bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physiological and Biochemical Traits of Dormancy Release and Growth Resumption in Japanese Cedar in the Warm-Temperate Zone
Authors: Hiejima Shoma , Seino Hiroto , Hachisuka Rico , Watanabe Yuka , Matsuura Takakazu , Mori Izumi C. , Ugawa Shin 
Published: February 2025

Abstract
Global warming will disturb dormancy release and growth resumption of trees. To better understand this process, it is important to investigate physiological and biochemical traits related to these stages. We examined dormancy release and growth resumption in Japanese cedar (Cryptomeria japonica [L.] D. Don), an evergreen needle-leaved tree, in the warm-temperate zone by evaluating budbreak under growth-promoting conditions, and simultaneously examining respiration rates and contents of carbohydrates and phytohormones in shoots from November 2022 to March 2023. A long time to budbreak and the lowest budbreak rates of 75% in November indicated shallow dormancy. Budbreak rates of 98%, short time to budbreak, and first appearance of budbreak in the field in March indicated growth resumption. Continuous changes in budbreak rates and time to budbreak between dormancy and growth resumption indicated dormancy was gradually released. Surges in budbreak rates in December indicated dormancy was almost completely released by early winter. Contents of abscisic acid (ABA) and salicylic acid (SA) decreased from November, remained low in March, and were strongly associated with budbreak rates according to principal component analysis. It was suggested that the depletion of SA led to the depletion of ABA, contributing to dormancy release and growth resumption. Fructose and trans-zeatin accumulated until February, and low levels of starch, indole-3-acetic acid, jasmonic acid, and jasmonic acid-isoleucine during winter was followed by accumulation in March. Although these biochemical traits were less related to budbreak rates compared to ABA and SA, they seemed to assist either dormancy release or growth resumption.
Risk management in the era of data-centric engineering
Authors: Di Francesco Domenic 
Published: February 2025

Abstract
Novel methods of data collection and analysis can enhance traditional risk management practices that rely on expert engineering judgment and established safety records, specifically when key conditions are met: Analysis is linked to the decisions it is intended to support, standards and competencies remain up to date, and assurance and verification activities are performed. This article elaborates on these conditions. The reason engineers are required to perform calculations is to support decision-making. Since humans are famously weak natural statisticians, rather than ask stakeholders to implicitly assimilate data, and arrive at a decision, we can instead rely on subject matter experts to explicitly define risk management decision problems. The results of engineering calculation can then also communicate which interventions (if any) are considered to be risk-optimal. It is also proposed that the next generation of engineering standards should learn from the success of open source software development in community building. Interacting with open datasets and code can promote engagement, identification (and resolution) of errors, training and ultimately competence. Finally, the profession’s tradition of independent verification should also be applied to the complex models that will increasingly contribute to the safety of the built environment. Model assurance will be required to keep pace with model development to identify suitable use cases as adequately safe. These are considered to be increasingly important components in ensuring that methods of data-centric engineering can be safely and appropriately adopted in industry.
EFFECTS OF DIETARY RECOMMENDATIONS FOR REDUCING FREE SUGAR INTAKES, ON FREE SUGAR INTAKES, DIETARY PROFILES AND ANTHROPOMETRY: A RANDOMISED CONTROLLED TRIAL
Authors: Boxall Lucy R , Arden-Close Emily , James Janet , Appleton Katherine M 
Published: February 2025

ABSTRACT
Free sugar intakes are currently higher than recommended for health, yet effective strategies for reducing consumption are yet to be elucidated. This work investigated the effects of different dietary recommendations for reducing free sugar intakes, on relevant outcomes, in UK adults consuming >5% total energy intake (TEI) from free sugars. Using a randomized controlled parallel-group design, 242 adults received nutrient-based (N=61), nutrient- and food-based (N=60), nutrient-, food- and food-substitution-based (N=63) or no (N=58) recommendations for reducing free sugars at a single timepoint, with effects assessed for the following 12 weeks. Primary outcomes were free sugar intakes as a percentage of TEI (%FS) and adherence to the recommendations at week 12. Secondary outcomes included TEI, diet composition, sugar-sweetened and low-calorie-sweetened food consumption and anthropometry. In Intention-to-Treat analyses adjusted for baseline measures, %FS reduced in intervention groups (%FSchange=-2.5 to -3.3%) compared to control (%FSchange=-1.2%) (smallest B=-0.573, p=0.03), with effects from week 1 until week 12, and no differences between interventions (largest B=0.352, p=0.42). No effects of intervention were found in dietary profiles, but change in %FS was associated with change in %TEI from non-sugar carbohydrate (B=0.141, p<0.01) and from protein (B=-0.171, p=0.02). Body weight was also lower at week 12 in intervention groups compared to control (B=-0.377, p<0.05), but associations with %FS were weak. Our findings demonstrate benefit from dietary recommendations for reducing free sugar intakes in UK adults. Limited advantages were found for the different dietary recommendations, but variety may offer individual choice.
Trial Registration: Clinicaltrials.gov: NCT04816955, registration date: 24.03.21.
Francis Fearon’s Ideas and Hidden Network of African Antislavery in Nineteenth-Century Gold Coast
Authors: Odijie Michael Ehis 
Published: February 2025

