bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibacterial activity of Dioscorea bulbifera Linn. extract and its active component flavanthrinin against skin-associated bacteria
Authors: Sanguansermsri Donruedee , Sanguansermsri Phanchana , Buaban Kittisak , Choommongkol Vachira , Akekawatchai Chareeporn , Charoensri Noree , Fraser Ian , Wongkattiya Nalin 
Published: May 2024

Abstract
Background
Dioscorea bulbifera Linn. has been used for wound care in Thailand. However, a comprehensive evaluation of its antibacterial activity is required. This study aimed to investigate the antibacterial efficacy of D. bulbifera extract against skin-associated bacteria and isolate and characterize its active antibacterial agent, flavanthrinin.

Methods
Air-dried bulbils of D. bulbifera were pulverised and extracted with hexane, dichloromethane, ethyl acetate, methanol, ethanol, and distilled water; vacuum filtered; concentrated; freeze-dried; and stored at -20 ºC. Antibacterial activity of the extracts was assessed using microdilution techniques against several skin-associated bacteria. Thin-layer chromatography (TLC) bioautography was used to identify the active compounds in the extract, which were fractionated by column chromatography and purified by preparative TLC. The chemical structures of the purified compounds were analysed using nuclear magnetic resonance (NMR). The cytotoxicity of the extract and its active compounds was evaluated in Vero cells.

Results
The ethyl acetate extract exhibited distinct inhibition zones against bacteria compared to other extracts. Therefore, the ethyl acetate extract of D. bulbifera in the ethyl acetate layer was used for subsequent analyses. D. bulbifera extract exhibited antibacterial activity, with minimum inhibitory concentrations (MICs) of 0.78–1.56 mg/mL. An active compound, identified through TLC-bioautography, demonstrated enhanced antibacterial activity, with MICs of 0.02–0.78 mg/mL. NMR analysis identified this bioactive compound as flavanthrinin. Both D. bulbifera extract and flavanthrinin-containing fraction demonstrated potent antibacterial activity against Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), and S. epidermidis. The flavanthrinin containing fraction demonstrated low cytotoxicity against Vero cells, showing CC50 values of 0.41 ± 0.03 mg/mL. These values are lower than the MIC value, indicating that this fraction is safer than the initial ethyl acetate extract.

Conclusions
Dioscorea bulbifera extract and its bioactive component flavanthrinin demonstrated significant antibacterial activity against the skin-associated bacteria Staphylococci, including MRSA. Flavanthrinin has potential as a complementary therapeutic agent for managing skin infections owing to its potent antibacterial effects and low cytotoxicity.
Exploring machine learning strategies for predicting cardiovascular disease risk factors from multi-omic data
Authors: Drouard Gabin , Mykkänen Juha , Heiskanen Jarkko , Pohjonen Joona , Ruohonen Saku , Pahkala Katja , Lehtimäki Terho , Wang Xiaoling , Ollikainen Miina , Ripatti Samuli , Pirinen Matti , Raitakari Olli , Kaprio Jaakko 
Published: May 2024

Abstract
Background
Machine learning (ML) classifiers are increasingly used for predicting cardiovascular disease (CVD) and related risk factors using omics data, although these outcomes often exhibit categorical nature and class imbalances. However, little is known about which ML classifier, omics data, or upstream dimension reduction strategy has the strongest influence on prediction quality in such settings. Our study aimed to illustrate and compare different machine learning strategies to predict CVD risk factors under different scenarios.

Methods
We compared the use of six ML classifiers in predicting CVD risk factors using blood-derived metabolomics, epigenetics and transcriptomics data. Upstream omic dimension reduction was performed using either unsupervised or semi-supervised autoencoders, whose downstream ML classifier performance we compared. CVD risk factors included systolic and diastolic blood pressure measurements and ultrasound-based biomarkers of left ventricular diastolic dysfunction (LVDD; E/e' ratio, E/A ratio, LAVI) collected from 1,249 Finnish participants, of which 80% were used for model fitting. We predicted individuals with low, high or average levels of CVD risk factors, the latter class being the most common. We constructed multi-omic predictions using a meta-learner that weighted single-omic predictions. Model performance comparisons were based on the F1 score. Finally, we investigated whether learned omic representations from pre-trained semi-supervised autoencoders could improve outcome prediction in an external cohort using transfer learning.

