bluuebunny/crossref_metadata_2025_split huggingface dataset:
CSTF2 Supports Hypoxia Tolerance in Hepatocellular Carcinoma by Enabling m6A Modification Evasion of PGK1 to Enhance Glycolysis
Authors: Zhang Qiangnu , Zhang Yusen , Fu Chuli , He Xiaoyan , Huang Zuotian , Wu Geyan , Wei Teng , Jin Wen , Yan Lesen , Wu Meilong , Peng Gongze , Fan LinLan , Li Mingyue , Guo Yuehua , Bi Jiangang , Bai Yu , Roessler Stephanie , Yan Guang-Rong , Liu Liping 
Published: November 2024

Abstract
Cleavage stimulation factor subunit 2 (CSTF2) is a fundamental factor in the regulation of 3′-end cleavage and alternative polyadenylation of pre-mRNAs. Previous work has identified a tumor-promoting role of CSTF2, suggesting that it may represent a potential therapeutic target. In this study, we aimed to elucidate the mechanistic function of CSTF2 in hepatocellular carcinoma (HCC). CSTF2 upregulation was frequent in HCC, and elevated levels of CSTF2 correlated with poor patient prognosis. Although CSTF2 inhibition did not suppress HCC growth under nonstress conditions, it supported tolerance and survival of HCC cells under hypoxic conditions. Mechanistically, CSTF2 increased phosphoglycerate kinase 1 (PGK1) protein production to enhance glycolysis, thereby sustaining the energy supply under hypoxic conditions. CSTF2 shortened the 3′ untranslated region of PGK1 pre-mRNA by binding near the proximal polyadenylation site. This shortening led to a loss of N6-methyladenosine (m6A) modification sites that are bound by YTH m6A RNA-binding protein F2 and increase degradation of PGK1 mRNA. Concurrently, hypoxia increased m6A modification of PGK1 mRNA near the proximal polyadenylation site that was recognized by the YTH m6A RNA-binding protein C1, which recruited CSTF2 to enhance the shortening of the PGK1 3′ untranslated region. A small-molecule screen identified masitinib as an inhibitor of CSTF2. Masitinib counteracted PGK1 upregulation by CSTF2 and suppressed the growth of HCC xenograft and patient-derived organoid models. In conclusion, this study revealed a function of CSTF2 in supporting HCC survival under hypoxia conditions through m6A modification evasion and metabolic reprogramming, indicating that inhibiting CSTF2 may overcome hypoxia tolerance in HCC.
Significance: Targeting CSTF2 inhibits hepatocellular carcinoma survival in hypoxic microenvironments, which may be a promising therapeutic strategy for treating liver cancer.
Genomic, Epigenomic, and Transcriptomic Inter- and Intratumor Heterogeneity in Desmoid Tumors
Authors: De Bellis Chelsea , Vennam Sujay , Eeles Christopher , Rahimizadeh Pegah , Cates Justin , Stricker Thomas , Hoffman Jenny , Ganjoo Kristen , Charville Gregory W. , Haibe-Kains Benjamin , van de Rijn Matt , Przybyl Joanna 
Published: November 2024

Abstract

Purpose:
Desmoid tumors are bland fibroblastic tumors that do not metastasize but have a high rate of local recurrence. Previously published studies proposed two different transcriptomic signatures to predict relapse. Molecular heterogeneity has been well established in high-grade sarcomas, but little is known about molecular variability within locally aggressive tumors such as desmoids.

Experimental Design:
We performed transcriptomic profiling of 31 specimens from 20 primary desmoid tumors to identify genes predictive of relapse. We also performed multiomic analysis including DNA methylation, copy-number alterations, point mutations, and gene expression on 24 specimens from different regions of primary and recurrent desmoid tumors from three patients (7–9 specimens per patient).

Results:
We observed highly variable expression of transcriptomic prognostic signatures both in patients who did and did not progress. Signatures associated with favorable and unfavorable outcomes were detected in different regions within the same tumor. Further multiomic studies showed remarkable intra- and intertumor heterogeneity of genomic, epigenomic, and transcriptomic patterns. The transcriptomic profiles showed the highest degree of variability within tumors and between primary and recurrent tumors from the same patient.

