bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel 8-Methoxycoumarin-3-Carboxamides with potent anticancer activity against liver cancer via targeting caspase-3/7 and β-tubulin polymerization
Authors: Alzamami Ahmad , Radwan Eman M. , Abo-Elabass Eman , Behery Mohammed El , Alshwyeh Hussah Abdullah , Al-Olayan Ebtesam , Altamimi Abdulmalik S. , Attallah Nashwah G. M. , Altwaijry Najla , Jaremko Mariusz , Saied Essa M. 
Published: December 2023

AbstractIn the present study, we explored the potential of coumarin-based compounds, known for their potent anticancer properties, by designing and synthesizing a novel category of 8-methoxycoumarin-3-carboxamides. Our aim was to investigate their antiproliferative activity against liver cancer cells. Toward this, we developed a versatile synthetic approach to produce a series of 8-methoxycoumarin-3-carboxamide analogues with meticulous structural features. Assessment of their antiproliferative activity demonstrated their significant inhibitory effects on the growth of HepG2 cells, a widely studied liver cancer cell line. Among screened compounds, compound 5 exhibited the most potent antiproliferative activity among the screened compounds (IC50 = 0.9 µM), outperforming the anticancer drug staurosporine (IC50 = 8.4 µM), while showing minimal impact on normal cells. The flow cytometric analysis revealed that compound 5 induces cell cycle arrest during the G1/S phase and triggers apoptosis in HepG2 cells by increasing the percentage of cells arrested in the G2/M and pre-G1 phases. Annexin V-FITC/PI screening further supported the induction of apoptosis without significant necrosis. Further, compound 5 exhibited the ability to activate caspase3/7 protein and substantially inhibited β-tubulin polymerization activity in HepG2 cells. Finally, molecular modelling analysis further affirmed the high binding affinity of compound 5 toward the active cavity of β-tubulin protein, suggesting its mechanistic involvement. Collectively, our findings highlight the therapeutic potential of the presented class of coumarin analogues, especially compound 5, as promising candidates for the development of effective anti-hepatocellular carcinoma agents.
Alterations in lipidome profiles distinguish early-onset hyperuricemia, gout, and the effect of urate-lowering treatment
Authors: Kvasnička Aleš , Friedecký David , Brumarová Radana , Pavlíková Markéta , Pavelcová Kateřina , Mašínová Jana , Hasíková Lenka , Závada Jakub , Pavelka Karel , Ješina Pavel , Stibůrková Blanka 
Published: December 2023

Abstract
Background
Currently, it is not possible to predict whether patients with hyperuricemia (HUA) will develop gout and how this progression may be affected by urate-lowering treatment (ULT). Our study aimed to evaluate differences in plasma lipidome between patients with asymptomatic HUA detected ≤ 40 years (HUA ≤ 40) and > 40 years, gout patients with disease onset ≤ 40 years (Gout ≤ 40) and > 40 years, and normouricemic healthy controls (HC).

Methods
Plasma samples were collected from 94 asymptomatic HUA (77% HUA ≤ 40) subjects, 196 gout patients (59% Gout ≤ 40), and 53 HC. A comprehensive targeted lipidomic analysis was performed to semi-quantify 608 lipids in plasma. Univariate and multivariate statistics and advanced visualizations were applied.

Results
Both HUA and gout patients showed alterations in lipid profiles with the most significant upregulation of phosphatidylethanolamines and downregulation of lysophosphatidylcholine plasmalogens/plasmanyls. More profound changes were observed in HUA ≤ 40 and Gout ≤ 40 without ULT. Multivariate statistics differentiated HUA ≤ 40 and Gout ≤ 40 groups from HC with an overall accuracy of > 95%.

Conclusion
Alterations in the lipidome of HUA and Gout patients show a significant impact on lipid metabolism. The most significant glycerophospholipid dysregulation was found in HUA ≤ 40 and Gout ≤ 40 patients, together with a correction of this imbalance with ULT.
Antibiotic-Resistant Arcobacter spp. in commercial and smallholder farm animals in Asante Akim North Municipality, Ghana and Korogwe Town Council, Tanzania: a cross-sectional study
Authors: Paintsil Ellis Kobina , Ofori Linda Aurelia , Akenten Charity Wiafe , Zautner Andreas E. , Mbwana Joyce , Khan Neyaz Ahmed , Lusingu John P. A. , Kaseka Joseph , Minja Daniel T. R. , Gesase Samwel , Jaeger Anna , Lamshöft Maike , May Jürgen , Obiri-Danso Kwasi , Krumkamp Ralf , Dekker Denise 
Published: December 2023

