bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bibliometric analysis and visualization of transdermal drug delivery research in the last decade: global research trends and hotspots
Authors: Chen Xinghan , Xiao Haitao , Shi Xiujun , Zhao Qiao , Xu Xuewen , Fan Ping , Xiao Dongqin 
Published: June 2023

Background: Transdermal delivery has become a crucial field in pharmaceutical research. There has been a proliferation of innovative methods for transdermal drug delivery. In recent years, the number of publications regarding transdermal drug delivery has been rising rapidly. To investigate the current research trends and hotspots in transdermal drug delivery, a comprehensive bibliometric analysis was performed.Methods: An extensive literature review was conducted to gather information on transdermal drug delivery that had been published between 2003 and 2022. The articles were obtained from the Web of Science (WOS) and the National Center for Biotechnology Information (NCBI) databases. Subsequently, the collected data underwent analysis and visualization using a variety of software tools. This approach enables a deeper exploration of the hotspots and emerging trends within this particular research domain.Results: The results showed that the number of articles published on transdermal delivery has increased steadily over the years, with a total of 2,555 articles being analyzed. The most frequently cited articles were related to the optimization of drug delivery and the use of nanotechnology in transdermal drug delivery. The most active countries in the field of transdermal delivery research were the China, United States, and India. Furthermore, the hotspots over the past 2 decades were identified (e.g., drug therapy, drug delivery, and pharmaceutical preparations and drug design). The shift in research focus reflects an increasing emphasis on drug delivery and control release, rather than simply absorption and penetration, and suggests a growing interest in engineering approaches to transdermal drug delivery.Conclusion: This study provided a comprehensive overview of transdermal delivery research. The research indicated that transdermal delivery would be a rapidly evolving field with many opportunities for future research and development. Moreover, this bibliometric analysis will help researchers gain insights into transdermal drug delivery research’s hotspots and trends accurately and quickly.
Design, in silico and pharmacological evaluation of a peptide inhibitor of BACE-1
Authors: Boldin Renata , Zychar Bianca Cestari , Gonçalves Luis Roberto C. , Sciani Juliana Mozer 
Published: June 2023

Introduction: Alzheimer’s disease (AD) is the main type of dementia, caused by the accumulation of amyloid plaques, formed by amyloid peptides after being processed from amyloid precursor protein (APP) by γ- and ß-secretases (BACE-1). Although amyloid peptides have been well established for AD, they have been found in other neurodegenerative diseases, such as Parkinson’s disease, Lewy body dementia, and amyotrophic lateral sclerosis. Inhibitors of BACE-1 have been searched and developed, but clinical trials failed due to lack of efficacy or toxicity. Nevertheless, it is still considered a good therapeutic target, as it was proven to remove amyloid peptides and improve memory.Methods: In this work, we designed a peptide based on a sequence obtained from the marine fish Merluccius productus and evaluated it by molecular docking to verify its binding to BACE-1, which was tested experimentally by enzymatic kinetics and cell culture assays. The peptide was injected in healthy mice to study its pharmacokinetics and toxicity.Results: We could obtain a new sequence in which the first N-terminal amino acids and the last one bound to the catalytic site of BACE-1 and showed high stability and hydrophobicity. The synthetic peptide showed a competitive inhibition of BACE-1 and Ki = 94 nM, and when injected in differentiated neurons, it could reduce Aβ42o production. In plasma, its half-life is ∼1 h, clearance is 0.0015 μg/L/h, and Vss is 0.0015 μg/L/h. The peptide was found in the spleen and liver 30 min after injection and reduced its level after that, when it was quantified in the kidneys, indicating its fast distribution and urinary excretion. Interestingly, the peptide was found in the brain 2 h after its administration. Histological analysis showed no morphological alteration in any organ, as well as the absence of inflammatory cells, indicating a lack of toxicity.Discussion: We obtained a new BACE-1 inhibitor peptide with fast distribution to the tissues, without accumulation in any organ, but found in the brain, with the possibility to reach its molecular target, BACE-1, contributing to the reduction in the amyloid peptide, which causes amyloid-linked neurodegenerative diseases.
Utilization patterns and prescription characteristics of traditional Chinese medicine among patients with irritable bowel syndrome in Taiwan
Authors: Gu Ye , Lai Yu-Tung , Chang Fang-Rong , Chen Chung-Yu 
Published: June 2023

