bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual functionality of pyrimidine and flavone in targeting genomic variants of EGFR and ER receptors to influence the differential survival rates in breast cancer patients
Authors: Avti Pramod K , Singh Jitender , Dahiya Divya , Khanduja Krishan L 
Published: December 2023

Abstract
Breast cancer ranks as one of the most prevalent forms of cancer and stands as the primary global cause of mortality among women. Overexpression of EGFR and ER receptors or their genomic alterations leads to malignant transformation, disease aggression and is linked to poor patient survival outcomes. The clinical breast cancer patient’s genomic expression, survival analysis, and computational drug-targeting approaches were used to identify best-hit phytochemicals for therapeutic purposes. Breast cancer patients have genomic alterations in EGFR (4%, n = 5699) and ER (9%, n = 8461), with the highest proportion being missense mutations. No statistically significant difference was observed in the patient survival rates between the altered and unaltered ER groups, unlike EGFR, with the lowest survival rates in the altered group. Computational screening of natural compound libraries (7711) against each EGFR (3POZ) and ER (3ERT) receptor shortlists the best-hit 3 compounds with minimum docking score (ΔG = −7.9 to −10.8), MMGBSA (−40.16 to −51.91 kcal/mol), strong intermolecular H-bonding, drug-like properties with least kd, and ki. MD simulation studies display stable RMSD, RMSF, and good residual correlation of best-hit common compounds (PubChem ID: 5281672 and 5280863) targeting both EGFR and ER receptors. In vitro, studies revealed that these common drugs exhibited a high anti-proliferative effect on MCF-7 and MDA-MB-231 breast cancer cells, with effective IC50 values (15–40 μM) and lower free energy, kd, and ki (5281672 &gt; 5280863 &gt; 5330286) much affecting HEK-293 non-cancerous cells, indicating the safety profile. The experimental and computational correlation studies suggest that the highly expressed EGFR and ER receptors in breast cancer patients having poor survival rates can be effectively targeted with best-hit common potent drugs with a multi-target therapeutic approach.
Insight Box: The findings of this study provide valuable insights into the genomic/proteomic data, breast cancer patient’s survival analysis, and EGFR and ER receptor variants structural analysis. The genetic alterations analysis of EGFR and ER/ESR1 in breast cancer patients reveals the high frequency of mutation types, which affect patient’s survival rate and targeted therapies. The common best-hit compounds affect the cell survival patterns with effective IC50, drug-like properties having lower equilibrium and dissociation constants demonstrating the anti-proliferative effects. This work integrates altered receptor structural analysis, molecular interaction-based simulations, and ADMET properties to illuminate the identified best hits phytochemicals potential efficacy targeting both EGFR and ER receptors, demonstrating a multi-target therapeutic approach.
Confusion, unfair competition and legal action in OAPI countries
Authors: Lowe Gnintedem Patrick Juvet 
Published: December 2023

Abstract
This paper analyses the interpretation of confusion and the consequences it has on legal action, considering its compliance with the international framework and with regard to the case law of the African Intellectual Property Organization (OAPI) Member States. It argues that provisions of the Bangui Agreement (2015), in particular Annex VIII on unfair competition, are in compliance with international agreements, and the substantial interpretation of confusion made by the case law of the OAPI countries is appropriate. Although OAPI statutory bodies have the possibility to appreciate likelihood of confusion, only the judicial judges have the ultimate authority to give a binding interpretation. When confusion concerns a registered intellectual property right (IPR), a plaintiff can introduce both an action for infringement and an action for unfair competition, or only one of these actions. However, the action for unfair competition has a larger spectrum; it can be introduced even when there is no registered IPR, provided that a separate fault is demonstrated, in combination with the other constitutive elements of unfair competition. Reference made by judges either to national civil liability provisions, to Annex VIII, or to both provisions, as the legal basis of the action for unfair competition, should be harmonized in favour of Annex VIII, even if, in practice, it has not proved to be damaging for any litigant.
Leaf and root traits are partially coordinated but they show contrasting multi-trait-based community trait dispersion patterns in a subtropical forest
Authors: Luo Wenqi , Valverde-Barrantes Oscar J , Weemstra Monique , Cahill James F , Wang Zi , He Dong , Chen Yongfa , Chu Chengjin , Wang Youshi 
Published: December 2023

