bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synergistic effects of the KDM4C inhibitor SD70 and the menin inhibitor MI‐503 against MLL::AF9‐driven acute myeloid leukaemia
Authors: Zhu Wenqi , Ding Yiyi , Huang Wanling , Guo Nini , Ren Qian , Wang Nan , Ma Xiaotong 
Published: June 2024

SummaryMLL‐rearranged (MLL‐r) leukaemia is observed in approximately 10% of acute myeloid leukaemia (AML) and is associated with a relatively poor prognosis, highlighting the need for new treatment regimens. MLL fusion proteins produced by MLL rearrangements recruit KDM4C to mediate epigenetic reprogramming, which is required for the maintenance of MLL‐r leukaemia. In this study, we used a combinatorial drug screen to selectively identify synergistic treatment partners for the KDM4C inhibitor SD70. The results showed that the drug combination of SD70 and MI‐503, a potent menin‐MLL inhibitor, induced synergistically enhanced apoptosis in MLL::AF9 leukaemia cells without affecting normal CD34+ cells. In vivo treatment with SD70 and MI‐503 significantly prolonged survival in AML xenograft models. Differential gene expression analysis by RNA‐seq following combined pharmacological inhibition of SD70 and MI‐503 revealed changes in numerous genes, with MYC target genes being the most significantly downregulated. Taken together, these data provide preclinical evidence that the combination of SD70 and MI‐503 is a potential dual‐targeted therapy for MLL::AF9 AML.
Dasatinib induces endothelial dysfunction leading to impaired recovery from ischaemia
Authors: Gover‐Proaktor Ayala , Leshem‐Lev Dorit , Winograd‐Katz Sabina , Partouche Shirly , Samara Aladin , Shapira Saar , Nardi‐Agmon Inbar , Harari Emanuel , Younis Aseel , Najjar Abderrahman , Kornowski Ran , Geiger Benjamin , Raanani Pia , Leader Avi , Granot Galit 
Published: June 2024

SummaryChronic myeloid leukaemia (CML) management is complicated by treatment‐emergent vascular adverse events seen with tyrosine kinase inhibitors (TKIs) such as nilotinib, dasatinib and ponatinib. Pleural effusion and pulmonary arterial hypertension (PAH) have been associated with dasatinib treatment. Endothelial dysfunction and impaired angiogenesis are hallmarks of PAH. In this study, we explored, at cellular and whole animal levels, the connection between dasatinib exposure and disruption of endothelial barrier integrity and function, leading to impaired angiogenesis. Understanding the mechanisms whereby dasatinib initiates PAH will provide opportunities for intervention and prevention of such adverse effects, and for future development of safer TKIs, thereby improving CML management.
An agonist of the adenosine A2A receptor, CGS21680, promotes corneal epithelial wound healing via the YAP signalling pathway
Authors: Sun Qiuqin , Jiang Nan , Yao Rui , Song Yue , Li Zewen , Wang Wei , Chen Jiangfan , Guo Wei 
Published: June 2024

AbstractBackground and PurposeThe adenosine A2A receptor (A2AR) is involved in various physiological and pathological processes in the eye; however, the role of the A2AR signalling in corneal epithelial wound healing is not known. Here, the expression, therapeutic effects and signalling mechanism of A2AR in corneal epithelial wound healing were investigated using the A2AR agonist CGS21680.Experimental ApproachA2AR localization and expression during wound healing in the murine cornea were determined by immunofluorescence staining, quantitative reverse transcription polymerase chain reaction (RT‐qPCR) and western blotting. The effect of CGS21680 on corneal epithelial wound healing in the lesioned corneal and cultured human corneal epithelial cells (hCECs) by modulating cellular proliferation and migration was critically evaluated. The role of Hippo–YAP signalling in mediating the CGS21680 effect on wound healing by pharmacological inhibition of YAP signalling was explored.Key ResultsA2AR expression was up‐regulated after corneal epithelial injury. Topical administration of CGS21680 dose‐dependently promoted corneal epithelial wound healing in the injured corneal epithelium by promoting cellular proliferation. Furthermore, CGS21680 accelerated the cellular proliferation and migration of hCECs in vitro. A2AR activation promoted early up‐regulation and later down‐regulation of YAP signalling molecules, and pharmacological inhibition of YAP signalling reverted CGS21680‐mediated wound healing effect in vivo and in vitro.Conclusion and ImplicationsA2AR activation promotes wound healing by enhancing cellular proliferation and migration through the YAP signalling pathway. A2ARs play an important role in the maintenance of corneal epithelium integrity and may represent a novel therapeutic target for facilitating corneal epithelial wound healing.
Re‐routing of submarine channels by Plio‐Quaternary extensional tectonics along the Tanzania margin and implications for an offshore branch of the East African Rift System
Authors: Dottore Stagna Marina , Maselli Vittorio , Reynolds David J. , Grujic Djordje , Iacopini David , Reynolds Pamela , Tewari Sugandha , van Vliet Arjan 
Published: June 2024

