bluuebunny/crossref_metadata_2025 huggingface dataset:
RFBoost: Understanding and Boosting Deep WiFi Sensing via Physical Data Augmentation
Authors: Hou Weiying , Wu Chenshu
Published: May 2024

Deep learning shows promising performance in wireless sensing. However, deep wireless sensing (DWS) heavily relies on large datasets. Unfortunately, building comprehensive datasets for DWS is difficult and costly, because wireless data depends on environmental factors and cannot be labeled offline. Despite recent advances in few-shot/cross-domain learning, DWS is still facing data scarcity issues. In this paper, we investigate a distinct perspective of radio data augmentation (RDA) for WiFi sensing and present a data-space solution. Our key insight is that wireless signals inherently exhibit data diversity, contributing more information to be extracted for DWS. We present RFBoost, a simple and effective RDA framework encompassing novel physical data augmentation techniques. We implement RFBoost as a plug-and-play module integrated with existing deep models and evaluate it on multiple datasets. Experimental results demonstrate that RFBoost achieves remarkable average accuracy improvements of 5.4% on existing models without additional data collection or model modifications, and the best-boosted performance outperforms 11 state-of-the-art baseline models without RDA. RFBoost pioneers the study of RDA, an important yet currently underexplored building block for DWS, which we expect to become a standard DWS component of WiFi sensing and beyond. RFBoost is released at https://github.com/aiot-lab/RFBoost.
TeleAware Robot: Designing Awareness-augmented Telepresence Robot for Remote Collaborative Locomotion
Authors: Li Ruyi , Zhu Yaxin , Liu Min , Zeng Yihang , Zhuang Shanning , Fu Jiayi , Lu Yi , Zhou Guyue , Liu Can , Gong Jiangtao
Published: May 2024

Telepresence robots can be used to support users to navigate an environment remotely and share the visiting experience with their social partners. Although such systems allow users to see and hear the remote environment and communicate with their partners via live video feed, this does not provide enough awareness of the environment and their remote partner's activities. In this paper, we introduce an awareness framework for collaborative locomotion in scenarios of onsite and remote users visiting a place together. From an observational study of small groups of people visiting exhibitions, we derived four design goals for enhancing the environmental and social awareness between social partners, and developed a set of awareness-enhancing techniques to add to a standard telepresence robot - named TeleAware robot. Through a controlled experiment simulating a guided exhibition visiting task, TeleAware robot showed the ability to lower the workload, facilitate closer social proximity, and improve mutual awareness and social presence compared with the standard one. We discuss the impact of mobility and roles of local and remote users, and provide insights for the future design of awareness-enhancing telepresence robot systems that facilitate collaborative locomotion.
G-VOILA: Gaze-Facilitated Information Querying in Daily Scenarios
Authors: Wang Zeyu , Shi Yuanchun , Wang Yuntao , Yao Yuchen , Yan Kun , Wang Yuhan , Ji Lei , Xu Xuhai , Yu Chun
Published: May 2024

Modern information querying systems are progressively incorporating multimodal inputs like vision and audio. However, the integration of gaze --- a modality deeply linked to user intent and increasingly accessible via gaze-tracking wearables --- remains underexplored. This paper introduces a novel gaze-facilitated information querying paradigm, named G-VOILA, which synergizes users' gaze, visual field, and voice-based natural language queries to facilitate a more intuitive querying process. In a user-enactment study involving 21 participants in 3 daily scenarios (p = 21, scene = 3), we revealed the ambiguity in users' query language and a gaze-voice coordination pattern in users' natural query behaviors with G-VOILA. Based on the quantitative and qualitative findings, we developed a design framework for the G-VOILA paradigm, which effectively integrates the gaze data with the in-situ querying context. Then we implemented a G-VOILA proof-of-concept using cutting-edge deep learning techniques. A follow-up user study (p = 16, scene = 2) demonstrates its effectiveness by achieving both higher objective score and subjective score, compared to a baseline without gaze data. We further conducted interviews and provided insights for future gaze-facilitated information querying systems.
Digital Forms for All: A Holistic Multimodal Large Language Model Agent for Health Data Entry
Authors: Cuadra Andrea , Breuch Justine , Estrada Samantha , Ihim David , Hung Isabelle , Askaryar Derek , Hassanien Marwan , Fessele Kristen L. , Landay James A.
Published: May 2024

Digital forms help us access services and opportunities, but they are not equally accessible to everyone, such as older adults or those with sensory impairments. Large language models (LLMs) and multimodal interfaces offer a unique opportunity to increase form accessibility. Informed by prior literature and needfinding, we built a holistic multimodal LLM agent for health data entry. We describe the process of designing and building our system, and the results of a study with older adults (N =10). All participants, regardless of age or disability status, were able to complete a standard 47-question form independently using our system---one blind participant said it was "a prayer answered." Our video analysis revealed how different modalities provided alternative interaction paths in complementary ways (e.g., the buttons helped resolve transcription errors and speech helped provide more options when the pre-canned answer choices were insufficient). We highlight key design guidelines, such as designing systems that dynamically adapt to individual needs.
Predicting Multi-dimensional Surgical Outcomes with Multi-modal Mobile Sensing
Authors: Xu Ziqi , Zhang Jingwen , Greenberg Jacob , Frumkin Madelyn , Javeed Saad , Zhang Justin K. , Benedict Braeden , Botterbush Kathleen , Rodebaugh Thomas L. , Ray Wilson Z. , Lu Chenyang
Published: May 2024

