bluuebunny/crossref_metadata_2025 huggingface dataset:
Combining GitHub, Chat, and Peer Evaluation Data to Assess Individual Contributions to Team Software Development Projects
Authors: Hundhausen Christopher , Conrad Phill , Adesope Olusola , Tariq Ahsun
Published: May 2023

Assessing team software development projects is notoriously difficult and typically based on subjective metrics. To help make assessments more rigorous, we conducted an empirical study to explore relationships between subjective metrics based on peer and instructor assessments, and objective metrics based on GitHub and chat data. We studied 23 undergraduate software teams (
n
= 117 students) from two undergraduate computing courses at two North American research universities. We collected data on teams’ (a) commits and issues from their GitHub code repositories, (b) chat messages from their Slack and Microsoft Teams channels, (c) peer evaluation ratings from the CATME peer evaluation system, and (d) individual assignment grades from the courses. We derived metrics from (a) and (b) to measure both individual team members’
contributions
to the team, and the
equality
of team members’ contributions. We then performed Pearson analyses to identify correlations among the metrics, peer evaluation ratings, and individual grades. We found significant positive correlations between team members’ GitHub contributions, chat contributions, and peer evaluation ratings. In addition, the equality of teams’ GitHub contributions was positively correlated with teams’ average peer evaluation ratings and negatively correlated with the variance in those ratings. However, no such positive correlations were detected between the equality of teams’ chat contributions and their peer evaluation ratings. Our study extends previous research results by providing evidence that (a) team members’ chat contributions, like their GitHub contributions, are positively correlated with their peer evaluation ratings; (b) team members’ chat contributions are positively correlated with their GitHub contributions; and (c) the equality of team’ GitHub contributions is positively correlated with their peer evaluation ratings. These results lend further support to the idea that combining objective and subjective metrics can make the assessment of team software projects more comprehensive and rigorous.
Deep Learning Inferencing with High-performance Hardware Accelerators
Authors: Kljucaric Luke , George Alan D.
Published: May 2023

As computer architectures continue to integrate application-specific hardware, it is critical to understand the relative performance of devices for maximum app acceleration. The goal of benchmarking suites, such as MLPerf for analyzing machine learning (ML) hardware performance, is to standardize a fair comparison of different hardware architectures. However, there are many apps that are not well represented by these standards that require different workloads, such as ML models and datasets, to achieve similar goals. Additionally, many apps, like real-time video processing, are focused on latency of computations rather than strictly on throughput. This research analyzes multiple compute architectures that feature ML-specific hardware on a case study of handwritten Chinese character recognition. Specifically, AlexNet and a custom version of GoogLeNet are benchmarked in terms of their streaming latency and maximum throughput for optical character recognition. Considering that these models are composed of fundamental neural network operations yet architecturally different from each other, these models can stress devices in different yet insightful ways that generalizations of the performance of other models can be drawn from. Many devices featuring ML-specific hardware and optimizations are analyzed including Intel and AMD CPUs, Xilinx and Intel FPGAs, NVIDIA GPUs, and Google TPUs. Overall, ML-oriented hardware added to the Intel Xeon CPUs helps to boost throughput by 3.7× and to reduce latency by up to 34.7×, which makes the latency of Intel Xeon CPUs competitive on more parallel models. The TPU devices were limited in terms of throughput due to large data transfer times and not competitive in terms of latency. The FPGA frameworks showcase the lowest latency on the Xilinx Alveo U200 FPGA achieving 0.48 ms on AlexNet using Mipsology Zebra and 0.39 ms on GoogLeNet using Vitis-AI. Through their custom acceleration datapaths coupled with high-performance SRAM, the FPGAs are able to keep critical model data closer to processing elements for lower latency. The massively parallel and high-memory GPU devices with Tensor Core accelerators achieve the best throughput. The NVIDIA Tesla A100 GPU showcases the highest throughput at 42,513 and 52,484 images/second for AlexNet and GoogLeNet, respectively.

1
Keeping Up with the Emotets: Tracking a Multi-infrastructure Botnet
Authors: Boyarchuk Oleg , Mariani Sebastiano , Ortolani Stefano , Vigna Giovanni
Published: May 2023

Throughout its eight-year history, Emotet has caused substantial damage. This threat reappeared at the beginning of 2022 following a take-down by law enforcement in November 2021. Emotet is arguably one of the most notorious advanced persistent threats, causing substantial damage during its earlier phases and continuing to pose a danger to organizations everywhere. In this article, we present a longitudinal study of several waves of Emotet-based attacks that we observed in VMware’s customer telemetry. By analyzing Emotet’s software development life cycle, we were able to dissect how it quickly changes its command and control (C2) infrastructure, obfuscates its configuration, adapts and tests its evasive execution chains, deploys different attack vectors at different stages, laterally propagates, and continues to evolve using numerous tactics and techniques.
Toward a Distributed Trust Management System for Misbehavior Detection in the Internet of Vehicles
Authors: Mahmood Adnan , Sheng Quan Z. , Zhang Wei Emma , Wang Yan , Sagar Subhash
Published: May 2023

Recent considerable state-of-the-art advancements within the automotive sector, coupled with an evolution of the promising paradigms of vehicle-to-everything communication and the Internet of Vehicles (IoV), have facilitated vehicles to generate and, accordingly, disseminate an enormous amount of safety-critical and non-safety infotainment data in a bid to guarantee a highly safe, convenient, and congestion-aware road transport. These dynamic networks require intelligent security measures to ensure that the malicious messages, along with the vehicles that disseminate them, are identified and subsequently eliminated in a timely manner so that they are not in a position to harm other vehicles. Failing to do so could jeopardize the entire network, leading to fatalities and injuries amongst road users. Several researchers, over the years, have envisaged conventional cryptographic-based solutions employing certificates and the public key infrastructure for enhancing the security of vehicular networks. Nevertheless, cryptographic-based solutions are not optimum for an IoV network primarily, since the cryptographic schemes could be susceptible to compromised trust authorities and insider attacks that are highly deceptive in nature and cannot be noticed immediately and are, therefore, capable of causing catastrophic damage. Accordingly, in this article, a distributed trust management system has been proposed that ascertains the trust of all the reputation segments within an IoV network. The envisaged system takes into consideration the salient characteristics of familiarity, i.e., assessed via a subjective logic approach, similarity, and timeliness to ascertain the weights of all the reputation segments. Furthermore, an intelligent trust threshold mechanism has been developed for the identification and eviction of the misbehaving vehicles. The experimental results suggest the advantages of our proposed IoV-based trust management system in terms of optimizing the misbehavior detection and its resilience to various sorts of attacks.
STExplorer: A Hierarchical Autonomous Exploration Strategy with Spatio-temporal Awareness for Aerial Robots
Authors: Chen Bolei , Cui Yongzheng , Zhong Ping , Yang Wang , Liang Yixiong , Wang Jianxin
Published: May 2023