Background: Few studies have investigated traditional Chinese medicine (TCM) utilization patterns for irritable bowel syndrome (IBS), despite the potential benefits of exploring TCM utilization patterns in optimizing TCM management. This study aimed to evaluate TCM utilization patterns and clinical features for IBS patterns in Taiwan.Methods: This was a population-based cross-sectional study using claim data from the National Health Insurance Research Database between 2012 and 2018. Patients newly diagnosed with IBS and aged over 20 years were included. The TCM utilization patterns and characteristics, including Chinese herbal medicine (CHM) treatment types and prescription patterns, were evaluated.Results: A total of 73,306 patients newly diagnosed with IBS used TCM for IBS at least once. Females used TCM for IBS more than males (female-to-male ratio = 1.89: 1). The age distribution showed a peak at 30–39 years (27.29%), followed by 40–49 years (20.74%) and 20–29 years (20.71%). Patients who received Western medications for IBS had a lower tendency to seek TCM. CHM was the most commonly used TCM modality (98.22%), with Jia-wei-xiao-yao-san being the most commonly prescribed Chinese herbal formula and Bai-zhu being the most frequently prescribed single Chinese herb.Conclusion: This study enhances our understanding of TCM usage patterns for IBS, particularly CHM prescriptions. Further research is needed to investigate commonly used TCM formulas and individual herbs.
Multi-omics research on common allergens during the ripening of pollen and poplar flocs of Populus deltoides
Authors: Guo Wei , Luo Hui , Cao Yi , Jiang Ziyun , Liu Hui , Zou Jie , Sheng Changle , Xi Yilong 
Published: June 2023

BackgroundPopulus deltoides is widely cultivated in China and produces a large number of pollen and poplar flocs from March to June per year. Previous studies have found that the pollen of P. deltoides contains allergens. However, studies on the ripening mechanism of pollen/poplar flocs and their common allergens are very limited.MethodsProteomics and metabolomics were used to study the changes of proteins and metabolites in pollen and poplar flocs of P. deltoides at different developmental stages. Allergenonline database was used to identify common allergens in pollen and poplar flocs at different developmental stages. Western blot (WB) was used to detect the biological activity of common allergens between mature pollen and poplar flocs.ResultsIn total, 1400 differently expressed proteins (DEPs) and 459 different metabolites (DMs) were identified from pollen and poplar flocs at different developmental stages. KEGG enrichment analysis showed that DEPs in pollen and poplar flocs were significantly enriched in ribosome and oxidative phosphorylation signaling pathways. The DMs in pollen are mainly involved in aminoacyl-tRNA biosynthesis and arginine biosynthesis, while the DMs in poplar flocs are mainly involved in glyoxylate and dicarboxylate metabolism. Additionally, 72 common allergens were identified in pollen and poplar flocs at different developmental stages. WB showed that there were distinct binding bands between 70 and 17KD at the two groups of allergens.ConclusionsA multitude of proteins and metabolites are closely related to the ripening of pollen and poplar flocs of Populus deltoides, and they contain common allergens between mature pollen and poplar flocs.
Fear of COVID-19 among cancer patients in Henan Province, Central China: causes, results, and coping factors
Authors: Mao Yiqing , Ma Wenjie , Kang Dingding , Miao Yudong , Fu Hang , Zhang Bowen , Zhang Jiangong , Wu Jian 
Published: June 2023