Pre-operative prediction of post-surgical recovery for patients is vital for clinical decision-making and personalized treatments, especially with lumbar spine surgery, where patients exhibit highly heterogeneous outcomes. Existing predictive tools mainly rely on traditional Patient-Reported Outcome Measures (PROMs), which fail to capture the long-term dynamics of patient conditions before the surgery. Moreover, existing studies focus on predicting a single surgical outcome. However, recovery from spine surgery is multi-dimensional, including multiple distinctive but interrelated outcomes, such as pain interference, physical function, and quality of recovery. In recent years, the emergence of smartphones and wearable devices has presented new opportunities to capture longitudinal and dynamic information regarding patients' conditions outside the hospital. This paper proposes a novel machine learning approach, Multi-Modal Multi-Task Learning (M3TL), using smartphones and wristbands to predict multiple surgical outcomes after lumbar spine surgeries. We formulate the prediction of pain interference, physical function, and quality of recovery as a multi-task learning (MTL) problem. We leverage multi-modal data to capture the static and dynamic characteristics of patients, including (1) traditional features from PROMs and Electronic Health Records (EHR), (2) Ecological Momentary Assessment (EMA) collected from smartphones, and (3) sensing data from wristbands. Moreover, we introduce new features derived from the correlation of EMA and wearable features measured within the same time frame, effectively enhancing predictive performance by capturing the interdependencies between the two data modalities. Our model interpretation uncovers the complementary nature of the different data modalities and their distinctive contributions toward multiple surgical outcomes. Furthermore, through individualized decision analysis, our model identifies personal high risk factors to aid clinical decision making and approach personalized treatments. In a clinical study involving 122 patients undergoing lumbar spine surgery, our M3TL model outperforms a diverse set of baseline methods in predictive performance, demonstrating the value of integrating multi-modal data and learning from multiple surgical outcomes. This work contributes to advancing personalized peri-operative care with accurate pre-operative predictions of multi-dimensional outcomes.
Scoring Multi-hop Question Decomposition Using Masked Language Models
Authors: Hamouda Sidhoum Abdellah , Mataoui Mhamed , Sebbak Faouzi , Hosni Adil Imad Eddine , Smaili Kamel
Published: May 2024

Question answering (QA) is a sub-field of Natural Language Processing (NLP) that focuses on developing systems capable of answering natural language queries. Within this domain, multi-hop question answering represents an advanced QA task that requires gathering and reasoning over multiple pieces of information from diverse sources or passages. To handle the complexity of multi-hop questions, question decomposition has been proven to be a valuable approach. This technique involves breaking down complex questions into simpler sub-questions, reducing the complexity of the problem. However, it’s worth noting that existing question decomposition methods often rely on training data, which may not always be readily available for low-resource languages or specialized domains. To address this issue, we propose a novel approach that utilizes pre-trained masked language models to score decomposition candidates in a zero-shot manner. The method involves generating decomposition candidates, scoring them using a pseudo-log likelihood estimation, and ranking them based on their scores. To evaluate the efficacy of the decomposition process, we conducted experiments on two datasets annotated on decomposition in two different languages, Arabic and English. Subsequently, we integrated our approach into a complete QA system and conducted a reading comprehension performance evaluation on the HotpotQA dataset. The obtained results emphasize that while the system exhibited a small drop in performance, it still maintained a significant advance compared to the baseline model. The proposed approach highlights the efficiency of the language model scoring technique in complex reasoning tasks such as multi-hop question decomposition.
A Review of Olfactory Display Designs for Virtual Reality Environments
Authors: Tewell Jordan , Ranasinghe Nimesha
Published: May 2024

The field of Virtual Reality continues to evolve to provide an ever-greater sense of immersion to the user. However, VR experiences are still primarily constrained through the human senses of vision and audition, with some interest in haptic (mainly vibrotactile) applications. Only recently have olfactory displays—technologies that generate and deliver scent stimuli—been examined to provide the sense of smell to the human olfactory organ in virtual environments. This article presents a classification and review of olfactory-enhanced virtual reality systems, particularly those that deployed a Head-mounted Display or Cave Automatic Virtual Environment system. In addition, the article provides a discussion of the various technological and design challenges for developing an olfactory display suitable for enhancing virtual reality experiences. Finally, the article proposes future perspectives on the field and includes a table summarizing the characteristics and features of the reviewed systems.
Urban Transport Policies and Net Zero Emissions in the European Union
Authors: Hart Rob , Kyriakopoulou Efthymia , Lu Tingmingke
Published: May 2024

This review discusses the role of road transport policies in achieving the European Union's ambitious zero-emission target for the transportation sector by 2050 and provides an overview of the empirical literature that studies the effectiveness of urban transport policies. The analysis is divided into two parts. First, we study policies that are relevant in the transitional phase from internal combustion engine vehicles to battery electric vehicles (BEVs), then we discuss policies that will remain relevant as we switch entirely to BEVs. In the best-case scenario, the transition can be driven by fuel taxes, but in case fuel taxes are not feasible or acceptable, a combination of penalties for buying polluting vehicles and subsidies for scrappage of such vehicles might be the best compromise. In the long run, road space will be increasingly at a premium, and to ensure its efficient use, increasingly sophisticated road-pricing policies will be needed.
Central Serous Chorioretinopathy: Epidemiology, Genetics and Clinical Features
Authors: Khan Adnan H. , Lotery Andrew J.
Published: May 2024

Central serous chorioretinopathy (CSCR) is the fourth most common medical retinal disease. Moderate vision loss occurs in approximately one-third of patients who have the chronic form of the disease. CSCR has a multifactorial etiology, with acquired risk factors and increasing evidence of genetic susceptibility factors. The detection of new gene variants in CSCR and association of these variants with age-related macular degeneration provide insights into possible disease mechanisms. The contribution of multimodal ocular imaging and associated research studies to the modern-day clinical investigation of CSCR has been significant. This review aims to provide an overview of the most significant epidemiological and genetic studies of CSCR, in addition to describing its clinical and multimodal imaging features. The review also provides an update of the latest evidence from studies investigating pathophysiological mechanisms in CSCR and current opinions on multimodal imaging to better classify this complex retinal disease.
Effects of Process-Induced Defects on the Corrosion of Additively Manufactured Stainless Steel 304L
Authors: Saberi Leila , Liou Frank W. , Amiri Mehdi
Published: May 2024

This study investigates the impact of process-induced defects such as gas pores, lack of fusions, and surface roughness on corrosion behavior of stainless steel 304L (SS304L) fabricated by laser powder bed fusion additive manufacturing. Specimens are printed with optimized process parameters but selected from different locations on the build plate. Parallel and perpendicular surfaces to the build direction are investigated and compared with corrosion properties of wrought SS304L in 5 wt% NaCl. The results reveal significant difference in corrosion behavior among specimens due to variations in their defect features. Pitting potential, pit initiation, and growth rates are found to be influenced by specimen location on the build plate. The specimen located in downstream of the shielding gas flow shows the least corrosion resistance. While no clear trends are observed between some corrosion properties and defect features, other properties show strong correlations. For example, no trend is observed for the corrosion properties in relation to pore average area fraction. However, strong correlations are observed for the corrosion properties as functions of defects maximum area. Corrosion properties linearly deteriorate as the defects maximum area increases. Roughness shows a mixed relationship with pitting potential. Comprehensive discussions on all these effects are presented.
Sex and APOE genotype influence respiratory function under hypoxic and hypoxic-hypercapnic conditions
Authors: Taylor Chase E. , Mendenhall Laura E. , Sunshine Michael D. , Wilson Jessica N. , Calulot Chris M. , Sun Ramon C. , Johnson Lance A. , Alilain Warren J.
Published: May 2024