AbstractThe distribution and timing of Neogene extensional structures along the offshore Tanzania margin and their influence on submarine sediment dispersal pathways remain poorly constrained. This knowledge gap limits understanding of the propagation of the East African Rift System (EARS) in the western Indian Ocean. In this study, we use 2D and 3D seismic reflection data to explore a portion of the upper slope region offshore the Rufiji River delta which led to the discovery of a new extensional structure. Horizon maps and seismic sections extracted from the 3D volume reveal that the slope was intersected by W‐E‐oriented turbidite channels during the Cenozoic until the early Pliocene (5.3 Ma). Since then, the opening of this graben, whose timing is also constrained by stratigraphic horizon flattening, has led to a southward reorientation of these channels, a pattern that persists today, as evidenced by the flow direction of the channels at the modern seafloor. 2D seismic profiles reaching depths of 10 s two‐way travel time (TWT) indicate that the formation of this graben is not related to the reactivation of Mesozoic structures. In detail, seismic data show that the acoustic basement is intersected by extensional faults, likely related to the Jurassic rift tectonics, which is reactivated during the middle Cretaceous forming a gentle monocline. The lack of deformation in the post‐Cretaceous suggests a period of tectonic quiescence which persists until the establishment of a new extensional regime responsible for the graben's opening, indicating a decoupling between Mesozoic and Neogene tectonics. Considering the similarity in kinematics, orientation and timing between the graben and other structures along the margin, onshore and offshore, we interpret this graben to be generated by a later tectonic phase of the EARS. These new results may indicate that tectonic stresses associated with the EARS migrated from the Tanzania craton, where the oldest rift structures are dated to ca. 25 Ma, to the western Indian Ocean, where the tectonic activity started during the middle‐late Miocene to Pliocene.
Alternative magnetic field exposure suppresses tumor growth via metabolic reprogramming
Authors: Akimoto Taisuke , Islam Md Rafikul , Nagasako Akane , Kishi Kazuhito , Nakakaji Rina , Ohtake Makoto , Hasumi Hisashi , Yamaguchi Takashi , Yamada Shigeki , Yamamoto Tetsuya , Ishikawa Yoshihiro , Umemura Masanari 
Published: June 2024

AbstractApplication of physical forces, ranging from ultrasound to electric fields, is recommended in various clinical practice guidelines, including those for treating cancers and bone fractures. However, the mechanistic details of such treatments are often inadequately understood, primarily due to the absence of comprehensive study models. In this study, we demonstrate that an alternating magnetic field (AMF) inherently possesses a direct anti‐cancer effect by enhancing oxidative phosphorylation (OXPHOS) and thereby inducing metabolic reprogramming. We observed that the proliferation of human glioblastoma multiforme (GBM) cells (U87 and LN229) was inhibited upon exposure to AMF within a specific narrow frequency range, including around 227 kHz. In contrast, this exposure did not affect normal human astrocytes (NHA). Additionally, in mouse models implanted with human GBM cells in the brain, daily exposure to AMF for 30 min over 21 days significantly suppressed tumor growth and prolonged overall survival. This effect was associated with heightened reactive oxygen species (ROS) production and increased manganese superoxide dismutase (MnSOD) expression. The anti‐cancer efficacy of AMF was diminished by either a mitochondrial complex IV inhibitor or a ROS scavenger. Along with these observations, there was a decrease in the extracellular acidification rate (ECAR) and an increase in the oxygen consumption rate (OCR). This suggests that AMF‐induced metabolic reprogramming occurs in GBM cells but not in normal cells. Our results suggest that AMF exposure may offer a straightforward strategy to inhibit cancer cell growth by leveraging oxidative stress through metabolic reprogramming.
Prognostic and therapeutic potential of imbalance between PD‐1+CD8 and ICOS+Treg cells in advanced HBV‐HCC
Authors: Yan Fengna , Zhu Bingbing , Shi Ke , Zhang Yi , Zeng Xuanwei , Zhang Qun , Yang Zhiyun , Wang Xianbo 
Published: June 2024

