bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ethylbenzene oxidation by a hybrid catalysis system of reconstituted myoglobin and silica-protected PdAu nanoparticles under a hydrogen-oxygen mixed atmosphere
Authors: Oohora Koji , Kagawa Yoshiyuki , Kuwahara Yasutaka , Yamashita Hiromi , Hayashi Takashi 
Published: May 2023

C–H bond oxidation using molecular oxygen as a terminal oxidant is an important reaction in molecular conversions. This reaction is achieved by several enzymes such as cytochrome P450s in biological systems, whereas artificial catalytic systems for this reaction are limited. In this work, the oxidation of ethylbenzene was promoted by a hybrid catalysis system consisting of myoglobin reconstituted with manganese porphycene as an artificial peroxygenase in combination with PdAu nanoparticles encapsulated in hollow mesoporous silica spheres as a solid catalyst to produce hydrogen peroxide, respectively. Neither catalyst alone provides hydroxylated products. Favorable conditions for hydrogen peroxide generation and subsequent C–H bond hydroxylation are different from each other and require optimization of pH and salt concentration. The optimized conditions are found to be 0.5 atm of H2 and 0.5 atm of O2 at pH 8.5 in the presence of 10 mM NaCl. The total optimized turnover number of the hybrid catalysis system for ethyl benzene hydroxylation is 3.6, which is consistent with 97% of the turnover number value of the same reaction catalyzed by reconstituted myoglobin using 0.5 mM hydrogen peroxide under the hydrogen-oxygen mixed atmosphere. This finding indicates that the hybrid catalyst system operates without any negative effects for both catalytic reactions.
CellMinerCDB: NCATS Is a Web-Based Portal Integrating Public Cancer Cell Line Databases for Pharmacogenomic Explorations
Authors: Reinhold William C. , Wilson Kelli , Elloumi Fathi , Bradwell Katie R. , Ceribelli Michele , Varma Sudhir , Wang Yanghsin , Duveau Damien , Menon Nikhil , Trepel Jane , Zhang Xiaohu , Klumpp-Thomas Carleen , Micheal Samuel , Shinn Paul , Luna Augustin , Thomas Craig , Pommier Yves 
Published: May 2023

Abstract

Major advances have been made in the field of precision medicine for treating cancer. However, many open questions remain that need to be answered to realize the goal of matching every patient with cancer to the most efficacious therapy. To facilitate these efforts, we have developed CellMinerCDB: National Center for Advancing Translational Sciences (NCATS; https://discover.nci.nih.gov/rsconnect/cellminercdb_ncats/), which makes available activity information for 2,675 drugs and compounds, including multiple nononcology drugs and 1,866 drugs and compounds unique to the NCATS. CellMinerCDB: NCATS comprises 183 cancer cell lines, with 72 unique to NCATS, including some from previously understudied tissues of origin. Multiple forms of data from different institutes are integrated, including single and combination drug activity, DNA copy number, methylation and mutation, transcriptome, protein levels, histone acetylation and methylation, metabolites, CRISPR, and miscellaneous signatures. Curation of cell lines and drug names enables cross-database (CDB) analyses. Comparison of the datasets is made possible by the overlap between cell lines and drugs across databases. Multiple univariate and multivariate analysis tools are built-in, including linear regression and LASSO. Examples have been presented here for the clinical topoisomerase I (TOP1) inhibitors topotecan and irinotecan/SN-38. This web application provides both substantial new data and significant pharmacogenomic integration, allowing exploration of interrelationships.

Significance:
CellMinerCDB: NCATS provides activity information for 2,675 drugs in 183 cancer cell lines and analysis tools to facilitate pharmacogenomic research and to identify determinants of response.
TIGIT Expression Delineates T-cell Populations with Distinct Functional and Prognostic Impact in Pancreatic Cancer
Authors: Heiduk Max , Klimova Anna , Reiche Charlotte , Digomann David , Beer Carolin , Aust Daniela E. , Distler Marius , Weitz Jürgen , Seifert Adrian M. , Seifert Lena 
Published: May 2023

Abstract

Purpose:
Immunotherapy has led to a fundamental shift in the treatment of several cancers. However, its efficacy in pancreatic ductal adenocarcinoma (PDAC) is limited. Understanding the expression of inhibitory immune checkpoint receptors (ICR) by intratumoral T cells may help to unravel their involvement in insufficient T-cell–mediated antitumor immunity.