The autonomous exploration task we consider requires Unmanned Aerial Vehicles (UAVs) to actively navigate through unknown environments with the goal of fully perceiving and mapping the environments. Some existing exploration strategies suffer from rough cost budgets, ambiguous Information Gain (IG), and unnecessary backtracking exploration caused by Fragmented Regions (FRs). In our work, a hierarchical spatio-temporal-aware exploration framework is proposed to alleviate these problems. At the local exploration level, the Asymmetrical Traveling Salesman Problem (ATSP) is solved by comprehensively considering exploration time, IG, and heading consistency to avoid blindly exploring. Specifically, the exploration time is reasonably budgeted by fast marching in an artificial potential field. Meanwhile, a transformer-based map occupancy predictor is designed to assist in IG calculation by imagining spatial clues out of the Field of View (FoV), facilitating the prescient exploration. We verify that our local exploration is effective in alleviating the unnecessary back-and-forth movements caused by FRs and the interference of potential obstacle occlusion on the IG calculation. At the global exploration level, the classical Next Best View Points (NBVP) are generalized to Next Best Sub-Regions (NBSR) to choose informative sub-regions for further forward-looking exploration based on a well-designed utility function. Safe flight paths and dynamically feasible trajectories are reasonably generated throughout the exploration process by fast marching and B-spline curve optimization. Comparative simulations and benchmark tests demonstrate that our proposed exploration strategy is quite competitive in terms of exploration path length, total exploration time, and exploration ratio.
Research on Interface Properties of Thermally Grown SiO2 and ALD SiO2 Stacked Structures
Authors: Li Shuai , Luo Jun , Ye Tianchun
Published: May 2023

This study presents a stacked process of thermal and atomic layer deposition (ALD) SiO2 that reduces the interface trap density of 4H-SiC metal-oxide-semiconductor (MOS) capacitors. The channel mobility of metal-oxide-semiconductor field effect transistors (MOSFETS) are reduced due to the high interface trap density as well as coulomb scattering mechanism. Herein, we investigate SiO2/SiC interface properties of a stacked process, which is accomplished via reducing the thickness of thermal oxidation film. Notably, MOS capacitors fabricated with thermal and ALD SiO2 stacked structures can reduce the interface states density (Dit) by twofold at 0.2 eV below the conduction band energy compared with thermally grown SiO2. Additionally, the leakage current increases at a relatively slow rate in the electric field of 5–10 MV cm−1, whereas the leakage current increases sharply when the electric field is higher than 10 MV cm−1. The resultant ALD SiO2 stacked structure provides a new approach to improving interface quality, which allows a reduction in the thermal budget involved in the fabrication of devices.
Performance Analysis of Voltage-Controlled Magnetic Anisotropy MRAM-Based Logic Gates and Full Adder
Authors: Jangra Payal , Duhan Manoj
Published: May 2023

In the last decade, spintronics technology has been extensively researched for future non-volatile memories use. VCMA-MRAM exploits the voltage-controlled magnetic anisotropy (VCMA) principle to write data into magnetic tunnel junctions. In this paper, analysis, and comparison of the Energy consumption and delay performance parameter of Voltage Controlled Magnetic Anisotropy (VCMA) based logic gates are being done. This paper has implemented AND/NAND, OR/NOR, XOR/XNOR, and Full Adder using CMOS/VCMA models. Three models of VCMA have been used in this paper for performance analysis and comparison—STT-assisted thermally activated VCMA, STT-assisted precessional VCMA, and Precessional VCMA. The performance of these circuits has been analyzed, and the results have been compared within VCMA modules. Performance parameters like energy consumption and delay has been analyzed in this paper. From the gate latency (delay) and energy consumption analysis, it has been derived that the precessional VCMA-based gates perform better in these domains as compared to the other VCMA model-based gates. It is observed that performance improvements of ∼20% and ∼60% have been seen over STT-assisted precessional VCMA and STT-assisted thermally activated VCMA based gates in terms of gate latency at 1.2 V operating voltage and improvement of around 80% is seen in terms of energy over STT assisted thermally activated magnetic anisotropic MRAM, respectively.
Heterozygous midnolin knockout attenuates severity of nonalcoholic fatty liver disease in mice fed a Western-style diet high in fat, cholesterol, and fructose
Authors: Kweon Soo-Mi , Irimia-Dominguez Jose , Kim Gayeoun , Fueger Patrick T. , Asahina Kinji , Lai Keith K. , Allende Daniela S. , Lai Quincy R. , Lou Chih-Hong , Tsark Walter M. , Yang Ju Dong , Ng Dominic S. , Lee Ju-Seog , Tso Patrick , Huang Wendong , Lai Keane K. Y.
Published: May 2023

We have developed and now report on the first functional global midnolin knockout mouse model. We found that global heterozygous midnolin knockout attenuated the severity of nonalcoholic fatty liver disease (NAFLD) in mice fed a Western-style diet, high in fat, cholesterol, and fructose, and this attenuation in disease was associated with significantly reduced levels of large lipid droplets, hepatic free cholesterol, and serum LDL, with significantly differential gene expression involved in cholesterol/lipid metabolism.
Probiotics, prebiotics, and synbiotics in nonalcoholic fatty liver disease and alcohol-associated liver disease
Authors: Kaufmann Benedikt , Seyfried Nick , Hartmann Daniel , Hartmann Phillipp
Published: May 2023