ObjectivesCancer patients exhibit fear of COVID-19, which could lead to serious consequences. However, minimal information is available about the effect of the COVID-19 pandemic on the mental health of cancer patients. Therefore, this study aims to examine the fear level of COVID-19 among cancer patients in Henan Province, Central China and to identify its causes, results, and coping factors.MethodsAn online survey was conducted among 1,067 cancer patients. The participants reported their individual fear level of COVID-19, risk of COVID-19 infection, risk of death from COVID-19, COVID-19 vaccination concerns, influence level of COVID-19 pandemic on their disease treatment, loneliness due to COVID-19, economic burden from COVID-19, quality of life, safety behavior, information regarding COVID-19 vaccination, psychological guidance, physical activities, and demographic characteristics. Chi-square and cumulative logistic regression were used to determine the predictors of COVID-19 fear level.ResultsThis study indicates that cancer patients report moderate fear level of COVID-19 in Central China (66.9%). The six cause factors (risk of COVID-19 infection, risk of death from COVID-19, COVID-19 vaccination concerns, influence level of COVID-19 pandemic on disease treatment, loneliness due to COVID-19, and economic burden from COVID-19) were positively associated with COVID-19 fear level. Three coping factors (information regarding COVID-19 vaccination, psychological guidance, and physical activities) were negatively associated with COVID-19 fear level. COVID-19 fear level was negatively associated with quality of life and positively associated with safety behavior.ConclusionOur results suggest that governments should improve access to personalized vaccine counseling and psychological guidance by undertaking the responsibility of patients’ attending physicians and increasing publicity. Physical activities should be included in the treatment program to help cancer patients better recover their physical and mental health.
What constitutes victims of toxicity - identifying drivers of toxic victimhood in multiplayer online battle arena games
Authors: Kordyaka Bastian , Laato Samuli , Weber Sebastian , Niehaves Bjoern 
Published: June 2023

IntroductionToxic behavior (i.e., toxicity) is a pervasive problem in online gaming communities such as League of Legends. This issue arises from factors such as frustrating and stressful in-game experiences and online disinhibition. Prior research on addressing toxicity has focused primarily on the perpetrators and how to mitigate their negative behavior and the consequences. The aim of this study was to approach toxicity from the perspective of the victims instead, and consequently, to investigate the factors that contribute to the experience of victimhood in multiplayer online battle arena games.MethodsA global sample of League of Legends and Defense of the Ancients 2 players (n=313) was collected to test hypotheses based on three theoretical approaches drawn from previous work, namely, the online disinhibition effect, social cognitive theory and theory of planned behavior. Participants were asked to complete a survey that included variables related to the three theoretical approaches.ResultsThe results of the study indicated that self-efficacy, and benign and toxic disinhibition, were the most relevant antecedents for the experience of being a victim of toxicity. Accordingly, the findings thus suggest that players with low self-efficacy and high online disinhibition may be more likely to experience victimhood in multiplayer online battle arena games. In general, insights based on our study demonstrate that individual characteristics partially explain why some players are more susceptible to toxic behavior than others.DiscussionThe study’s results have practical implications for game developers and policymakers, particularly in the areas of community management and player education. For example, game developers may consider incorporating self-efficacy training and disinhibition reduction programs into their games. Overall, this study contributes to the growing body of literature on toxicity in online gaming communities and invites further research into toxicity from the perspective of the victims.
Implementation of cross-sector partnerships: a description of implementation factors related to addressing social determinants to reduce racial disparities in adverse birth outcomes
Authors: Blebu Bridgette E. , Liu Patrick Y. , Harrington Maura , Nicholas William , Jackson Ashaki , Saleeby Erin 
Published: June 2023

IntroductionTraditional perinatal care alone cannot address the social and structural determinants that drive disparities in adverse birth outcomes. Despite the wide acceptance of partnerships between healthcare systems and social service agencies to address this challenge, there needs to be more research on the implementation factors that facilitate (or hinder) cross-sector partnerships, particularly from the perspective of community-based organizations. This study aimed to integrate the views of healthcare staff and community-based partner organizations to describe the implementation of a cross-sector partnership designed to address social and structural determinants in pregnancy.MethodsWe used a mixed methods design (in-depth interviews and social network analysis) to integrate the perspectives of healthcare clinicians and staff with those of community-based partner organizations to identify implementation factors related to cross-sector partnerships.ResultsWe identified seven implementation factors related to three overarching themes: relationship-centered care, barriers and facilitators of cross-sector partnerships, and strengths of a network approach to cross-sector collaboration. Findings emphasized establishing relationships between healthcare staff, patients, and community-based partner organizations.ConclusionThis study provides practical insights for healthcare organizations, policymakers, and community organizations that aim to improve access to social services among historically marginalized perinatal populations.
The assessment and validation of the depression, anxiety, and stress scale (DASS-21) among frontline doctors in Pakistan during fifth wave of COVID-19
Authors: Nadeem Muhammad Umar , Kulich Steve J. , Bokhari Ijaz Hussain 
Published: June 2023