Experimental Design:
Using multicolor flow cytometry, we analyzed circulating and intratumoral T cells from blood (n = 144) and matched tumor samples (n = 107) of patients with PDAC. We determined the expression of programmed cell death protein 1 (PD-1) and T-cell immunoreceptor with Ig and immunoreceptor tyrosine-based inhibition motif (ITIM) domains (TIGIT) by CD8+ T-cells, conventional CD4+ T-cells (Tconv) and regulatory T cells (Treg) and their association with T-cell differentiation, tumor reactivity, and cytokine expression. A comprehensive follow-up was used to determine their prognostic value.

Results:
Intratumoral T cells were characterized by increased PD-1 and TIGIT expression. Both markers delineated distinct T-cell subpopulations. PD-1+TIGIT− T cells highly expressed proinflammatory cytokines and markers of tumor reactivity (CD39, CD103), whereas TIGIT expression was linked to antiinflammatory and exhausted phenotypes. In addition, the enhanced presence of intratumoral PD-1+TIGIT− Tconv was associated with improved clinical outcomes, while high ICR expression on blood T cells was a significant hazard for overall survival (OS).

Conclusions:
Our results uncover the association between ICR expression and T-cell functionality. PD-1 and TIGIT characterized intratumoral T cells with highly divergent phenotypes linked to clinical outcomes, further underscoring the relevance of TIGIT for immunotherapeutic approaches in PDAC. The prognostic value of ICR expression in patient blood may be a valuable tool for patient stratification.
Discovery of a Small-Molecule Inhibitor Targeting the Androgen Receptor N-Terminal Domain for Castration-Resistant Prostate Cancer
Authors: Yi Qianhui , Liu Weiguo , Seo Jung Hwa , Su Jie , Alaoui-Jamali Moulay A. , Luo Jun , Lin Rongtuan , Wu Jian Hui 
Published: May 2023

Abstract
The current mainstay therapeutic strategy for advanced prostate cancer is to suppress androgen receptor (AR) signaling. However, castration-resistant prostate cancer (CRPC) invariably arises with restored AR signaling activity. To date, the AR ligand-binding domain (LBD) is the only targeted region for all clinically available AR signaling antagonists, such as enzalutamide (ENZ). Major resistance mechanisms have been uncovered to sustain the AR signaling in CRPC despite these treatments, including AR amplification, AR LBD mutants, and the emergence of AR splice variants (AR-Vs) such as AR-V7. AR-V7 is a constitutively active truncated form of AR that lacks the LBD; thus, it can not be inhibited by AR LBD-targeting drugs. Therefore, an approach to inhibit AR through the regions outside of LBD is urgently needed. In this study, we have discovered a novel small molecule SC428, which directly binds to the AR N-terminal domain (NTD) and exhibits pan-AR inhibitory effect. SC428 potently decreased the transactivation of AR-V7, ARv567es, as well as full-length AR (AR-FL) and its LBD mutants. SC428 substantially suppressed androgen-stimulated AR-FL nuclear translocation, chromatin binding, and AR-regulated gene transcription. Moreover, SC428 also significantly attenuated AR-V7–mediated AR signaling that does not rely on androgen, hampered AR-V7 nuclear localization, and disrupted AR-V7 homodimerization. SC428 inhibited in vitro proliferation and in vivo tumor growth of cells that expressed a high level of AR-V7 and were unresponsive to ENZ treatment. Together, these results indicated the potential therapeutic benefits of AR-NTD targeting for overcoming drug resistance in CRPC.
Weighing Antitumor Immunity against Life-threatening Myocarditis from Immune-Checkpoint Inhibitors
Authors: Dougan Michael 
Published: May 2023

Summary:In this issue of Cancer Discovery, Salem and colleagues report a combination therapy for immune-checkpoint inhibitor (ICI) myocarditis using high-dose glucocorticoids, abatacept, and the JAK inhibitor ruxolitinib. The apparent efficacy of their strategy and an accompanying animal model provide further evidence for common immune mechanisms underlying ICI toxicities.See related article by Salem et al., p. 1100 (2).
Prevalence and Procedural Risk of Intracranial Atherosclerotic Stenosis Coexisting With Unruptured Intracranial Aneurysm
Authors: Yin Zihan , Zhang Qihang , Zhao Yahui , Lu Junlin , Ge Peicong , Xie Hutao , Wu Delong , Yu Shaochen , Kang Shuai , Zhang Qian , Zhang Yan , Zhang Dong , Zhao Jizong , Liu Xingju 
Published: May 2023

Background:
Coexistence of intracranial atherosclerotic stenosis (ICAS) and unruptured intracranial aneurysms (UIAs) is increasingly encountered in clinical practice. This study aims to determine the prevalence of ICAS in patients with UIAs and procedural ischemic risk associated with ICAS when treating UIAs.