The use of probiotics, prebiotics, and synbiotics has become an important therapy in numerous gastrointestinal diseases in recent years. Modifying the gut microbiota, this therapeutic approach helps to restore a healthy microbiome. Nonalcoholic fatty liver disease and alcohol-associated liver disease are among the leading causes of chronic liver disease worldwide. A disrupted intestinal barrier, microbial translocation, and an altered gut microbiome metabolism, or metabolome, are crucial in the pathogenesis of these chronic liver diseases. As pro-, pre-, and synbiotics modulate these targets, they were identified as possible new treatment options for liver disease. In this review, we highlight the current findings on clinical and mechanistic effects of this therapeutic approach in nonalcoholic fatty liver disease and alcohol-associated liver disease.
Exohedral Adsorption of N-(4-Methoxybenzylidene) Isonicotinohydrazone Molecule onto X12N12 Nanocages (where X=B and Al) and the Effect on Its NLO Properties by DFT and TD-DFT
Authors: Tsapi Charly Tedjeuguim , Tasheh Stanley Numbonui , Nkungli Nyiang Kennet , Fouegue Aymard Didier Tamafo , Alongamo Caryne Isabelle Lekeufack , Ghogomu Julius Numbonui
Published: May 2023

This study reports the nonlinear optical (NLO) properties of the exohedral adsorption of N-(4-methoxybenzylidene) isonicotinohydrazone (INH) onto B12N12 and Al12N12 nanocages. All ground state computations were performed using the density functional theory (DFT) method at the B3LYP-D3/6-311G(d,p) level of theory in the gaseous phase. Excited state computations were achieved via the time-dependent density functional theory (TD-DFT) at the CAM-B3LYP/6-311G(d,p) level of theory. Molecular electrostatic potential (MEP) analysis of INH reveals the presence of three preferential interaction sites: the O-atom of carbonyl (site 1), the N-atom of pyridine (site 2), and the N-atom of the azomethine group (site 3). The highest interaction energy values for the adsorption of INH onto the B12N12 and Al12N12 were −43.560 and −52.724 kcal·mol−1, respectively, indicating a chemisorption process. The computed Gibbs free energy change (ΔGad) and adsorption enthalpy change (ΔHad) values for all complexes studied are negative, indicating that the adsorption process is spontaneous and exothermic. Quantum theory of atoms in molecules (QTAIM) analysis reveals that the adsorbate-adsorbent interactions are partially covalent, which agrees with the reduced density gradient (RDG) analysis. Exohedral adsorption on the nanocages reduces the band gap, which ranges between 2.851 eV and 6.748 eV, according to density of state (DOS) diagrams. Furthermore, the first and second hyperpolarizabilities (βtot and γtot) were also determined. The outcomes show that adsorption improves these values over INH, and the complexes could be useful materials in optoelectronics and the development of more responsive NLO devices.
Utilization of Plastic Waste for Developing Composite Bricks and Enhancing Mechanical Properties: A Review on Challenges and Opportunities
Authors: Singh Aditya , Srivastava Ashish Kumar , Singh Gyanendra , Singh Akash Deep , Singh Hritik Kumar , Kumar Ajay , Singh Gyanendra Kumar
Published: May 2023

The population increases demand for plastic in every sector along with single-use plastic rapidly increasing, but it still has a low recycling rate. The use of plastic in the form of brick is challenging and overall has a better impact on the ecosystem, economy, and industrial revolution. In this paper, a study has been done of the available research work on plastic bricks from different plastic waste materials. It discusses the processes used to make bricks from plastic waste materials, the possibility of contamination from the waste materials utilized, the lack of pertinent standards, and the public adoption of waste materials-based bricks. Furthermore, it focused on research and development required for the widespread production and use of bricks made from waste materials, not only in terms of technical, economic, and environmental considerations but also in terms of standardization, governmental policy, and public awareness of waste recycling and sustainable development. It has been observed from the study that PET has mostly recycled plastic with greater efficiency compared to other plastics. However, worldwide global production is followed by PE, PVC, and PP. PET has only 5% contribution to the global recycling of plastics.
Heel‐Strike and Toe‐Off Detection Algorithm Based on Deep Neural Networks Using Shank‐Worn Inertial Sensors for Clinical Purpose
Authors: Skvortsov Dmitry , Chindilov Denis , Painev Nikita , Rozov Alexey
Published: May 2023

A foot placement of inertial sensors is commonly used for heel‐strike (HS) and toe‐off (TO) event detection. However, in clinical practice, such sensor placement may be difficult or even impossible due to the deformity of patients’ feet. The first contribution of this paper is a new algorithm for HS and TO event detection for cases when the sensors are placed on the lateral malleolus. Such sensor placement allows gait analysis in patients with foot deformities. In addition, the placement of the sensor directly on the wide bone surface of the lateral malleolus ensures secure fixation of the sensor during walking. The proposed algorithm is based on deep neural networks, which can be easily adapted (by retraining the neural networks) for analysis of various pathological gait patterns. It is especially important in clinical practice when the number of possible pathological gait patterns is very large. The algorithm proposed in this paper was implemented in a new wearable system for the clinical gait analysis. The second contribution is a validation of this new wearable system. The performance of both proposed algorithm and gait analysis system was evaluated against a reference treadmill system where a capacitance–based pressure platform was used. A total of 117 healthy volunteers participated in the comparison (62 males and 55 females, age 24–55 years, height 162–183 cm). They were asked to perform 2 min walking trials with different speed. Mean accuracy ± precision was –0.021 ± 0.091 s for gait cycle, 0.589 ± 1.144 steps/min for cadence, –0.051 ± 0.544% for stance phase, –0.37 ± 0.649% for single support, 0.296 ± 0.711% for double support, 0.132 ± 0.561% for load response, and 0.106 ± 0.661% for preswing. Limitations of the proposed algorithm and its compassion with state‐of‐the‐art algorithms were discussed.
Supplementary Table 4 from Spatial Transcriptomics Depict Ligand–Receptor Cross-talk Heterogeneity at the Tumor-Stroma Interface in Long-Term Ovarian Cancer Survivors
Authors: Ferri-Borgogno Sammy , Zhu Ying , Sheng Jianting , Burks Jared K. , Gomez Javier A. , Wong Kwong Kwok , Wong Stephen T.C. , Mok Samuel C.
Published: May 2023

