bluuebunny/crossref_metadata_2025_split huggingface dataset:
Value of GPR, APPRI and FIB-4 in the early diagnosis of hepatocellular carcinoma: a prospective cohort study
Authors: Zhang Lizhen , Li Siyu , Zhang Desheng , Yin Chun , Wang Zhongge , Chen Ruirui , Cheng Ning , Bai Yana 
Published: October 2023

Abstract

Objective
There is an urgent need for novel biomarkers that are inexpensive, effective and easily accessible to complement the early diagnosis of hepatocellular carcinoma. This study aimed to analyze the relationship between serum gamma-glutamate-transpeptidase to platelet ratio, alkaline phosphatase-to-platelet ratio index, fibrosis index based on four factors and the risk of hepatocellular carcinoma, and to determine the optimal cut-offs for predicting hepatocellular carcinoma.

Methods
Based on a prospective cohort study, 44 215 participants who were cancer-free at baseline (2011–13) were included in the study. Cox proportional hazard models and receiver operating characteristics curves were used to analyze the diagnostic value and optimal cut-off value of gamma-glutamyl-transpeptidase to platelet ratio, alkaline phosphatase-to-platelet ratio index and fibrosis index based on four factors in predicting hepatocellular carcinoma patients.

Results
Gamma-glutamyl-transpeptidase to platelet ratio, alkaline phosphatase-to-platelet ratio index and fibrosis index based on four factors can be used as early independent predictors of hepatocellular carcinoma risk. The risk of hepatocellular carcinoma in the fourth quantile of gamma-glutamyl-transpeptidase to platelet ratio and alkaline phosphatase-to-platelet ratio index was 4.04 times (hazard ratio = 4.04, 95% confidence interval: 2.09, 7.80) and 2.59 times (hazard ratio = 2.59, 95% confidence interval: 1.45, 4.61), respectively, compared with the first quantile. With fibrosis index based on four factors first quantile as a reference, fibrosis index based on four factors fourth quantile had the highest risk (hazard ratio = 18.58, 95% confidence interval: 7.55, 45.72). Receiver operating characteristic results showed that fibrosis index based on four factors had a stronger ability to predict the risk of hepatocellular carcinoma (area under curve = 0.81, 95% confidence interval: 0.80, 0.81), and similar results were shown for gender stratification. In the total population, the optimal cut-off values of gamma-glutamyl-transpeptidase to platelet ratio, alkaline phosphatase-to-platelet ratio index and fibrosis index based on four factors were 0.208, 0.629 and 1.942, respectively.

Conclusions
Gamma-glutamyl-transpeptidase to platelet ratio, alkaline phosphatase-to-platelet ratio index and fibrosis index based on four factors were independent predictors of hepatocellular carcinoma risk. Amongst them, fibrosis index based on four factors shows a stronger predictive ability for hepatocellular carcinoma risk, and gamma-glutamyl-transpeptidase to platelet ratio and alkaline phosphatase-to-platelet ratio index can be used as complementary indicators.
A quantitative model for spatio-temporal dynamics of root gravitropism
Authors: Porat Amir , Rivière Mathieu , Meroz Yasmine 
Published: October 2023

Abstract
Plant organs adapt their morphology according to environmental signals through growth-driven processes called tropisms. While much effort has been directed towards the development of mathematical models describing the tropic dynamics of aerial organs, these cannot provide a good description of roots due to intrinsic physiological differences. Here we present a mathematical model informed by gravitropic experiments on Arabidopsis thaliana roots, assuming a subapical growth profile and apical sensing. The model quantitatively recovers the full spatio-temporal dynamics observed in experiments. An analytical solution of the model enables us to evaluate the gravitropic and proprioceptive sensitivities of roots, while also allowing us to corroborate the requirement for proprioception in describing root dynamics. Lastly, we find that the dynamics are analogous to a damped harmonic oscillator, providing intuition regarding the source of the observed oscillatory behavior and the importance of proprioception for efficient gravitropic control. In all, the model provides not only a quantitative description of root tropic dynamics, but also a mathematical framework for the future investigation of roots in complex media.
The spin measurement of MAXI J1348-630 using the Insight-HXMT data
Authors: Song Yujia , Jia Nan , Yang Jun , Feng Ye , Gou Lijun , Lu Tianhua 
Published: October 2023