Results
Depending on the ML classifier or omic used, the quality of single-omic predictions varied. Multi-omics predictions outperformed single-omics predictions in most cases, particularly in the prediction of individuals with high or low CVD risk factor levels. Semi-supervised autoencoders improved downstream predictions compared to the use of unsupervised autoencoders. In addition, median gains in Area Under the Curve by transfer learning compared to modelling from scratch ranged from 0.09 to 0.14 and 0.07 to 0.11 units for transcriptomic and metabolomic data, respectively.

Conclusions
By illustrating the use of different machine learning strategies in different scenarios, our study provides a platform for researchers to evaluate how the choice of omics, ML classifiers, and dimension reduction can influence the quality of CVD risk factor predictions.
Barriers and facilitators to implementing a Canadian shared-care ADHD program in pediatric settings in Shanghai: a consolidated framework for implementation research approach
Authors: Bahraini Sayna , Maisonneuve Alexander R. , Wu Danping , Huang Minhui , Xu Mingyu , Yang Li , Li Fei , Samson André , Li Feng , Robaey Philippe 
Published: May 2024

Abstract
Objectives
The vast majority of children with Attention-Deficit Hyperactivity Disorder (ADHD) do not have access to proper diagnosis and treatment in China. The goal of this project is to identify the challenges and facilitators in implementing a Canadian ADHD Shared Care Pathways program in pediatric settings in Shanghai region.

Methods
Purposive semi-structured focus groups were conducted on a total of 13 healthcare practitioners from the Shanghai Xinuha, Ninghai and Chongming hospitals. Two independent researchers conducted a thematic analysis of the data with themes emerging based on the Consolidated Framework for Implementation Research (CFIR).

Results
Notable barriers identified by participants included: (1) lack of knowledge in the management of ADHD, primarily among general practitioners; (2) lack of resources such as lack of staff, time, and medication for ADHD; (3) challenges in implementing an international multicentre intervention (such as communication difficulties between teams and integration of resources available in different hospitals); and (4) mental health stigma, difficulties in identifying ADHD patients, and logistical problems related to medication procurement rules put in place by provincial governments. Notable facilitators included: (1) the strong motivation of stakeholders and their confidence in their ability to learn and subsequently execute action plans to achieve the implementation goal; (2) the compatibility between the values and goals of the stakeholders and those of the program despite some cultural tension, a positive learning climate, strong tensions for change, and the high interest of organization leaders in engaging in the program (3) the perceived benefits of the program, such as standardization of the diagnostic and treatment process, and engaging primary care providers in ADHD management; and (4) the strong relationship between participating institutions and schools as well as provincial health initiatives available to support collaborative models of care. Mixed factors to implementation were also explored.

Conclusions
Appropriate training of health care providers, cultural adaptation of the program, increase public awareness about ADHD to decrease stigma, as well as strong project management and guidelines that clearly describe the role and expectations of each team member appeared essential to successful implementation.
Digital dermatitis in Swedish dairy herds assessed by ELISA targeting Treponema phagedenis in bulk tank milk
Authors: Roelofs Lex , Frössling Jenny , Rosander Anna , Bjerketorp Joakim , Belaghi Reza Arabi , Hansson Ingrid , Frosth Sara 
Published: May 2024

Abstract
Background
Digital dermatitis (DD) is a contagious hoof infection affecting cattle worldwide. The disease causes lameness and a reduction in animal welfare, which ultimately leads to major decreases in milk production in dairy cattle. The disease is most likely of polymicrobial origin with Treponema phagedenis and other Treponema spp. playing a key role; however, the etiology is not fully understood. Diagnosis of the disease is based on visual assessment of the feet by trained hoof-trimmers and veterinarians, as a more reliable diagnostic method is lacking. The aim of this study was to evaluate the use of an enzyme-linked immunosorbent assay (ELISA) on bulk tank milk samples testing for the presence of T. phagedenis antibodies as a proxy to assess herd prevalence of DD in Swedish dairy cattle herds.

Results
Bulk tank milk samples were collected in 2013 from 612 dairy herds spread across Sweden. A nationwide DD apparent prevalence of 11.9% (8.1–14.4% CI95%) was found, with the highest proportion of test-positive herds in the South Swedish regions (31.3%; 19.9–42.4% CI95%).