Abstract
This article critically examines the antislavery activism of Francis P. Fearon, an African activist based in late nineteenth-century Accra. His correspondence with the Aborigines’ Protection Society (APS) provides a profound insight into the dynamics of African abolitionism. By analysing a collection of letters housed in the APS archive, this study sheds light on Fearon’s commitment to abolishing slavery, driven by his principled opposition to family separation. The article underscores Fearon’s active involvement in a network of African antislavery advocates who sought to disrupt the institution of slavery through legal challenges and international advocacy. This research extends the growing literature on African abolitionism, which primarily focuses on the efforts of African missionaries, educated elites, and grassroots movements, adding a new dimension by exploring the operations of a dedicated network committed to the abolitionist cause.
Disrupted intersubject variability architecture in structural and functional brain connectomes in major depressive disorder
Authors: Fang Keke , Wen Baohong , Liu Liang , Han Shaoqiang , Zhang Wenzhou 
Published: February 2025

Abstract

Background
Major depressive disorder (MDD) is a heterogeneous condition characterized by significant intersubject variability in clinical presentations. Recent neuroimaging studies have indicated that MDD involves altered brain connectivity across widespread regions. However, the variability in abnormal connectivity among MDD patients remains understudied.

Methods
Utilizing a large, multi-site dataset comprising 1,276 patients with MDD and 1,104 matched healthy controls, this study aimed to investigate the intersubject variability of structural covariance (IVSC) and functional connectivity (IVFC) in MDD.

Results
Patients with MDD demonstrated higher IVSC in the precuneus and lingual gyrus, but lower IVSC in the medial frontal gyrus, calcarine, cuneus, and cerebellum anterior lobe. Conversely, they exhibited an overall increase in IVFC across almost the entire brain, including the middle frontal gyrus, anterior cingulate cortex, hippocampus, insula, striatum, and precuneus. Correlation and mediation analyses revealed that abnormal IVSC was positively correlated with gray matter atrophy and mediated the relationship between abnormal IVFC and gray matter atrophy. As the disease progressed, IVFC increased in the left striatum, insula, right lingual gyrus, posterior cingulate, and left calcarine. Pharmacotherapy significantly reduced IVFC in the right insula, superior temporal gyrus, and inferior parietal lobule. Furthermore, we found significant but distinct correlations between abnormal IVSC and IVFC and the distribution of neurotransmitter receptors, suggesting potential molecular underpinnings. Further analysis confirmed that abnormal patterns of IVSC and IVFC were reproducible and MDD specificity.

Conclusions
These results elucidate the heterogeneity of abnormal connectivity in MDD, underscoring the importance of addressing this heterogeneity in future research.
Law and Emotion: The Lexicon of ‘Enmity’ in Early Modern Inner Austria
Authors: Oman Žiga 
Published: February 2025

Abstract
This article investigates the lexicon of dispute settlement in early modern Inner Austria, exploring the broadest legal, social, and emotional dimensions of the concept of “enmity” to better understand the nature of dispute settlement and social relations in coeval Central Europe. In particular, the article examines how litigants and courts understood and used “enmity” and its cognates, and how changes in criminal law impacted its usage. The article focuses on interpersonal conflicts and violence among nonnobles, who constituted the vast majority of Inner Austria’s population. It demonstrates that well into the 1700s among local urbanites and peasants, “enmity” and its key synonyms expressing ill-will, discord, or hatred—as opposites of love, concord, and friendship—signified a social state of mutual hostility closely related to violent retribution rather than unrestrained feeling.
Increased Rotational Coupling Between Antarctic Sea Ice and the Atmosphere Over the Last 30 Years
Authors: de Jager Wayne , Vichi Marcello 
Published: February 2025