This study is the first to use whole body plethysmography (WBP) to measure the impact of APOE alleles on breathing under normoxia and during adverse respiratory challenges in a targeted replacement Alzheimer’s model. Both sex and genotype were shown to affect breathing under normoxia, hypoxic challenge, and hypoxic-hypercapnic challenge. This work has important implications regarding the impact of genetics on respiratory control as well as applications pertaining to conditions of disordered breathing including sleep apnea and neurotrauma.
Figure S5 from Bile Acid Metabolism Mediates Cholesterol Homeostasis and Promotes Tumorigenesis in Clear Cell Renal Cell Carcinoma
Authors: Riscal Romain , Gardner Sarah M. , Coffey Nathan J. , Carens Madeleine , Mesaros Clementina , Xu Jimmy P. , Xue Yizheng , Davis Leah , Demczyszyn Sara , Vogt Austin , Olia Adam , Finan Jennifer M. , Godfrey Jason , Schultz David C. , Blair Ian A. , Keith Brian , Marmorstein Ronen , Skuli Nicolas , Simon M. Celeste
Published: May 2024

Figure S5
Figure S3 from Bile Acid Metabolism Mediates Cholesterol Homeostasis and Promotes Tumorigenesis in Clear Cell Renal Cell Carcinoma
Authors: Riscal Romain , Gardner Sarah M. , Coffey Nathan J. , Carens Madeleine , Mesaros Clementina , Xu Jimmy P. , Xue Yizheng , Davis Leah , Demczyszyn Sara , Vogt Austin , Olia Adam , Finan Jennifer M. , Godfrey Jason , Schultz David C. , Blair Ian A. , Keith Brian , Marmorstein Ronen , Skuli Nicolas , Simon M. Celeste
Published: May 2024

Figure S3
Figure 6 from FUME-TCRseq Enables Sensitive and Accurate Sequencing of the T-cell Receptor from Limited Input of Degraded RNA
Authors: Baker Ann-Marie , Nageswaran Gayathri , Nenclares Pablo , Ronel Tahel , Smith Kane , Kimberley Christopher , Laclé Miangela M. , Bhide Shreerang , Harrington Kevin J. , Melcher Alan , Rodriguez-Justo Manuel , Chain Benny , Graham Trevor A.
Published: May 2024

A, Bar plots showing the proportion of each V gene detected by FUME-TCRseq (right column) and immunoSEQ (left column) in three representative FFPE head and neck cancer samples (HN1, HN2, HN3). B, Bar chart showing the numbers of unique TCR clonotypes detected in the three samples with FUME-TCRseq and immunoSEQ methodologies. C, Heat map showing the Morisita overlap between each sample. D, Plots showing the frequencies of the 10 most common clonotypes detected in each sample by immunoSEQ and the frequencies at which they appear in the FUME-TCRseq data.
Figure 3 from FUME-TCRseq Enables Sensitive and Accurate Sequencing of the T-cell Receptor from Limited Input of Degraded RNA
Authors: Baker Ann-Marie , Nageswaran Gayathri , Nenclares Pablo , Ronel Tahel , Smith Kane , Kimberley Christopher , Laclé Miangela M. , Bhide Shreerang , Harrington Kevin J. , Melcher Alan , Rodriguez-Justo Manuel , Chain Benny , Graham Trevor A.
Published: May 2024

A, Hematoxylin and eosin images and annotated BaseScope staining for point mutations in PIK3CA (Case C537, top) or KRAS (Case 539, bottom). Scale bars, 5 mm (top) and 1 mm (bottom). Regions circled in green were macrodissected for FUME-TCRseq. B, Bar chart showing the numbers of unique TCR clonotypes detected in the PIK3CA WT and mutant (E545K) subclones of Case C537. C, Bar chart showing the diversity of the TCR repertoire in PIK3CA WT and mutant subclones of Case C537. D, Plot showing the frequencies of the 10 most common clonotypes detected in the PIK3CA E545K mutant subclone and the frequencies at which they appear in the WT subclone. Arrow, TCR sequence CASSYGHPNTEAFF. E, Bar chart showing the numbers of unique TCR clonotypes detected in the KRAS WT and mutant (G12C) subclones of Case C539. F, Bar chart showing the diversity of the TCR repertoire in KRAS WT and mutant subclones of Case C539. G, Plot showing the frequencies of the 10 most common clonotypes detected in the KRAS G12C mutant subclone and the frequencies at which they appear in the WT subclone.
Supplementary Tables from NPEPPS Is a Druggable Driver of Platinum Resistance
Authors: Jones Robert T. , Scholtes Mathijs , Goodspeed Andrew , Akbarzadeh Maryam , Mohapatra Saswat , Feldman Lily Elizabeth , Vekony Hedvig , Jean Annie , Tilton Charlene B. , Orman Michael V. , Romal Shahla , Deiter Cailin , Kan Tsung Wai , Xander Nathaniel , Araki Stephanie P. , Joshi Molishree , Javaid Mahmood , Clambey Eric T. , Layer Ryan , Laajala Teemu D. , Parker Sarah J. , Mahmoudi Tokameh , Zuiverloon Tahlita C.M. , Theodorescu Dan , Costello James C.
Published: May 2024

Supplementary Tables 9-16
Supplementary Data from β-Catenin Activation Reprograms Ammonia Metabolism to Promote Senescence Resistance in Hepatocellular Carcinoma
Authors: Wang Ye , Cheng Chunxiao , Lu Yanjun , Lian Zhaowu , Liu Qi , Xu Yanchao , Li Yunzheng , Li Huan , Zhang Laizhu , Jiang Xiang , Li Binghua , Yu Decai
Published: May 2024