Abstract
The ecology of plant species relies on the synchronous functioning of leaves and roots, but few studies have simultaneously examined the community trait dispersion (CTD) patterns of both organs. We measured 16 analogous leaf and root traits on 44 co-occurring woody species in a subtropical forest in southern China, aiming to examine whether leaf and root traits were coordinated, organized into parallel trait axes, exhibited similar CTD, and displayed consistent responses in CTD and community-weighted means of (CWM) traits over environmental gradients. While the first axes of leaf and root trait variation similarly exhibited a fast–slow continuum, leaf traits covered a secondary “carbon economics” axis, contrasting to root traits depicting a collaboration axis reflecting species’ mycorrhizal dependency. Analogous leaf and root chemical traits were generally coordinated but less so for morphological traits. At the community level, changes in the CWM of the first axes were generally consistent among organs with more conservative traits found as increasing elevation but not for the second axis. While root traits became thinner and more conservative as soil phosphorus concentration decreased, leaf traits rarely varied. When different trait axes were combined, leaf traits were overdispersed but tended to converge with increased elevation and soil potassium and phosphorus levels, whereas root traits were clustered but tended to diverge along the same gradients. Our study highlights fine filtering of different suites of traits above- and belowground, which in turn might reduce overall niche overlap among species and promote coexistence with diverse functional designs.
Quality, diversity, and impact: (The first) 10 years of theJournal of Professions and Organization
Authors: Brock David M 
Published: December 2023

AbstractThis essay marks, reviews, and celebrates the first decade of the Journal of Professions and Organization. It begins with a brief review of the journal’s founding, initial scope, and objectives. This is followed by an analysis of all the articles published in the first decade (2014–23) of the journal’s existence. Finally, turning to the future, we consider at topics and initiatives that are becoming relevant as we approach JPO’s second decade.
The Forgotten Dreams of History-from-Below
Authors: Satia Priya 
Published: December 2023

Abstract
In his 2003 essay, “On Agency,” Walter Johnson faulted the way scholars’ focus on agency presumed a “unidirectional trade between past and present,” treating “history writing as a mode of redress.” It marginalized “human-ness lived outside the conventions” of a “liberal notion of selfhood.” Restoring agency to the enslaved made the scholar feel better about themselves without making the world any better: “therapy rather than politics.” Looking back on this pivotal assessment of social history from the vantage of twenty years, its criticisms seem relevant to the use of agency in its time (and ours) more than to the concept’s original invention in the era of decolonization after World War II. In that time, drawing on anticolonial thought, history-from-below emerged precisely to contest liberal notions of selfhood and reform the existing, whiggish two-way trade between past and present. Revisiting that turn reminds us that questions raised by the category of “agency” were present at its making and that it is unlikely that academic scholarship can fulfill more than a therapeutic function without affiliated struggles to remake the academy and popular politics. Reminding us of history-from-below's foundational commitment to building up “the present-life of the past” and challenging the individuated ideal of selfhood, this essay notes the continued urgency of recovering alternative subjectivities as we face the planetary crisis created by dominance of Enlightenment notions of history and selfhood. Though scholarship in the academy may not be capable of the political impact Johnson imagined, it nevertheless furthers history’s actual end of internal transformation.
On the Agency of Environmental History
Authors: Demuth Bathsheba 
Published: December 2023

Abstract
Twenty years ago, Walter Johnson warned historians not to rely on a concept that let both user and audience alike feel better without doing better. The concept in question was agency. Down the metaphorical hall and many a literal one, environmental historians were also talking about agency. The proximity is not surprising: the new social history Johnson addressed in 2003 came up alongside environmental history.
Introducing a randomized controlled trial into Family Proceedings: Describing the ‘how?’ and defending the ‘why?’
Authors: Atkinson Carol , Forde Matt , Crawford Karen , Henderson Marion , Wilson Philip , Ougrin Dennis , Minnis Helen 
Published: December 2023