AbstractOver 50% of patients with hepatitis B virus‐associated hepatocellular carcinoma (HBV‐HCC) are diagnosed at an advanced stage, which is characterized by immune imbalance between CD8+ T cells and regulatory T (Treg) cells that accelerates disease progression. However, there is no imbalance indicator to predict clinical outcomes. Here, we show that the proportion of CD8+ T cells decreases and Treg cells increases in advanced HBV‐HCC patients. During this stage, CD8+ T cells and Treg cells expressed the coinhibitory molecule PD‐1 and the costimulatory molecule ICOS, respectively. Additionally, the ratio between PD‐1+CD8 and ICOS+Tregs showed significant changes. Patients were further divided into high‐ and low‐ratio groups: PD‐1+CD8 and ICOS+Tregs high‐ (PD‐1/ICOShi) and low‐ratio (PD‐1/ICOSlo) groups according to ratio median. Compared with PD‐1/ICOSlo patients, the PD‐1/ICOShi group had better clinical prognosis and weaker CD8+ T cells exhaustion, and the T cell‐killing and proliferation functions were more conservative. Surprisingly, the small sample analysis found that PD‐1/ICOShi patients exhibited a higher proportion of tissue‐resident memory T (TRM) cells and had more stable killing capacity and lower apoptosis capacity than PD‐1/ICOSlo advanced HBV‐HCC patients treated with immune checkpoint inhibitors (ICIs). In conclusion, the ratio between PD‐1+CD8 and ICOS+Tregs was associated with extreme immune imbalance and poor prognosis in advanced HBV‐HCC. These findings provide significant clinical implications for the prognosis of advanced HBV‐HCC and may serve as a theoretical basis for identifying new targets in immunotherapy.
Assessing the efficacy of celecoxib after tonsillectomy and/or adenoidectomy: A systematic review and meta‐analysis of randomised control trials
Authors: Banatwala Umm E Salma Shabbar , Syed Abdul Rehman Shah , Ain Noor Ul , Zulfikar Aimen , Akhund Ilqa Ikram , Lodhi Rija , Baig Rameesha , Ghufran Laiba , Rizwan Ayesha , Bai Meena , Khatri Mahima , Kumar Satesh 
Published: June 2024

AbstractObjectivesTonsillectomy and adenoidectomy are common surgical procedures that cause persistent pain, bleeding, and functional limitations. We aimed to investigate the efficacy of celecoxib compared with a placebo for managing post‐tonsillectomy or adenoidectomy pain and other adverse events.DesignSystematic review and meta‐analysis.MethodsWe conducted a systematic literature search in the PubMed, Cochrane, and Google Scholar databases from inception until July 2023. Dichotomous outcomes have been reported as risk ratios (RR) while continuous outcomes were reported using mean differences (MD). A funnel plot was drawn to investigate publication bias.ResultsFrom 1394 records identified, 6 randomised double‐blind trials comprising 591 participants undergoing tonsillectomy and/or adenoidectomy were eligible for inclusion. A high dose (400 mg) of celecoxib was effective in decreasing the pain score for ‘worst pain’ after the procedure (MD: −10.98, [95% CI: −11.53, −10.42], p < .01, I2 = 0%) while a low dose (200 mg) was not significantly effective (p = 0.31). For managing other outcomes such as vomiting (RR: 1.37 [95% CI: 0.69, 2.68], p = 0.37, I2 = 67%), diarrhoea (RR: 1.41, [95% CI: 0.75, 2.64], p = .29, I2 = 42%), dizziness/drowsiness (RR: 0.90, [95% CI: 0.71, 1.15], p = .48, I2 = 0%), functional recovery time (p = .74), and headache (p = .91), there was no significant difference between the group on celecoxib and the placebo group regardless of dosage. Finally, there was no significant difference (RR: 1.02, [95% CI: 0.91, 1.15], p = .69, I2 = 0%) in the effect of the intervention on minimum bleeding, moderate bleeding, and profuse bleeding.ConclusionThis meta‐analysis provides robust evidence pooled from high‐quality trials and raises questions about the efficacy of celecoxib for tonsillectomy and/or adenoidectomy, challenging existing perceptions.
The mathematical model for colour preference in Chinese painting within museum lighting environments
Authors: Dang Rui , Wang Shuning , Sun Xingcan , Tang Ming , Yang Di 
Published: June 2024