Supplementary Figures: S1-S16;
Supplementary Methods;
Supplementary Materials;
Supplementary Cell lines authentication
Figure S8 from DNA of Neutrophil Extracellular Traps Binds TMCO6 to Impair CD8+ T-cell Immunity in Hepatocellular Carcinoma
Authors: Song Mengjia , Zhang Chaoqi , Cheng Shaoyan , Ouyang Dijun , Ping Yu , Yang Jieying , Zhang YaoJun , Tang Yan , Chen Hao , Wang Qi-jing , Li Yong-qiang , He Jia , Xiang Tong , Zhang Yizhuo , Xia Jian-Chuan
Published: May 2024

NET-DNA regulates CD8+ T cell-immunity via TMCO6.
Figure S15 from DNA of Neutrophil Extracellular Traps Binds TMCO6 to Impair CD8+ T-cell Immunity in Hepatocellular Carcinoma
Authors: Song Mengjia , Zhang Chaoqi , Cheng Shaoyan , Ouyang Dijun , Ping Yu , Yang Jieying , Zhang YaoJun , Tang Yan , Chen Hao , Wang Qi-jing , Li Yong-qiang , He Jia , Xiang Tong , Zhang Yizhuo , Xia Jian-Chuan
Published: May 2024

The prognostic value of TMCO6 in HB and its role in HB cell behaviors.
Supplementary Tables from Ketogenic Diet Alters the Epigenetic and Immune Landscape of Prostate Cancer to Overcome Resistance to Immune Checkpoint Blockade Therapy
Authors: Murphy Sean , Rahmy Sharif , Gan Dailin , Liu Guoqiang , Zhu Yini , Manyak Maxim , Duong Loan , He Jianping , Schofield James H. , Schafer Zachary T. , Li Jun , Lu Xuemin , Lu Xin
Published: May 2024

Supplementary Table S1, S2, S3, S4, S5
Figure S12 from DNA of Neutrophil Extracellular Traps Binds TMCO6 to Impair CD8+ T-cell Immunity in Hepatocellular Carcinoma
Authors: Song Mengjia , Zhang Chaoqi , Cheng Shaoyan , Ouyang Dijun , Ping Yu , Yang Jieying , Zhang YaoJun , Tang Yan , Chen Hao , Wang Qi-jing , Li Yong-qiang , He Jia , Xiang Tong , Zhang Yizhuo , Xia Jian-Chuan
Published: May 2024

Pancancer analysis for the expression and prognosis value of TMCO6 in multiple cancer types.
Figure S11 from DNA of Neutrophil Extracellular Traps Binds TMCO6 to Impair CD8+ T-cell Immunity in Hepatocellular Carcinoma
Authors: Song Mengjia , Zhang Chaoqi , Cheng Shaoyan , Ouyang Dijun , Ping Yu , Yang Jieying , Zhang YaoJun , Tang Yan , Chen Hao , Wang Qi-jing , Li Yong-qiang , He Jia , Xiang Tong , Zhang Yizhuo , Xia Jian-Chuan
Published: May 2024

The expression of TMCO6 in HCC tissues and its role in HCC cell behaviors.
Data from Transcriptomic Profiling of Plasma Extracellular Vesicles Enables Reliable Annotation of the Cancer-Specific Transcriptome and Molecular Subtype
Authors: Bahrambeigi Vahid , Lee Jaewon J. , Branchi Vittorio , Rajapakshe Kimal I. , Xu Zhichao , Kui Naishu , Henry Jason T. , Kun Wang , Stephens Bret M. , Dhebat Sarah , Hurd Mark W. , Sun Ryan , Yang Peng , Ruppin Eytan , Wang Wenyi , Kopetz Scott , Maitra Anirban , Guerrero Paola A.
Published: May 2024

Abstract
Longitudinal monitoring of patients with advanced cancers is crucial to evaluate both disease burden and treatment response. Current liquid biopsy approaches mostly rely on the detection of DNA-based biomarkers. However, plasma RNA analysis can unleash tremendous opportunities for tumor state interrogation and molecular subtyping. Through the application of deep learning algorithms to the deconvolved transcriptomes of RNA within plasma extracellular vesicles (evRNA), we successfully predicted consensus molecular subtypes in patients with metastatic colorectal cancer. Analysis of plasma evRNA also enabled monitoring of changes in transcriptomic subtype under treatment selection pressure and identification of molecular pathways associated with recurrence. This approach also revealed expressed gene fusions and neoepitopes from evRNA. These results demonstrate the feasibility of using transcriptomic-based liquid biopsy platforms for precision oncology approaches, spanning from the longitudinal monitoring of tumor subtype changes to the identification of expressed fusions and neoantigens as cancer-specific therapeutic targets, sans the need for tissue-based sampling.
Significance:
The development of an approach to interrogate molecular subtypes, cancer-associated pathways, and differentially expressed genes through RNA sequencing of plasma extracellular vesicles lays the foundation for liquid biopsy–based longitudinal monitoring of patient tumor transcriptomes.
Data from NPEPPS Is a Druggable Driver of Platinum Resistance
Authors: Jones Robert T. , Scholtes Mathijs , Goodspeed Andrew , Akbarzadeh Maryam , Mohapatra Saswat , Feldman Lily Elizabeth , Vekony Hedvig , Jean Annie , Tilton Charlene B. , Orman Michael V. , Romal Shahla , Deiter Cailin , Kan Tsung Wai , Xander Nathaniel , Araki Stephanie P. , Joshi Molishree , Javaid Mahmood , Clambey Eric T. , Layer Ryan , Laajala Teemu D. , Parker Sarah J. , Mahmoudi Tokameh , Zuiverloon Tahlita C.M. , Theodorescu Dan , Costello James C.
Published: May 2024