ABSTRACT
We report the results of fitting Insight-HXMT data to the black hole X-ray binary MAXI J1348-430, which was discovered on January 26th, 2019, We also inferred the ionization state and iron abundancewith the Gas Slit Camera on-board MAXI. Several observations at the beginning of the first burst were selected, with a total of 10 spectra. From the residuals of fits using disc plus power-law models, X-ray reflection signatures were clearly visible in some of these observations. We use the state-of-the-art $\tt {relxill}$ series reflection model to fit six spectra with distinct reflection signatures and a joint fit to these spectra. In particular, we focus on the results for the black hole spin values. Assuming Rin = RISCO, the spin parameter is constrained to be $0.82^{+0.04}_{-0.03}$ with 90 per cent confidence level (statistical only).
Optical variability in quasars: scalings with black hole mass and Eddington ratio depend on the observed time-scales
Authors: Arévalo P , Lira P , Sánchez-Sáez P , Patel P , López-Navas E , Churazov E , Hernández-García L 
Published: October 2023

ABSTRACT
Quasars emission is highly variable, and this variability gives us clues to understand the accretion process onto supermassive black holes. We can expect variability properties to correlate with the main physical properties of the accreting black hole, i.e. its mass and accretion rate. It has been established that the relative amplitude of variability anticorrelates with the accretion rate. The dependence of the variance on black hole mass has remained elusive, and contradicting results, including positive, negative, or no correlation, have been reported. In this work, we show that the key to these contradictions lies in the times-cales of variability studied (e.g. the length of the light curves available). By isolating the variance on different time-scales in well-defined mass and accretion rate bins we show that there is indeed a negative correlation between black hole mass and variance and that this anticorrelation is stronger for shorter time-scale fluctuations. The behaviour can be explained in terms of a universal variability power spectrum for all quasars, resembling a broken power law where the variance is constant at low temporal frequencies and then drops continuously for frequencies higher than a characteristic (break) frequency fb, where fb correlates with the black hole mass. Furthermore, to explain all the variance results presented here, not only the normalization of this power spectrum must anticorrelate with the accretion rate, but also the shape of the power spectra at short time-scales must depend on this parameter as well.
Hypernova signatures of the first stars in dwarf galaxies in the local group
Authors: Lee Teayong , Jeon Myoungwon , Bromm Volker 
Published: October 2023

ABSTRACT
Observing the first generation of stars, Population III (Pop III), is still a challenge even with the JWST due to their faintness. Instead, searching for fossil records of Pop III stars in nearby dwarf galaxies provides an alternative method for studying their physical properties. It is intriguing that a star recently discovered in the Sculptor dwarf galaxy, named AS0039, is considered to show the unique signature of a Pop III star. The detailed abundance patterns of AS0039 are well matched with those predicted by nucleosynthesis models for Pop III exploding as an energetic hypernova (HN), confirming its potential to provide insight into the properties of the first stars. This study aims to explore the environmental conditions required for the formation of such a unique star using cosmological hydrodynamic zoom-in simulations on dwarf galaxies with a mass of $M_{\rm vir}\approx 10^8{\ \mathrm{ M}_\odot }$ at z = 0 while varying the fraction of Pop III stars that undergo HNe. Our simulations identify rapid gas inflow ($\dot{M}_{\rm gas}\sim 0.08{\ \mathrm{ M}_\odot }$ $\rm yr^{-1}$) as a possible factor in facilitating the formation of stars similar to AS0039. Alternatively, the delayed formation of subsequent Population II (Pop II) stars in the gas-enriched environment may lead to low-metallicity stars like AS0039. Additionally, using the a-sloth code, we investigate the probability of finding remnants of Pop II stars with HN signatures in nearby dwarf satellite galaxies. We suggest that the most likely dwarf galaxies to contain HN signatures are massive satellites with a probability of 40 per cent in the range of $M_{\rm peak}\approx 10^{10}\ \mathrm{ to} \ 10^{11}{\ \mathrm{ M}_\odot }$ and $M_{\ast }\approx 10^7 \ \mathrm{ to} \ 10^8{\ \mathrm{ M}_\odot }$, considering observational limitations.
Evolutionary Insights from a Large-Scale Survey of Population-Genomic Variation
Authors: Ye Zhiqiang , Wei Wen , Pfrender Michael E , Lynch Michael 
Published: October 2023