AbstractColour in a Chinese painting not only conveys cultural, historical, and philosophical concepts but also carries specific symbolic meanings and emotions, possessing a high level of artistic value. However, the sensitivity of Chinese paintings to light results in exhibition environments being characterised by low illuminance and low colour temperature. Therefore, accurately assessing colour preferences in Chinese paintings under such conditions is an issue that needs to be addressed. This study conducted simulated experiments in real museum exhibition halls, with 36 participants providing subjective evaluations of Chinese paintings, to explore the effects of various lighting parameters on colour preferences. Through statistical analysis and multiple linear regression, the relationship between lighting parameters and colour preferences in a Chinese painting was determined, and an evaluation model was established. This research outcome provides important mathematical tools for selecting appropriate lighting and developing dedicated lighting for Chinese paintings, ensuring the artistic inheritance of Chinese painting colours.
Lichen biocrusts contribute to soil microbial biomass carbon in the northern temperate zone: A meta‐analysis
Authors: Tian Chang , Bu Chongfeng , Wu Shufang , Siddique Kadambot H. M. 
Published: June 2024

AbstractBiological soil crusts (biocrusts) have crucial ecological functions in dryland ecosystems, yet understanding the variations in soil microbial biomass within biocrusts across diverse ecosystems, climates and soil conditions remains limited. This knowledge gap constrains our understanding of how microbial communities within biocrusts regulate terrestrial carbon and nitrogen cycling. Hence, we conducted a meta‐analysis using 255 paired observations from 42 study sites across the northern temperate ecosystem. The analysis revealed that biocrusts harbour significantly higher soil microbial biomass carbon and nitrogen (SMBC and SMBN, respectively) levels than bare (non‐biocrust) soil across all habitat types. Notably, deeper soil layers (5–10 and >10 cm) accumulated less SMBC and SMBN than biocrust and biocrust–5‐cm soil, revealing that biocrusts influence shallow soil environments. Ecosystem type, soil texture, depth and season emerged as key factors influencing the distribution of SMBC within biocrusts. Of particular interest, lichen biocrusts accumulated the most SMBC compared with other biocrust types. Furthermore, the difference in SMBC between biocrust and non‐biocrust soils was more pronounced in oligotrophic habitats (e.g., desert, grassland, sand and sandy loam soils) than in eutrophic habitats (e.g., forest and loam soils). Random forest analysis confirmed that soil variables affected SMBC accumulation in biocrusts more than climatic factors. Soil organic carbon (SOC), as the primary source of SMBC, could be the most important determinant. Moreover, the disparity between non‐biocrust SMBC and biocrust SMBC increased with increasing mean annual temperature (MAT) or decreasing altitude. These insights underscore the substantial contribution of lichen biocrusts to SMBC and emphasize the need to incorporate this knowledge into regional models for predicting the effects of climate change on soil carbon budgets within biocrust microbiomes in temperate ecosystems of the Northern Hemisphere.
Principles for area‐based biodiversity conservation
Authors: Riva Federico , Haddad Nick , Fahrig Lenore , Banks‐Leite Cristina 
Published: June 2024

AbstractRecent international agreements have strengthened and expanded commitments to protect and restore native habitats for biodiversity protection (“area‐based biodiversity conservation”). Nevertheless, biodiversity conservation is hindered because how such commitments should be implemented has been strongly debated, which can lead to suboptimal habitat protection decisions. We argue that, despite the debates, there are three essential principles for area‐based biodiversity conservation. These principles are related to habitat geographic coverage, amount, and connectivity. They emerge from evidence that, while large areas of nature are important and must be protected, conservation or restoration of multiple small habitat patches is also critical for global conservation, particularly in regions with high land use. We contend that the many area‐based conservation initiatives expected in the coming decades should follow the principles we identify, regardless of ongoing debates. Considering the importance of biodiversity for maintenance of ecosystem services, we suggest that this would bring widespread societal benefits.
Mast seeding in European beech (Fagus sylvaticaL.) is associated with reduced fungal sporocarp production and community diversity
Authors: Michaud Talia J. , Pearse Ian S. , Kauserud Håvard , Andrew Carrie J. , Kennedy Peter G. 
Published: June 2024

AbstractMast seeding is a well‐documented phenomenon across diverse forest ecosystems. While its effect on aboveground food webs has been thoroughly studied, how it impacts the soil fungi that drive soil carbon and nutrient cycling has not yet been explored. To evaluate the relationship between mast seeding and fungal resource availability, we paired a Swiss 29‐year fungal sporocarp census with contemporaneous seed production for European beech (Fagus sylvaticaL.). On average, mast seeding was associated with a 55% reduction in sporocarp production and a compositional community shift towards drought‐tolerant taxa across both ectomycorrhizal and saprotrophic guilds. Among ectomycorrhizal fungi, traits associated with carbon cost did not explain species' sensitivity to seed production. Together, our results support a novel hypothesis that mast seeding limits annual resource availability and reproductive investment in soil fungi, creating an ecosystem ‘rhythm’ to forest processes that is synchronized above‐ and belowground.
Internal versus external CSR practices: The trade‐off in family firms
Authors: Rivera‐Franco Pilar , Requejo Ignacio , Suárez‐González Isabel 
Published: June 2024