Abstract
There is an unmet need to improve the efficacy of platinum-based cancer chemotherapy, which is used in primary and metastatic settings in many cancer types. In bladder cancer, platinum-based chemotherapy leads to better outcomes in a subset of patients when used in the neoadjuvant setting or in combination with immunotherapy for advanced disease. Despite such promising results, extending the benefits of platinum drugs to a greater number of patients is highly desirable. Using the multiomic assessment of cisplatin-responsive and -resistant human bladder cancer cell lines and whole-genome CRISPR screens, we identified puromycin-sensitive aminopeptidase (NPEPPS) as a driver of cisplatin resistance. NPEPPS depletion sensitized resistant bladder cancer cells to cisplatin in vitro and in vivo. Conversely, overexpression of NPEPPS in sensitive cells increased cisplatin resistance. NPEPPS affected treatment response by regulating intracellular cisplatin concentrations. Patient-derived organoids (PDO) generated from bladder cancer samples before and after cisplatin-based treatment, and from patients who did not receive cisplatin, were evaluated for sensitivity to cisplatin, which was concordant with clinical response. In the PDOs, depletion or pharmacologic inhibition of NPEPPS increased cisplatin sensitivity, while NPEPPS overexpression conferred resistance. Our data present NPEPPS as a druggable driver of cisplatin resistance by regulating intracellular cisplatin concentrations.
Significance:
Targeting NPEPPS, which induces cisplatin resistance by controlling intracellular drug concentrations, is a potential strategy to improve patient responses to platinum-based therapies and lower treatment-associated toxicities.
Data from Mutant U2AF1-Induced Mis-Splicing of mRNA Translation Genes Confers Resistance to Chemotherapy in Acute Myeloid Leukemia
Authors: Jin Peng , Wang Xiaoling , Jin Qiqi , Zhang Yi , Shen Jie , Jiang Ge , Zhu Hongming , Zhao Ming , Wang Dan , Li Zeyi , Zhou Yan , Li Wenzhu , Zhang Wei , Liu Yabin , Wang Siyang , Jin Wen , Cao Yuncan , Sheng Guangying , Dong Fangyi , Wu Shishuang , Li Xiaoyang , Jin Zhen , He Mengke , Liu Xiaxin , Chen Luonan , Zhang Yunxiang , Wang Kankan , Li Junmin
Published: May 2024

Abstract
Patients with primary refractory acute myeloid leukemia (AML) have a dismal long-term prognosis. Elucidating the resistance mechanisms to induction chemotherapy could help identify strategies to improve AML patient outcomes. Herein, we retrospectively analyzed the multiomics data of more than 1,500 AML cases and found that patients with spliceosome mutations had a higher risk of developing refractory disease. RNA splicing analysis revealed that the mis-spliced genes in refractory patients converged on translation-associated pathways, promoted mainly by U2AF1 mutations. Integrative analyses of binding and splicing in AML cell lines substantiated that the splicing perturbations of mRNA translation genes originated from both the loss and gain of mutant U2AF1 binding. In particular, the U2AF1S34F and U2AF1Q157R mutants orchestrated the inclusion of exon 11 (encoding a premature termination codon) in the eukaryotic translation initiation factor 4A2 (EIF4A2). This aberrant inclusion led to reduced eIF4A2 protein expression via nonsense-mediated mRNA decay. Consequently, U2AF1 mutations caused a net decrease in global mRNA translation that induced the integrated stress response (ISR) in AML cells, which was confirmed by single-cell RNA sequencing. The induction of ISR enhanced the ability of AML cells to respond and adapt to stress, contributing to chemoresistance. A pharmacologic inhibitor of ISR, ISRIB, sensitized U2AF1 mutant cells to chemotherapy. These findings highlight a resistance mechanism by which U2AF1 mutations drive chemoresistance and provide a therapeutic approach for AML through targeting the ISR pathway.
Significance:
U2AF1 mutations induce the integrated stress response by disrupting splicing of mRNA translation genes that improves AML cell fitness to enable resistance to chemotherapy, which can be targeted to improve AML treatment.
Data from DNA of Neutrophil Extracellular Traps Binds TMCO6 to Impair CD8+ T-cell Immunity in Hepatocellular Carcinoma
Authors: Song Mengjia , Zhang Chaoqi , Cheng Shaoyan , Ouyang Dijun , Ping Yu , Yang Jieying , Zhang YaoJun , Tang Yan , Chen Hao , Wang Qi-jing , Li Yong-qiang , He Jia , Xiang Tong , Zhang Yizhuo , Xia Jian-Chuan
Published: May 2024

Abstract
Neutrophil extracellular traps (NET), formed by the extracellular release of decondensed chromatin and granules, have been shown to promote tumor progression and metastasis. Tumor-associated neutrophils in hepatocellular carcinoma (HCC) are prone to NET formation, highlighting the need for a more comprehensive understanding of the mechanisms of action of NETs in liver cancer. Here, we showed that DNA of NETs (NET-DNA) binds transmembrane and coiled-coil domains 6 (TMCO6) on CD8+ T cells to impair antitumor immunity and thereby promote HCC progression. TGFβ1 induced NET formation, which recruited CD8+ T cells. Binding to NET-DNA inhibited CD8+ T cells function while increasing apoptosis and TGFβ1 secretion, forming a positive feedback loop to further stimulate NET formation and immunosuppression. Mechanistically, the N-terminus of TMCO6 interacted with NET-DNA and suppressed T-cell receptor signaling and NFκB p65 nuclear translocation. Blocking NET formation by inhibiting PAD4 induced potent antitumor effects in wild-type mice but not TMCO6−/− mice. In clinical samples, CD8+ T cells expressing TMCO6 had an exhausted phenotype. TGFβ1 signaling inhibition or TMCO6 deficiency combined with anti-PD-1 abolished NET-driven HCC progression in vivo. Collectively, this study unveils the role of NET-DNA in impairing CD8+ T-cell immunity by binding TMCO6 and identifies targeting this axis as an immunotherapeutic strategy for blocking HCC progression.
Significance:
TMCO6 is a receptor for DNA of NETs that mediates CD8+ T-cell dysfunction in HCC, indicating that the NET-TMCO6 axis is a promising target for overcoming immunosuppression in liver cancer.
Data from Ketogenic Diet Alters the Epigenetic and Immune Landscape of Prostate Cancer to Overcome Resistance to Immune Checkpoint Blockade Therapy
Authors: Murphy Sean , Rahmy Sharif , Gan Dailin , Liu Guoqiang , Zhu Yini , Manyak Maxim , Duong Loan , He Jianping , Schofield James H. , Schafer Zachary T. , Li Jun , Lu Xuemin , Lu Xin
Published: May 2024