Abstract
The field of genomics has ushered in new methods for studying molecular-genetic variation in natural populations. However, most population-genomic studies still rely on small sample sizes (typically, &lt;100 individuals) from single time points, leaving considerable uncertainties with respect to the behavior of relatively young (and rare) alleles and, owing to the large sampling variance of measures of variation, to the specific gene targets of unusually strong selection. Genomic sequences of ∼1,700 haplotypes distributed over a 10-year period from a natural population of the microcrustacean Daphnia pulex reveal evolutionary-genomic features at a refined scale, including previously hidden information on the behavior of rare alleles predicted by recent theory. Background selection, resulting from the recurrent introduction of deleterious alleles, appears to strongly influence the dynamics of neutral alleles, inducing indirect negative selection on rare variants and positive selection on common variants. Temporally fluctuating selection increases the persistence of nonsynonymous alleles with intermediate frequencies, while reducing standing levels of variation at linked silent sites. Combined with the results from an equally large metapopulation survey of the study species, classes of genes that are under strong positive selection can now be confidently identified in this key model organism. Most notable among rapidly evolving Daphnia genes are those associated with ribosomes, mitochondrial functions, sensory systems, and lifespan determination.
Association between matrix metalloprotease-3 levels and radiographic progression in patients with rheumatoid arthritis: A post hoc analysis from a Japanese Phase 3 clinical trial of peficitinib (RAJ4)
Authors: Takeuchi Tsutomu , Tanaka Yoshiya , Morita Yoshiaki , Kato Daisuke , Kaneko Yuichiro , Terada Wataru 
Published: October 2023

ABSTRACT

Objectives
The current study assesses the utility of matrix metalloprotease-3 (MMP-3) as a biomarker for joint damage in patients with rheumatoid arthritis receiving peficitinib.

Methods
Rheumatoid arthritis patients with inadequate response to methotrexate were randomised to peficitinib 100 mg, peficitinib 150 mg, or placebo, combined with methotrexate, for 52 weeks; patients receiving placebo switched to peficitinib 100/150 mg at Week (W)12/28. This post hoc analysis investigated association between MMP-3 above/below upper limit of normal (ULN) at W12/28 and radiographic progression [modified total Sharp score (mTSS), joint space narrowing score, or erosion score &gt;0.5] at W52 or swollen joint count 66 at W28, stratified by baseline glucocorticoid use and renal function.

Results
MMP-3 levels decreased in both peficitinib-treated groups but more slowly in patients with baseline glucocorticoids and those with radiographic progression at W52. There was no clear correlation between MMP-3 change from baseline (CFB) at W12, CFB in mTSS, joint space narrowing score, or erosion score at W52, or CFB in swollen joint count 66 at W28. More patients with MMP-3 ≤ULN versus &gt;ULN at W12 had radiographic non-progression at W52. MMP-3 normalisation at W12 was significantly associated with mTSS non-progression at W52.

Conclusions
Normalisation of MMP-3 at W12 may be a predictor for subsequent non-progression of joint damage at W52.
Total knee arthroplasty for neuropathic arthropathy in a patient with leprosy
Authors: Kii Sakumo , Sonohata Motoki , Mawatari Masaaki 
Published: October 2023

ABSTRACT
Patients with leprosy are known to tend to develop neuropathic arthropathy, known as Charcot joint. There are no case reports of total knee arthroplasty (TKA) in patients with leprosy with polyarticular neuropathic arthropathy, and the results are unknown. In this study, we report a case of TKA in a patient with leprosy with polyarticular neuropathic arthropathy and discuss its outcomes and indications. Right TKA using the NexGen Legacy Constrained Condylar Knee implant was performed in a 62-year-old man with neuropathic arthropathy in multiple joints with clinical symptoms, particularly in the right knee. Seven years post-operation, the American Knee Society Score-knee and -function, which represent knee function and activities of daily living on a scale of 100 points, were significantly improved compared with preoperative values, from 30 to 99 points and 0 to 60 points, respectively. Indications for arthroplasty for neuropathic arthropathy should be carefully considered in each individual case. In this case, the patient had neuropathic arthropathy in multiple joints; however, TKA was performed because recovery of function in the right knee was expected to significantly improve the patient’s activities of daily living, and a good mid-term clinical outcome was achieved. Therefore, indications for arthroplasty should be considered in patients with systemic neuropathic arthropathy such as leprosy, and with accurate assessment and appropriate implant selection, good long-term outcomes may be expected.
RNA sequestration driven by amyloid formation: the alpha synuclein case
Authors: Rupert Jakob , Monti Michele , Zacco Elsa , Tartaglia Gian Gaetano 
Published: October 2023