Abstract
Background
Arcobacter species are considered emerging foodborne pathogens that can potentially cause serious infections in animals and humans. This cross-sectional study determined the frequency of potentially pathogenic Arcobacter spp. in both commercial and smallholder farm animals in Ghana and Tanzania. A total of 1585 and 1047 (poultry and livestock) samples were collected in Ghana and Tanzania, respectively. Selective enrichment media, along with oxidase and Gram testing, were employed for isolation of suspected Arcobacter spp. and confirmation was done using MALDI-TOF MS. Antibiotic susceptibility was assessed through disk diffusion method and ECOFFs were generated, for interpretation, based on resulting inhibition zone diameters.

Results
The overall Arcobacter frequency was higher in Ghana (7.0%, n = 111) than in Tanzania (2.0%, n = 21). The frequency of Arcobacter in commercial farms in Ghana was 10.3% (n/N = 83/805), while in Tanzania, it was 2.8% (n/N = 12/430). Arcobacter was detected in only 3.6% (n/N = 28/780) of the samples from smallholder farms in Ghana and 1.5% (n/N = 9/617) of the samples from Tanzania. For commercial farms, in Ghana, the presence of Arcobacter was more abundant in pigs (45.1%, n/N = 37/82), followed by ducks (38.5%, n/N = 10/26) and quails (35.7%, n/N = 10/28). According to MALDI-TOF-based species identification, Arcobacter butzleri (91.6%, n/N = 121/132), Arcobacter lanthieri (6.1%, n/N = 8/132), and Arcobacter cryaerophilus (2.3%, n/N = 3/132) were the only three Arcobacter species detected at both study sites. Almost all of the Arcobacter from Ghana (98.2%, n/N = 109/111) were isolated during the rainy season. The inhibition zone diameters recorded for penicillin, ampicillin, and chloramphenicol allowed no determination of an epidemiological cut-off value. However, the results indicated a general resistance to these three antimicrobials. Multidrug resistance was noted in 57.1% (n/N = 12/21) of the Arcobacter isolates from Tanzania and 45.0% (n/N = 50/111) of those from Ghana. The type of farm (commercial or smallholder) and source of the sample (poultry or livestock) were found to be associated with multi-drug resistance.

Conclusions
The high levels of MDR Arcobacter detected from farms in both countries call for urgent attention and comprehensive strategies to mitigate the spread of antimicrobial resistance in these pathogens.
RPU-PVB: robust object detection based on a unified metric perspective with bilinear interpolation
Authors: Yang Hao , Wang Xuewei , Chen Yuling , Dou Hui , Zhang Yangwen 
Published: December 2023

AbstractWith the development of cloud computing and deep learning, an increasing number of artificial intelligence models have been applied to reality. Such as videos on cell phones can be uploaded to the cloud for storage, which is detected by cloud arithmetic. Nevertheless, achieving this goal requires frequent consideration of the security of the model, since videos or images that go to the cloud, it is very likely to receive an adversarial attack. Regarding object detection, there has however been slow advancement in robustness research in this area. This is because training a target detection model requires a lot of arithmetic and time. Moreover, the current research has only slightly reduced the gap between clean and adversarial samples. To alleviate this problem, we propose a uniform perspective object detection robustness model based on bilinear interpolation that can accurately identify clean and adversarial samples. We propose the robustness optimization based on uniform metric perspective (RPU) for feature learning of clean and adversarial samples, drawing on the fine-grained idea. Following this, we analyze the fragility of the adversarial samples and consequently use the proposed perturbation filtering verification (PVB) based on bilinear interpolation. With slightly degraded clean sample detection performance, it substantially improves the robustness of object detection. Extensive experiments on PASCAL VOC and MS COCO show that our model guarantees the detection performance of clean samples and increases the detection performance of adversarial samples. The work we did has been open-sourced on GitHub: https://github.com/KujouRiu/RPU-PVB.
“It feels like I’m coming to a friend’s house”: an interpretive descriptive study of an integrated care site offering iOAT (Dr. Peter Centre)
Authors: Dobischok Sophia , Carvajal José R. , Turner Kyle , Jaffe Kaitlyn , Lehal Eisha , Blawatt Sarinn , Redquest Casey , Baltzer Turje Rosalind , McDougall Patrick , Koch Bryce , McDermid Cheryl , Hassan Damon , Harrison Scott , Oviedo-Joekes Eugenia 
Published: December 2023