ObjectiveThe study aims to document sociodemographic features, address the symptoms and levels of depression, anxiety, and stress among frontline doctors in Pakistan, and validate the depression, anxiety, stress scale (DASS-21) on the context of Pakistan.MethodA cross-sectional survey was conducted throughout the regions of Pakistan on frontline doctors to document their sociodemographic patterns and the levels of depression, anxiety, and stress while dealing with the fifth wave (Omicron-variant) of the coronavirus (SARS-CoV-2) pandemic in Pakistan (December 2021–April 2022). Respondents (N = 319) were recruited through a snowball sampling process.ResultsThough previous literature reported declines in psychological symptoms after earlier waves of COVID-19, these DASS-21 findings show that as the pandemic has worn on, frontline doctors in Pakistan are having considerable personal symptoms of depression (72.7%), anxiety (70.2%), and stress (58.3%). Though specifically related to the COVID-19 pandemic, they rated only moderate levels of depression and stress, however they reported severe levels of anxiety. The results also revealed a positive correlation between depression and anxiety (r = 0.696, p &lt; 0.001), depression and stress (r = 0.761, p &lt; 0.001), and anxiety and stress (r = 0.720, p &lt; 0.001).ConclusionThrough the application of all required statistical procedures, DASS-21 is validated in the cultural context of Pakistan among this group of frontline doctors. The findings of this study can provide new directions for the policy makers (government and hospitals' administration) of Pakistan to focus on the mental wellbeing of the doctors under similar enduring public health crises and to protect them from short- or long-term disorders.
Embolo/sclerotherapy for the treatment of hand arteriovenous malformations: a single-center retrospective cohort experience
Authors: Fan Xueqiang , Zhang Jianbin , Liu Peng , Ye Zhidong 
Published: June 2023

PurposeTo retrospectively report our preliminary experience of treating hand arteriovenous malformations (AVMs) with embolo/sclerotherapy.Materials and methodsRetrospectively review the demographics, treatment detail, outcome data, and complications of 13 consecutive patients with hand AVMs from January 2018 to December 2021. We embolize the dominant outflow vein with elastic coils and then use absolute ethanol or polidocanol for intravascular sclerotherapy and bleomycin for interstitial sclerotherapy.ResultsYakes type II presents in four lesions, type IIIa in six, and type IIIb in three. A total of 29 treatment episodes were conducted for the 13 patients (1 episode for 3 patients, 2 for 4 patients, and 3 for 6 patients; the repeated treatment rate was 76.9%). The mean stretched length of coils for 1 treatment episode was 95 cm. The mean absolute ethanol dosage was 6.8 ml (range 4–30 ml). In addition, 10 ml of 3% polidocanol foam was injected and interstitial sclerotherapy with 150,000 IU bleomycin was performed on every patient. The post-operative arterial-dominant outflow vein pressure index (AVI) increased in the 29 procedures (6.55 ± 1.68 vs. 9.38 ± 2.80, P &lt; 0.05). The Mann–Whitney U test showed that the post-operative AVI was higher in patients without re-intervention (P &lt; 0.05). Local swelling occurred after all the procedures. Blistering occurred in 6 of the patients in 13 (44.8%) of the 29 procedures. Superficial skin necrosis occurred in 3 of the patients in 5 (17.2%) of the 29 procedures. The swelling, blistering, and superficial skin necrosis recovered within 4 weeks. No finger amputation occurred. The follow-up time was 6 months. The 6-month assessment of clinical improvement after the last treatment episode showed that 2 patients were cured, 10 were improved, and 1 remained unchanged. With regard to angiographic evaluation, 9 showed partial response and 4 complete response.ConclusionEmbolo/sclerotherapy can be effective and safe for hand AVM. The AVI increased significantly after embolo/sclerotherapy, and the index may be valuable in predicting recurrence in further study.
Ionizing Radiation Induced Removal of Ofloxacin, Abatement of Its Toxicity and Antibacterial Activity in Various Water Matrices
Authors: Wojnárovits László , Homlok Renáta , Kovács Krisztina , Bezsenyi Anikó , Takács Erzsébet 
Published: June 2023