Methods:
Based on the CAIASA study (Coexistence of Atherosclerotic Intracranial Arterial Stenosis With Intracranial Aneurysms), we prospectively included patients undergoing treatment procedures for UIAs from October 2015 to December 2020 at Beijing Tiantan Hospital, China. We used computed tomography angiography or digital subtraction angiography to diagnose ICAS (stenosis≥50%). Multivariable logistic regression and propensity-score matching were performed to evaluate the risk of procedure-related ischemic stroke and unfavorable outcome associated with ICAS. The ICAS score was used to explore the association between different burden of ICAS and procedure-related ischemic risk.

Results:

Among 3949 patients who underwent endovascular or open surgical procedures for UIAs, 245 (6.2%) had ICAS. After exclusion, 15.7% (32/204) of patients with ICAS experienced procedure-related ischemic stroke compared with 5.0% (141/2825) of patients without ICAS. From the unmatched and matched cohort, ICAS was significantly associated with increased risk of procedure-related ischemic stroke (unmatched: adjusted odds ratio=3.11 [1.89–5.11]; and matched: adjusted odds ratio=2.99 [1.38–6.48]). This association became more evident among patients not receiving antiplatelet therapy (
P
interaction
=0.022). For patients undergoing different treatment modalities, similar increased risks were observed (clipping: adjusted odds ratio=3.43 [1.73–6.79]; and coiling: adjusted odds ratio=3.59 [1.94–6.65]). Higher ICAS score was correlated with higher procedural ischemic risk (
P
trend
<0.001).

Conclusions:
The occurrence of ICAS is not infrequent in patients with UIAs. ICAS confers an ~2-fold increased procedural ischemic risk, irrespective of clipping or coiling. Previous antiplatelet therapy may decrease the risk.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02795078.
Dimensions of Explanatory Value in NLP Models
Authors: Deemter Kees van 
Published: May 2023

AbstractPerformance on a dataset is often regarded as the key criterion for assessing NLP models. I argue for a broader perspective, which emphasizes scientific explanation. I draw on a long tradition in the philosophy of science, and on the Bayesian approach to assessing scientific theories, to argue for a plurality of criteria for assessing NLP models. To illustrate these ideas, I compare some recent models of language production with each other. I conclude by asking what it would mean for institutional policies if the NLP community took these ideas onboard.
The morphosyntax of imperative agreement in Amharic
Authors: Kramer Ruth 
Published: May 2023

Abstract
Discontinuous agreement has been the focus of considerable research, especially within the Afroasiatic language family. However, most previous work has focused on how discontinuous agreement is generated and has relied on data from verbs with relatively basic tense, aspect and mood. In this paper, I investigate a different kind of discontinuous agreement puzzle in an atypical kind of verb, namely, why and how the agreement prefix (but not the agreement suffix) is lacking from imperative verbs in Amharic. I argue that the agreement prefix undergoes morphological haplology because it repeats the second person features found in the imperative head. I then demonstrate how a haplology approach decides between two different analyses of discontinuous agreement: it furnishes evidence against a Linearization analysis (Harbour 2008a, 2016, this issue) and in favor of a Metathesis analysis (Hewett 2022, this issue). Overall, this paper develops a novel approach to imperative inflection, supports a Metathesis approach to discontinuous agreement, and advances our understanding of morphological haplology.
Discontinuous agreement
Authors: Harbour Daniel 
Published: May 2023

Abstract
Nine characteristics of discontinuous agreement are shown to flow from a syntax that deals in whole phi structures and a linearisation algorithm that renders these discontinuous when conditions converge. This approach is demonstrably superior to reliance solely on syntax, morphology, or the lexicon, outperforming these across a range morphological and syntactic data from Afroasiatic languages and those of Australia and Papua New Guinea.
Critique and Catharsis: Jain-Vaiṣṇava Polemics in Early Modern Karnataka
Authors: Peterson Jonathan 
Published: May 2023