Abstract
In 2011, a randomized controlled trial (RCT) of a mental health intervention for families with children under the age of 5 years coming into the Scottish care system was launched, called the Best Services Trial (BeST). When attempts were made to expand the study to English sites, the local leadership Judge objected, concerned that randomization in family proceedings was unfair, potentially discriminatory, and unlawful. Considerations about parental consent, fairness of randomization, and an understanding that the new intervention might be no better, or even harmful, compared to current best practices were crucial in addressing these concerns. In 2017, BeST was launched in England utilizing a randomized methodology. Significant input into the design of BeST came from the leadership Judge who had previously considered randomization unlawful. In July 2021, 383 families with 488 children had been recruited across both Scottish and English sites. Follow-up continues and 76 per cent of families continue to participate at 2.5 years after entering the study. Although there were undoubted challenges in designing and implementing BeST, with hindsight, the objections raised to the testing of interventions randomly were demonstrably resolvable and the process of randomization encountered no legal challenges. This is the first time an RCT has been accommodated within live proceedings in the family justice arena in England and Wales and one of a relatively few such RCTs conducted internationally.
DNA Conserved in Diverse Animals Since the Precambrian Controls Genes for Embryonic Development
Authors: Frith Martin C , Ni Shengliang 
Published: December 2023

Abstract
DNA that controls gene expression (e.g. enhancers, promoters) has seemed almost never to be conserved between distantly related animals, like vertebrates and arthropods. This is mysterious, because development of such animals is partly organized by homologous genes with similar complex expression patterns, termed “deep homology.” Here, we report 25 regulatory DNA segments conserved across bilaterian animals, of which 7 are also conserved in cnidaria (coral and sea anemone). They control developmental genes (e.g. Nr2f, Ptch, Rfx1/3, Sall, Smad6, Sp5, Tbx2/3), including six homeobox genes: Gsx, Hmx, Meis, Msx, Six1/2, and Zfhx3/4. The segments contain perfectly or near-perfectly conserved CCAAT boxes, E-boxes, and other sequences recognized by regulatory proteins. More such DNA conservation will surely be found soon, as more genomes are published and sequence comparison is optimized. This reveals a control system for animal development conserved since the Precambrian.
A bromodomain-independent mechanism of gene regulation by the BET inhibitor JQ1: direct activation of nuclear receptor PXR
Authors: Huber Andrew D , Poudel Shyaron , Wu Jing , Miller Darcie J , Lin Wenwei , Yang Lei , Bwayi Monicah N , Rimmer Mary Ashley , Gee Rebecca R Florke , Seetharaman Jayaraman , Chai Sergio C , Chen Taosheng 
Published: December 2023

Abstract
Bromodomain and extraterminal (BET) proteins are extensively studied in multiple pathologies, including cancer. BET proteins modulate transcription of various genes, including those synonymous with cancer, such as MYC. Thus, BET inhibitors are a major area of drug development efforts. (+)-JQ1 (JQ1) is the prototype inhibitor and is a common tool to probe BET functions. While showing therapeutic promise, JQ1 is not clinically usable, partly due to metabolic instability. Here, we show that JQ1 and the BET-inactive (−)-JQ1 are agonists of pregnane X receptor (PXR), a nuclear receptor that transcriptionally regulates genes encoding drug-metabolizing enzymes such as CYP3A4, which was previously shown to oxidize JQ1. A PXR-JQ1 co-crystal structure identified JQ1′s tert-butyl moiety as a PXR anchor and explains binding by (−)-JQ1. Analogs differing at the tert-butyl lost PXR binding, validating our structural findings. Evaluation in liver cell models revealed both PXR-dependent and PXR-independent modulation of CYP3A4 expression by BET inhibitors. We have characterized a non-BET JQ1 target, a mechanism of physiological JQ1 instability, a biological function of (−)-JQ1, and BET-dependent transcriptional regulation of drug metabolism genes.
Visualizing cancer-originating acetate uptake through monocarboxylate transporter 1 in reactive astrocytes in the glioblastoma tumor microenvironment
Authors: Kim Dongwoo , Ko Hae Young , Chung Jee-In , Park Yongmin Mason , Lee Sangwon , Kim Seon Yoo , Kim Jisu , Chun Joong-Hyun , Han Kyung-Seok , Lee Misu , Ju Yeon Ha , Park Sun Jun , Park Ki Duk , Nam Min-Ho , Kim Se Hoon , Shim Jin-Kyoung , Park Youngjoo , Lim Hyunkeong , Park Jaekyung , Lee Gwan-Ho , Kim Hyunjin , Kim Suhyun , Park Uiyeol , Ryu Hoon , Lee So Yun , Park Sunghyouk , Kang Seok-Gu , Chang Jong Hee , Lee C Justin , Yun Mijin 
Published: December 2023

