bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design, synthesis of novel chromene‐based scaffolds targeting hepatocellular carcinoma: Cell cycle arrest, cytotoxic effect against resistant cancer cells, apoptosis induction, and c‐Src inhibition
Authors: Abdelall Eman K. A. , Elshemy Heba A. H. , Labib Madlen B. , Mohamed Fatma E. A. 
Published: November 2023

AbstractNew chromene derivatives were synthesized based on 4‐(3,4‐dimethoxy)‐4H‐chromene scaffold. All target compounds exhibited cytotoxic activity against HepG2 cells (IC50 = 2.40–141.22 μM). Chromens 5 and 9 showed superior cytotoxicity over staurosporine (IC50 = 18.27 μM) and vinblastine (IC50 = 5.20 μM). c‐Src kinase inhibition assay of compounds 5 and 9 displayed the dominant c‐Src inhibitory activity of 5 (IC50 = 0.184 μM) over 9 (IC50 = 0.288 μM). The safety of the most potent compound 5 against normal WI‐38 cells was confirmed via its IC50 of 115.75 μM comparable with 5‐FU (IC50 = 16.28 μM). Moreover, the promising chromene 5 displayed potent cytotoxicity against resistant HepG2 cells with IC50 of 26.03 μM comparable with 5‐FU (IC50 = 42.68 μM). The most active chromene 5 arrested the HepG2 cell cycle at the S phase and induced a 29‐fold increase in the total number of apoptotic cells indicating pre‐G1 apoptosis. The ability of compound 5 to induce apoptosis was supported via elevation of caspase‐3, caspase‐7, caspase‐9 and proapoptotic Bax protein levels in addition to downregulation of the antiapoptotic Bcl2 protein. Molecular docking studies of compound 5 showed good binding interaction pattern inside c‐Src kinase enzyme active site.
Energy governance in China: A mixture of democratic environmentalism and authoritarian environmentalism
Authors: Zhang Chenxi 
Published: November 2023

AbstractThis paper challenges the conventional wisdom that environmental governance in China is a typical example of authoritarian environmentalism. By analyzing the case of energy governance, it indicates that China has become aware that energy and environmental issues are inter‐related and complicated and that more diverse and multi‐level solutions are required to reach increasingly ambitious national goals. In the context of ongoing state reform, local governments, enterprises, and civil society have played more active roles during the process of policy formulation and implementation. But meanwhile, the central government is tightening regulation and supervision to reduce non‐compliance with its energy initiatives and to safeguard national security and social stability. Therefore, energy governance in China has displayed a mixture of democratic and authoritarian elements. The state can adopt different measures based on the specific situation it faces and the final outcome it wants to reach. More broadly, this case reveals that there is no simple relationship between the regime type and its corresponding energy governance model. The study of environmental politics should not be confined to the examination of formal institutional features but also needs to take concrete practices in every country into account.
Empagliflozin cost‐effectiveness analysis in Japanese heart failure with mildly reduced and preserved ejection fraction
Authors: Tsutsui Hiroyuki , Sakamaki Hiroyuki , Momomura Shin‐ichi , Sakata Yasushi , Kotobuki Yutaro , Linden Stephan , Idehara Koki , Nitta Daisuke 
Published: November 2023