Abstract
Background
Injectable opioid agonist treatment (iOAT) has proven to be a safe and effective treatment option for severe opioid use disorder (OUD). Yet, iOAT is often isolated from other health and social services. To align with a person-centered care approach, iOAT can be embedded in sites that combine systems and services that have been historically fragmented and that address multiple comorbidities (integrated care sites). The present study investigates the addition of iOAT at an integrated care in Vancouver, British Columbia. We aimed to capture what it means for service users and service providers to incorporate iOAT in an integrated care site and describe the processes by which the site keeps people engaged.

Methods
We conducted 22 interviews with 15 service users and 14 interviews with 13 service providers across two rounds of individual semi-structured interviews (Fall 2021, Summer 2022). The second interview round was precipitated by a service interruption in medication dispensation. Interview audio was recorded, transcribed, and then analysed in NVivo 1.6 following an interpretive description approach.

Results
The emergent themes from the analysis are represented in two categories: (1) a holistic approach (client autonomy, de-medicalized care, supportive staff relationships, multiple opportunities for engagement, barriers to iOAT integration) and (2) a sense of place (physical location, social connection and community belonging, food).

Conclusion
Incorporating iOAT at an integrated care site revealed how iOAT delivery can be strengthened through its direct connection to a diverse, comprehensive network of health and social services that are provided in a community atmosphere with high quality therapeutic relationships.
Antibiotic prophylaxis after 48 h postoperatively are not associated with decreased surgical site infections and other healthcare associated infections in pancreatic surgery patients: a retrospective cohort study
Authors: Ma Xiaoju , He Qiangsheng , Chen Youpeng , Lu Yan , Zhu Ping , Zhang Ji , Chen Wen-sen , Zhang Yongxiang , Zhang Wei-hong , Zhu Chuanlong , Li Qiang , Li Zhanjie 
Published: December 2023

Abstract
Background
It is controversial whether antibiotic should be used prophylactically 48 h after pancreatic surgery. Hence, the association of antibiotic prophylaxis (AP) after 48 h postoperatively with the incidence of surgical site infections (SSIs) and other healthcare-associated infections (HAIs) in patients receiving pancreatic surgery was evaluated.

Methods
A retrospective cohort analysis was performed on 1073 patients who underwent pancreatic surgery. These patients were categorized into the non-AP after 48 h postoperatively group (n = 963) and the AP after 48 h postoperatively group (n = 110) based on whether or not they obtained AP from 48 h to 30 days after surgery. Outcomes included SSIs and other HAIs.

Results
The incidence of SSIs in the non-AP after 48 h postoperatively group (98/963, 10.2%) was notably lower than that in the AP after 48 h postoperatively group (22/110, 20.0%) (P = 0.002). Other HAIs incidence was not significantly different between the non-AP after 48 h postoperatively group (77/963, 8.0%) and the AP after 48 h postoperatively group (11/110, 10.0%) (P = 0.468). Multiple regression analysis demonstrated that AP after 48 h postoperatively was a risk factor for SSIs (OR = 2.14, 95% CI 1.28–3.59) but not for other HAIs (OR = 1.24, 95% CI 0.63–2.42) after adjustment for age, gender, and diabetes. Subsequent to adjustment for all confounding factors, AP after 48 h postoperatively was not a influence factor for SSIs (OR = 2.13, 95% CI 0.76–5.99) and other HAIs (OR = 3.69, 95% CI 0.99–13.81).

Conclusions
AP after 48 h postoperatively following pancreatic surgery was not associated with the lower morbidity rate of SSIs and other HAIs. Nonetheless, this study may facilitate further development of strategies towards standardization of the duration of AP management of pancreatic surgery.
Role of advanced glycation end products in diabetic vascular injury: molecular mechanisms and therapeutic perspectives
Authors: Liu Jing , Pan Shuo , Wang Xiqiang , Liu Zhongwei , Zhang Yong 
Published: December 2023

Abstract
Background
In diabetic metabolic disorders, advanced glycation end products (AGEs) contribute significantly to the development of cardiovascular diseases (CVD).

Aims
This comprehensive review aims to elucidate the molecular mechanisms underlying AGE-mediated vascular injury.