Conclusions:
This study shows an unexpected degree of intra- and intertumor heterogeneity in desmoid tumors. Our analysis indicates that molecular analysis of a single-tumor biopsy may underestimate the magnitude of molecular alterations in desmoid tumors. Our study also shows that recurrent desmoid tumors acquire multiple new molecular alterations. Thus, molecular heterogeneity is an important consideration in drug development and validation of prognostic and predictive biomarkers for desmoid tumors.
A Tumor-Naïve ctDNA Assay Detects Minimal Residual Disease in Resected Stage II or III Colorectal Cancer and Predicts Recurrence: Subset Analysis from the GALAXY Study in CIRCULATE-Japan
Authors: Nakamura Yoshiaki , Kaneva Kristiyana , Lo Christine , Neems Daniel , Freaney Jonathan E. , Boulos Hala , Hyun Seung Won , Islam Farahnaz , Yamada-Hanff Jason , Driessen Terri M. , Sonnenschein Anne , DeSantis Dana F. , Kotani Daisuke , Watanabe Jun , Kotaka Masahito , Mishima Saori , Bando Hideaki , Yamazaki Kentaro , Taniguchi Hiroya , Takemasa Ichiro , Kato Takeshi , Sangli Chithra , Tell Robert , Blidner Richard , Yoshino Takayuki , Sasser Kate , Oki Eiji , Nimeiri Halla 
Published: November 2024

Abstract

Purpose:
Analysis of ctDNA may enable early identification of patients likely to relapse, presenting an opportunity for early interventions and improved outcomes. Tumor-naïve plasma-only approaches for minimal residual disease (MRD) assessment accelerate turnaround time, enabling rapid treatment decisions and ongoing surveillance.

Experimental Design:
Plasma samples were obtained from 80 study participants with stage II or III colorectal cancer selected from CIRCULATE-Japan GALAXY. MRD status was assessed using a tumor-naïve ctDNA assay (xM) that integrates methylation and genomic variant data, delivering a binary call. MRD was assessed at 4 weeks postsurgery [landmark time point (LMT)] using methylation and genomic variant data and longitudinally (median, 22.1 months) using only methylation data.

Results:
At LMT, 69/80 study participants were evaluable (36 recurrent; 33 nonrecurrent). Of recurrent study participants, 22/36 had detectable ctDNA (MRD-positive) at LMT and 29/33 nonrecurrent study participants had undetectable ctDNA (MRD-negative), yielding a clinical sensitivity of 61.1% and specificity of 87.9%. Additionally, 74 study participants were evaluable for longitudinal performance with a clinical sensitivity of 83.3% and specificity of 89.5%. The median lead time from the first MRD-positive result to recurrence was 4.77 months overall, and 5.30 months for study participants with no adjuvant treatment. At 12 weeks postsurgery, MRD status strongly correlated with disease-free survival (adjusted HR, 9.69), outperforming carcinoembryonic antigen correlation (HR, 2.13).

Conclusions:
This tumor-naïve MRD assay demonstrated clinically meaningful performance at LMT and longitudinally, accurately predicting clinical recurrence. MRD status was a stronger prognostic biomarker for disease-free survival compared with standard-of-care carcinoembryonic antigen.
HPV and p53 Status as Precision Determinants of Head and Neck Cancer Response to DNA-PKcs Inhibition in Combination with Irradiation
Authors: Hayrapetyan Liana , Roth Selina M. , Quintin Aurélie , Hovhannisyan Lusine , Medo Matúš , Riedo Rahel , Ott Julien G. , Albers Joachim , Aebersold Daniel M. , Zimmer Yitzhak , Medová Michaela 
Published: November 2024