AbstractAimsEmpagliflozin, a sodium‐glucose co‐transporter 2 inhibitor, was shown to be effective in patients with heart failure with preserved ejection fraction (HFpEF) in the EMPEROR‐Preserved trial. The present study aims to evaluate the cost‐effectiveness of empagliflozin among Japanese patients with HFpEF.Methods and resultsA Markov cohort model was developed to evaluate the cost‐effectiveness of empagliflozin added to standard of care (SoC) compared with SoC alone in patients with HFpEF from the perspective of the Japanese healthcare system and with a lifetime horizon. In addition to clinical events, the progression of disease severity was modelled based on the migration of Kansas City Cardiomyopathy Questionnaire‐Clinical Summary Scores (KCCQ‐CSS). Model inputs, including risk of clinical events, costs, and utilities/disutilities, were derived from EMPEROR‐Preserved trial data, a claims database and published literature. The generalizability of model results was investigated by applying various subgroups including age, body mass index (BMI), and region Asia, based on the subgroup analysis of EMPEROR‐Preserved data. In the base‐case analysis, empagliflozin yielded additional quality‐adjusted life years (QALYs; 0.11) with an incremental cost of $1408 per patient for Japanese patients with HFpEF. Incremental cost, mainly derived from drug acquisition cost ($1963 per patient), was largely offset by reduced cost in hospitalization for heart failure (HHF) and cardiovascular death (−$537 per patient and −$166 per patient, respectively). Treatment of empagliflozin provided incremental 0.11 QALYs and 0.08 life years compared with SoC alone. The incremental cost‐effectiveness ratio (ICER) was $12 772 (¥1 662 689)/QALY, which was below the Japanese willingness‐to‐pay (WTP) threshold of $38 408 (¥5 000 000)/QALY. The results were consistent across all the subgroups considered, and empagliflozin was dominant over SoC alone in the region Asia and BMI < 25 kg/m2 subgroups. ICERs for the remaining subgroups ranged from $7520/QALY (¥978 972/QALY, patients with baseline age ≥ 75 years) to $31 049/QALY (¥4 041 896/QALY, patients with baseline New York Heart Association class III/IV). Deterministic sensitivity analysis result showed that the treatment effect on HHF is the biggest driver of the cost‐effectiveness analysis, while the ICER will be still under the threshold even if no effect of empagliflozin on HHF was assumed. The probabilistic sensitivity analysis result showed that 64% of simulations were cost‐effective based on the Japanese WTP threshold.ConclusionsEmpagliflozin was demonstrated to be cost‐effective for patients with HFpEF in Japan based on EMPEROR‐Preserved trial data.
Identification of the communal pathogenesis and immune landscape between viral myocarditis and dilated cardiomyopathy
Authors: Lei Zhe , Cao Jianlei , Wu Jiahe , Lu Yi , Ni Lihua , Hu Xiaorong 
Published: November 2023

AbstractAimsStudies have confirmed that viral myocarditis (VMC) is one of the risk factors for dilated cardiomyopathy (DCM). The molecular mechanisms underlying the progression from VMC to DCM remain unclear and require further investigation.Methods and resultsThe mRNA microarray datasets GSE57338 (DCM) and GSE1145 (VMC) were obtained from the Gene Expression Omnibus database. The candidate key genes were further screened using weighted correlation network analysis (WGCNA), protein–protein interaction and external dataset validation, and the correlation between the candidate key genes and immune cells and the signalling pathways of the candidate key genes were observed by enrichment analysis and immune infiltration analysis. The expression of key genes was validated in the external dataset GSE35182. The crosstalk genes between DCM and VMC were mainly enriched in ‘transcriptional misregulation in cancer’, ‘FoxO signalling pathway’, ‘AGE‐RAGE signalling pathway in diabetic complications’, ‘thyroid hormone signalling pathway’, ‘AMPK signalling pathway’, and other signalling pathways. The immune infiltration analysis indicated that VMC was mainly associated with resting dendritic cells and M0 macrophages, while DCM was mainly associated with monocytes, M0 macrophages, CD8+ T cells, resting CD4 memory T cells, naive CD4+ T cells, and resting mast cells. In DCM‐related dataset GSE57338 and VMC‐related dataset GSE1145, a total of 18 candidate key genes were differentially expressed. BLC6, FOXO1, and UBE2M were identified as the key genes that lead to the progression from VMC to DCM by GSE35182.ConclusionsThree key genes (BLC6, FOXO1, and UBE2M) were identified and provided new insights into the diagnosis and treatment of VMC with DCM.
Improved seismic risk evaluation for high‐voltage switchgear equipment: A copula‐based framework considering joint failure modes
Authors: Wen Jiayi , Li Xiaoxuan , Zhu Yuxiang 
Published: November 2023