Conclusions
We discuss the formation and accumulation of AGEs, their interactions with cellular receptors, and the subsequent activation of signaling pathways leading to oxidative stress, inflammation, endothelial dysfunction, smooth muscle cell proliferation, extracellular matrix remodeling, and impaired angiogenesis. Moreover, we explore potential therapeutic strategies targeting AGEs and related pathways for CVD prevention and treatment in diabetic metabolic disorders. Finally, we address current challenges and future directions in the field, emphasizing the importance of understanding the molecular links between AGEs and vascular injury to improve patient outcomes.
Top 100 cited articles in the thromboangiitis obliterans: a bibliometric analysis and visualized study
Authors: Liu Zhenxing , Ning Weiwei , Liang Jinlong , Zhang Tao , Yang Qingxu , Zhang Jie , Xie Ming 
Published: December 2023

Abstract
Objective
Thromboangiitis obliterans (TAO) is one of the most common types of peripheral arterial disease (PAD). This study aimed to explore the characteristics of the top 100 most cited articles in the TAO.

Methods
A bibliometric analysis based on the Web of Science (WOS) database was performed. Literature was retrieved and ranked by the citations. Listed below are the top 100 citations, including original articles, reviews, full-length proceeding papers, and case reports that were included for analysis. The type of literature, research areas, and languages were recorded. The trends of citations including the total citations, an analysis of publication and citation numbers were conducted each year. We analyzed citations from highly cited countries, authors, institutions, and journals. Research hotspots were gathered by a visualized analysis of author keywords.

Results
Most of the highly cited literature was original articles. A rising trend was observed in the number of citations per year. The peaks in the number of highly cited articles appeared in the year 1998 and 2006. The majority of the articles focused on the cardiovascular system and surgery. Journal of Vascular Surgery published most of the highly cited articles. The USA and Japan contributed nearly half the number of highly cited articles. Mayo Clinic and Nagoya University were highly cited institutions. Shionoya S and Olin JW were both the author with the largest number of citations and the most highly cited author in the reference. Articles that were highly cited most often addressed the following topics: “vasculitis”, “autoimmune disease”, and “critical limb ischemia”. Keywords that were mostly used in recent years were “stem cell therapy”, “progenitor therapy”, and “immunoadsorption”. The detection of bursts of author keywords showed the following: “permeability”, “differentiation”, and “critical limb ischemia” are recent keywords that have burst.

Conclusions
In this study, the highly cited contributors in the field of TAO research were identified. Most cited articles in the top 100 focused on the cardiovascular system and surgery. Treatment and pathophysiology including stem cell therapy, progenitor therapy, genetics, autoimmunity, and inflammation are the hotspots of TAO.
Electroacupuncture promotes neurogenesis in the dentate gyrus and improves pattern separation in an early Alzheimer's disease mouse model
Authors: Ding Yanyi , Li Long , Wang Sinuo , Cao Yajun , Yang Minguang , Dai Yaling , Lin Huawei , Li Jianhong , Liu Yulu , Wang Zhifu , Liu Weilin , Tao Jing 
Published: December 2023

Abstract
Background
Impaired pattern separation occurs in the early stage of Alzheimer’s disease (AD), and hippocampal dentate gyrus (DG) neurogenesis participates in pattern separation. Here, we investigated whether spatial memory discrimination impairment can be improved by promoting the hippocampal DG granule cell neogenesis-mediated pattern separation in the early stage of AD by electroacupuncture (EA).

Methods
Five familial AD mutations (5 × FAD) mice received EA treatment at Baihui and Shenting points for 4 weeks. During EA, mice were intraperitoneally injected with BrdU (50 mg/kg) twice a day. rAAV containing Wnt5a shRNA was injected into the bilateral DG region, and the viral efficiency was evaluated by detecting Wnt5a mRNA levels. Cognitive behavior tests were conducted to assess the impact of EA treatment on cognitive function. The hippocampal DG area Aβ deposition level was detected by immunohistochemistry after the intervention; The number of BrdU+/CaR+ cells and the gene expression level of calretinin (CaR) and prospero homeobox 1(Prox1) in the DG area of the hippocampus was detected to assess neurogenesis by immunofluorescence and western blotting after the intervention; The gene expression levels of FZD2, Wnt5a, DVL2, p-DVL2, CaMKII, and p-CaMKII in the Wnt signaling pathway were detected by Western blotting after the intervention.