Abstract
The popularization of Madhva’s realist Vedānta was accompanied by forceful critiques of its alleged enemies. Although the movement’s challenges to other Vedāntas has been well studied, its sustained engagement with Jainism has not. The anti-Jain writings of Madhva’s followers offer an important but neglected perspective on the early history of Mādhva Vedānta and its rise to power. This article examines the anti-Jain polemics of an influential intellectual named Vādirāja Tīrtha (c. 1520–1600). By situating Vādirāja and his writings in the vibrant and volatile world of post-Vijayanagara coastal Karnataka, this paper treats the archive of anti-Jain polemics not as a record of timeless doctrinal disagreement, but as a repository of local struggles over patronage, livelihood, and influence. Reading interreligious disputes with an eye to local context allows me to make a larger point about polemics and community formation. Work on polemics has tended to focus on ideas of verbal warfare and destructive debate; this paper suggests, however, that acts of polemical othering in early modern South Asia were productive forms of boundary keeping and community formation. This paper argues that Vādirāja constructed and ridiculed the Jain other as a way to galvanize a coterie of beleaguered Brahmans in a moment of duress. Vādirāja’s anti-Jain writings, in other words, were condemnation as catharsis and community-building.
The European Court of Human Rights and its Search for Common Values
Authors: Lewis Carl Emilio 
Published: May 2023

Abstract
Values play a significant role in the jurisprudence of the European Court of Human Rights (Court), and carry the potential to influence the Court’s interpretation of the European Convention on Human Rights (Convention). This is particularly evident when the Court refers to common values whilst engaging in European consensus analysis. By exploring sociological approaches to the concept of values and Gilbert’s summative and plural subject accounts of shared values, this article argues that it is reasonable for the Court to search for common values amongst the member states of the Convention, in an effort to align its interpretation of Convention rights with such values. However, the article contends that when the Court ascribes normative authority to shared values identified purely through a comparative analysis of state practice, it is confounding the summative and plural subject accounts of common values in its reasoning, thus raising legitimacy concerns.
Analyzing How the Philippine Government Shapes Gender Norms through Migration: The Case of an Institutionalized Award System
Authors: Llige Aurora S. 
Published: May 2023

Abstract
This study analyzes how the Philippine government shapes gender norms through the awardees of an institutionalized award system called the “Presidential Awards for Filipino Individuals and Organizations Overseas” (PAFIOO). Publicly available biennial books of awardees that span 30 years (1991–2021) were obtained from the Commission on Filipinos Overseas archives, and the narrative data of the 342 awardees were thematically analyzed. This study argues that the state reinforces gender norms within migration and development through two identity frames bestowed on the winners of PAFIOO. First, the hero/heroine identity emphasizes the traditional views of gender roles, where women awardees, regardless of their civil status, are framed as sacrificing mother figures. Second, the commodity identity highlights men awardees and their masculine-related fields. Consequently, their contribution to development reflected this. Further, the PAFIOO selection is imbalanced, consistently awarding more men than women in the past three decades.
The impacts of total body irradiation on umbilical cord blood hematopoietic stem cell transplantation
Authors: Wang Hao , Berger Kristin N. , Miller Elizabeth L. , Fu Wei , Broglie Larisa , Goldman Frederick D. , Konig Heiko , Lim Su Jin , Berg Arthur S. , Talano Julie-An , Comito Melanie A. , Farag Sherif S. , Pu Jeffrey J. 
Published: May 2023

Background: Umbilical cord blood hematopoietic stem cells are commonly used for hematopoietic system reconstitution in recipients after umbilical cord blood transplantation (UCBT). However, the optimal conditioning regimen for UCBT remains a topic of debate. The exact impact of total body irradiation (TBI) as a part of conditioning regimens remains unknown. Objectives: The aim of this study was to evaluate the impacts of TBI on UCBT outcomes. Design: This was a multi-institution retrospective study. Methods: A retrospective analysis was conducted on the outcomes of 136 patients receiving UCBT. Sixty-nine patients received myeloablative conditioning (MAC), in which 33 underwent TBI and 36 did not, and 67 patients received reduced-intensity conditioning (RIC), in which 43 underwent TBI and 24 did not. Univariate and multivariate analyses were conducted to compare the outcomes and the post-transplant complications between patients who did and did not undergo TBI in the MAC subgroup and RIC subgroup, respectively. Results: In the RIC subgroup, patients who underwent TBI had superior overall survival (adjusted hazard ratio [aHR] = 0.25, 95% confidence interval [CI]: 0.09–0.66, p = 0.005) and progression-free survival (aHR = 0.26, 95% CI: 0.10–0.66, p = 0.005). However, in the MAC subgroup, there were no statistically significant differences between those receiving and not receiving TBI. Conclusion: In the setting of RIC in UCBT, TBI utilization can improve overall survival and progression-free survival. However, TBI does not show superiority in the MAC setting.
Estimating the Cost of 3 Risk Prediction Strategies for Potential Use in the United Kingdom National Breast Screening Program
Authors: Wright Stuart J. , Eden Martin , Ruane Helen , Byers Helen , Evans D. Gareth , Harvie Michelle , Howell Sacha J. , Howell Anthony , French David , Payne Katherine 
Published: May 2023