MIA immune enrichment group comparison
Supplementary Table 2 from Spatial Transcriptomics Depict Ligand–Receptor Cross-talk Heterogeneity at the Tumor-Stroma Interface in Long-Term Ovarian Cancer Survivors
Authors: Ferri-Borgogno Sammy , Zhu Ying , Sheng Jianting , Burks Jared K. , Gomez Javier A. , Wong Kwong Kwok , Wong Stephen T.C. , Mok Samuel C.
Published: May 2023

Spatial Transcriptomics differentially expressed genes
Supplementary file 2: Supplementary Figures and Legends. from circFNDC3B Accelerates Vasculature Formation and Metastasis in Oral Squamous Cell Carcinoma
Authors: Li Xiang , Wang Chenxing , Zhang Hang , Li Yangjie , Hou Deqiang , Liu Dingshan , Xu Rongyao , Cheng Jie , Liu Laikui , Fu Yu , Ye Jinhai , Jiang Hongbing
Published: May 2023

Supplementary Figures and Legends.
Supplementary Materials and Methods from Spatial Transcriptomics Depict Ligand–Receptor Cross-talk Heterogeneity at the Tumor-Stroma Interface in Long-Term Ovarian Cancer Survivors
Authors: Ferri-Borgogno Sammy , Zhu Ying , Sheng Jianting , Burks Jared K. , Gomez Javier A. , Wong Kwong Kwok , Wong Stephen T.C. , Mok Samuel C.
Published: May 2023

Supplementary Materials and Methods
Supplementary Figures 1-11 from Spatial Transcriptomics Depict Ligand–Receptor Cross-talk Heterogeneity at the Tumor-Stroma Interface in Long-Term Ovarian Cancer Survivors
Authors: Ferri-Borgogno Sammy , Zhu Ying , Sheng Jianting , Burks Jared K. , Gomez Javier A. , Wong Kwong Kwok , Wong Stephen T.C. , Mok Samuel C.
Published: May 2023

Supplementary Figures 1-11
Supplementary Data from FOXA2 Cooperates with Mutant KRAS to Drive Invasive Mucinous Adenocarcinoma of the Lung
Authors: Tomoshige Koichi , Stuart William D. , Fink-Baldauf Iris M. , Ito Masaoki , Tsuchiya Tomoshi , Nagayasu Takeshi , Yamatsuji Tomoki , Okada Morihito , Fukazawa Takuya , Guo Minzhe , Maeda Yutaka
Published: May 2023

Supplementary Tables
Supplementary Data from FOXA2 Cooperates with Mutant KRAS to Drive Invasive Mucinous Adenocarcinoma of the Lung
Authors: Tomoshige Koichi , Stuart William D. , Fink-Baldauf Iris M. , Ito Masaoki , Tsuchiya Tomoshi , Nagayasu Takeshi , Yamatsuji Tomoki , Okada Morihito , Fukazawa Takuya , Guo Minzhe , Maeda Yutaka
Published: May 2023

Supplementary Materials and Methods and Supplementary Figures
Supplementary Data from Spatial Positioning of Immune Hotspots Reflects the Interplay between B and T Cells in Lung Squamous Cell Carcinoma
Authors: Zhang Hanyun , AbdulJabbar Khalid , Moore David A. , Akarca Ayse , Enfield Katey S.S. , Jamal-Hanjani Mariam , Raza Shan E. Ahmed , Veeriah Selvaraju , Salgado Roberto , McGranahan Nicholas , Le Quesne John , Swanton Charles , Marafioti Teresa , Yuan Yinyin
Published: May 2023

Table S3 and Fig. S1-S10
Supplementary Data from Polyunsaturated Fatty Acid–Bound α-Fetoprotein Promotes Immune Suppression by Altering Human Dendritic Cell Metabolism
Authors: Munson Paul V. , Adamik Juraj , Hartmann Felix J. , Favaro Patricia M.B. , Ho Daniel , Bendall Sean C. , Combes Alexis J. , Krummel Matthew F. , Zhang Karen , Kelley Robin K. , Butterfield Lisa H.
Published: May 2023

Supplementary Figures, Table, Supplementary Tables
Figure 6 from Spatial Positioning of Immune Hotspots Reflects the Interplay between B and T Cells in Lung Squamous Cell Carcinoma
Authors: Zhang Hanyun , AbdulJabbar Khalid , Moore David A. , Akarca Ayse , Enfield Katey S.S. , Jamal-Hanjani Mariam , Raza Shan E. Ahmed , Veeriah Selvaraju , Salgado Roberto , McGranahan Nicholas , Le Quesne John , Swanton Charles , Marafioti Teresa , Yuan Yinyin
Published: May 2023

The relationship among B-cell, T-cell percentages and CD8+/CD4+FOXP3+ ratio in individual intratumoral IH and peritumoral IH without TLS or LAG. A, Percentages of B-cell subsets in individual intratumoral (n = 262) and peritumoral IH (n = 392) classified by CD8+/CD4+FOXP3+ ratio. The high and low groups were determined by the cut-off of median CD8+/CD4+FOXP3+ ratio in intratumoral and peritumoral IH, respectively. B, Percentages of CD8+ T cells and CD4+FOXP3+ Treg cells in individual intratumoral (n = 262) and peritumoral IH (n = 392) classified by the percentage of B cells. This B-cell percentage was calculated as the total count of all B-cell subsets divided by the total count of all 6 immune cell types. C, Percentages of CD8+ T cells in individual intratumoral (n = 262) and peritumoral IH (n = 392) classified by CD4+FOXP3+ Treg-cell percentages. Statistical significance was evaluated by the Wilcoxon rank sum test and adjusted by the Benjamini–Hochberg method.
Supplementary Data from Computational and Functional Analyses of HER2 Mutations Reveal Allosteric Activation Mechanisms and Altered Pharmacologic Effects
Authors: Ishiyama Noboru , O'Connor Matthew , Salomatov Andrei , Romashko Darlene , Thakur Shalabh , Mentes Ahmet , Hopkins Julia F. , Frampton Garrett M. , Albacker Lee A. , Kohlmann Anna , Roberts Christopher , Buck Elizabeth
Published: May 2023