Abstract
Resistance to immune checkpoint blockade (ICB) therapy represents a formidable clinical challenge limiting the efficacy of immunotherapy. In particular, prostate cancer poses a challenge for ICB therapy due to its immunosuppressive features. A ketogenic diet (KD) has been reported to enhance response to ICB therapy in some other cancer models. However, adverse effects associated with continuous KD were also observed, demanding better mechanistic understanding and optimized regimens for using KD as an immunotherapy sensitizer. In this study, we established a series of ICB-resistant prostate cancer cell lines and developed a highly effective strategy of combining anti-PD1 and anti-CTLA4 antibodies with histone deacetylase inhibitor (HDACi) vorinostat, a cyclic KD (CKD), or dietary supplementation of the ketone body β-hydroxybutyrate (BHB), which is an endogenous HDACi. CKD and BHB supplementation each delayed prostate cancer tumor growth as monotherapy, and both BHB and adaptive immunity were required for the antitumor activity of CKD. Single-cell transcriptomic and proteomic profiling revealed that HDACi and ketogenesis enhanced ICB efficacy through both cancer cell–intrinsic mechanisms, including upregulation of MHC class I molecules, and -extrinsic mechanisms, such as CD8+ T-cell chemoattraction, M1/M2 macrophage rebalancing, monocyte differentiation toward antigen-presenting cells, and diminished neutrophil infiltration. Overall, these findings illuminate a potential clinical path of using HDACi and optimized KD regimens to enhance ICB therapy for prostate cancer.
Significance:
Optimized cyclic ketogenic diet and 1,3-butanediol supplementation regimens enhance the efficacy of immune checkpoint blockade in prostate cancer through epigenetic and immune modulations, providing dietary interventions to sensitize tumors to immunotherapy.
Data from ATG-101 Is a Tetravalent PD-L1×4-1BB Bispecific Antibody That Stimulates Antitumor Immunity through PD-L1 Blockade and PD-L1–Directed 4-1BB Activation
Authors: Yuwen Hui , Wang Huajing , Li Tengteng , Ren Yijing , Zhang Yun-kai , Chen Peng , Sun Ao , Bian Gang , Li Bohua , Flowers David , Presler Marc , Subramanian Kalyanasundaram , Xue Jia , Wang Jingjing , Lynch Kevin , Mei Jay , He Xiaowen , Shan Bo , Hou Bing
Published: May 2024

Abstract
Immune checkpoint inhibitors (ICI) have transformed cancer treatment. However, only a minority of patients achieve a profound response. Many patients are innately resistant while others acquire resistance to ICIs. Furthermore, hepatotoxicity and suboptimal efficacy have hampered the clinical development of agonists of 4-1BB, a promising immune-stimulating target. To effectively target 4-1BB and treat diseases resistant to ICIs, we engineered ATG-101, a tetravalent "2+2″ PD-L1×4-1BB bispecific antibody. ATG-101 bound PD-L1 and 4-1BB concurrently, with a greater affinity for PD-L1, and potently activated 4-1BB+ T cells when cross-linked with PD-L1–positive cells. ATG-101 activated exhausted T cells upon PD-L1 binding, indicating a possible role in reversing T-cell dysfunction. ATG-101 displayed potent antitumor activity in numerous in vivo tumor models, including those resistant or refractory to ICIs. ATG-101 greatly increased the proliferation of CD8+ T cells, the infiltration of effector memory T cells, and the ratio of CD8+ T/regulatory T cells in the tumor microenvironment (TME), rendering an immunologically “cold” tumor “hot.” Comprehensive characterization of the TME after ATG-101 treatment using single-cell RNA sequencing further revealed an altered immune landscape that reflected increased antitumor immunity. ATG-101 was well tolerated and did not induce hepatotoxicity in non-human primates. According to computational semimechanistic pharmacology modeling, 4-1BB/ATG-101/PD-L1 trimer formation and PD-L1 receptor occupancy were both maximized at around 2 mg/kg of ATG-101, providing guidance regarding the optimal biological dose for clinical trials. In summary, by localizing to PD-L1–rich microenvironments and activating 4-1BB+ immune cells in a PD-L1 cross-linking–dependent manner, ATG-101 safely inhibits growth of ICI resistant and refractory tumors.
Significance:
The tetravalent PD-L1×4-1BB bispecific antibody ATG-101 activates 4-1BB+ T cells in a PD-L1 cross-linking–dependent manner, minimizing the hepatotoxicity of existing 4-1BB agonists and suppressing growth of ICI-resistant tumors.

See related commentary by Ha et al., p. 1546
The DRAP1/DR1 Repressor Complex Increases mTOR Activity to Promote Progression and Confer Everolimus Sensitivity in Triple-Negative Breast Cancer
Authors: Huang Min-Ying , Hu Shu-Yuan , Dong Jia , Deng Ling , Andriani Lisa , Ma Xiao-Yan , Zhang Yin-Ling , Zhang Fang-Lin , Shao Zhi-Ming , Li Da-Qiang
Published: May 2024

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Transcriptional dysregulation is a hallmark of cancer, and several transcriptional regulators have been demonstrated to contribute to cancer progression. In this study, we identified an upregulation of the transcriptional corepressor downregulator of transcription 1–associated protein 1 (DRAP1) in TNBC, which was closely associated with poor recurrence-free survival in patients with TNBC. DRAP1 promoted TNBC proliferation, migration, and invasion in vitro and tumor growth and metastasis in vivo. Mechanistically, the downregulator of transcription 1 (DR1)/DRAP1 heterodimer complex inhibited expression of the cytosolic arginine sensor for mTORC1 subunit 1 (CASTOR1) and thereby increased activation of mTOR, which sensitized TNBC to treatment with the mTOR inhibitor everolimus. DRAP1 and DR1 also formed a positive feedback loop. DRAP1 enhanced the stability of DR1 by recruiting the deubiquitinase USP7 to inhibit its proteasomal degradation; in turn, DR1 directly promoted DRAP1 transcription. Collectively, this study uncovered a DRAP1–DR1 bidirectional regulatory pathway that promotes TNBC progression, suggesting that targeting the DRAP1/DR1 complex might be a potential therapeutic strategy to treat TNBC.

