bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancing Code Understanding for Impact Analysis by Combining Transformers and Program Dependence Graphs
Authors: Yan Yanfu , Cooper Nathan , Moran Kevin , Bavota Gabriele , Poshyvanyk Denys , Rich Steve 
Published: July 2024

Impact analysis (IA) is a critical software maintenance task that identifies the effects of a given set of code changes on a larger software project with the intention of avoiding potential adverse effects. IA is a cognitively challenging task that involves reasoning about the abstract relationships between various code constructs. Given its difficulty, researchers have worked to automate IA with approaches that primarily use coupling metrics as a measure of the "connectedness" of different parts of a software project. Many of these coupling metrics rely on static, dynamic, or evolutionary information and are based on heuristics that tend to be brittle, require expensive execution analysis, or large histories of co-changes to accurately estimate impact sets.
In this paper, we introduce a novel IA approach, called ATHENA, that combines a software system's dependence graph information with a conceptual coupling approach that uses advances in deep representation learning for code without the need for change histories and execution information. Previous IA benchmarks are small, containing less than ten software projects, and suffer from tangled commits, making it difficult to measure accurate results. Therefore, we constructed a large-scale IA benchmark, from 25 open-source software projects, that utilizes fine-grained commit information from bug fixes. On this new benchmark, our best performing approach configuration achieves an mRR, mAP, and HIT@10 score of 60.32%, 35.19%, and 81.48%, respectively. Through various ablations and qualitative analyses, we show that ATHENA's novel combination of program dependence graphs and conceptual coupling information leads it to outperform a simpler baseline by 10.34%, 9.55%, and 11.68% with statistical significance.
Metamorphic Testing of Secure Multi-party Computation (MPC) Compilers
Authors: Li Yichen , Xiao Dongwei , Liu Zhibo , Pang Qi , Wang Shuai 
Published: July 2024

The demanding need to perform privacy-preserving computations among multiple

data owners has led to the prosperous development of secure multi-party

computation (MPC) protocols. MPC offers protocols for parties to jointly compute

a function over their inputs while keeping those inputs private. To date, MPC

has been widely adopted in various real-world, privacy-sensitive sectors, such

as healthcare and finance. Moreover, to ease the adoption of MPC, industrial and academic

MPC compilers have been developed to automatically translate

programs describing arbitrary MPC procedures into low-level MPC executables.
Compiling high-level descriptions into high-efficiency MPC executables is

challenging: the compilation often involves converting high-level languages into

several intermediate representations (IR), e.g., arithmetic or boolean circuits,

optimizing the computation/communication cost, and picking proper MPC protocols (and

underlying virtual machines) for a particular task and threat model. Various

optimizations and heuristics are employed during the compilation procedure to

improve the efficiency of the generated MPC executables.
Despite the prosperous adoption of MPC compilers by industrial vendors and

academia, a principled and systematic understanding of the correctness of

MPC compilers does not yet exist. To fill this critical gap, this paper

introduces MT-MPC, a metamorphic testing (MT) framework specifically designed for

MPC compilers to effectively uncover erroneous compilations. Our approach

proposes three metamorphic relations (MRs) that are tailored for MPC programs to

mutate high-level MPC programs (compiler inputs). We then examine if MPC

compilers yield semantics-equivalent MPC executables regarding the original and

mutated MPC programs by comparing their execution results.
Real-world MPC compilers exhibit a high level of engineering quality.

Nevertheless, we detected 4,772 inputs that can result in erroneous

compilations in three popular MPC compilers available on the market. While the

discovered error-triggering inputs do not cause the MPC compilers to crash

directly, they can lead to the generation of incorrect MPC executables,

jeopardizing the underlying dependability of the computation.