Supplementary Data
Figure 4 from Spatial Positioning of Immune Hotspots Reflects the Interplay between B and T Cells in Lung Squamous Cell Carcinoma
Authors: Zhang Hanyun , AbdulJabbar Khalid , Moore David A. , Akarca Ayse , Enfield Katey S.S. , Jamal-Hanjani Mariam , Raza Shan E. Ahmed , Veeriah Selvaraju , Salgado Roberto , McGranahan Nicholas , Le Quesne John , Swanton Charles , Marafioti Teresa , Yuan Yinyin
Published: May 2023

Lymphocyte composition and the presence of TLS at intratumoral and peritumoral IH. A, Example regions showing annotations of TLS at the IH and pathologically defined lymphoid aggregates without a prominent germinal center (LAG) at the intratumoral IH. B, Lymphocyte subset densities at intratumoral (n = 10) and peritumoral IH (n = 10). Cell densities were measured as the cell counts divided by the total area of IHs. C, Pie chart displaying the average percentages of peritumoral IH and intratumoral IH identified as TLS, LAG, and non-TLS/LAG IH. D, Densities of TLS and LAG at intratumoral (n = 10) and peritumoral IH (n = 10). E, Densities of B- and T-cell subsets in TLS (n = 10), LAG (n = 10), and non-TLS/LAG IH (n = 10). Statistical significance was evaluated by the Wilcoxon signed-rank test, followed by the Benjamini–Hochberg method for P value adjustment. *, P < 0.05; **, P < 0.01. The median is marked by the horizontal line; the first and third quartiles are shown as box edges; whiskers indicate the range of error.
Figure 3 from Spatial Positioning of Immune Hotspots Reflects the Interplay between B and T Cells in Lung Squamous Cell Carcinoma
Authors: Zhang Hanyun , AbdulJabbar Khalid , Moore David A. , Akarca Ayse , Enfield Katey S.S. , Jamal-Hanjani Mariam , Raza Shan E. Ahmed , Veeriah Selvaraju , Salgado Roberto , McGranahan Nicholas , Le Quesne John , Swanton Charles , Marafioti Teresa , Yuan Yinyin
Published: May 2023

The deep learning pipeline to map T-cell and B-cell subsets at intratumoral and peritumoral IH. A, Framework of the deep learning pipeline for spatial analysis. The pipeline comprised 3 steps: serial section alignment, deep learning–based cell classification, and hotspots mapping. IHC staining with a B-cell panel (CD20/CXCR5/CD79b/P40) and a T-cell panel (CD4/FOXP3/CD8) was performed on serial sections, which were then aligned to the corresponding H&E section. Dominant B-cell subsets (CD20+CXCR5−, CD20+CXCR5+, CD79b+) and T-cell subsets (CD4+FOXP3−, CD4+FOXP3+, CD8+) were detected and classified by deep learning models and projected to the H&E slide. The magnified region example illustrates this entire framework, which combines immune cell detection from the B-/T-cell IHC sections together with hotspot identification on the corresponding H&E slide. B–E, Representative TLS, LAG, non-TLS/LAG intratumoral IH, and non-TLS/LAG peritumoral IH. Cell classification results are shown below the original image, with color codes for each cell type shown at the bottom. Scale bar, 100 μm.
Supplementary Information from Ablation of p57+ Quiescent Cancer Stem Cells Suppresses Recurrence after Chemotherapy of Intestinal Tumors
Authors: Oka Takeru , Higa Tsunaki , Sugahara Osamu , Koga Daisuke , Nakayama Shogo , Nakayama Keiichi I.
Published: May 2023

Supplementary Table InformationSupplementary Figures S1–S5Supplementary Figure Legends
Figure 1 from Spatial Positioning of Immune Hotspots Reflects the Interplay between B and T Cells in Lung Squamous Cell Carcinoma
Authors: Zhang Hanyun , AbdulJabbar Khalid , Moore David A. , Akarca Ayse , Enfield Katey S.S. , Jamal-Hanjani Mariam , Raza Shan E. Ahmed , Veeriah Selvaraju , Salgado Roberto , McGranahan Nicholas , Le Quesne John , Swanton Charles , Marafioti Teresa , Yuan Yinyin
Published: May 2023

Immune hotspots in LUSC. A, Illustrative examples of automatic cell classification results and hotspot distribution with zoomed-in regions showing areas enriched with immune cells and cancer–immune coclustering. Cancer hotspots (red) and IHs were identified based on the local clustering of cancer and lymphocytes. Intratumoral IH (green) was determined as regions enriched with both immune and cancer cells, while peritumoral IH (blue) were regions enriched with only immune cells. B, Schematic representations of tissue compartments including cancer hotspots, peritumoral IH, intratumoral IH based on automated spatial analysis, and pathologically defined TLSs and lymphoid aggregates without clear separation of T- and B-cell zones (LAG). The three spatial scores Sintra/immune, Sintra/cancer, and Sintra/tissue were determined as the proportion of intratumoral IH in the immune-rich area (intratumoral IH and peritumoral IH), cancer-rich area (intratumoral IH and cancer hotspots), and the entire tissue, respectively. C, Kaplan–Meier curves to illustrate the difference in OS in LUSC patients stratified by Sintra/immune, with the dichotomization optimized for the discovery cohort (n = 231) and assessed in the validation cohort (n = 231). D, Forest plots to show the prognostic value of Sintra/immune in multivariate models adjusted for stage, age, and smoking pack years in the validation cohort. E, Spearman correlation between lymphocyte percentage and Sintra/immune in the TCGA LUSC cohort (n = 462). F, Kaplan–Meier curve to illustrate the difference in OS in LUSC patients stratified by both Sintra/immune and lymphocyte percentage, with the stratification of the entire cohort shown (n = 462).
Supplementary Table S4 from RBM10 Loss Promotes EGFR-Driven Lung Cancer and Confers Sensitivity to Spliceosome Inhibition
Authors: Bao Yufang , Zhang Sirui , Zhang Xiaoyu , Pan Yunjian , Yan Yueren , Wang Ning , Ren Yunpeng , Zuo Ji , Zong Wei-Xing , Wang Zefeng , Wang Yongbo
Published: May 2023

