bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phosphotyrosine Signal Profiling of Clinical CAR-T Reveals Tonic Signaling Associated with Therapeutic Efficacy
Authors: Yao Bin , Ye Xueting , Kong Qian , Chen Wendong , Li Wentao , Feng Chun , He An , Li Guoqiang , Chen Lan , Chen Xiong , Hu Lina , Xie Lifen , Qiu Xiao , Wang Xi , Lin Yuhong , Cao Yixuan , Zhou Jihao , Zhang Xinyou , Wang Haopeng , Tian Ruijun 
Published: December 2024

SummaryChimeric Antigen Receptor T (CAR-T) therapies have revolutionized the treatment of cancers such as relapsed and refractory B cell malignancies. However, the precise therapeutic mechanism of CAR-T action remain to be elucidated. In this study, we systematically analyzed CAR signaling via phosphotyrosine (pTyr) proteomics in CAR-T cells from both clinical patients and healthy donors. We found that CAR-T products from clinical patients displayed heightened tyrosine phosphorylation, particularly in the JAK-STAT, MAPK and TCR signaling cascades. We also identified the significantly regulated pTyr sites in primary CAR-T cells under tonic signaling or upon stimulation by antigen-presenting CD19-K562 cells. Although both CD28ζ and 4-1BBζ CAR-T cells exhibited comparable pTyr changes, CD28ζ CAR-T cells displayed a more pronounced activation in the TCR signaling pathway. Additionally, comparative analysis between clinical and primary CAR-T cells suggested that CAR-T products were subject to heightened tonic signaling, which may be related to therapeutic relapse. Our findings reveal the state of clinical CAR-T products and refine the CAR-T signal transduction network, providing comprehensive insights and informed guidance for CAR-T therapies.
VSIG4-Expressing Macrophages Contribute To Anti-Parasitic And Anti-Metastatic Responses In The Peritoneal Cavity
Authors: Lebegge Els , Kancheva Daliya , Van Craenenbroeck Jolien , Ernst Sam , Bardet Pauline M.R. , Caro Aarushi A. , Kiss Maté , Jumapili Neema Ahishakiye , Mora Barthelmess Romina , Zivalj Maida , Assaf Naela , Elkrim Yvon , Demuytere Jesse , De Jonge Jan , Raes Geert , Hadadi Eva , Devoogdt Nick , Vincke Cécile , Vereecke Lars , Ceelen Wim , Stijlemans Benoit , Laoui Damya , Arnouk Sana M. , Van Ginderachter Jo A. 
Published: December 2024

ABSTRACTPeritoneal tissue-resident macrophages, also referred to as large peritoneal macrophages (LPMs), play an important role as gatekeepers of peritoneal homeostasis by providing a first line of defense against pathogenic threats. About a third of the LPMs express the surface receptor V-set and Immunoglobulin domain containing 4 (VSIG4), but it is unclear to what extent these cells differ from their VSIG4-negative counterparts and perform dedicated functions. Here, we demonstrate that VSIG4+LPMs, in contrast to VSIG4-LPMs, are in majority derived from embryonal precursors and their occurrence is to a large extent independent from sex and microbiota. Although their transcriptome and surface proteome are indistinguishable from VSIG4-LPMs at steady-state, VSIG4+LPMs are superior in phagocytosing Gram-positive bacteria and colorectal carcinoma (CRC) cells. In-house generated anti-VSIG4 nanobody constructs that are antibody-dependent cell-mediated cytotoxicity (ADCC)-enabled allowed a selective elimination of the VSIG4+LPM subset without affecting the overall LPM content of the peritoneal cavity. This strategy uncovered a role for VSIG4+LPMs in lowering the first peak of parasitemia in aTrypanosoma brucei bruceiinfection model and in reducing the outgrowth of CRC cells in the peritoneal cavity, a prime metastatic site in CRC patients. Altogether, our data uncover a protective role for VSIG4+LPMs in infectious and oncological diseases in the peritoneal cavity.
Gene expression is globally regulated by interacting nucleobase supply and mRNA composition demand: a mechanism disrupted by multiple disease states and drug treatments
Authors: Pickard Benjamin S. 
Published: December 2024