AbstractFirms face the challenge of choosing between corporate social responsibility (CSR) practices aimed at different stakeholders (internal and external). Striking the right balance is particularly complex in family firms (FFs), in which CSR practices become a vehicle to express their identity. Our goal is to study FFs' trade‐off between internal and external CSR practices compared to non‐FFs by drawing on the FF identity and socioemotional wealth perspectives. We analyze a panel of 423 European listed companies (3,918 observations) from 2008 to 2017. Our results show that FFs outperform non‐FFs in overall CSR, with FFs' stronger efforts in internal CSR driving their better CSR performance. We also find that FFs' prioritization of internal CSR is more pronounced when CSR credibility at a country level is lower. However, a greater exposure of the family name reverses FFs' preferences and leads them to prioritize external stakeholders' interests.
Behavioral response to chemical cues from injured conspecifics in the livebearing fish, Brachyrhaphis rhabdophora
Authors: Duffy Alexandra G. , Johnson Jerald B. 
Published: June 2024

AbstractPredator–prey dynamics have led to a strong selection of prey's ability to detect and respond to information about the risk environment. Further, intrinsic factors, such as sex, may cause prey to perceive and respond to information differently. Chemical alarm cues from injured conspecifics are a classic example of how prey have evolved to use publicly available information to shape their behavior and enhance fitness, yet sex‐specific alarm reactions are rarely considered. The purpose of our study was to compare how males and females respond to conspecific chemical alarm cues in the livebearing fish species, Brachyrhaphis rhabdophora. Furthermore, we tested males and females from populations with a high‐ or low‐predation environment. Brachyrhaphis rhabdophora showed strong alarm reactions, but contrary to our predictions, showed limited variation due to sex or predation environment. We found that males and females from both populations displayed lower activity levels and increased their swimming depth when exposed to an alarm cue, despite variable and consistent baseline behaviors among individuals. These data further contribute to our understanding of what factors shape the evolution of behavioral responses to chemical alarm cues in fishes.
Grip strength complements performance status in assessing general condition in patients with unresectable hepatocellular carcinoma treated with atezolizumab and bevacizumab
Authors: Endo Kei , Kakisaka Keisuke , Abe Tamami , Yusa Kenji , Nakaya Ippeki , Watanabe Takuya , Abe Hiroaki , Suzuki Akiko , Yoshida Yuichi , Oikawa Takayoshi , Miyasaka Akio , Kuroda Hidekatsu , Matsumoto Takayuki 
Published: June 2024

AbstractAimAn accurate assessment of the general condition of patients with hepatocellular carcinoma (HCC) is essential. We evaluated the impact of grip strength (GS) and Eastern Cooperative Oncology Group Performance Status (ECOG‐PS) on the clinical outcomes of patients with unresectable HCC (u‐HCC) treated with atezolizumab plus bevacizumab.MethodsThis observational cohort study analyzed 89 patients with u‐HCC treated with atezolizumab plus bevacizumab between October, 2020 and October, 2023. A Cox proportional hazards model and Kaplan–Meier curve were used to identify the prognostic factors associated with survival outcomes.ResultsThere were 33 patients who had low GS and 16 had an ECOG‐PS ≥1. The frequency of patients with low GS increased as the ECOG‐PS score increased. The overall survival of the normal GS group was significantly higher than that of the low GS group (p < 0.01). There was no significant difference in progression‐free survival between the normal GS group and low‐GS group (p = 0.28). Among the patients in the ECOG‐PS 0 groups, the overall survival in the normal GS group was significantly higher than that in the low GS group (p < 0.01). A multivariate analysis revealed that modified albumin‐bilirubin 2b (HR 2.24; 95% confidence interval [CI] 1.06–4.73), α‐fetoprotein ≥100 ng/mL (HR 2.35; 95% CI 1.20–4.58), and low GS (HR 2.87; 95% CI 1.31–6.27) were independently associated with a poor overall survival.ConclusionsThe present study demonstrated that GS is a sensitive marker for detecting a subclinical decline in the general condition and is therefore a potential predictor of the outcome of u‐HCC patients treated with atezolizumab plus bevacizumab.