Abstract
Major risk factors of head and neck squamous cell carcinoma (HNSCC) are tobacco use and human papillomavirus (HPV). HPV E6 oncoprotein leads to p53 degradation, whereas HPV-negative cancers are frequently associated with TP53 mutations. Peposertib is a potent and selective, orally administered small-molecule inhibitor of the catalytic subunit of the DNA-dependent kinase (DNA-PKcs), a key regulator of nonhomologous end joining (NHEJ). NHEJ inhibition along with irradiation (IR)-induced DNA double-strand breaks has the potential to increase antitumor treatment efficacy. In this study, we investigated the responses of a panel of HNSCC models with distinct HPV and p53 status to treatments with IR, DNA-PKcs inhibition, and their combination in vitro and in vivo. IR-induced DNA damage combined with peposertib administration shortly before IR results in decreased cell viability and proliferation and causes DNA repair delay in all studied HNSCC cell lines. However, our data confirm that the actual cell fate upon this treatment is determined by cellular p53 and/or HPV status. Cells lacking functional p53 due to its degradation by HPV or due to a loss-of-function mutation are arrested in the G2/M phase of the cell cycle and eliminated by apoptosis, whereas p53-proficient HNSCC cell lines preferentially undergo senescence. This is also recapitulated in vivo, where HPV+ UD-SCC-2 xenografts display stronger and more durable responses to the combined treatment as compared with p53 wild-type UM-SCC-74A tumors. In conclusion, DNA-PKcs inhibitor peposertib should be further studied as a potential radiosensitizer for HNSCCs, taking into consideration the genetic background and the HPV status of a particular tumor.
Sympathetic Neurons Promote Small Cell Lung Cancer through the β2-Adrenergic Receptor
Authors: FNU Tala , Shi Peiguo , Zhang Wanwei , Chung Sanny S.W. , Damoci Christopher B. , Fang Yinshan , Chen Qi-Yue , Saqi Anjali , Huang Yuefeng , Wu Xuebing , Lu Chao , Yang Dian , Wang Timothy C. , Que Jianwen 
Published: November 2024

Abstract
The vagal nerve is linked to tumorigenesis in multiple tissues, including small cell lung cancer (SCLC). However, the role of sympathetic neurons in SCLC development remains unknown. In this study, we observed a significant reduction in tumor growth following chemical denervation of local sympathetic nerves in a mouse model of SCLC. Further study identified that β2-adrenergic receptor (ADRB2) expression on cancer cells mediated the cross-talk with nerve fibers. Genetic deletion or pharmacological inhibition of ADRB2 led to reduced tumor growth and improved survival. Moreover, blocking ADRB2 also reduced the growth of human SCLC organoids and xenografts. Further studies revealed that ADRB2 promoted cancer cell expansion through activating protein kinase A (PKA) signaling. Consistently, inhibition of PKA also reduced the growth of SCLC cells. These findings offer the initial insight into the role played by sympathetic neurons in the development of SCLC and may open a new therapeutic avenue to treat this deadly malignancy.

Significance:
SCLC is highly aggressive, with limited effective treatment options. We show that ablating sympathetic nerves or inhibiting the ADRB2 receptor slows SCLC progression and prolongs survival in mice. Additionally, ADRB2 inhibition reduces the growth of human SCLC organoids and xenografts by disrupting PKA signaling, identifying a new therapeutic target.
Leptolaimus petrelense n. sp. (Plectida: Leptolaimidae), a new nematode species from the Petrel lagoon, central Chile
Authors: Bastidas Brynelly , Morales-Montero Patricia , Holovochov Oleksandr , Sulbarán Yoelvis , San-Blas Ernesto 
Published: November 2024

Summary
During a survey on the biodiversity of nematodes in the Petrel lagoon (central Chile), a population of Leptolaimus was found in sediment samples. Morphological, morphometric and molecular data indicated that the recovered nematode is a new species. This nematode belongs to the group in which the males only have four pre-cloacal tubular supplements present, and females have no supplements. The new species can be separated from the other species of the group by the length of both males and females (843-1060 μm), the tail length (118-208 μm), the shape of the gubernaculum, and the arrangement of the caudal setae in males (a pair of ventral precloacal setae at level of spicules, a pair of dorsal post-cloacal setae, two subventral and two subdorsal caudal pairs. The differences from closely related species L. gerlachi, L. praeclarus, L. octavus, L. hydrothermalis, L. vipriensis, and L. hadalis are discussed. The recovered population is described herein as Leptolaimus petrelense n. sp.
Nakba and the US-Israel Imperial Regime
Authors: Sussman Gerald 
Published: November 2024