Abstract

Background
Reactive astrogliosis is a hallmark of various brain pathologies, including neurodegenerative diseases and glioblastomas. However, the specific intermediate metabolites contributing to reactive astrogliosis remain unknown. This study investigated how glioblastomas induce reactive astrogliosis in the neighboring microenvironment and explore 11C-acetate PET as an imaging technique for detecting reactive astrogliosis.

Methods
Through in vitro, mouse models, and human tissue experiments, we examined the association between elevated 11C-acetate uptake and reactive astrogliosis in gliomas. We explored acetate from glioblastoma cells, which triggers reactive astrogliosis in neighboring astrocytes by upregulating MAO-B and monocarboxylate transporter 1 (MCT1) expression. We evaluated the presence of cancer stem cells in the reactive astrogliosis region of glioblastomas and assessed the correlation between the volume of 11C-acetate uptake beyond MRI and prognosis.

Results
Elevated 11C-acetate uptake is associated with reactive astrogliosis and astrocytic MCT1 in the periphery of glioblastomas in human tissues and mouse models. Glioblastoma cells exhibit increased acetate production as a result of glucose metabolism, with subsequent secretion of acetate. Acetate derived from glioblastoma cells induces reactive astrogliosis in neighboring astrocytes by increasing the expression of MAO-B and MCT1. We found cancer stem cells within the reactive astrogliosis at the tumor periphery. Consequently, a larger volume of 11C-acetate uptake beyond contrast-enhanced MRI was associated with a worse prognosis.

Conclusions
Our results highlight the role of acetate derived from glioblastoma cells in inducing reactive astrogliosis and underscore the potential value of 11C-acetate PET as an imaging technique for detecting reactive astrogliosis, offering important implications for the diagnosis and treatment of glioblastomas.
Impact of unhealthy food and beverage consumption on children’s risk of dental caries: a systematic review
Authors: Large Jessica F , Madigan Claire , Pradeilles Rebecca , Markey Oonagh , Boxer Benjamin , Rousham Emily K 
Published: December 2023

Abstract

Context
The impact of unhealthy foods and beverages, namely those high in sugar, salt, and saturated or trans fats, has been studied extensively in relation to weight, body composition, and noncommunicable diseases, but less so in relation to the risk of dental caries. Few previous reviews have examined the evidence from all countries globally.

Objective
A systematic review was conducted to assess the impact of unhealthy food and beverage consumption on the risk of dental caries in children aged ≤10 years, commissioned by the World Health Organization to inform updated complementary feeding recommendations.

Data Sources
Systematic searches were conducted in the PubMed, Cochrane, and Embase databases for articles meeting the inclusion criteria dating from January 1971 to March 2022; supplementary searches were undertaken for articles from that period to June 2022.

Data Extraction
Unhealthy foods and beverages were identified using nutrient- and food-based approaches. Risk of bias was assessed using the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I).

Data Analysis
A total of 30 023 unique citations were screened, yielding 37 studies for inclusion. Studies were conducted in high-income (n = 23 [62.2%]) or middle-income countries (n = 14 [37.8%]). Evidence synthesis was performed narratively, stratified by age (0 years to &lt;2 years, 2 years to &lt;5 years, and 5 years to ≤10 years) and exposure (unhealthy foods and unhealthy beverages). The heterogeneity of the exposures and comparators across studies was high. Almost all studies (n = 34) reported positive associations between the consumption of sugar-sweetened beverages or foods high in free sugars and dental caries. However, 67.6% of studies were assessed as having serious risk of bias.