With substantial manual effort and help from the MPC compiler developers, we

uncovered thirteen bugs in these MPC compilers by debugging them using the

error-triggering inputs. Our proposed testing frameworks and findings can be

used to guide developers in their efforts to improve MPC compilers.
Improved Stability of Oxysulfide Solid-State Electrolytes in Li(G3)TFSI Solvate Ionic Liquid Electrolyte
Authors: Yersak Thomas A. , Zhang Yubin , Hafiz Hasnain , Pieczonka Nicholas P. W. , Gonzalez Malabet Hernando J. , Cunningham Hayden , Cai Mei 
Published: July 2024

The performance of all solid-state batteries is limited by poor interfacial contact between active material and solid-state electrolyte (SSE) particles. Semi-solid batteries utilize a secondary electrolyte phase to wet the SSE/AM interface to improve cell performance. Solvate ionic liquids (SILs) are one class of liquid electrolytes under consideration for use in semi-solid batteries. This paper focuses on the Li(G3)TFSI SIL consisting of the bis(trifluoromethanesulfonyl)imide (TFSI−) anion coupled to a [Li(G3)]+ solvate cation. Sulfide SSEs are normally subject to nucleophilic attack by trigylme (G3), however, strong coordination of Li+ to G3 in the [Li(G3)]+ solvate cation prevents this reaction from taking place. Consequently, the stability of sulfide SSE depends on the ideal 1:1 molar ratio of G3 to TFSI, which may be difficult to maintain. We studied the chemical stability of 70Li2S·(30-x)P2S5·xP2O5 (x = 0, 2, 5, 10) (oxy)sulfide solid-state electrolyte in Li(G3)TFSI SIL. By physical measurement, UV–vis spectroscopy, electrochemical evaluation, X-ray photoelectron spectroscopy, and first principles calculation it is shown that increased oxygen content improves the stability of SSE in various Li(G3)xTFSI (x = 1, 2, 3, 4) liquid electrolytes. The results suggest that an oxysulfide SSE + SIL semi-solid electrolyte is a good choice for future semi-solid battery designs.
HER2DX Genomic Assay in HER2-Positive Early Breast Cancer Treated with Trastuzumab and Pertuzumab: A Correlative Analysis from the PHERGain Phase II Trial
Authors: Llombart-Cussac Antonio , Pérez-García Jose , Brasó-Maristany Fara , Paré Laia , Villacampa Guillermo , Gion Maria , Schmid Peter , Colleoni Marco , Borrego Manuel R. , Galván Patricia , Parker Joel S. , Buckingham Wesley , Perou Charles M. , Villagrasa Patricia , Guerrero Jose A. , Sampayo-Cordero Miguel , Mancino Mario , Prat Aleix , Cortés Javier 
Published: July 2024

Abstract

Purpose:
The purpose of this study was to assess the predictive capability of HER2DX assay following (neo)adjuvant trastuzumab–pertuzumab (HP)–based therapy in HER2-positive (HER2+) early breast cancer.

Experimental Design:
HER2DX was analyzed in baseline pretreatment tumors from the PHERGain trial. Patients with stage I–IIIA HER2+ early breast cancer were randomized to group A [docetaxel, carboplatin, and HP (TCHP)] and group B (HP ± endocrine therapy). PET response was evaluated after two cycles. Group A received TCHP for six cycles regardless of PET response. Group B continued with HP ± endocrine therapy for six cycles (PET responders) or with TCHP for six cycles (PET nonresponders). The primary objective of this retrospective study was to associate the HER2DX pathologic complete response (pCR) score with pCR. The secondary objective was the association of the HER2DX risk score with 3-year invasive disease-free survival (iDFS).

Results:
HER2DX was performed on 292 (82.0%) tumors. The overall pCR rate was 38.0%, with pCR rates of 56.4% in group A and 33.8% in group B. In multivariable analysis including treatment and clinicopathologic factors, the HER2DX pCR score (continuous variable) significantly correlated with pCR [OR, 1.29; 95% confidence interval (CI), 1.10–1.54; P &lt; 0.001]. HER2DX-defined pCR-high, -med, and -low groups exhibited pCR rates of 50.4%, 35.8%, and 23.2%, respectively (pCR-high vs. pCR-low OR, 3.27; 95% CI, 1.54–7.09; P &lt; 0.001). In patients with residual disease, the HER2DX high-risk group demonstrated numerically worse 3-year iDFS than the low-risk group (89.8% vs. 100%; HR, 2.70; 95% CI, 0.60–12.18; P = 0.197).