AbstractTraditional seismic evaluations for high‐voltage switchgear equipment, the critical power facilities, consider only structural failure mode and may underestimate the actual seismic risk. By additionally introducing a probable functional failure mode caused by the excessive deformation of the switchable blade of equipment, a novel copula‐based framework is proposed to utilize limited samples to generate simulation data and evaluate the joint failure probability (JFP). The correlation index and Akaike Information Criterion are employed to optimize the Copula function. For illustration, a disconnector, representative switchgear equipment, was selected as an example and modeled with the experiment validation. Model analysis results demonstrate the Clayton type is the most competent for evaluation. Neglecting functional failure can significantly underestimate the actual failure probability at various seismic intensities, up to 50%. Furthermore, it was found that the current equipment material strength level already meets the requirements, and enhancing strength alone does not effectively improve reliability under strong earthquakes. For PGA intensities ≥0.7 g, the blade deformation capacity plays the primary reliability constraint, independent of material stress. A cost‐effective seismic design should optimize the combination of allowable material stress and blade deformation based on the JFP considering seismic intensity and targeted reliability.
Deep Learning‐Assisted Design of Novel Promoters in Escherichia coli
Authors: Wang Xinglong , Xu Kangjie , Tan Yameng , Yu Shangyang , Zhao Xinyi , Zhou Jingwen 
Published: November 2023

AbstractDeep learning (DL) approaches have the ability to accurately recognize promoter regions and predict their strength. Here, the potential for controllably designing active Escherichia coli promoter is explored by combining multiple deep learning models. First, “DRSAdesign,” which relies on a diffusion model to generate different types of novel promoters is created, followed by predicting whether they are real or fake and strength. Experimental validation showed that 45 out of 50 generated promoters are active with high diversity, but most promoters have relatively low activity. Next, “Ndesign,” which relies on generating random sequences carrying functional −35 and −10 motifs of the sigma70 promoter is introduced, and their strength is predicted using the designed DL model. The DL model is trained and validated using 200 and 50 generated promoters, and displays Pearson correlation coefficients of 0.49 and 0.43, respectively. Taking advantage of the DL models developed in this work, possible 6‐mers are predicted as key functional motifs of the sigma70 promoter, suggesting that promoter recognition and strength prediction mainly rely on the accommodation of functional motifs. This work provides DL tools to design promoters and assess their functions, paving the way for DL‐assisted metabolic engineering.
iPSC‐derived microglia carrying the TREM2 R47H/+ mutation are proinflammatory and promote synapse loss
Authors: Penney Jay , Ralvenius William T. , Loon Anjanet , Cerit Oyku , Dileep Vishnu , Milo Blerta , Pao Ping‐Chieh , Woolf Hannah , Tsai Li‐Huei 
Published: November 2023

AbstractGenetic findings have highlighted key roles for microglia in the pathology of neurodegenerative conditions such as Alzheimer's disease (AD). A number of mutations in the microglial protein triggering receptor expressed on myeloid cells 2 (TREM2) have been associated with increased risk for developing AD, most notably the R47H/+ substitution. We employed gene editing and stem cell models to gain insight into the effects of the TREM2 R47H/+ mutation on human‐induced pluripotent stem cell‐derived microglia. We found transcriptional changes affecting numerous cellular processes, with R47H/+ cells exhibiting a proinflammatory gene expression signature. TREM2 R47H/+ also caused impairments in microglial movement and the uptake of multiple substrates, as well as rendering microglia hyperresponsive to inflammatory stimuli. We developed an in vitro laser‐induced injury model in neuron–microglia cocultures, finding an impaired injury response by TREM2 R47H/+ microglia. Furthermore, mouse brains transplanted with TREM2 R47H/+ microglia exhibited reduced synaptic density, with upregulation of multiple complement cascade components in TREM2 R47H/+ microglia suggesting inappropriate synaptic pruning as one potential mechanism. These findings identify a number of potentially detrimental effects of the TREM2 R47H/+ mutation on microglial gene expression and function likely to underlie its association with AD.
Dynamic saturation area and water balance modelling of karstic basins
Authors: Mohseni Bilehsavarchi Shayan , Nasiri Saleh Farzin , Zahraie Banafsheh 
Published: November 2023