Significance: DR1 and DRAP1 form a positive feedback loop and a repressor complex to cooperatively inhibit cytosolic arginine sensor for mTORC1 subunit 1 transcription and stimulate mTOR signaling, leading to progression and increased everolimus sensitivity in triple-negative breast cancer.
Suppl Table S8 from Targeting CCL2/CCR2 Signaling Overcomes MEK Inhibitor Resistance in Acute Myeloid Leukemia
Authors: Modak Rucha V. , de Oliveira Rebola Katia G. , McClatchy John , Mohammadhosseini Mona , Damnernsawad Alisa , Kurtz Stephen E. , Eide Christopher A. , Wu Guanming , Laderas Ted , Nechiporuk Tamilla , Gritsenko Marina A. , Hansen Joshua R. , Hutchinson Chelsea , Gosline Sara J.C. , Piehowski Paul , Bottomly Daniel , Short Nicholas , Rodland Karin , McWeeney Shannon K. , Tyner Jeffrey W. , Agarwal Anupriya
Published: May 2024

GSEA analysis from trametinib-sensitive and resistant cells
Suppl Table S7 from Targeting CCL2/CCR2 Signaling Overcomes MEK Inhibitor Resistance in Acute Myeloid Leukemia
Authors: Modak Rucha V. , de Oliveira Rebola Katia G. , McClatchy John , Mohammadhosseini Mona , Damnernsawad Alisa , Kurtz Stephen E. , Eide Christopher A. , Wu Guanming , Laderas Ted , Nechiporuk Tamilla , Gritsenko Marina A. , Hansen Joshua R. , Hutchinson Chelsea , Gosline Sara J.C. , Piehowski Paul , Bottomly Daniel , Short Nicholas , Rodland Karin , McWeeney Shannon K. , Tyner Jeffrey W. , Agarwal Anupriya
Published: May 2024

Phosphopeptides identified by trametinib and CCL2 treatments using a KSEA analysis
Suppl Table S10 from Targeting CCL2/CCR2 Signaling Overcomes MEK Inhibitor Resistance in Acute Myeloid Leukemia
Authors: Modak Rucha V. , de Oliveira Rebola Katia G. , McClatchy John , Mohammadhosseini Mona , Damnernsawad Alisa , Kurtz Stephen E. , Eide Christopher A. , Wu Guanming , Laderas Ted , Nechiporuk Tamilla , Gritsenko Marina A. , Hansen Joshua R. , Hutchinson Chelsea , Gosline Sara J.C. , Piehowski Paul , Bottomly Daniel , Short Nicholas , Rodland Karin , McWeeney Shannon K. , Tyner Jeffrey W. , Agarwal Anupriya
Published: May 2024

CRISPR pathway enrichment analysis
Supp Table S6 from Targeting CCL2/CCR2 Signaling Overcomes MEK Inhibitor Resistance in Acute Myeloid Leukemia
Authors: Modak Rucha V. , de Oliveira Rebola Katia G. , McClatchy John , Mohammadhosseini Mona , Damnernsawad Alisa , Kurtz Stephen E. , Eide Christopher A. , Wu Guanming , Laderas Ted , Nechiporuk Tamilla , Gritsenko Marina A. , Hansen Joshua R. , Hutchinson Chelsea , Gosline Sara J.C. , Piehowski Paul , Bottomly Daniel , Short Nicholas , Rodland Karin , McWeeney Shannon K. , Tyner Jeffrey W. , Agarwal Anupriya
Published: May 2024

Whole exome sequencing of mutations within trametinib resistant lines grown under trametinib or trametinib +CCL2
Supp Table S3 from Targeting CCL2/CCR2 Signaling Overcomes MEK Inhibitor Resistance in Acute Myeloid Leukemia
Authors: Modak Rucha V. , de Oliveira Rebola Katia G. , McClatchy John , Mohammadhosseini Mona , Damnernsawad Alisa , Kurtz Stephen E. , Eide Christopher A. , Wu Guanming , Laderas Ted , Nechiporuk Tamilla , Gritsenko Marina A. , Hansen Joshua R. , Hutchinson Chelsea , Gosline Sara J.C. , Piehowski Paul , Bottomly Daniel , Short Nicholas , Rodland Karin , McWeeney Shannon K. , Tyner Jeffrey W. , Agarwal Anupriya
Published: May 2024

RNA-seq gene list and pathway correlation with drug resistance
Supplementary Figure S7 from Developing Novel Genomic Risk Stratification Models in Soft Tissue and Uterine Leiomyosarcoma
Authors: Dermawan Josephine K. , Chiang Sarah , Singer Samuel , Jadeja Bhumika , Hensley Martee L. , Tap William D. , Movva Sujana , Maki Robert G. , Antonescu Cristina R.
Published: May 2024

Supplementary Figure S7. Modified 3-tier genomic risk stratification in STLMS cohort. DSS represented by Kaplan-Meier curves.
Supplementary Figure S5 from Developing Novel Genomic Risk Stratification Models in Soft Tissue and Uterine Leiomyosarcoma
Authors: Dermawan Josephine K. , Chiang Sarah , Singer Samuel , Jadeja Bhumika , Hensley Martee L. , Tap William D. , Movva Sujana , Maki Robert G. , Antonescu Cristina R.
Published: May 2024

Supplementary Figure S5. A. Forest plot depicting univariate Cox regression analysis for clinicopathologic and genomic risk variables for DSS in STLMS patients. B. Forest plot depicting multivariate Cox regression analysis comparing mitotic rate and necrosis with high genomic risk group for DSS in STLMS patients.
Supplementary Figure S12 from Developing Novel Genomic Risk Stratification Models in Soft Tissue and Uterine Leiomyosarcoma
Authors: Dermawan Josephine K. , Chiang Sarah , Singer Samuel , Jadeja Bhumika , Hensley Martee L. , Tap William D. , Movva Sujana , Maki Robert G. , Antonescu Cristina R.
Published: May 2024

Supplementary Figure S12. A. Forest plot depicting univariate Cox regression analysis for clinicopathologic and genomic risk variables for DSS in ULMS patients. B. Forest plot depicting multivariate Cox regression analysis comparing tumor size, mitotic rate and necrosis with high genomic risk group for DSS in ULMS patients.
Supplementary Figure S10 from Developing Novel Genomic Risk Stratification Models in Soft Tissue and Uterine Leiomyosarcoma
Authors: Dermawan Josephine K. , Chiang Sarah , Singer Samuel , Jadeja Bhumika , Hensley Martee L. , Tap William D. , Movva Sujana , Maki Robert G. , Antonescu Cristina R.
Published: May 2024