AbstractConventional expression studies quantify messenger RNA (mRNA) transcript levels gene-by-gene. We recently showed that protein expression is modulated at a global scale by amino acid availability, suggesting that mRNA expression levels might be similarly affected by nucleobase supply. Re-analysis of transcriptomic datasets confirmed that nucleobase supply and mRNA A+U:C+G sequence composition interact to shape a global profile of expression which can be represented by simple numerical outputs.In mammals, each separate organ and cell-type displays a distinct baseline profile of expression, influenced by differentiation state. Expression profiles shift dynamically across the circadian day and the menstrual cycle. They are also significantly distorted by viral infection, multiple complex genetic disorders (including Alzheimer’s disease, schizophrenia, and autoimmune disorders), and after treatment with 115 of the 597 chemical entities analysed. These entities included known toxins, but also many commonly prescribed medications such as antibiotics and proton pump inhibitors, thus revealing a new mechanism of drug action and side-effect.A role for nucleobase supply is supported by the actions of nucleobase analogue treatments and by a model of the nucleobase metabolism disorder, Lesch-Nyhan syndrome. On the demand-side, mRNAs at compositional extremes are over-represented in key gene ontologies including transcription and cell division, making these processes particularly sensitive to swings in global expression. This permits efficienten blocreprogramming of cell state through simple changes in nucleobase proportion and supply. It is also proposed that this mechanism helped mitigate the loss of essential amino acid synthesis in higher organisms.In summary, global expression regulation is invisible to conventional transcriptomic analysis, but its measurement allows a useful distinction between active, promoter-mediated gene expression changes and passive, cell state-dependent transcriptional competence. Linking metabolism directly to expression offers an entirely new perspective on evolution, disease aetiopathology (including GxE interactions), and the nature of the pharmacological response.
Structure and dynamics ofBurkholderia pseudomalleiOXA-57, a distinctive low efficiency class D β-lactamase with carbapenem-hydrolyzing activity
Authors: Bragginton Éilís C. , Colenso Charlotte K. , Calvopiña Karina , Hinchliffe Philip , Shaw John M. , Tooke Catherine. L. , Seng Rathanin , Chantratita Narisara , Mulholland Adrian J. , Schofield Christopher J. , Spencer James 
Published: December 2024

AbstractThe Gram-negative bacteriumBurkholderia pseudomalleicauses the severe disease melioidosis. β-Lactams, including carbapenems, are the primary treatment, but are susceptible to chromosomal β-lactamases, including the class D enzyme OXA-57. Here we show recombinant OXA-57 is active towards penicillins and first-generation cephalosporins, slowly hydrolyzes carbapenems including imipenem and meropenem, but is inactive towards oxyimino-cephalosporins (e.g., ceftazidime). Unlike many OXA enzymes, OXA-57 is sensitive to the mechanism-based inhibitor clavulanic acid, but less so to the diazabicyclooctane avibactam and not to the cyclic boronate vaborbactam. Crystal structures of covalent OXA-57:avibactam and OXA-57:meropenem complexes reveal limited hydrogen- bonding interactions with bound ligands. In molecular dynamics simulations, bound meropenem is mobile, while the water necessary for deacylation has only limited active site access. These observations are consistent with the low level of meropenem turnover, supporting proposals that OXA β-lactamases generally possess limited carbapenemase activity, and highlight the potential importance of OXA-57 inB. pseudomalleiβ-lactam resistance.Graphical Abstract
Using deep generative models for simultaneous representational and predictive modeling of brain and behavior: A graded unsupervised-to-supervised modeling framework
Authors: McVeigh Kieran , Singh Ashutosh , Erdogmus Deniz , Feldman Barrett Lisa , Satpute Ajay B. 
Published: December 2024