Abstract
The US-Israeli genocide is best understood as the end game of empire, the culmination of failed Anglo-American and Zionist policies in the Middle East and, indeed, virtually the entire non-Western world. It is the outcome of a US-sponsored apartheid system in Israel, largely carried out by the IDF and other militarist forces in the West Bank, East Jerusalem, Gaza, and Israel itself and funded by American financial assistance and weapons transfers to the Israeli army. The threats of multipolarity to US/NATO hegemony, Britain being the major junior partner, pushed the Trump and Biden administrations, along with the British Tories and post-Corbyn Labour Party, to support de facto the “final solution” in Gaza and the rest of Palestine. This article puts the Israeli assault on the people of Gaza, the Hamas-led attack on October 7 being the main pretext, in historical perspective. It argues that it is a logical sequence of the pre-war Zionist idea of an exclusive Jewish state and US and UK post-war power politics in the Middle East and in two imperial states’ respective domestic electoral politics.
Marxism and Ukraine’s Struggle for Independence and Self-Determination
Authors: Harris Jerry 
Published: November 2024

Abstract
This article traces the historic development of socialist thought on the importance of upholding independence and self-determination for oppressed nations. The examination starts with Marx on independence for Ireland and Lenin’s political and theoretical principals on nations oppressed by the Tsarist dictatorship. It proceeds to Ho Chi Minh’s address to the Comintern, Chou En Lai at the Bandung Conference, and Mao’s writings on contradictions. This article then applies these principals to the Russian invasion of Ukraine, debates in the Left, and the need to support Ukraine.
The Ukrainian Crisis: a Game-Theoretic Analysis of the Complex Interplay between Ukraine, Russia, and the West
Authors: Alibeli Madalla Awad 
Published: November 2024

Abstract
This study gives a general overview of the Ukrainian crisis through the lens of game theory, examining the motivations and constraints of Ukraine, Russia, and the West. Game theory provides structural concepts that explore trust, cooperation, risk-taking, and coordination challenges within the crisis. The analysis considers the impact of power imbalances and external factors like alliances and historical ties, strategic behavior, and other factors. The article concludes by highlighting key takeaways from the game-theoretic approach that can provide a roadmap towards a deeper analysis, and a structural diplomatic approach to conflict resolution.
China’s Connectivity Politics vis-à-vis Global Challenges: a Roadmap to Strategic Development?
Authors: Chajdas Tymoteusz 
Published: November 2024

Abstract
This article examines the transformative role of connectivity politics amid global upheaval, focusing on China’s Belt and Road Initiative (BRI) and Western connectivity strategies. It explores how China’s strategic use of connectivity has enabled it to navigate crises and exert global influence, while also analyzing the strengths and weaknesses of both Chinese and Western approaches. The article highlights the importance of multilateral collaboration, environmental sustainability, local empowerment, and adaptive policies for future connectivity initiatives. By synthesizing lessons from both the BRI and Western models, the article proposes a balanced and sustainable framework for global development, offering insights into fostering a more interconnected, equitable, and resilient world.
The Value of Negotiation Research in Perilous Times
Authors: Druckman Daniel , Wagner Lynn 
Published: November 2024

Abstract
Over the past 30 years, articles in this journal and elsewhere have offered insights and advice about making our world more peaceful through negotiation. This time in history provides a moment for reflection about the contributions we have made. This article shows how research findings add value for solving practical problems. Examples include two contemporaneous conflicts, the Russian invasion of Ukraine and the war in Gaza. We also explore issues that could trigger tipping points and spur greater global unrest, as well as avenues that could help reduce growing tensions: the world of international diplomacy, global climate diplomacy, insights on summitry, and negotiation skills training. These contributions are evaluated for ease of application, attentiveness of practitioners, and impact. We conclude optimistically: While research will not save us from the horrors of war, it can enhance our understanding of how to make the world a little safer for peace.
Penguin Books
Authors: Graham Tim 
Published: November 2024

Abstract
This article is an edited version of a public lecture that addressed three main areas of the history of Penguin Books Ltd: the origin and initial history of the company and its books; some aspects of the development of the design of the books; and the impact the publisher had on 20th-century society, principally in the UK. The article argues that this impact was greater than that of any other publisher in the last century.
A Typology of Authorship
Authors: Span Madeleine 
Published: November 2024