Supplementary Figure S10. ULMS genomic risk stratification for disease-specific survival (DSS). A 3-tier genomic risk group is proposed for DSS. DSS for 238 ULMS patients from the MSK cohort in low, intermediate, and high-risk genomic groups is represented by Kaplan-Meier curves (global log-rank P and Benjamin-Hochberg adjusted P-values by pairwise analysis).
Supplementary Figure S1 from Developing Novel Genomic Risk Stratification Models in Soft Tissue and Uterine Leiomyosarcoma
Authors: Dermawan Josephine K. , Chiang Sarah , Singer Samuel , Jadeja Bhumika , Hensley Martee L. , Tap William D. , Movva Sujana , Maki Robert G. , Antonescu Cristina R.
Published: May 2024

Supplementary Figure S1. A. Lollipop plots depicting the distribution of point mutations in TP53, RB1 and ATRX in STLMS and ULMS. B-C. Oncoprints in STLMS (B) and ULMS (C) depicting the distribution of recurrent genetic alterations in primary versus metastatic samples (unpaired).
Supplementary Table S3 from Tumor-Infiltrating Lymphocytes Refine Outcomes in Triple-Negative Breast Cancer Treated with Anthracycline-Free Neoadjuvant Chemotherapy
Authors: Martín Miguel , Yoder Rachel , Salgado Roberto , del Monte-Millán María , Álvarez Enrique L. , Echavarría Isabel , Staley Joshua M. , O'Dea Anne P. , Nye Lauren E. , Stecklein Shane R. , Bueno Coralia , Jerez Yolanda , Cebollero María , Bueno Oscar , García Saenz José Ángel , Moreno Fernando , Bohn Uriel , Gómez Henry , Massarrah Tatiana , Khan Qamar J. , Godwin Andrew K. , López-Tarruella Sara , Sharma Priyanka
Published: May 2024

Survival by availability of sTILs data
Supplementary Figure S3 from Tumor-Infiltrating Lymphocytes Refine Outcomes in Triple-Negative Breast Cancer Treated with Anthracycline-Free Neoadjuvant Chemotherapy
Authors: Martín Miguel , Yoder Rachel , Salgado Roberto , del Monte-Millán María , Álvarez Enrique L. , Echavarría Isabel , Staley Joshua M. , O'Dea Anne P. , Nye Lauren E. , Stecklein Shane R. , Bueno Coralia , Jerez Yolanda , Cebollero María , Bueno Oscar , García Saenz José Ángel , Moreno Fernando , Bohn Uriel , Gómez Henry , Massarrah Tatiana , Khan Qamar J. , Godwin Andrew K. , López-Tarruella Sara , Sharma Priyanka
Published: May 2024

Survival by pathologic response
Supplementary Figure S4 from Targeting SMAD3 Improves Response to Oxaliplatin in Esophageal Adenocarcinoma Models by Impeding DNA Repair
Authors: Ballout Farah , Lu Heng , Bhat Nadeem , Chen Lei , Peng Dunfa , Chen Zheng , Chen Steven , Sun Xiaodian , Giordano Silvia , Corso Simona , Zaika Alexander , McDonald Oliver , Livingstone Alan S. , El-Rifai Wael
Published: May 2024

Supplementary Figure 4. SMAD3 inhibition induces apoptosis in oxaliplatin sensitized EAC cells.
Supplementary Figure S3 from The Irreversible FGFR Inhibitor KIN-3248 Overcomes FGFR2 Kinase Domain Mutations
Authors: Balasooriya Eranga R. , Wu Qibiao , Ellis Haley , Zhen Yuanli , Norden Bryanna L. , Corcoran Ryan B. , Mohan Adithi , Martin Eric , Franovic Aleksandra , Tyhonas John , Lardy Matthew , Grandinetti Kathryn B. , Pelham Robert , Soroceanu Liliana , Silveira Vanessa S. , Bardeesy Nabeel
Published: May 2024

Supplementary Figure S3. Treatment with KIN-3248 is well-tolerated when administered orally at doses up to 15 mg/kg daily. Data are from the CCLP-1 model engineered with the FGFR2-PHGDH fusion (n=8 mice/group) and are presented as mean ± SEM.
Supplementary Figure S2 from The Irreversible FGFR Inhibitor KIN-3248 Overcomes FGFR2 Kinase Domain Mutations
Authors: Balasooriya Eranga R. , Wu Qibiao , Ellis Haley , Zhen Yuanli , Norden Bryanna L. , Corcoran Ryan B. , Mohan Adithi , Martin Eric , Franovic Aleksandra , Tyhonas John , Lardy Matthew , Grandinetti Kathryn B. , Pelham Robert , Soroceanu Liliana , Silveira Vanessa S. , Bardeesy Nabeel
Published: May 2024

Supplementary Figure S2. A. Cell viability assays were conducted to assess IC50 measurements in FGFR3S249C UM-UC-14 parental cells (left) and wild-type, mock-transfected cells (right) when treated with specific FGFR inhibitors. B-C. Cell viability curves for FGFR3S249C UM-UC-14 cells carrying N540K (B) or V555M (C) kinase domain mutations and their response to KIN-3248 and other designated FGFR inhibitors.
Supplementary Figure S1 from Response Rate and Molecular Correlates to Encorafenib and Binimetinib in BRAF-V600E Mutant High-Grade Glioma
Authors: Schreck Karisa C. , Strowd Roy E. , Nabors Louis B. , Ellingson Benjamin M. , Chang Michael , Tan Sze K. , Abdullaev Zied , Turakulov Rust , Aldape Kenneth , Danda Neeraja , Desideri Serena , Fisher Joy , Iacoboni Michaella , Surakus Trisha , Rudek Michelle A. , Bettegowda Chetan , Grossman Stuart A. , Ye Xiaobu
Published: May 2024

Supplementary Figure S1: Study schema.
Supplementary Table S2 from FDA Approval Summary: Enfortumab Vedotin plus Pembrolizumab for Cisplatin-Ineligible Locally Advanced or Metastatic Urothelial Carcinoma
Authors: Maguire William F. , Lee Daniel , Weinstock Chana , Gao Xin , Bulik Catharine C. , Agrawal Sundeep , Chang Elaine , Hamed Salaheldin S. , Bloomquist Erik W. , Tang Shenghui , Pazdur Richard , Kluetz Paul G. , Amiri-Kordestani Laleh , Suzman Daniel L.
Published: May 2024

Table S2 presents a summary of exposure and safety data by performance status in patients receiving combination treatment in EV-103