AbstractAntarctic sea ice has been characterized by high temporal and spatial variability since the inception of reliable satellite records. The complex oceanic and atmospheric mechanisms driving this variability present ongoing challenges in determining their respective contributions. We examine the cyclonic and anticyclonic rotation dynamics within the sea ice and overlying atmosphere at daily timescales from 1991 to 2020 using a new generation remote‐sensing product for sea‐ice drift. A two‐dimensional pattern similarity comparison between the ice and atmospheric vorticity fields demonstrated a noteworthy increase in pattern similarity over the past 3 decades, despite the absence of any discernible trends in the mean intensity of either field. This escalating coupling suggests an increasing responsiveness of sea ice to atmospheric forcing, a phenomenon observed across all regions of the Southern Ocean. Notably, sea ice in the Weddell Sea experienced a sharp decline in the intensity of its clockwise and anticlockwise components from 2002 onwards. The increased coupling of sea‐ice drift at the synoptic scale with no discernible trends in the atmospheric forcing points to a plausible role of the ocean in modifying the rheology of pack‐ice. Analysis of the southern annular mode (SAM) reveals its winter correlation with sea‐ice vorticity but not to the observed strengthening of the coupling trend since the winter SAM trend is negligible. Our findings reiterate the predominant role of the atmosphere in driving rotation within Antarctic sea ice, while highlighting a knowledge gap on the possibly increasing influence of the under‐ice ocean on drift dynamics.
Innovations in bulk photovoltaics: design strategies for boosted photocurrent
Authors: Sreevalsan Akhil , Choi Hyosung 
Published: February 2025

Abstract
The limitations imposed by low contact resistance, restricted polarization access, and tensile strain in bulk photovoltaic systems were mitigated by the engineering and optimization of edge semimetal contacts using Bi/Au. Improved bulk PV photocurrent and intriguing prospective applications are made possible by this effort.
Precise targeting of transcriptional co-activators YAP/TAZ annihilates chemoresistant brCSCs by alteration of their mitochondrial homeostasis
Authors: Talukdar Priyanka Dey , Pramanik Kunal , Gatti Priya , Mukherjee Pritha , Ghosh Deepshikha , Roy Himansu , Germain Marc , Chatterji Urmi 
Published: February 2025

Abstract
Persistence of drug-resistant breast cancer stem cells (brCSCs) after a chemotherapeutic regime correlates with disease recurrence and elevated mortality. Therefore, deciphering mechanisms that dictate their drug-resistant phenotype is imperative for designing targeted and more effective therapeutic strategies. The transcription factor SOX2 has been recognized as a protagonist in brCSC maintenance, and previous studies have confirmed that inhibition of SOX2 purportedly eliminated these brCSCs. However, pharmacological targeting of transcription factors like SOX2 is challenging due to their structural incongruities and intrinsic disorders in their binding interfaces. Therefore, transcriptional co-activators may serve as a feasible alternative for effectively targeting the brCSCs. Incidentally, transcriptional co-activators YAP/TAZ were found to be upregulated in CD44+/CD24-/ALDH+ cells isolated from patient breast tumors and CSC-enriched mammospheres. Interestingly, it was observed that YAP/TAZ exhibited direct physical interaction with SOX2 and silencing YAP/TAZ attenuated SOX2 expression in mammospheres, leading to significantly reduced sphere forming efficiency and cell viability. YAP/TAZ additionally manipulated redox homeostasis and regulated mitochondrial dynamics by restraining the expression of the mitochondrial fission marker, DRP1. Furthermore, YAP/TAZ inhibition induced DRP1 expression and impaired OXPHOS, consequently inducing apoptosis in mammospheres. In order to enhance clinical relevance of the study, an FDA-approved drug verteporfin (VP), was used for pharmacological inhibition of YAP/TAZ. Surprisingly, VP administration was found to reduce tumor-initiating capacity of the mammospheres, concomitant with disrupted mitochondrial homeostasis and significantly reduced brCSC population. Therefore, VP holds immense potential for repurposing and decisively eliminating the chemoresistant brCSCs, offering a potent strategy for managing tumor recurrence effectively.
A first-in-class selective inhibitor of ERK1/2 and ERK5 overcomes drug resistance with a single-molecule strategy
Authors: Xiao Huan , Wang Aoxue , Shuai Wen , Qian Yuping , Wu Chengyong , Wang Xin , Yang Panpan , Sun Qian , Wang Guan , Ouyang Liang , Sun Qiu 
Published: February 2025