Abstract
The growing share of self-publishing titles on the book market has sparked debates about their position within the literary sphere. Although some consider self-publishing to be a parallel universe in its own right, our understanding of self-publishing’s links to traditional structures is still evolving. This study showcases three distinct types of perspectives. The first type strategically utilizes self-publishing to build authorial renown and increase their likelihood of securing a contract with a royalty publisher. The second type makes use of self-publishing to measure the quality of authors’ work, assessing the work’s popularity with readers and comparing its quality with that of competing authors and titles. Finally, the third type sees self-publishing as a way to preserve creative autonomy and self-determined authorial work. Drawing further on the broader sociocultural context of these findings, the research contributes to our understanding of self-publishing’s diverse landscape as well as its implications for the contemporary literary sphere.
Amino acid requirements of yellow mealworm and black soldier fly larvae
Authors: Spranghers T. , Moradei A. , Vynckier K. , Boudrez M. , Pinotti L. , Ottoboni M. 
Published: November 2024

Abstract
In order to achieve optimal growth and health of farm animals, a different amount/ratio of essential amino acids in the feed is necessary in each phase of life. Knowledge about which amino acids are essential and in which quantities/proportions they are best administered has already greatly advanced the pig and poultry sector and is still being generated today. For the still young, rapidly developing insect sector, this knowledge could mean a major step forward towards breeding optimization. Therefore, in this research the needs of the 2 most commercially reared insect species, namely mealworms (Tenebrio molitor) (MW) and black soldier fly larvae (Hermetia illucens) (BSF), were investigated. The focus was on requirements for lysine, methionine, threonine, phenylalanine and tryptophan based on evidence from the literature and those of pigs. Semi-artificial diets based on at least 25% wheat bran (MW) and chicken feed/water (30/70) (BSF) (basic feed important for structure and certain micronutrients) supplemented with sugar and synthetic amino acids were tested. The diets were isoenergetic and isoproteinous. Of the amino acids studied, one was administered in different doses per experiment. The non-essential glutamic acid was used as a substitute at lower doses. Growth, as measured by weight gain, and survival were observed. The following results were for MW and BSF respectively. For lysine from a content of 0.35 g/100 g diet and 0.53 g/100 g diet no extra growth was noticeable. For methionine this was from 0.13 g/100 g and 0.16 g/100 g. Each time more threonine was given, a significant difference could be noticed and the minimum doses were around 0.42 g/100 g and 0.49 g/100 g. With tryptophan, for MW, there were no differences between the different concentrations. At the lowest dose of 0.06 g/100 g the maximum growth was already reached, whereas for BSF this was at 0.13 g/100 g.
Sex Robot Utopianism and the Transhumanist Vision: A Critical Reflection
Authors: Kwan Kai-man 
Published: November 2024

Abstract
The sex robots (or sexbots) are coming, and this has generated a lot of discussion. The scholarly debate on love & sex with sexbots has been ignited mostly by David Levy’s book in 2007, Love + Sex with Robots: The Evolution of Human-Robot Relationships. There exist many perspectives on sexbots, and one way to assess them is to view this as an embodiment of the transhumanist or posthumanist vision (see Michael Hauskeller’s book, Sex and the Posthuman Condition, in 2014). Some enthusiasts for sexbots such as David Levy espouse a kind of sex robot utopianism that largely mirrors the transhumanist vision of posthuman transformation. Thus, this essay will first introduce transhumanism as well as the major philosophical and theological criticisms of transhumanism. In a second step, it will introduce Levy’s sex robot utopianism and then critically assess his arguments. The critical discussions of both parts will prove to be mutually illuminating and reinforcing.
A Requiem for “Jadidism”? Debates on Islamic Education in Contemporary Tatarstan
Authors: Almazova Leila , Kemper Michael 
Published: November 2024

Abstract
Over the last two decades, the public discourse on Islam in Tatarstan has seen a shift from celebrating “Jadidism” to a new emphasis on “Qadimism”. This paper explores the Tatar national movement’s use of “Jadidism” in the 1990s and 2000s and then reconstructs the “Qadimist” countertrend which started to gain visibility with the works of DUM RT deputy mufti Valiulla Yakupov (d. 2012), and which became dominant in the religious establishment of DUM RT under Mufti Kamil’ Samigullin (in office since 2013). In the second part of the paper we trace the marginalization of “Jadid” literature in Tatarstan’s Islamic teaching institutions. We argue that also “Qadimism”, as the discursive counterpart of “Jadidism”, has undergone changes in scope and meaning over time, and eventually became a self-ascription of the current Islamic leadership. Furthermore, our paper compares the attack on “Jadidophilia” by religious leaders in Tatarstan with the ongoing critique of “Jadidophilia” by Western academic scholars.