Conclusion
The evidence indicates that the consumption of unhealthy food and beverages in children ≤10 years appears to increase the risk of dental caries. Further longitudinal studies with high-quality dietary assessments, including studies in low-income countries and children aged &gt;5 years at baseline, are recommended in order to build a more robust evidence base for use in the development of policy recommendations.

Systematic Review Registration
PROSPERO registration no. CRD42020218109.
The microtubule-nucleating factor MACERATOR tethers AUGMIN7 to microtubules and governs phragmoplast architecture
Authors: Schmidt-Marcec Sharol , Parish Alyssa , Smertenko Tetyana , Hickey Matthew , Piette Bernard M A G , Smertenko Andrei 
Published: December 2023

AbstractThe plant cytokinetic microtubule array, called the phragmoplast, exhibits higher microtubule dynamics in its center (midzone) than at the periphery (distal zone). This behavior is known as the axial asymmetry. Despite being a major characteristic of the phragmoplast, little is known about regulators of this phenomenon. Here we address the role of microtubule nucleation in axial asymmetry by characterizing MACERATOR (MACET) proteins in Arabidopsis thaliana and Nicotiana benthamiana with a combination of genetic, biochemical, and live-cell imaging assays, using photo-convertible microtubule probes, and modeling. MACET paralogs accumulate at the shrinking microtubule ends and decrease the tubulin OFF rate. Loss of MACET4 and MACET5 function abrogates axial asymmetry by suppressing microtubule dynamicity in the midzone. MACET4 also narrows the microtubule nucleation angle at the phragmoplast leading edge and functions as a microtubule tethering factor for AUGMIN COMPLEX SUBUNIT 7 (AUG7). The macet4 macet5 double mutant shows diminished clustering of AUG7 in the phragmoplast distal zone. Knockout of AUG7 does not affect MACET4 localization, axial asymmetry, or microtubule nucleation angle, but increases phragmoplast length and slows down phragmoplast expansion. The mce4-1 mce5 aug7-1 triple knockout is not viable. Experimental data and modeling demonstrate that microtubule nucleation factors regulate phragmoplast architecture and axial asymmetry directly by generating new microtubules and indirectly by modulating the abundance of free tubulin.
The E3 ligase TaGW2 mediates transcription factor TaARR12 degradation to promote drought resistance in wheat
Authors: Li Shumin , Zhang Yifang , Liu Yuling , Zhang Peiyin , Wang Xuemin , Chen Bin , Ding Li , Nie Yingxiong , Li Fangfang , Ma Zhenbing , Kang Zhensheng , Mao Hude 
Published: December 2023

Abstract
Drought stress limits crop yield, but the molecular modulators and their mechanisms underlying the trade-off between drought resistance and crop growth and development remain elusive. Here, a grain width and weight2 (GW2)-like really interesting new gene finger E3 ligase, TaGW2, was identified as a pivotal regulator of both kernel development and drought responses in wheat (Triticum aestivum). TaGW2 overexpression enhances drought resistance but leads to yield drag under full irrigation conditions. In contrast, TaGW2 knockdown or knockout attenuates drought resistance but remarkably increases kernel size and weight. Furthermore, TaGW2 directly interacts with and ubiquitinates the type-B Arabidopsis response regulator TaARR12, promoting its degradation via the 26S proteasome. Analysis of TaARR12 overexpression and knockdown lines indicated that TaARR12 represses the drought response but does not influence grain yield in wheat. Further DNA affinity purification sequencing combined with transcriptome analysis revealed that TaARR12 downregulates stress-responsive genes, especially group-A basic leucine zipper (bZIP) genes, resulting in impaired drought resistance. Notably, TaARR12 knockdown in the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated nuclease 9 (Cas9)-mediated tagw2 knockout mutant leads to significantly higher drought resistance and grain yield compared to wild-type plants. Collectively, these findings show that the TaGW2–TaARR12 regulatory module is essential for drought responses, providing a strategy for improving stress resistance in high-yield wheat varieties.