Abstract
Despite significant advancements in kinase-targeted therapy, the emergence of acquired drug resistance to targets such as KRAS and MEK remains a challenge. Extracellular-regulated kinase 1/2 (ERK1/2), positioned at the terminus of this pathway, is highly conserved and less susceptible to mutations, thereby garnering attention as a crucial therapeutical target. However, attempts to use monotherapies that target ERK1/2 have achieved only limited clinical success, mainly due to the issues of limited efficacy and the emergence of drug resistance. Herein, we present a proof of concept that extracellular-regulated kinase 5 (ERK5) acts as a compensatory pathway after ERK1/2 inhibition in triple-negative breast cancer (TNBC). By utilizing the principle of polypharmacology, we computationally designed SKLB-D18, a first-in-class molecule that selectively targets ERK1/2 and ERK5, with nanomolar potency and high specificity for both targets. SKLB-D18 demonstrated excellent tolerability in mice and demonstrated superior in vivo anti-tumor efficacy, not only exceeding the existing clinical ERK1/2 inhibitor BVD-523, but also the combination regimen of BVD-523 and the ERK5 inhibitor XMD8-92. Mechanistically, we showed that SKLB-D18, as an autophagy agonist, played a role in mammalian target of rapamycin (mTOR)/70 ribosomal protein S6 kinase (p70S6K) and nuclear receptor coactivator 4 (NCOA4)-mediated ferroptosis, which may mitigate multidrug resistance.
Inactivation of necroptosis-promoting protein MLKL creates a therapeutic vulnerability in colorectal cancer cells
Authors: Jiang Peijia , Chipurupalli Sandhya , Yoo Byong Hoon , Liu Xiaoyang , Rosen Kirill V. 
Published: February 2025

Abstract
Mortality from colorectal cancer (CRC) is significant, and novel CRC therapies are needed. A pseudokinase MLKL typically executes necroptotic cell death, and MLKL inactivation protects cells from such death. However, we found unexpectedly that MLKL gene knockout enhanced CRC cell death caused by a protein synthesis inhibitor homoharringtonine used for chronic myeloid leukemia treatment. In an effort to explain this finding, we observed that MLKL gene knockout reduces the basal CRC cell autophagy and renders such autophagy critically dependent on the presence of VPS37A, a component of the ESCRT-I complex. We further found that the reason why homoharringtonine enhances CRC cell death caused by MLKL gene knockout is that homoharringtonine activates p38 MAP kinase and thereby prevents VPS37A from supporting autophagy in MLKL-deficient cells. We observed that the resulting inhibition of the basal autophagy in CRC cells triggers their parthanatos, a cell death type driven by poly(ADP-ribose) polymerase hyperactivation. Finally, we discovered that a pharmacological MLKL inhibitor necrosulfonamide strongly cooperates with homoharringtonine in suppressing CRC cell tumorigenicity in mice. Thus, while MLKL promotes cell death during necroptosis, MLKL supports the basal autophagy in CRC cells and thereby protects them from death. MLKL inactivation reduces such autophagy and renders the cells sensitive to autophagy inhibitors, such as homoharringtonine. Hence, MLKL inhibition creates a therapeutic vulnerability that could be utilized for CRC treatment.
Can virtual reality reduce anxiety and pain in dental patients?
Authors: Goodship Nicola , Taylor Greig 
Published: February 2025

Abstract

A Commentary on

Nezhad H M, Ashourioun A, Sadeghdaghighi A

The effect of virtual reality for anxiety and pain in dentistry: a systematic review and meta-analysis. Community Dent Health 2024; 41: 248–255.

Data sources
A systematic search was conducted across PubMed and Cochrane Library up to April 2024.

Study selection
The article type was limited to Randomised Controlled Trials, comparing virtual reality (VR) interventions with non-VR methods in dental settings. The selection followed the PRISMA-P guidelines. Using the PICOS framework, studies involving dental patients of any age utilising VR during dental treatments and reporting outcomes on anxiety and pain were included.