Abstract
Nucleic acids can act as potent modulators of protein aggregation, and RNA has the ability to either hinder or facilitate protein assembly, depending on the molecular context. In this study, we utilized a computational approach to characterize the physico-chemical properties of regions involved in amyloid aggregation. In various experimental datasets, we observed that while the core is hydrophobic and highly ordered, external regions, which are more disordered, display a distinct tendency to interact with nucleic acids. To validate our predictions, we performed aggregation assays with alpha-synuclein (aS140), a non-nucleic acid-binding amyloidogenic protein, and a mutant truncated at the acidic C-terminus (aS103), which is predicted to have a higher tendency to interact with RNA. For both aS140 and aS103, we observed an acceleration of aggregation upon RNA addition, with a significantly stronger effect for aS103. Due to favorable electrostatics, we noted an enhanced nucleic acid sequestration ability for the aggregated aS103, allowing it to entrap a larger amount of RNA compared to the aggregated wild-type counterpart. Overall, our research suggests that RNA sequestration might be a common phenomenon linked to protein aggregation, constituting a gain-of-function mechanism that warrants further investigation.
ASD2023: towards the integrating landscapes of allosteric knowledgebase
Authors: He Jixiao , Liu Xinyi , Zhu Chunhao , Zha Jinyin , Li Qian , Zhao Mingzhu , Wei Jiacheng , Li Mingyu , Wu Chengwei , Wang Junyuan , Jiao Yonglai , Ning Shaobo , Zhou Jiamin , Hong Yue , Liu Yonghui , He Hongxi , Zhang Mingyang , Chen Feiying , Li Yanxiu , He Xinheng , Wu Jing , Lu Shaoyong , Song Kun , Lu Xuefeng , Zhang Jian 
Published: October 2023

Abstract
Allosteric regulation, induced by perturbations at an allosteric site topographically distinct from the orthosteric site, is one of the most direct and efficient ways to fine-tune macromolecular function. The Allosteric Database (ASD; accessible online at http://mdl.shsmu.edu.cn/ASD) has been systematically developed since 2009 to provide comprehensive information on allosteric regulation. In recent years, allostery has seen sustained growth and wide-ranging applications in life sciences, from basic research to new therapeutics development, while also elucidating emerging obstacles across allosteric research stages. To overcome these challenges and maintain high-quality data center services, novel features were curated in the ASD2023 update: (i) 66 589 potential allosteric sites, covering &gt; 80% of the human proteome and constituting the human allosteric pocketome; (ii) 748 allosteric protein–protein interaction (PPI) modulators with clear mechanisms, aiding protein machine studies and PPI-targeted drug discovery; (iii) ‘Allosteric Hit-to-Lead,’ a pioneering dataset providing panoramic views from 87 well-defined allosteric hits to 6565 leads and (iv) 456 dualsteric modulators for exploring the simultaneous regulation of allosteric and orthosteric sites. Meanwhile, ASD2023 maintains a significant growth of foundational allosteric data. Based on these efforts, the allosteric knowledgebase is progressively evolving towards an integrated landscape, facilitating advancements in allosteric target identification, mechanistic exploration and drug discovery.
FusionPDB: a knowledgebase of human fusion proteins
Authors: Kumar Himansu , Tang Lin-Ya , Yang Chengyuan , Kim Pora 
Published: October 2023

Abstract
Tumorigenic functions due to the formation of fusion genes have been targeted for cancer therapeutics (i.e. kinase inhibitors). However, many fusion proteins involved in various cellular processes have not been studied for targeted therapeutics. This is because the lack of complete fusion protein sequences and their whole 3D structures has made it challenging to develop new therapeutic strategies. To fill these critical gaps, we developed a computational pipeline and a resource of human fusion proteins named FusionPDB, available at https://compbio.uth.edu/FusionPDB. FusionPDB is organized into four levels: 43K fusion protein sequences (14.7K in-frame fusion genes, Level 1), over 2300 + 1267 fusion protein 3D structures (from 2300 recurrent and 266 manually curated in-frame fusion genes, Level 2), pLDDT score analysis for the 1267 fusion proteins from 266 manually curated fusion genes (Level 3), and virtual screening outcomes for 68 selected fusion proteins from 266 manually curated fusion genes (Level 4). FusionPDB is the only resource providing whole 3D structures of fusion proteins and comprehensive knowledge of human fusion proteins. It will be regularly updated until it covers all human fusion proteins in the future.
Systematic characterization of antibody–drug conjugate targets in central nervous system tumors
Authors: Coy Shannon , Lee Jong Suk , Chan Sabrina J , Woo Terri , Jones Jacquelyn , Alexandrescu Sanda , Wen Patrick Y , Sorger Peter K , Ligon Keith L , Santagata Sandro 
Published: October 2023