AbstractWater balance models are known as major tools for simulation of basin‐wide water cycle components. Considering the complexity of the runoff generation processes in karstic basins, it is crucial to bring the model processes closer to the physical reality of karstic springs and their contribution to runoff formation. One of the challenges in basin‐scale modelling of karstic basins is that the basin response to precipitation is highly influenced by the soil saturation condition and its seasonal variability. One way to address this challenge is to include a dynamic structure for the water balance model. In this research, the structure of SAM‐KARST water balance model for estimation of monthly streamflows in the outlet of karst basins was presented. Moreover, to better simulate the basin response fluctuations in different seasons, the SAMdyn‐KARST model with a dynamic storage structure was introduced and developed. The results of the SAMdyn‐KARST model were compared with the saturation area model (SAM) and SAM‐KARST models for the Shapur river basin in southwest of Iran. The results confirmed the importance of considering larger saturation storage in the karst basins. The case study results also showed that SAMdyn‐KARST outperformed SAM‐KARST model and provided higher accuracy in estimating seasonal variations of surface streamflows at the basin outlet.
Observing and modelling dynamic changes in temperature and volumetric fluxes within a riverbank aquifer under the influence of seasonal river stage fluctuations
Authors: Ren Jie , Xu Song , Ma Chen , Dai Juan , Zhang Nan , Li Suping 
Published: November 2023

AbstractSeasonal variation causes regular fluctuations in river water levels and water temperatures, which affects the distribution of temperature fields and seepage fields in riparian zones. In this paper, the monitoring device was used to continuously monitor Dongting Lake for a period of 1 year, and the temperature distribution characteristics of the riparian hyporheic zone under seasonal variation were analysed. Ten riparian hydrothermal coupling models based on different soil thermal conductivity models were verified, and the optimal model was used to simulate the influence of the flood process on the temperature field and seepage field of the riparian hyporheic zone. The results show that the changes in groundwater level and temperature in the riparian hyporheic zone had obvious lag and attenuation phenomena compared with the changes in river water level and ambient temperature. The temperature field of the riparian hyporheic zone changed obviously in the year. The vertical temperature gradient was large in summer and winter, the stratification phenomenon was obvious, and the temperature field fluctuation was small. The effect of the flood process on the temperature field and seepage velocity in the riparian hyporheic zone was obviously hysteretic. The effect of the flood‐withdrawing process on the temperature change of the shallow layer was greater than that of the flood‐rising process, while the response of the deep layer temperature change to flood‐rising and flood‐withdrawing processes was the opposite. The effect of floods on the variation in groundwater velocity was that the flood‐rising process was greater than the flood‐withdrawing process.
Hemihysterectomy in a patient with uterus didelphys, vaginal septum and ipsilateral renal agenesis: A case report and literature review
Authors: Peixoto Silva Ananda , Souza Neves Sasha , Tannure Saraiva Pedro Henrique , Bicalho Bretas Tancredo Alberto 
Published: November 2023

AbstractUterus didelphys is a rare Müllerian anomaly, often diagnosed during menarche or in women with a personal history of infertility and/or recurrent pregnancy loss. Its association with other genitourinary anomalies is frequent and may determine the existence of established syndromes. This case report refers to a 13‐year‐old female patient diagnosed with OHVIRA syndrome (Obstructed Hemivagina with Ipsilateral Renal Agenesis), a condition wherein the presence of a didelphic uterus is associated with hemivagina obstruction and ipsilateral renal agenesis. The patient presented with cyclic pelvic pain, related to the presence of hematocolpos and hematometra, which persisted despite several surgical approaches, including vaginal septum excision and correction of cervical stenosis. The recurrence of the condition indicated exploratory laparotomy, revealing two hemi‐uteri and two uterine cervixes, with hematometra on the right. A subtotal hemihysterectomy was performed on the right. Post‐procedure, the patient developed with regular menstrual cycles and improvement of pelvic pain complaints. Given the limited prevalence and low index of suspicion, the potential requirement for surgical intervention and its potential impact on reproductive future, diagnosing and treating OHVIRA syndrome and other Müllerian anomalies poses notable challenges in clinical practice. Hence, sharing different therapeutic approaches of a rare diagnosis with the scientific community is of paramount importance to aid in early diagnosis and effective management of similar clinical cases.
Efficient feature recognition and matching technology for IoT‐enabled sports training
Authors: Du Meng , Liu Zhongliang 
Published: November 2023