Conclusions:
HER2DX predicts pCR in the context of neoadjuvant HP-based therapy, regardless of chemotherapy addition, and might identify patients at higher risk of recurrence among patients with residual disease.
Spatial Landscape of Malignant Pleural and Peritoneal Mesothelioma Tumor Immune Microenvironments
Authors: Ma Xiaojun , Lembersky David , Kim Elena S. , Becich Michael J. , Testa Joseph R. , Bruno Tullia C. , Osmanbeyoglu Hatice U. 
Published: July 2024

Abstract

Immunotherapies have demonstrated limited clinical efficacy in malignant mesothelioma treatment. We conducted multiplex immunofluorescence analyses on tissue microarrays (n = 3) from patients with malignant pleural mesothelioma (MPM, n = 88) and malignant peritoneal mesothelioma (MPeM, n = 25). Our study aimed to elucidate spatial distributions of key immune cell populations and their association with lymphocyte activation gene 3 (LAG3), BRCA1-associated protein 1 (BAP1), neurofibromatosis type 2 (NF2), and methylthioadenosine phosphorylase (MTAP), with MTAP serving as a cyclin-dependent kinase inhibitor 2A/2B (CDKN2A/B) surrogate marker. Additionally, we examined the relationship between the spatial distribution of major immune cell types and prognosis and clinical characteristics of patients with malignant mesothelioma. We observed a higher degree of interaction between immune cells and tumor cells in MPM compared with MPeM. Notably, within MPM tumors, we detected a significantly increased interaction between tumor cells and CD8+ T cells in tumors with low BAP1 expression compared with those with high BAP1 expression. To support the broader research community, we have developed The Human Spatial Atlas of Malignant Mesothelioma, containing hematoxylin and eosin and multiplex immunofluorescence images with corresponding metadata.

Significance:
Considering the limited therapeutic options available to patients with malignant mesothelioma, there is substantial translational potential in understanding the correlation between the spatial architecture of the malignant mesothelioma tumor immune microenvironment and tumor biology. Our investigation reveals critical cell–cell interactions that may influence the immune response against malignant mesothelioma tumors, potentially contributing to the differential behaviors observed in MPM and MPeM. These findings represent a valuable resource for the malignant mesothelioma cancer research community.
p300 KAT Regulates SOX10 Stability and Function in Human Melanoma
Authors: Waddell Aaron , Grbic Nicole , Leibowitz Kassidy , Wyant William Austin , Choudhury Sabah , Park Kihyun , Collard Marianne , Cole Philip A. , Alani Rhoda M. 
Published: July 2024

Abstract

SOX10 is a lineage-specific transcription factor critical for melanoma tumor growth; on the other hand, SOX10 loss-of-function drives the emergence of therapy-resistant, invasive melanoma phenotypes. A major challenge has been developing therapeutic strategies targeting SOX10’s role in melanoma proliferation while preventing a concomitant increase in tumor cell invasion. In this study, we report that the lysine acetyltransferase (KAT) EP300 and SOX10 gene loci on chromosome 22 are frequently co-amplified in melanomas, including UV-associated and acral tumors. We further show that p300 KAT activity mediates SOX10 protein stability and that the p300 inhibitor A-485 downregulates SOX10 protein levels in melanoma cells via proteasome-mediated degradation. Additionally, A-485 potently inhibits proliferation of SOX10+ melanoma cells while decreasing invasion in AXLhigh/MITFlow melanoma cells through downregulation of metastasis-related genes. We conclude that the SOX10/p300 axis is critical to melanoma growth and invasion and that inhibition of p300 KAT activity through A-485 may be a worthwhile therapeutic approach for SOX10-reliant tumors.

Significance:
The p300 KAT inhibitor A-485 blocks SOX10-dependent proliferation and SOX10-independent invasion in hard-to-treat melanoma cells.
Composite Pulmonary Embolism Shock Score and Risk of Adverse Outcomes in Patients With Pulmonary Embolism
Authors: Zhang Robert S. , Yuriditsky Eugene , Zhang Peter , Maqsood Muhammad H. , Amoroso Nancy E. , Maldonado Thomas S. , Xia Yuhe , Horowitz James M. , Bangalore Sripal 
Published: July 2024

BACKGROUND:
In hemodynamically stable patients with acute pulmonary embolism (PE), the Composite Pulmonary Embolism Shock (CPES) score predicts normotensive shock. However, it is unknown if CPES predicts adverse clinical outcomes. The objective of this study was to determine whether the CPES score predicts in-hospital mortality, resuscitated cardiac arrest, or hemodynamic deterioration.