Supplementary Table S4
Supplementary Table 1 from The Macrophage-Associated LncRNA MALR Facilitates ILF3 Liquid–Liquid Phase Separation to Promote HIF1α Signaling in Esophageal Cancer
Authors: Liu Jia , Liu Ze-Xian , Li Jia-Jun , Zeng Zhao-Lei , Wang Jin-Hong , Luo Xiao-Jing , Wong Chau-Wei , Zheng Jia-Bo , Pu Heng-Ying , Mo Hai-Yu , Sheng Hui , Wu Qi-Nian , Li Hao , Wan Gang , Li Bo , Wang De-shen , Xu Rui-Hua , Ju Huai-Qiang
Published: May 2023

Supplementary Table 1
Supplementary Table S2 from RBM10 Loss Promotes EGFR-Driven Lung Cancer and Confers Sensitivity to Spliceosome Inhibition
Authors: Bao Yufang , Zhang Sirui , Zhang Xiaoyu , Pan Yunjian , Yan Yueren , Wang Ning , Ren Yunpeng , Zuo Ji , Zong Wei-Xing , Wang Zefeng , Wang Yongbo
Published: May 2023

Supplementary Table S2
Figure S7 from Comprehensive Metabolic Tracing Reveals the Origin and Catabolism of Cysteine in Mammalian Tissues and Tumors
Authors: Yoon Sang Jun , Combs Joseph A. , Falzone Aimee , Prieto-Farigua Nicolas , Caldwell Samantha , Ackerman Hayley D. , Flores Elsa R. , DeNicola Gina M.
Published: May 2023

Figure S7 contains mRNA expression of cysteine metabolic enzymes in patient liver, pancreas and lung tumors
TableS3 from Enhancer Coamplification and Hijacking Promote Oncogene Expression in Liposarcoma
Authors: Liu Tingting , Wang Juan , Yang Hongbo , Jin Qiushi , Wang Xiaotao , Fu Yihao , Luan Yu , Wang Qixuan , Youngblood Mark W. , Lu Xinyan , Casadei Lucia , Pollock Raphael , Yue Feng
Published: May 2023

Patient Sample Hi-C data Statistics
Figure S4 from Comprehensive Metabolic Tracing Reveals the Origin and Catabolism of Cysteine in Mammalian Tissues and Tumors
Authors: Yoon Sang Jun , Combs Joseph A. , Falzone Aimee , Prieto-Farigua Nicolas , Caldwell Samantha , Ackerman Hayley D. , Flores Elsa R. , DeNicola Gina M.
Published: May 2023

Figure S4 contains the total metabolite levels in healthy mouse tissues related to Figure 3
Figure S2 from Comprehensive Metabolic Tracing Reveals the Origin and Catabolism of Cysteine in Mammalian Tissues and Tumors
Authors: Yoon Sang Jun , Combs Joseph A. , Falzone Aimee , Prieto-Farigua Nicolas , Caldwell Samantha , Ackerman Hayley D. , Flores Elsa R. , DeNicola Gina M.
Published: May 2023

Figure S2 demonstrates that transsulfuration intermediates are limiting for activity in NSCLC cells
Supplementary Figures from Enhancer Coamplification and Hijacking Promote Oncogene Expression in Liposarcoma
Authors: Liu Tingting , Wang Juan , Yang Hongbo , Jin Qiushi , Wang Xiaotao , Fu Yihao , Luan Yu , Wang Qixuan , Youngblood Mark W. , Lu Xinyan , Casadei Lucia , Pollock Raphael , Yue Feng
Published: May 2023

All Supplementary Figures
Data from FOXA2 Cooperates with Mutant KRAS to Drive Invasive Mucinous Adenocarcinoma of the Lung
Authors: Tomoshige Koichi , Stuart William D. , Fink-Baldauf Iris M. , Ito Masaoki , Tsuchiya Tomoshi , Nagayasu Takeshi , Yamatsuji Tomoki , Okada Morihito , Fukazawa Takuya , Guo Minzhe , Maeda Yutaka
Published: May 2023

Abstract
The endoderm-lineage transcription factor FOXA2 has been shown to inhibit lung tumorigenesis in in vitro and xenograft studies using lung cancer cell lines. However, FOXA2 expression in primary lung tumors does not correlate with an improved patient survival rate, and the functional role of FOXA2 in primary lung tumors remains elusive. To understand the role of FOXA2 in primary lung tumors in vivo, here, we conditionally induced the expression of FOXA2 along with either of the two major lung cancer oncogenes, EGFRL858R or KRASG12D, in the lung epithelium of transgenic mice. Notably, FOXA2 suppressed autochthonous lung tumor development driven by EGFRL858R, whereas FOXA2 promoted tumor growth driven by KRASG12D. Importantly, FOXA2 expression along with KRASG12D produced invasive mucinous adenocarcinoma (IMA) of the lung, a fatal mucus-producing lung cancer comprising approximately 5% of human lung cancer cases. In the mouse model in vivo and human lung cancer cells in vitro, FOXA2 activated a gene regulatory network involved in the key mucous transcription factor SPDEF and upregulated MUC5AC, whose expression is critical for inducing IMA. Coexpression of FOXA2 with mutant KRAS synergistically induced MUC5AC expression compared with that induced by FOXA2 alone. ChIP-seq combined with CRISPR interference indicated that FOXA2 bound directly to the enhancer region of MUC5AC and induced the H3K27ac enhancer mark. Furthermore, FOXA2 was found to be highly expressed in primary tumors of human IMA. Collectively, this study reveals that FOXA2 is not only a biomarker but also a driver for IMA in the presence of a KRAS mutation.
Significance:
FOXA2 expression combined with mutant KRAS drives invasive mucinous adenocarcinoma of the lung by synergistically promoting a mucous transcriptional program, suggesting strategies for targeting this lung cancer type that lacks effective therapies.
Understanding Long-Term Survival of Patients with Ovarian Cancer—The Tumor Microenvironment Comes to the Forefront
Authors: Kelliher Lucy , Lengyel Ernst
Published: May 2023