Conclusions
This study reveals an underestimation of DD prevalence based on test results compared to hoof trimming data, highlighting the critical need for a reliable and accurate diagnostic method. Such a method is essential for disease monitoring and the development of effective control strategies. The novelty of ELISA-based diagnostic methods for DD, coupled with the disease’s polymicrobial origin, suggests an avenue for improvement. Developing an expanded ELISA, incorporating antigens from various bacterial species implicated in the disease, could enhance diagnostic accuracy. The significance of this study is underscored by the extensive analysis of a substantial sample size (612). Notably, this investigation stands as the largest assessment to date, evaluating the application of ELISA on bulk tank milk for DD diagnosis at the herd level.
A lava-inspired proteolytic enzyme therapy on cancer with a PEG-based hydrogel enhances tumor distribution and penetration of liposomes
Authors: Li Jiaojiao , Mi Dandan , Wang Rujing , Li Yuke , Zhao Mengnan , Shi Sanjun 
Published: May 2024

AbstractThe enhanced permeability and retention (EPR) effect has become the guiding principle for nanomedicine against cancer for a long time. However, several biological barriers severely resist therapeutic agents’ penetration and retention into the deep tumor tissues, resulting in poor EPR effect and high tumor mortality. Inspired by lava, we proposed a proteolytic enzyme therapy to improve the tumor distribution and penetration of nanomedicine. A trypsin-crosslinked hydrogel (Trypsin@PSA Gel) was developed to maintain trypsin’s activity. The hydrogel postponed trypsin’s self-degradation and sustained the release. Trypsin promoted the cellular uptake of nanoformulations in breast cancer cells, enhanced the penetration through endothelial cells, and degraded total and membrane proteins. Proteomic analysis reveals that trypsin affected ECM components and down-regulated multiple pathways associated with cancer progression. Intratumoral injection of Trypsin@PSA Gel significantly increased the distribution of liposomes in tumors and reduced tumor vasculature. Combination treatment with intravenous injection of gambogic acid-loaded liposomes and intratumoral injection of Trypsin@PSA Gel inhibited tumor growth. The current study provides one of the first investigations into the enhanced tumor distribution of liposomes induced by a novel proteolytic enzyme therapy.
Graphic Abstract
Two remarkable serine/leucine polymorphisms in Helicobacter pylori: functional importance for serine protease HtrA and adhesin BabA
Authors: Backert Steffen , Tegtmeyer Nicole , Horn Anselm H. C. , Sticht Heinrich , Linz Bodo 
Published: May 2024

AbstractSingle nucleotide polymorphisms (SNPs) account for significant genomic variability in microbes, including the highly diverse gastric pathogen Helicobacter pylori. However, data on the effects of specific SNPs in pathogen-host interactions are scarce. Recent functional studies unravelled how a serine/leucine polymorphism in serine protease HtrA affects the formation of proteolytically active trimers and modulates cleavage of host cell-to-cell junction proteins during infection. A similar serine/leucine mutation in the carbohydrate binding domain of the adhesin BabA controls binding of ABO blood group antigens, enabling binding of either only the short Lewis b/H antigens of blood group O or also the larger antigens of blood groups A and B. Here we summarize the functional importance of these two remarkable bacterial SNPs and their effect on the outcome of pathogen-host interactions.
Knowledge and practices of traditional management of child malnutrition and associated pathologies in Benin
Authors: Vissoh Ahamidé Carel Sosthène , Klotoé Jean Robert , Fah Lauris , Agbodjento Eric , Koudokpon Hornel , Togbe Eskyl , Saïdou Souad , Dougnon Victorien 
Published: May 2024

Abstract
Background
Child malnutrition is a major public health challenge, affecting millions of children worldwide, with alarming proportions of children under five in Benin. The complexity of managing this condition is increased by its potential association with opportunistic pathologies. An interesting approach arises from the use of medicinal plants, to address child malnutrition and its associated pathologies. This study aimed to document the knowledge and practices of Beninese mothers and traditional practitioners with regard to the use of medicinal plants to treat child malnutrition and associated diseases.

Methods
A total of 844 Beninese mothers and 201 traditional healers were surveyed between March 2022 and August 2023 in the communes of Karimama, Bopa and Za-Kpota in Benin. The respondents’ knowledge of child malnutrition and associated pathologies was explored. The ethnobotanical data collected from the subjects concerned the medicinal recipes used to treat child malnutrition, the medicinal plants that make them up and the methods of use. These data were analyzed using ethnobotanical indices such as the Informant Consensus Factor, the frequency of citation of medicinal recipes types and medicinal plants, and the contribution of plants to medicinal recipes.