Abstract

Background
Antibody–drug conjugates (ADCs) enhance the specificity of cytotoxic drugs by directing them to cells expressing target antigens. Multiple ADCs are FDA-approved for solid and hematologic malignancies, including those expressing HER2, TROP2, and NECTIN4. Recently, an ADC targeting HER2 (Trastuzumab-Deruxtecan) increased survival and reduced growth of brain metastases in treatment-refractory metastatic breast cancer, even in tumors with low HER2 expression. Thus, low-level expression of ADC targets may be sufficient for treatment responsiveness. However, ADC target expression is poorly characterized in many central nervous system (CNS) tumors.

Methods
We analyzed publicly available RNA-sequencing and proteomic data from the children’s brain tumor network (N = 188 tumors) and gene-expression-omnibus RNA-expression datasets (N = 356) to evaluate expression of 14 potential ADC targets that are FDA-approved or under investigation in solid cancers. We also used immunohistochemistry to measure the levels of HER2, HER3, NECTIN4, TROP2, CLDN6, CLDN18.2, and CD276/B7-H3 protein in glioblastoma, oligodendroglioma, meningioma, ependymoma, pilocytic astrocytoma, medulloblastoma, atypical teratoid/rhabdoid tumor (AT/RT), adamantinomatous craniopharyngioma (ACP), papillary craniopharyngioma (PCP), and primary CNS lymphoma (N = 575).

Results
Pan-CNS analysis showed subtype-specific expression of ADC target proteins. Most tumors expressed HER3, B7-H3, and NECTIN4. Ependymomas strongly expressed HER2, while meningiomas showed weak-moderate HER2 expression. ACP and PCP strongly expressed B7-H3, with TROP2 expression in whorled ACP epithelium. AT/RT strongly expressed CLDN6. Glioblastoma showed little subtype-specific marker expression, suggesting a need for further target development.

Conclusions
CNS tumors exhibit subtype-specific expression of ADC targets including several FDA-approved for other indications. Clinical trials of ADCs in CNS tumors may therefore be warranted.
The Origin of Asymmetric Information: Revisiting the Rationale for Regulation
Authors: Downing Gareth 
Published: October 2023

Abstract
Akerlof’s seminal model on asymmetric information forms the basis for a broad range of regulatory interventions aimed at addressing the adverse effects of unequal information between transacting parties. While a groundbreaking model of the effects of information asymmetries in markets, Akerlof’s model does not examine why information asymmetries emerge. This article argues that an examination of the underlying drivers and origins of information asymmetries revitalises the policy rationale for regulatory intervention.
Horațiu Rădulescu and the Intangible Dimensions of Plasmatic Music
Authors: Marinescu Liviu 
Published: October 2023

Abstract
As early as his student years at the Bucharest Conservatory, Horațiu Rădulescu developed an interest in transcending established musical syntaxes by moving beyond the use of heterophony, favored by the Romanian post-war avant-garde. Yet, the temporal dimension of his music remains inextricably bonded with the ancient traditions and rituals of the Carpathian Mountains, where musicians and artists still preserve a mystical relationship with nature. In these lands, the flow of time seems to have no discrete entities. Sound plasma can be achieved when the relationship between cause and effect is obscured, and all musical elements are in a constant state of flux. While his poetic manifesto on the future of plasmatic music, published by Edition Modern in 1975, did little to clarify his theories, his works from the same decade had a strong impact on the evolution of avant-garde music throughout Western Europe. This chapter focuses on investigating the origins and spectral dimensions of plasmatic music, through a thorough examination of interviews with his classmates from the Bucharest Conservatory, articles written by Bob Gilmore, Horia Șurianu, and Livia Teodorescu, and an overview of Rădulescu’s music written since his defection to Western Europe in 1969. By unearthing the roots of plasmatic music and examining its later development, this chapter will provide the Western reader a more refined context for Rădulescu’s music, ultimately revealing the unique facets of Romanian spectralism.