High-grade serous ovarian cancer (HGSOC) is the deadliest subtype of ovarian cancer, and most patients do not survive more than 5 years after diagnosis. Yet, for reasons that are often elusive, approximately 15% of women with advanced-stage HGSOC will survive longer than 10 years. An understanding of the biological basis of long-term survival with HGSOC may elucidate novel prognostic factors and targets for treatment. Past analyses of the clinicopathologic features of these women and genetic profiles of their tumors have not revealed a unifying explanation for their increased longevity. In this issue of Cancer Research, Ferri-Borgogno and colleagues investigate the tumor microenvironment (TME) in samples from both long- and short-term survivors using spatial transcriptomics and single-cell RNA sequencing. They found that, in metastatic tumors, various populations of cancer-associated fibroblasts (CAF) in the TME play different roles in supporting the malignant phenotype of ovarian cancer cells. Higher density of CAFs, particularly αSMA+VIM+PDGFRβ+ CAFs, was associated with lower tumor immune infiltration and short-term survival. There was also marked expression of periostin and CD36 in spatially resolved CAFs, as well as a prevalence of the APOE-LRP5 ligand-receptor pair at the tumor-stromal interface in tissue from short-term survivors. These findings suggest that, in short-term survivors, CAFs are able to more effectively promote tumorigenicity, stemness, and chemoresistance in the nearby tumor.

See related article by Ferri-Borgogno et al., p. 1503
Estimated Ovulatory Years Prior to Menopause and Postmenopausal Endogenous Hormone Levels
Authors: Cramer Daniel W. , Vitonis Allison F. , Huang Tianyi , Shafrir Amy L. , Eliassen A. Heather , Barbieri Robert L. , Hankinson Susan E.
Published: May 2023

Background:

Lifetime ovulatory years (LOY) is estimated by the difference between ages at menopause and menarche subtracting time for events interrupting ovulation. We tested whether LOY influences sex hormone levels in postmenopausal women with at least one intact ovary not using hormones.

Methods:

Estradiol, estrone, estrone sulfate, total testosterone, dehydroepiandrostendione sulfate, prolactin, and sex hormone binding globulin were measured in 1,976 postmenopausal women from the Nurses’ Health Study. Associations of age, body mass index (BMI), smoking, alcohol use, and other factors on hormones were assessed by t tests and ANOVA. Linear regression was used to assess multivariable adjusted associations between LOY and hormones and trends in hormone levels per 5-year increases in LOY were estimated.

Results:

Women averaged 61.4 years old, 11.0 years since menopause, with BMI of 25.8 kg/m2. A total of 13.6% had irregular cycles, 17.5% hysterectomy, 6.4% unilateral oophorectomy, and 13.8% were current smokers. Variables associated with one or more hormone levels were included as covariates. Each 5-year increase in LOY was significantly associated with a 5.2% increase in testosterone in women with BMI < 25 kg/m2 and a 7.4% increase in testosterone and 7.3% increase in estradiol in women with above-average BMI.

Conclusions:

This is the first study to show that greater LOY is associated with higher testosterone in postmenopausal women and higher estradiol in those with elevated BMI, suggesting accumulation of functioning stromal and thecal cells from repeated ovulations and peripheral conversion of testosterone.

Impact:

A possible explanation for why greater LOY increases risk for breast, endometrial, and ovarian cancer is offered.
Supplementary Table S1: Common co-occurring alterations with tissue-agnostic targets in select tumor types from Tumor-Agnostic Precision Medicine from the AACR GENIE Database: Clinical Implications
Authors: Gouda Mohamed A. , Nelson Blessie E. , Buschhorn Lars , Wahida Adam , Subbiah Vivek
Published: May 2023

Genes most frequently mutated in cases with tissue-agnostic targets in the overall altered population and top 5 cancers with highest number of profiled samples in each alteration
Supplementary Data 1 from The Negative Influence of Baseline Cell-free DNA on Long-term Survival in DLBCL Depends on Frontline Treatment Intensity
Authors: Desmots Fabienne , Rossille Delphine , Roussel Mikael , Pangault Céline , Louarn Laetitia , De Saint Jore Mylène , Le Gouill Steven , Bouabdallah Krimo , Delwail Vincent , Gressin Remy , Cornillon Jérôme , Damaj Gandhi , Maisonneuve Hervé , Damotte Diane , Kraeber-Bodere Françoise , Lamy Thierry , Parrens Marie-Cécile , Milpied Noël , Fest Thierry
Published: May 2023

supplemental methods, tables and figures
Supplementary Table S3 from Clinical Relevance of BRCA1 Promoter Methylation Testing in Patients with Ovarian Cancer
Authors: Blanc-Durand Félix , Tang Roseline , Pommier Margaux , Nashvi Marzieh , Cotteret Sophie , Genestie Catherine , Le Formal Audrey , Pautier Patricia , Michels Judith , Kfoury Maria , Hervé Robert , Mengue Sylvie , Wafo Estelle , Elies Antoine , Miailhe Gregoire , Uzan Jennifer , Rouleau Etienne , Leary Alexandra
Published: May 2023

Clinical characteristics according to BRCA status
Supplementary Table S7 from DNA-Methylome–Based Tumor Hypoxia Classifier Identifies HPV-Negative Head and Neck Cancer Patients at Risk for Locoregional Recurrence after Primary Radiochemotherapy
Authors: Tawk Bouchra , Rein Katrin , Schwager Christian , Knoll Maximilian , Wirkner Ute , Hörner-Rieber Juliane , Liermann Jakob , Kurth Ina , Balermpas Panagiotis , Rödel Claus , Linge Annett , Löck Steffen , Lohaus Fabian , Tinhofer Ingeborg , Krause Mechtild , Stuschke Martin , Grosu Anca Ligia , Zips Daniel , Combs Stephanie E. , Belka Claus , Stenzinger Albrecht , Herold-Mende Christel , Baumann Michael , Schirmacher Peter , Debus Jürgen , Abdollahi Amir
Published: May 2023