Results
All respondents cited a total of 82 plant species used to treat child malnutrition and associated diseases. These plants were grouped into 37 botanical families, the most common of which were Fabaceae, Malvaceae and Annonaceae. The leaves were the most commonly used part of the plant species identified. The mothers shared 122 medicinal recipes, ranging from recipes based on a single plant to more complex compositions involving five plants. The most notable plants were Moringa oleifera Lam, Phyllanthus amarus Schumach & Thonn, Senna siamea (Lam.) H.S.Irwin & Barneby, Carica papaya L. and Ocimum gratissimum L. Traditional healers provided 52 plants in 71 recipes, with Moringa oleifera featuring prominently in both single-plant and multiplant formulations.

Conclusion
This study made it possible to constitute a rich base of medicinal recipes used against malnutrition and associated pathologies, with the preponderant involvement of certain plant species. It is therefore necessary to deepen research on these different identified species in order to scientifically assess their potential.
Tunisian Artemisia campestris L.: a potential therapeutic agent against myeloma - phytochemical and pharmacological insights
Authors: Limam Inès , Ghali Ridha , Abdelkarim Mohamed , Ouni Anis , Araoud Manel , Abdelkarim Mouaadh , Hedhili Abderrazek , Ben-Aissa Fennira Fatma 
Published: May 2024

Abstract
Background
Artemisia campestris L. (AC) leaves are widely recognized for their importance in traditional medicine. Despite the considerable amount of research conducted on this plant overworld, the chemical composition and the biological activity of the leaves grown in Tunisia remains poorly investigated. In this study of AC, a successive extraction method was employed (hexane, ethyl acetate and methanol) to investigate its bioactive constituents by LC-MS analysis, and their antioxidant, antibacterial, antifungal, and anticancer activities.

Results
Data analysis revealed diverse compound profiles in AC extracts. Methanolic and ethyl acetate extracts exhibited higher polyphenolic content and antioxidant activities, while Hexane showed superior phytosterol extraction. Ethyl acetate extract displayed potent antibacterial activity against multi-resistant Staphylococcus aureus and Pseudomonas aeruginosa. Additionally, all extracts demonstrated, for the first time, robust antifungal efficacy against Aspergillus flavus and Aspergillus niger. Cytotoxicity assays revealed the significant impact of methanolic and ethyl acetate extracts on metastatic breast cancer and multiple myeloma, examined for the first time in our study. Moreover, further analysis on multiple myeloma cells highlighted that the ethyl acetate extract induced apoptotic and necrotic cell death and resulted in an S phase cell cycle blockage, underscoring its therapeutic potential.

Conclusions
This investigation uncovers novel findings in Tunisian AC, notably the identification of lupeol, oleanolic acid, ursolic acid, stigmasterol and β-sitosterol. The study sheds light on the promising role of AC extracts in therapeutic interventions and underscores the need for continued research to harness its full potential in medicine and pharmaceutical development.
GTSE1 promotes nasopharyngeal carcinoma proliferation and angiogenesis by upregulating STMN1
Authors: Dong Jiadi , Chen Jingjing , Wu Yidong , Yan Jiangyu 
Published: May 2024

Abstract
Background
Nasopharyngeal carcinoma (NPC) is a malignant tumor with poor survival rate. G2 and S phase-expressed‐1 (GTSE1) takes part in the progression of diverse tumors as an oncogene, but its role and potential mechanism in NPC remain unknown.

Methods
The GTSE1 expression was analyzed by western blot in NPC tissues and cells. Knock-down experiments were conducted to determine the function of GTSE1 in NPC by cell counting kit-8, the 5-ethynyl-2′-deoxyuridine (EdU) incorporation experiment, cell scratch wound-healing experiment, transwell assays, tube forming experiment and western blot. In addition, the in vivo role of GTSE1 was addressed in tumor-bearing mice.

Results
The expression of was increased in NPC. Silencing of GTSE1 suppressed cell viability, the percent of EdU positive cells, and the number of invasion cells and tubes, but enhanced the scratch ratio in NPC cells. Mechanically, downregulation of GTSE1 decreased the expressions of FOXM1 and STMN1, which were restored with the upregulation of FOXM1. Increased expression of STMN1 reversed the effects of the GTSE1 silencing on proliferation, migration, invasion and angiogenesis of NPC cells. Furthermore, knockdown of GTSE1 repressed the tumor volume and tumor weight of xenografted mice.