METHODS:
Patients with acute intermediate-risk PE admitted from October 2016 to July 2019 were included. CPES was calculated for each patient. The primary outcome was a composite of in-hospital mortality, resuscitated cardiac arrest, or hemodynamic decompensation. Secondary outcomes included individual components of the primary outcome. The association of CPES with primary and secondary outcomes was evaluated.

RESULTS:

Among the 207 patients with intermediate-risk PE (64.7% with intermediate-high risk PE), 29 (14%) patients had a primary outcome event. In a multivariable model, a higher CPES score was associated with a worse primary composite outcome (adjusted hazard ratio [aHR], 1.81 [95% CI, 1.29–2.54];
P
=0.001). Moreover, a higher CPES score predicted death (aHR, 1.76 [95% CI, 1.04–2.96];
P
=0.033), resuscitated cardiac arrest (aHR, 1.99 [95% CI, 1.17–3.38];
P
=0.011), and hemodynamic decompensation (aHR, 1.96 [95% CI, 1.34–2.89];
P
=0.001). A high CPES score (≥3) was associated with the worse primary outcome when compared with patients with a low CPES score (22% versus 2.4%;
P
=0.003; aHR, 6.48 [95% CI, 1.49–28.04];
P
=0.012). CPES score provided incremental prognostic value for the prediction of primary outcome over baseline demographics and European Society of Cardiology intermediate-risk subcategories (global Χ
2
value increased from 0.63 to 1.39 to 13.69;
P
=0.005)

CONCLUSIONS:
In patients with acute intermediate-risk PE, the CPES score effectively risk stratifies and prognosticates patients for the prediction of clinical events and provides incremental value over baseline demographics and European Society of Cardiology intermediate-risk subcategories.
Alone Together, Together Alone: The Effects of Social Context on Nonverbal Behavior in Virtual Reality
Authors: Han Eugy , DeVeaux Cyan , Miller Mark Roman , Harari Gabriella M. , Hancock Jeffrey T. , Ram Nilam , Bailenson Jeremy N. 
Published: July 2024

Abstract
Social virtual reality (VR), by definition, focuses on people using networked VR systems to bring avatars together. Previous studies have examined how different factors affect social interaction, in small groups such as dyads or triads. However, in a typical social VR scene there tends to be dozens of avatars, even those not directly interacting with a given user. Furthermore, beyond the virtual environment, VR users are also situated in various immediate physical social contexts. In two field experiments, we investigate how the presence of virtual and physical people contextualize and influence nonverbal behaviors. Study 1 examines virtual context and asks how interacting with others in a private or public virtual environment influences nonverbal outcomes during interactions in a social VR platform. Across two sessions, participants (n = 104) met either in a private virtual environment with their group members alone or in a public environment surrounded by four other groups. Results showed that participants moved their avatars slower and stood closer to group members in public versus private environments. Study 2 examines physical context and asks how interacting with virtual others while physically together or alone influences nonverbal behaviors. Participants (n = 61) met in virtual environments while they were in either a shared physical environment or separated physical environments. Results showed that, compared to remote participants, participants who were physically together moved their bodies more slowly, but their avatars faster. Moreover, there was more mutual gaze among remote participants. We discuss implications to theories of social influence in VR.
Risk prediction for clonal cytopenia: multicenter real-world evidence
Authors: Xie Zhuoer , Komrokji Rami , Al Ali Najla , Regelson Alexandra , Geyer Susan , Patel Anand , Saygin Caner , Zeidan Amer M. , Bewersdorf Jan Philipp , Mendez Lourdes , Kishtagari Ashwin , Zeidner Joshua F. , Coombs Catherine C. , Madanat Yazan F. , Chung Stephen , Badar Talha , Foran James , Desai Pinkal , Tsai Charlton , Griffiths Elizabeth A. , Al Malki Monzr M. , Amanam Idoroenyi , Lai Catherine , Deeg H. Joachim , Ades Lionel , Arana Yi Cecilia , Osman Afaf E. G. , Dinner Shira , Abaza Yasmin , Taylor Justin , Chandhok Namrata , Soong Deborah , Brunner Andrew M. , Carraway Hetty E. , Singh Abhay , Elena Chiara , Ferrari Jacqueline , Gallì Anna , Pozzi Sara , Padron Eric , Patnaik Mrinal M. , Malcovati Luca , Savona Michael R. , Al-Kali Aref 
Published: July 2024