The fluoroquinolone-type antibiotic ofloxacin is regularly detected in wastewaters. In this work, its hydroxyl radical (•OH) induced degradation was studied at a concentration of 0.1 mmol dm−3 in three water matrices, pure water, tap water, and purified wastewater (collected from a wastewater treatment plant). •OH was produced by γ-irradiation under conditions when it had a high yield. The •OH dosage dependencies of chemical (COD) and biochemical (BOD) oxygen demands, total organic carbon (TOC) content, oxygen uptake rate (OUR), Microtox® toxicity, and antibacterial activity values were evaluated. •OH effectively oxidized and mineralized ofloxacin; both processes were observed even at the lowest •OH dosage, 0.14 mmol dm−3 (0.5 kGy absorbed dose). When 0.28 mmol dm−3 •OH was introduced into pure or tap water, the antibacterial activity vanished. In purified wastewater, a higher dosage (0.56 mmol dm−3) was required to achieve the same effect as in pure water, due to the organic molecules of the matrix that quenched the •OH radicals. The products did not have antibacterial activity and showed little toxicity toward the test organism Vibrio fischeri. •OH preferentially attacks the pharmacophore part, the 4-quinolone unit of ofloxacin. •OH-induced reactions can be safely applied to destroy the antimicrobial potency of fluoroquinolone-type antibiotics in purified wastewater matrices.
Bioefficacy of Lecanoric Acid Produced by Parmotrema austrosinense (Zahlbr.) Hale against Tea Fungal Pathogens
Authors: Rajendran Kalidoss , Ponmurugan Ponnusamy , Gnanamangai Balasubramanian Mythili , Karuppiah Ponmurugan , Shaik Mohammed Rafi , Khan Mujeeb , Khan Merajuddin , Shaik Baji 
Published: June 2023

Lichens are symbiotic organisms that are composed of fungal partners and photosynthetic algal partners. During the symbiotic process in lichen thallus, the fungus synthesizes certain secondary metabolites in which lecanoric acid is very important in terms of antibiotic properties. Considering the vital importance of lecanoric acid, the present study aimed to produce lecanoric acid from the thallus of Parmotrema austrosinense lichen using Modified Bold’s basal salt medium and evaluate the bio-efficacy against tea fungal pathogens. Lecanoric acid was purified and confirmed by micro-crystallization method and subsequently bioassayed against tea fungal pathogens. The results revealed that lecanoric acid registered a significant antifungal activity in terms of the growth inhibition of test pathogens. Companion systemic and botanical fungicides were found to be inferior to lecanoric acid in the percentage of growth inhibition. The inhibition rate varied among tea pathogens. Of the tea pathogens tested, tea leaf disease-causing pathogens including Cercospora theae (C. theae), Glomerella cingulata (G. cingulate), and Phomopsis theae (P. theae) showed the highest percentage of growth inhibition followed by stem and root rot diseases. The present study suggests that lecanoric acid showed an inhibitory effect against tea pathogens, which might be due to antibiotic properties and fungicidal action of lecanoric acid.
(Iq)–Stability and Uniform Convergence of the Solutions of Singularly Perturbed Boundary Value Problems
Authors: Vrabel Robert 
Published: June 2023

In this paper, using the notion of (Iq)–stability and the method of a priori estimates, known as the method of lower and upper solutions, the sufficient conditions guaranteeing uniform convergence of solutions to the solution of a reduced problem on the entire interval [a,b] have been established for four different types of boundary conditions for a singularly perturbed differential equation εy″=f(x,y,y′), a≤x≤b. In the second part of the paper, by employing the Peano phenomenon, we analyzed the structure of the solutions of the reduced problem f(x,y,y′)=0.