AbstractThis paper uses a generative neural network architecture combining unsupervised (generative) and supervised (discriminative) models with a model comparison strategy to evaluate assumptions about the mappings between brain states and behavior. Most modeling in cognitive neuroscience publications assume a one-to-one brain-behavior relationship that is linear, but never test these assumptions or the consequences of violating them. We systematically varied these assumptions using simulations of four ground-truth brain-behavior mappings that involve progressively more complex relationships, ranging from one-to-one linear mappings to many-to-one nonlinear mappings. We then applied our Variational AutoEncoder-Classifier framework to the simulations to show how it accurately captured diverse brain-behavior mappings,provided evidence regarding which assumptions are supported by the data, and illustrated the problems that arise when assumptions are violated. This integrated approach offers a reliable foundation for cognitive neuroscience to effectively model complex neural and behavioral processes, allowing more justified conclusions about the nature of brain-behavior mappings.
Identification of SMARCA1 as a key regulator for Colorectal Cancer
Authors: Fu Chunqing , Duan Shoufeng , Zhang Chengwen , Cui Xinyu , Wang Fengxian , Wang Lichen , Hu Jinglei , Li Tengjiao , Li Lin 
Published: December 2024

AbstractEmerging evidence indicates that aberrations in the writing, reading, or erasure of chromatin modification codes are pivotal events in various human cancers. In this study, we conducted a systematic investigation of histone modification recognition proteins in a pair of colorectal cancer cell lines, SW480 and SW620. Using chromatin fractionation combined with data-independent acquisition mass spectrometry (DIA-MS), we developed a robust method to identify changes in histone modification recognition proteins during cancer progression. Our analysis revealed 22 proteins that were significantly upregulated and 22 proteins that were significantly downregulated in SW620 cells compared to SW480 cells. Notably, SMARCA1, a member of the ISWI family belonging to ATP-dependent chromatin remodeling complexes, was downregulated in SW620 cells compared to SW480 cells. Its high expression was strongly correlated with poor patient prognosis, aligning with the proposed role of SMARCA1 in promoting colorectal cancer (CRC) metastasis. Furthermore, reduced SMARCA1 expression altered the levels of metastasis-related matrix metalloproteinases (MMPs) in these cells. In conclusion, by systematically profiling histone modification recognition proteins in a matched pair of primary and metastatic CRC cell lines, we identified SMARCA1 as a potential driver of CRC metastasis and a promising therapeutic target for CRC patients.
Mechanistic studies of autophagic cargo recruitment and membrane expansion through in vitro reconstitution
Authors: Zhang Wenxin , Litschel Thomas , D’Antuono Rocco , Davis Colin , Schreiber Anne , Tooze Sharon A. 
Published: December 2024

AbstractAutophagy is a highly conserved catabolic pathway to remove deleterious cytosolic material to maintain cellular homeostasis and cell survival. Upon autophagy induction, a unique double-membraned structure, called a phagophore, forms and expands into a cup shape to engulf these cytosolic substrates. ATG8 proteins are covalently conjugated to autophagic membranes by lipidation of phosphatidylethanolamine (PE) and are thought to localise on both sides of the phagophore membrane. ATG8 conjugated on the inner membrane of the phagophore recruits autophagy cargo receptors, such as p62. To recapitulate events on the inner membrane, we used giant unilamellar vesicles (GUVs) as a model membrane and encapsulated proteins of interest inside GUVs, thus generating a membrane platform to which ATG8 proteins could be localised on the inner leaflet of the vesicles. We reconstituted WIPI2b-directed and cargo-directed ATG8 lipidation inside the GUVs and revealed distinct roles of WIPI2b and p62 in initiating the ATG conjugation cascade. Furthermore, we showed that p62 or p62 droplets were recruited to the inner membrane of the GUVs though interaction with membrane-bound ATG8s. Using a bead-based membrane expansion assay, we demonstrated a redistribution and local enrichment of membrane-bound ATG8s across the membrane upon interaction with p62 and p62 droplets. Our study provides novel model systems to investigate the interactions on the inner membrane of the phagophore and reveals fundamental molecular insights into phagophore membrane bending. This process is directed by ATG8-cargo interaction, during which cargo receptors concentrate ATG8 proteins on the inner surface of the phagophore membrane.
Origin of the Kerker phenomena
Authors: Lasa-Alonso Jon , Devescovi Chiara , Maciel-Escudero Carlos , García-Etxarri Aitzol , Molina-Terriza Gabriel 
Published: December 2024