Abstract
Clonal cytopenia of undetermined significance (CCUS) represents a distinct disease entity characterized by myeloid-related somatic mutations with a variant allele fraction of ≥2% in individuals with unexplained cytopenia(s) but without a myeloid neoplasm (MN). Notably, CCUS carries a risk of progressing to MN, particularly in cases featuring high-risk mutations. Understanding CCUS requires dedicated studies to elucidate its risk factors and natural history. Our analysis of 357 patients with CCUS investigated the interplay between clonality, cytopenia, and prognosis. Multivariate analysis identified 3 key adverse prognostic factors: the presence of splicing mutation(s) (score = 2 points), platelet count of &lt;100 × 109/L (score = 2.5), and ≥2 mutations (score = 3). Variable scores were based on the coefficients from the Cox proportional hazards model. This led to the development of the clonal cytopenia risk score (CCRS), which stratified patients into low- (score of &lt;2.5 points), intermediate- (score of 2.5 to &lt;5), and high-risk (score of ≥5) groups. The CCRS effectively predicted 2-year cumulative incidence of MN for low- (6.4%), intermediate- (14.1%), and high-risk (37.2%) groups, respectively, by the Gray test (P &lt; .0001). We further validated the CCRS by applying it to an independent CCUS cohort of 104 patients, demonstrating a c-index of 0.64 (P = .005) in stratifying the cumulative incidence of MN. Our study underscores the importance of integrating clinical and molecular data to assess the risk of CCUS progression, making the CCRS a valuable tool that is practical and easily calculable. These findings are clinically relevant, shaping the management strategies for CCUS and informing future clinical trial designs.
RNA editing regulates glutamatergic synapses in the frontal cortex of a molecular subtype of Amyotrophic Lateral Sclerosis
Authors: Karagianni Korina , Dafou Dimitra , Xanthopoulos Konstantinos , Sklaviadis Theodoros , Kanata Eirini 
Published: July 2024

Abstract
Background
Amyotrophic Lateral Sclerosis (ALS) is a highly heterogenous neurodegenerative disorder that primarily affects upper and lower motor neurons, affecting additional cell types and brain regions. Underlying molecular mechanisms are still elusive, in part due to disease heterogeneity. Molecular disease subtyping through integrative analyses including RNA editing profiling is a novel approach for identification of molecular networks involved in pathogenesis.

Methods
We aimed to highlight the role of RNA editing in ALS, focusing on the frontal cortex and the prevalent molecular disease subtype (ALS-Ox), previously determined by transcriptomic profile stratification. We established global RNA editing (editome) and gene expression (transcriptome) profiles in control and ALS-Ox cases, utilizing publicly available RNA-seq data (GSE153960) and an in-house analysis pipeline. Functional annotation and pathway analyses identified molecular processes affected by RNA editing alterations. Pearson correlation analyses assessed RNA editing effects on expression. Similar analyses on additional ALS-Ox and control samples (GSE124439) were performed for verification. Targeted re-sequencing and qRT-PCR analysis targeting CACNA1C, were performed using frontal cortex tissue from ALS and control samples (n = 3 samples/group).

Results
We identified reduced global RNA editing in the frontal cortex of ALS-Ox cases. Differentially edited transcripts are enriched in synapses, particularly in the glutamatergic synapse pathway. Bioinformatic analyses on additional ALS-Ox and control RNA-seq data verified these findings. We identified increased recoding at the Q621R site in the GRIK2 transcript and determined positive correlations between RNA editing and gene expression alterations in ionotropic receptor subunits GRIA2, GRIA3 and the CACNA1C transcript, which encodes the pore forming subunit of a post-synaptic L-type calcium channel. Experimental data verified RNA editing alterations and editing-expression correlation in CACNA1C, highlighting CACNA1C as a target for further study.

Conclusions
We provide evidence on the involvement of RNA editing in the frontal cortex of an ALS molecular subtype, highlighting a modulatory role mediated though recoding and gene expression regulation on glutamatergic synapse related transcripts. We report RNA editing effects in disease-related transcripts and validated editing alterations in CACNA1C. Our study provides targets for further functional studies that could shed light in underlying disease mechanisms enabling novel therapeutic approaches.