Results
Cognitive behavioral tests showed that 5 × FAD mice had impaired pattern separation (P < 0.001), which could be improved by EA (P < 0.01). Immunofluorescence and Western blot showed that the expression of Wnt5a in the hippocampus was decreased (P < 0.001), and the neurogenesis in the DG was impaired (P < 0.001) in 5 × FAD mice. EA could increase the expression level of Wnt5a (P < 0.05) and promote the neurogenesis of immature granule cells (P < 0.05) and the development of neuronal dendritic spines (P < 0.05). Interference of Wnt5a expression aggravated the damage of neurogenesis (P < 0.05), weakened the memory discrimination ability (P < 0.05), and inhibited the beneficial effect of EA (P < 0.05) in AD mice. The expression level of Wnt pathway related proteins such as FZD2, DVL2, p-DVL2, CAMKII, p-CAMKII increased after EA, but the effect of EA was inhibited after Wnt5a was knocked down. In addition, EA could reduce the deposition of Aβ plaques in the DG without any impact on Wnt5a.

Conclusion
EA can promote hippocampal DG immature granule cell neogenesis-mediated pattern separation to improve spatial memory discrimination impairment by regulating Wnt5a in 5 × FAD mice.
Melatonin alleviates pyroptosis by regulating the SIRT3/FOXO3α/ROS axis and interacting with apoptosis in Atherosclerosis progression
Authors: Cong Lin , Liu Xiankun , Bai Yiming , Qin Qin , Zhao Lili , Shi Ying , Bai Yunpeng , Guo Zhigang 
Published: December 2023

Abstract
Background
Atherosclerosis (AS), a significant contributor to cardiovascular disease (CVD), is steadily rising with the aging of the global population. Pyroptosis and apoptosis, both caspase-mediated cell death mechanisms, play an essential role in the occurrence and progression of AS. The human pineal gland primarily produces melatonin (MT), an indoleamine hormone with powerful anti-oxidative, anti-pyroptotic, and anti-apoptotic properties. This study examined MT’s anti-oxidative stress and anti-pyroptotic effects on human THP-1 macrophages treated with nicotine.

Methods
In vitro, THP-1 macrophages were induced by 1 µM nicotine to form a pyroptosis model and performed 30 mM MT for treatment. In vivo, ApoE-/- mice were administered 0.1 mg/mL nicotine solution as drinking water, and 1 mg/mL MT solution was intragastric administrated at 10 mg/kg/day. The changes in pyroptosis, apoptosis, and oxidative stress were detected.

Results
MT downregulated pyroptosis, whose changes were paralleled by a reduction in reactive oxygen species (ROS) production, reversal of sirtuin3 (SIRT3), and Forkhead box O3 (FOXO3α) upregulation. MT also inhibited apoptosis, mainly caused by the interaction of caspase-1 and caspase-3 proteins. Vivo studies confirmed that nicotine could accelerate plaque formation. Moreover, mice treated with MT showed a reduction in AS lesion area.

Conclusions
MT alleviates pyroptosis by regulating the SIRT3/FOXO3α/ROS axis and interacting with apoptosis. Importantly, our understanding of the inhibitory pathways for macrophage pyroptosis will allow us to identify other novel therapeutic targets that will help treat, prevent, and reduce AS-associated mortality.
Embeddedness at varying depths: interactions between rural e-commerce entrepreneurs and China’s local politico-economic contexts
Authors: You Tianlong 
Published: December 2023

AbstractUsing data collected from face-to-face interviews, on-site observations, and other archival records, this article builds upon the mixed embeddedness framework to develop four concepts—hyper-, hypo-, governed, and dis-embeddedness—to capture the varied depths of rural e-commerce entrepreneurs’ embeddedness within multiple levels of contexts in response to four different local politico-economic conditions in China. This study finds that entrepreneurs in coastal province interiors are hyper-embedded in multiple levels of contexts that are interlinked through personal ties, while in the Pearl River Delta area, entrepreneurs’ hypo-embeddedness within multiple levels of contexts both enables and constrains their abilities to develop rural e-commerce businesses. Moreover, in the Yangtze River Delta area, in addition to entrepreneurs making their own efforts, local governments mobilize a variety of resources to affect the size, depth, and dynamics of entrepreneurs’ embeddedness, while in central and western provinces, entrepreneurs have not completely embraced the e-commerce economy because they face weak politico-economic conditions. This article further explores policy changes that would help entrepreneurs take full advantage of rural e-commerce in China.