We provide an insight into the origin of the phenomena reported 40 years ago by Kerker []. We show that the impedance and refractive index matching conditions, discussed in Secs. II and IV of the seminal paper, are intertwined and both lead to the conservation of a Casimir invariant. We derive our results starting from the theory of representations of the Poincaré group, as it is a theory on which one of the most elemental descriptions of electromagnetic waves is based. We show that fundamental features of electromagnetic waves in continuous material environments can be derived by applying the symmetry-breaking principle. In particular, we identify the Casimir invariants of the P3,1 subgroup as the magnitudes that describe the nature of monochromatic electromagnetic waves propagating in matter. Finally, we show that the emergence of the Kerker phenomena is associated with the conservation of such Casimir invariants in piecewise homogeneous media.

Published by the American Physical Society
2024
Exploring Esports game addiction among college students in multiplayer online battle arena: a quantitative model centered on self-control and motivation
Authors: Wang Sisi , Chiu Dickson K. W. , Ho Kevin K.W. 
Published: December 2024

PurposeWith the widespread popularity of Esports, Esports game addiction has attracted wide attention. This research explores the causes of Esports game addiction among college students in Mainland China and the influence of specific participation motivation and self-control on college students’ Esports game addiction.Design/methodology/approachThis research applied the organismic integration theory (OIT) instead of the basic psychological needs theory using Honor of Kings, the most popular Esports game in the form of multiplayer online battle arena (MOBA) among Chinese college students. A total of 339 completed questionnaires were finally analyzed. SmartPLS 2.0 M3 was used to perform the PLS-SEM analysis on the relationship between self-control, participation motivation and Esports game addiction.FindingsOnly introjected regulation and a motivation positively impacted Esports game addiction, while intrinsic motivation, integrated regulation, identified regulation and external regulation had surprisingly no effect on Esports game addiction.Originality/valueScant studies have explored Esports game addiction in MOBA games, especially in Asia. Results showed that parents, schools and society should consciously strengthen the education and exercise of students’ self-control ability to prevent Esports game addiction. Game developers should appropriately adjust game structures and functions to prevent college students from using them as social tools or games to escape reality.
The impact of IFRS 15 on revenue and earnings quality: evidence from China
Authors: Chen Jerry 
Published: December 2024

PurposeThis study examines the impact of the International Financial Reporting Standard (IFRS) 15 on revenue and earnings quality in China.Design/methodology/approachThis study employs a difference-in-differences design with a treatment group and a control group, both listed in stock exchanges in China from 2015 to 2019. Entropy balancing is employed to mitigate any imbalanced distribution effects caused by the inherent difference within our sample.FindingsThis study reveals an enhancement in the quality of revenue and earnings accruals after implementing IFRS 15 in China. However, adopters tend to engage in more real earnings management, and their revenue and earnings exhibit less persistence. Additional analysis shows that the new revenue standard substitutes for firm-level control factors in shaping the trade-off between accrual-based and real earnings management in jurisdictions with weak legal enforcement.Research limitations/implicationsThis study focuses on the staggered implementation of IFRS 15 in the Chinese setting; hence, the findings of this study might not be generalised to other countries.Practical implicationsThe findings of this study will be of interest to investors, given its focus on the revenue and earnings quality of companies that have adopted IFRS 15. Additionally, it holds implications for standard-setting organisations, particularly regarding post-implementation reviews, to comprehend how managers adjust their earnings management strategies in response to the enactment of IFRS 15.Originality/valueTo the best of our knowledge, our study is one of the few to investigate the impact of mandatory adoption of new IFRS standards within jurisdictions using a difference-in-differences design. In addition, we provide evidence that the new revenue standards substitute for firm-level control factors in shaping the trade-off between accrual-based and real earnings management in jurisdictions with weak legal enforcement, addressing a gap in the literature.
Innovation in cheese preservation: antimicrobial starch-based films produced by casting and thermo-compression techniques
Authors: Berti Sofia , González-Martínez Chelo , Flores Silvia Karina , Jagus Rosa Juana 
Published: December 2024