Supplementary Table S7. Distribution of clinical and biomarker-related characteristics between Methylation Hypoxia High vs Low in the TCGA-pancancer cohort
Supplementary Table S5 from DNA-Methylome–Based Tumor Hypoxia Classifier Identifies HPV-Negative Head and Neck Cancer Patients at Risk for Locoregional Recurrence after Primary Radiochemotherapy
Authors: Tawk Bouchra , Rein Katrin , Schwager Christian , Knoll Maximilian , Wirkner Ute , Hörner-Rieber Juliane , Liermann Jakob , Kurth Ina , Balermpas Panagiotis , Rödel Claus , Linge Annett , Löck Steffen , Lohaus Fabian , Tinhofer Ingeborg , Krause Mechtild , Stuschke Martin , Grosu Anca Ligia , Zips Daniel , Combs Stephanie E. , Belka Claus , Stenzinger Albrecht , Herold-Mende Christel , Baumann Michael , Schirmacher Peter , Debus Jürgen , Abdollahi Amir
Published: May 2023

Supplementary Table S5. Distribution of clinical and biomarker-related characteristics between Methylation Hypoxia High vs Low in the validation cohort (DKTK-ROG)
Supplementary Table S4 from DNA-Methylome–Based Tumor Hypoxia Classifier Identifies HPV-Negative Head and Neck Cancer Patients at Risk for Locoregional Recurrence after Primary Radiochemotherapy
Authors: Tawk Bouchra , Rein Katrin , Schwager Christian , Knoll Maximilian , Wirkner Ute , Hörner-Rieber Juliane , Liermann Jakob , Kurth Ina , Balermpas Panagiotis , Rödel Claus , Linge Annett , Löck Steffen , Lohaus Fabian , Tinhofer Ingeborg , Krause Mechtild , Stuschke Martin , Grosu Anca Ligia , Zips Daniel , Combs Stephanie E. , Belka Claus , Stenzinger Albrecht , Herold-Mende Christel , Baumann Michael , Schirmacher Peter , Debus Jürgen , Abdollahi Amir
Published: May 2023

Supplementary Table S4. Correlations with CIBERSORT immune signature expressions in the TCGA-HNSCC cohort
Supplementary Table S3 from DNA-Methylome–Based Tumor Hypoxia Classifier Identifies HPV-Negative Head and Neck Cancer Patients at Risk for Locoregional Recurrence after Primary Radiochemotherapy
Authors: Tawk Bouchra , Rein Katrin , Schwager Christian , Knoll Maximilian , Wirkner Ute , Hörner-Rieber Juliane , Liermann Jakob , Kurth Ina , Balermpas Panagiotis , Rödel Claus , Linge Annett , Löck Steffen , Lohaus Fabian , Tinhofer Ingeborg , Krause Mechtild , Stuschke Martin , Grosu Anca Ligia , Zips Daniel , Combs Stephanie E. , Belka Claus , Stenzinger Albrecht , Herold-Mende Christel , Baumann Michael , Schirmacher Peter , Debus Jürgen , Abdollahi Amir
Published: May 2023

Supplementary Table S3. Distribution of clinical and biomarker-related characteristics between Methylation Hypoxia High vs Low in the training cohort (TCGA-HNSCC)
Supplementary Table S2 from DNA-Methylome–Based Tumor Hypoxia Classifier Identifies HPV-Negative Head and Neck Cancer Patients at Risk for Locoregional Recurrence after Primary Radiochemotherapy
Authors: Tawk Bouchra , Rein Katrin , Schwager Christian , Knoll Maximilian , Wirkner Ute , Hörner-Rieber Juliane , Liermann Jakob , Kurth Ina , Balermpas Panagiotis , Rödel Claus , Linge Annett , Löck Steffen , Lohaus Fabian , Tinhofer Ingeborg , Krause Mechtild , Stuschke Martin , Grosu Anca Ligia , Zips Daniel , Combs Stephanie E. , Belka Claus , Stenzinger Albrecht , Herold-Mende Christel , Baumann Michael , Schirmacher Peter , Debus Jürgen , Abdollahi Amir
Published: May 2023

Supplementary Table S2. Treatment Information for the validation cohort (n=88, DKTK-ROG)
Supplementary Table S1 from DNA-Methylome–Based Tumor Hypoxia Classifier Identifies HPV-Negative Head and Neck Cancer Patients at Risk for Locoregional Recurrence after Primary Radiochemotherapy
Authors: Tawk Bouchra , Rein Katrin , Schwager Christian , Knoll Maximilian , Wirkner Ute , Hörner-Rieber Juliane , Liermann Jakob , Kurth Ina , Balermpas Panagiotis , Rödel Claus , Linge Annett , Löck Steffen , Lohaus Fabian , Tinhofer Ingeborg , Krause Mechtild , Stuschke Martin , Grosu Anca Ligia , Zips Daniel , Combs Stephanie E. , Belka Claus , Stenzinger Albrecht , Herold-Mende Christel , Baumann Michael , Schirmacher Peter , Debus Jürgen , Abdollahi Amir
Published: May 2023

Supplementary Table S1. Multivariate Analysis for the Hypoxia-M and Brooks signature.
Supplementary Figures S2 from DNA-Methylome–Based Tumor Hypoxia Classifier Identifies HPV-Negative Head and Neck Cancer Patients at Risk for Locoregional Recurrence after Primary Radiochemotherapy
Authors: Tawk Bouchra , Rein Katrin , Schwager Christian , Knoll Maximilian , Wirkner Ute , Hörner-Rieber Juliane , Liermann Jakob , Kurth Ina , Balermpas Panagiotis , Rödel Claus , Linge Annett , Löck Steffen , Lohaus Fabian , Tinhofer Ingeborg , Krause Mechtild , Stuschke Martin , Grosu Anca Ligia , Zips Daniel , Combs Stephanie E. , Belka Claus , Stenzinger Albrecht , Herold-Mende Christel , Baumann Michael , Schirmacher Peter , Debus Jürgen , Abdollahi Amir
Published: May 2023

Supplementary Figure S2. (Top) Hypoxia-M V2 is prognostic in the DKTK-ROG cohort. Patients predicted to have higher tumor hypoxia by Hypoxia-M V2 had higher rates of death (p=0.0097), local recurrence (p=0.0037), distant metastasis (p=0.027) and disease progression (p=0.00096). (Bottom) Hypoxia-M V2 remains an independent prognosticator of OS, LR and disease progression after adjusting for age, smoking status, GTV and anatomical site. Additionally, there is a trend towards higher rates of distant metastasis (HR=2.33, p=0.13)