Background Economic evaluations have suggested that risk-stratified breast cancer screening may be cost-effective but have used assumptions to estimate the cost of risk prediction. The aim of this study was to identify and quantify the resource use and associated costs required to introduce a breast cancer risk-stratification approach into the English national breast screening program. Methods A micro-costing study, conducted alongside a cohort-based prospective trial (BC-PREDICT), identified the resource use and cost per individual (£; 2021 price year) of providing a risk-stratification strategy at a woman’s first mammography. Costs were calculated for 3 risk-stratification approaches: Tyrer-Cuzick survey, Tyrer-Cuzick with Volpara breast-density measurement, and Tyrer-Cuzick with Volpara breast-density measurement and testing for 142 single nucleotide polymorphisms (SNP). Costs were determined for the intervention as implemented in the trial and in the health service. Results The cost of providing the risk-stratification strategy was calculated to be £16.45 for the Tyrer-Cuzick survey approach, £21.82 for the Tyrer-Cuzick with Volpara breast-density measurement, and £102.22 for the Tyrer-Cuzick with Volpara breast-density measurement and SNP testing. Limitations This study did not use formal expert elicitation methods to synthesize estimates. Conclusion The costs of risk prediction using a survey and breast density measurement were low, but adding SNP testing substantially increases costs. Implementation issues present in the trial may also significantly increase the cost of risk prediction. Implications This is the first study to robustly estimate the cost of risk-stratification for breast cancer screening. The cost of risk prediction using questionnaires and automated breast density measurement was low, but full economic evaluations including accurate costs are required to provide evidence of the cost-effectiveness of risk-stratified breast cancer screening. Highlights Economic evaluations have suggested that risk-stratified breast cancer screening may be a cost-effective use of resources in the United Kingdom. Current estimates of the cost of risk stratification are based on pragmatic assumptions. This study provides estimates of the cost of risk stratification using 3 strategies and when these strategies are implemented perfectly and imperfectly in the health system. The cost of risk stratification is relatively low unless single nucleotide polymorphisms are included in the strategy.
AttSec: protein secondary structure prediction by capturing local patterns from attention map
Authors: Kim Youjin , Kwon Junseok 
Published: May 2023

Abstract
Background
Protein secondary structures that link simple 1D sequences to complex 3D structures can be used as good features for describing the local properties of protein, but also can serve as key features for predicting the complex 3D structures of protein. Thus, it is very important to accurately predict the secondary structure of the protein, which contains a local structural property assigned by the pattern of hydrogen bonds formed between amino acids. In this study, we accurately predict protein secondary structure by capturing the local patterns of protein. For this objective, we present a novel prediction model, AttSec, based on transformer architecture. In particular, AttSec extracts self-attention maps corresponding to pairwise features between amino acid embeddings and passes them through 2D convolution blocks to capture local patterns. In addition, instead of using additional evolutionary information, it uses protein embedding as an input, which is generated by a language model.

Results
For the ProteinNet DSSP8 dataset, our model showed 11.8% better performance on the entire evaluation datasets compared with other no-evolutionary-information-based models. For the NetSurfP-2.0 DSSP8 dataset, it showed 1.2% better performance on average. There was an average performance improvement of 9.0% for the ProteinNet DSSP3 dataset and an average of 0.7% for the NetSurfP-2.0 DSSP3 dataset.

Conclusion
We accurately predict protein secondary structure by capturing the local patterns of protein. For this objective, we present a novel prediction model, AttSec, based on transformer architecture. Although there was no dramatic accuracy improvement compared with other models, the improvement on DSSP8 was greater than that on DSSP3. This result implies that using our proposed pairwise feature could have a remarkable effect for several challenging tasks that require finely subdivided classification. Github package URL is https://github.com/youjin-DDAI/AttSec.