AbstractWith the development of the Internet of Things (IoT), the IoT technology is gradually applied to the sport training of athletes. According to the training feature of athletes collected by the IoT equipment, this paper proposes to use the method of feature image sequence analysis and feature extraction to automatically identify the training of athletes. The mathematical model of feature image recognition based on gray difference is established, and the pyramid iterative recognition algorithm is used to reduce the recognition error effectively. In addition, a mathematical model of image sequence feature extraction based on moment invariants is established, and the feature table for athlete matching is discussed in detail. Based on the concept of dynamic establishment of search area and the principle of two‐step template feature recognition and matching, through the analysis of the pictures of high jumpers, the change of the athlete angle of left knee in the process of high jump is obtained, which achieves the purpose of automatic identification of key actions. At the same time, the random error existing in manual recognition is completely eliminated.
Cover Image
Authors: Babu Aravinda , Sunil K. , Sajith Ayyiliath Meleveetil , Muthipeedika Nibin Joy , Santra Sougata , Zyryanov Grigory V. 
Published: November 2023

The cover image is based on the Short Communication Pd/Co2(CO)8‐mediated bi‐metallic catalysis: Facile synthesis of pharmacologically relevant novel tacrine analogues by Aravinda Babu et al., https://doi.org/10.1002/jhet.4713image
Synthesis and characterizations of some new selenolo[2,3‐b]quinoxaline derivatives
Authors: Abdelwadoud Fatma K. , Gomaa Gehad S. , Geies Ahmed A. 
Published: November 2023

AbstractIn this paper, we present the synthesis of new selenoloquinoxaline derivatives starting from 2‐chloroquinoxaline‐3‐carbonitrile 1. The compound 1 was subjected to a reaction with selenium metal in the presence of NaBH4 as a reducing agent in ethanol, under a nitrogen atmosphere. This reaction resulted in the formation of the sodium salt of 3‐cyanoquinoxaline‐2‐selenolate, which was subsequently reacted with α‐halogenated carbonyl compounds in situ. This reaction produced a series of newly synthesized 3‐aminoselenolo[2,3‐b]quinoxaline‐2‐substituents. Ethyl 3‐aminoselenolo[2,3‐b]quinoxaline‐2‐carboxylate 3a was hydrolyzed by sodium hydroxide to give the corresponding sodium salt 9. This salt was then refluxed with acetic anhydride to produce oxazinone compound 10. The reaction of compound 10 with ammonium acetate afforded pyrimidoselenolo[2,3‐b]quinoxaline derivative 11. Compound 11 was then chlorinated using phosphorous oxychloride to give the corresponding chlorocompound.
Would external debts promote sustainable development in emerging and low‐income countries?
Authors: Luu Hiep Ngoc , Luu Nguyen Hanh , Phung Huong Thi Thu 
Published: November 2023

AbstractThis paper investigates how external debts influence sustainable development in emerging economies and low‐income countries from 101 countries from 2016 to 2020. External debt significantly aids countries in achieving their sustainable development goals but affects individual goal differently. While external debts promote well‐being, education quality, gender equality, employment, economic growth, and institutional strength, they negatively affect the sustainability of cities, communities, and ecosystems. Long‐term external and public debts make a significant contribution to promoting sustainable development, but excessive external borrowing could hamper sustainable development progress.