Conclusion
GTSE1 was highly expressed in NPC, and silencing of GTSE1 ameliorated the malignant processes of NPC cells by upregulating STMN1, suggesting a possible therapeutical target for NPC.
Clinical characteristics, radiological features and outcomes in pulmonary involvement of cryoglobulinemia
Authors: Han Hong-xiao , Su Wei , Tian Xinlun , Zhou Dao-bin , Li Jian , Cao Xin-xin 
Published: May 2024

Abstract
Background
Cryoglobulinemia with pulmonary involvement is rare, and its characteristics, radiological findings, and outcomes are still poorly understood.

Methods
Ten patients with pulmonary involvement of 491 cryoglobulinemia patients at Peking Union Medical College Hospital were enrolled in this retrospective study. We analyzed the characteristics, radiological features and management of pulmonary involvement patients, and compared with those of non-pulmonary involvement with cryoglobulinemia.

Results
The 10 patients with pulmonary involvement (2 males; median age, 53 years) included three patients with type I cryoglobulinemia and seven patients with mixed cryoglobulinemia. All of 10 patients were IgM isotype cryoglobulinemia. All type I patients were secondary to B-cell non-Hodgkin lymphoma. Four mixed patients were essential, and the remaining patients were secondary to infections (n = 2) and systemic lupus erythematosus (n = 1), respectively. Six patients had additional affected organs, including skin (60%), kidney (50%), peripheral nerves (30%), joints (20%), and heart (20%). The pulmonary symptoms included dyspnea (50%), dry cough (30%), chest tightness (30%), and hemoptysis (10%). Chest computed tomography (CT) showed diffuse ground-glass opacity (80%), nodules (40%), pleural effusions (30%), and reticulation (20%). Two patients experienced life-threatening diffuse alveolar hemorrhage. Five patients received corticosteroid-based regimens, and four received rituximab-based regimens. All patients on rituximab-based regimens achieved clinical remission. The estimated two-year overall survival (OS) was 40%. Patients with pulmonary involvement had significantly worse OS and progression-free survival than non-pulmonary involvement patients of cryoglobulinemia (P < 0.0001).

Conclusions
A diagnosis of pulmonary involvement should be highly suspected for patients with cryoglobulinemia and chest CT-indicated infiltrates without other explanations. Patients with pulmonary involvement had a poor prognosis. Rituximab-based treatment may improve the outcome.
LncRNA PCED1B-AS1 mediates miR-3681-3p/MAP2K7 axis to promote metastasis, invasion and EMT in gastric cancer
Authors: Cao Jia , Yang Yicheng , Duan Bensong , Zhang Haibin , Xu Qinwei , Han Junyi , Lu Bing 
Published: May 2024

Abstract
Background
LncRNA PCED1B-AS1 is abnormally expressed in multiple cancers and has been confirmed as an oncogene. Our study aimed to investigate the regulatory mechanism of lncRNA PCED1B-AS1 in gastric cancer.

Methods
TCGA database was used to analyze the abnormal expression of lncRNA PCED1B-AS1 in gastric cancer. By database prediction and mass spectrometric analysis, miR-3681-3p and MAP2K7 are potential downstream target molecules of lncRNA PCED1B-AS1 and verified by dual-luciferase report assay. RT-qPCR analysis and western blot were performed to detect the expressions of PCED1B-AS1 and MAP2K7 in gastric cancer cell lines and tissues. CCK-8 kit was applied to measure the cell viability. Wound healing and Transwell experiment were used to detect the migration and invasion. Western blot and immunohistochemical staining were performed to detect the expressions of EMT-related proteins in tissues. The changes of tumor proliferation were detected by xenograft experiment in nude mice.

Results
PCED1B-AS1 expression was higher but miR-3681-3 expression was lower in gastric cancer cell lines or tissues, compared to normal group. Function analysis verified PCED1B-AS1 promoted cell proliferation and inhibited cell apoptosis in gastric cancer cells in vitro and in vivo. LncRNA PCED1B-AS1 could bind directly to miR-3681-3p, and MAP2K7 was found to be a downstream target of miR-3681-3p. MiR-3681-3p mimics or si-MAP2K7 could partly reverse the effect of PCED1B-AS1 on gastric cancer cells.

Conclusion
PCED1B-AS1 accelerated cell proliferation and inhibited cell apoptosis through sponging miR-3681-3p to upregulate MAP2K7 expression in gastric cancer, which indicated PCED1B-AS1/miR-3681-3p/MAP2K7 axis may serve as a potential therapeutic target for gastric cancer.