PurposeThis is one of the innovative studies that performs a comparative study of active and biodegradable starch-based films containing natamycin, produced by casting and thermo-compression methods to improve the microbiological stability of Argentinian Port Salut cheese.Design/methodology/approachBarrier and diffusion tests were carried out in order to evaluate the effectiveness of the films as antifungal packaging.FindingsFilms exhibited strong barrier action, with cast films proving to be the most effective yeast inhibitors. In the diffusion test, both types of films loaded with natamycin demonstrated a decrease in Zygosaccharomyces bailii counts after 48 h. Casting films significantly reduced Zygosaccharomyces rouxii and Saccharomyces cerevisiae counts after 48 h, while thermo-compression films partially inhibited yeasts. Casting films presented the most effective antimicrobial action in protecting cheese against yeast contamination.Originality/valueThis study provides a comparative analysis of the impact of processing methods on the properties of starch-based films incorporating the natural antimicrobial, natamycin. This research studies edible films based on tapioca starch, with or without natamycin, produced by means of casting and thermo-compression techniques, and compares the films antimicrobial properties against Z. bailli, Z. rouxii and S. cerevisiae using model systems and Argentinian Port Salut cheese.
Are all cracks bad? The influences of top management team relationship-related versus task-related demographic faultlines on corporate digital transformation
Authors: Gong Min , Wang Dandan 
Published: December 2024

PurposeWith the development of the digital economy, the pressure on firms to transform digitally continues to increase. The top management team (TMT) is the subject of decision-making, and its structure is expected to influence the process and outcome of corporate digital transformation. This study aims to explore the impact of the TMT structure on corporate digital transformation from perspectives on TMT relationship-related and task-related faultlines.Design/methodology/approachThis study obtained 7,510 observations belonging to 1,971 publicly listed Chinese manufacturing firms between 2011 and 2019. It analyzed the above data with ordinary least squares fixed-effects panel regression models and used instrumental variables to solve potential endogeneity problems.FindingsDrawing on social categorization theory and information processing theory and the concept of demographic faultlines, we proposed and found that relationship-related (i.e. gender and age) faultlines within a TMT may hinder digital transformation while task-related (i.e. education level, functional background and tenure) faultlines have an inverted U-shaped effect on digital transformation. In addition, we posited and confirmed that market competition weakens the negative effect of relationship-related faultlines but strengthens the inverted U-shaped effect of task-related faultlines.Originality/valueBy exploring the nuanced roles of TMT demographic faultlines in corporate digital transformation, our study enriches research on the antecedents of digital transformation from the TMT structure perspective and deepens the understanding of the decision process for digital transformation. In addition, this study extends existing claims about the contrasting roles of relationship-related and task-related faultlines, thereby enhancing our understanding of TMT demographic faultlines. Further, this study augments our knowledge about market competition by revealing its nuanced roles within TMT dynamics and providing supportive evidence for its positive impact on TMT function within firms. This study also offers managerial guidance for corporate digitization practice and the optimization of the internal structures of the TMTs.
Scientific and technological parks in innovation ecosystems: the proposition of an analytical structure
Authors: Coletto Camila , Caliari Leonardo , Callegaro-de-Menezes Daniela 
Published: December 2024

Purpose
This paper aims to propose an analytical structure for scientific and technological parks (STPs) as innovation ecosystems based on generating knowledge spillovers.

Design/methodology/approach
The analytical structure is constructed using a strategic approach, with STPs being viewed as an ecosystem and their interactions with the social context based on knowledge spillovers. In the empirical phase, a case study is developed in a Brazilian STP focused on food and renewable energy, enabling the application of the proposed analytical structure.

Findings
This study proposes that STPs can be central for innovation ecosystems, coordinating activities and resources. Also, STPs generate knowledge spillovers for geographically close and external actors, expanding the impact and benefits of innovation. The integration of these two propositions composes the proposed analytical structure that emphasizes the STP as the protagonist of the discussion on ecosystem management.

Originality/value
This study explores the relationship between STPs, innovation ecosystems and knowledge spillovers to clarify their strategic role in fostering innovation. It integrates multiple theoretical perspectives to propose new, broadly applicable frameworks. Given the limited and recent research on STPs within innovation ecosystems, the study provides a timely opportunity to investigate the management role of STPs at the organizational level.