Data extraction and synthesis
Data extraction and quality appraisal were conducted independently by two reviewers using both the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach and the Risk of Bias 2 (ROB-2) tool. Meta-analyses used a random-effects model.

Results
A total of 263 studies resulted in the inclusion of 27 studies, encompassing several dental treatments. Evidence quality ranged from low to moderate. Meta-analysis of 14 studies, encompassing 957 patients, revealed VR significantly reduced anxiety in children (SMD −1.44, 95% CI −2.24 to −0.63, low quality of evidence). Metal-analysis of five studies (485 patients) revealed VR had no effect on adults’ anxiety (SMD -0.35, 95% CI -1.11 to 0.4, low level of certainty). VR significantly reduced pain in both children (11 studies, 791 participants) (SMD −1.11, 95% CI −1.65 to −0.57, moderate level of certainty) and adults (6 studies, 557 participants) (SMD −0.59, 95% CI −1.187 to −0.001, low evidence quality). Heterogeneity was high across studies.

Conclusion
The study concluded that VR is a promising intervention for reducing anxiety and pain in children during dental procedures, and pain reduction in adults. The authors suggested further research is needed to standardise the VR content and explore its impact across different age groups and dental procedures.
Molecular basis of foreign DNA recognition by BREX anti-phage immunity system
Authors: Drobiazko Alena , Adams Myfanwy C. , Skutel Mikhail , Potekhina Kristina , Kotovskaya Oksana , Trofimova Anna , Matlashov Mikhail , Yatselenko Daria , Maxwell Karen L. , Blower Tim R. , Severinov Konstantin , Ghilarov Dmitry , Isaev Artem 
Published: February 2025

Abstract
Anti-phage systems of the BREX (BacteRiophage EXclusion) superfamily rely on site-specific epigenetic DNA methylation to discriminate between the host and invading DNA. We demonstrate that in Type I BREX systems, defense and methylation require BREX site DNA binding by the BrxX (PglX) methyltransferase employing S-adenosyl methionine as a cofactor. We determined 2.2-Å cryoEM structure of Escherichia coli BrxX bound to target dsDNA revealing molecular details of BREX DNA recognition. Structure-guided engineering of BrxX expands its DNA specificity and dramatically enhances phage defense. We show that BrxX alone does not methylate DNA, and BREX activity requires an assembly of a supramolecular BrxBCXZ immune complex. Finally, we present a cryoEM structure of BrxX bound to a phage-encoded inhibitor Ocr that sequesters BrxX in an inactive dimeric form. We propose that BrxX-mediated foreign DNA sensing is a necessary first step in activation of BREX defense.
QbD-steered HPTLC approach for concurrent estimation of six co-administered COVID-19 and cardiovascular drugs in different matrices: greenness appraisal
Authors: Mohamed Ahmed R. , Sayed Rania A. , Shalaby Abdalla , Ibrahim Hany 
Published: February 2025

Abstract
Many COVID-19 sufferers have a history of cardiovascular illnesses, which makes them more likely to develop severe COVID-19. Such patients were advised by experts to prioritize drug therapies based on their doctor’s commendations to avoid exacerbating their basic illnesses. Therefore, developing an analytical methodology for the concurrent estimation of medications prescribed for co-treating cardiovascular and COVID-19 illnesses is becoming critical in both bioavailability hubs and QC units. Herein, an inventive, rapid, and affordable HPTLC approach was developed, and its conditions were optimized employing the full factorial design approach for the concurrent estimation of aspirin, atorvastatin, atenolol, losartan, remdesivir, and favipiravir as co-administered medications, either with salicylic acid or not. Using the desirability function, the experimental design approach could forecast the best eluent system for optimal resolution results. On HPTLC-silica plates, the above-mentioned medications were separated utilizing an eluent system of ethyl acetate, methylene chloride, methanol, and ammonia (6:4:4:1 by volume), and their spots were detected at 232 nm. The proposed methodology was evaluated following ICH prerequisites and applied successfully to the medications’ dosage forms, human plasma, and buffered dissolution media with superb recovery proportions and no intrusiveness from formulations’ additives or plasma matrices. Five metrics were employed to appraise the suggested technique’s greenness: AGREE, eco-scale, Raynie and Driver, GAPI, and NEMI. The sensitivity, large sample capacity, and short run duration (15 min) of the proposed methodology confirm its appositeness for regular estimation of the above-mentioned medications.