblasts (CAF), plays a crucial role in driving the aggressiveness of esophageal cancer. In a previous study utilizing human-derived xenograft models, we successfully developed a novel cancer treatment that targeted CAFs with near-infrared photoimmunotherapy (NIR-PIT), as an adjuvant therapy. In this study, we sought to translate our findings toward clinical practice by employing patient-derived xenograft (PDX) models and utilizing humanized mAbs, specifically sibrotuzumab, which is an antihuman fibroblast activation protein (FAP) Ab and already being investigated in clinical trials as monotherapy. PDX models derived from patients with esophageal cancer were effectively established, preserving the expression of key biomarkers such as EGFR and FAP, as observed in primary tumors. The application of FAP-targeted NIR-PIT using sibrotuzumab, conjugated with the photosensitizer IR700DX, exhibited precise binding and selective elimination of FAP-expressing fibroblasts in vitro. Notably, in our in vivo investigations using both cell line–derived xenograft and PDX models, FAP-targeted NIR-PIT led to significant inhibition of tumor progression compared with control groups, all without inducing adverse events such as weight loss. Immunohistologic assessments revealed a substantial reduction in CAFs exclusively within the tumor microenvironment of both models, further supporting the efficacy of our approach. Thus, our study demonstrates the potential of CAF-targeted NIR-PIT employing sibrotuzumab as a promising therapeutic avenue for the clinical treatment of patients with esophageal cancer.
Data from Inhibition of MALT1 and BCL2 Induces Synergistic Antitumor Activity in Models of B-Cell Lymphoma
Authors: Plotnik Joshua P. , Richardson Adam E. , Yang Haopeng , Rojas Estela , Bontcheva Velitchka , Dowell Colleen , Parsons Sydney , Wilson Ashley , Ravanmehr Vida , Will Christine , Jung Paul , Zhu Haizhong , Partha Sarathy Karunan , Panchal Sanjay C. , Mali Raghuveer Singh , Kohlhapp Frederick J. , McClure Ryan A. , Ramathal Cyril Y. , George Mariam D. , Jhala Manisha , Elsen Nathaniel L. , Qiu Wei , Judge Russell A. , Pan Chin , Mastracchio Anthony , Henderson Jared , Meulbroek Jonathan A. , Green Michael R. , Pappano William N.
Published: July 2024

Abstract
The activated B cell (ABC) subset of diffuse large B-cell lymphoma (DLBCL) is characterized by chronic B-cell receptor signaling and associated with poor outcomes when treated with standard therapy. In ABC-DLBCL, MALT1 is a core enzyme that is constitutively activated by stimulation of the B-cell receptor or gain-of-function mutations in upstream components of the signaling pathway, making it an attractive therapeutic target. We discovered a novel small-molecule inhibitor, ABBV-MALT1, that potently shuts down B-cell signaling selectively in ABC-DLBCL preclinical models leading to potent cell growth and xenograft inhibition. We also identified a rational combination partner for ABBV-MALT1 in the BCL2 inhibitor, venetoclax, which when combined significantly synergizes to elicit deep and durable responses in preclinical models. This work highlights the potential of ABBV-MALT1 monotherapy and combination with venetoclax as effective treatment options for patients with ABC-DLBCL.
Data from The Novel ATR Inhibitor M1774 Induces Replication Protein Overexpression and Broad Synergy with DNA-targeted Anticancer Drugs
Authors: Jo Ukhyun , Arakawa Yasuhiro , Zimmermann Astrid , Taniyama Daiki , Mizunuma Makito , Jenkins Lisa M. , Maity Tapan , Kumar Suresh , Zenke Frank T. , Takebe Naoko , Pommier Yves
Published: July 2024

Abstract
Ataxia telangiectasia and Rad3-related (ATR) checkpoint kinase inhibitors are in clinical trials. Here we explored the molecular pharmacology and therapeutic combination strategies of the oral ATR inhibitor M1774 (Tuvusertib) with DNA-damaging agents (DDA). As single agent, M1774 suppressed cancer cell viability at nanomolar concentrations, showing greater activity than ceralasertib and berzosertib, but less potency than gartisertib and elimusertib in the small cell lung cancer H146, H82, and DMS114 cell lines. M1774 also efficiently blocked the activation of the ATR-CHK1 checkpoint pathway caused by replication stress induced by TOP1 inhibitors. Combination with non-toxic dose of M1774 enhanced TOP1 inhibitor-induced cancer cell death by enabling unscheduled replication upon replicative damage, thereby increasing genome instability. Tandem mass tag-based quantitative proteomics uncovered that M1774, in the presence of DDA, forces the expression of proteins activating replication (CDC45) and G2−M progression (PLK1 and CCNB1). In particular, the fork protection complex proteins (TIMELESS and TIPIN) were enriched. Low dose of M1774 was found highly synergistic with a broad spectrum of clinical DDAs including TOP1 inhibitors (SN-38/irinotecan, topotecan, exatecan, and exatecan), the TOP2 inhibitor etoposide, cisplatin, the RNA polymerase II inhibitor lurbinectedin, and the PARP inhibitor talazoparib in various models including cancer cell lines, patient-derived organoids, and mouse xenograft models. Furthermore, we demonstrate that M1774 reverses chemoresistance to anticancer DDAs in cancer cells lacking SLFN11 expression, suggesting that SLFN11 can be utilized for patient selection in upcoming clinical trials.