bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hesperidin identified from Citrus extracts potently inhibits HCV genotype 3a NS3 protease
Authors: Khan Mahim , Rauf Waqar , Habib Fazal-e- , Rahman Moazur , Iqbal Shoaib , Shehzad Aamir , Iqbal Mazhar 
Published: April 2022

Abstract
Background
Hepatitis C virus infection is the main cause of liver ailments across the globe. Several HCV genotypes have been identified in different parts of the world. Effective drugs for combating HCV infections are available but not affordable, particularly to infected individuals from resource-limited countries. Hence, cost-effective drugs need to be developed against important HCV drug targets. As Citrus fruits naturally contain bioactive compounds with antiviral activities, the current study was designed to identify antiviral inhibitors from Citrus fruit extracts against an important drug target, NS3 protease, of HCV genotype 3a which is found predominantly in South Asian countries.

Methods
The full-length NS3 protease alone and the NS3 protease domain in fusion with the cognate NS4A cofactor were expressed in Escherichia coli, and purified by chromatographic techniques. Using the purified protein as a drug target, Citrus extracts were evaluated in a FRET assay, and active ingredients, identified using ESI–MS/MS, were docked to observe the interaction with active site residues of NS3. The best interacting compound was further confirmed through the FRET assay as the inhibitor of NS3 protease.

Results
Fusion of the NS3 protease domain to the NS4A cofactor significantly improved the purification yield, and NS3-NS4A was functionally more active than the full-length NS3 alone. The purified protein (NS3-NS4A) was successfully employed in a validated FRET assay to evaluate 14 Citrus fruit extracts, revealing that the mesocarp extract of Citrus paradisi, and whole fruit extracts of C. sinesis, C. aurantinum, and C. reticulata significantly inhibited the protease activity of HCV NS3 protease (IC50 values of 5.79 ± 1.44 µg/mL, 37.19 ± 5.92 µg/mL, 42.62 ± 6.89 µg/mL, and 57.65 ± 3.81 µg/mL, respectively). Subsequent ESI-MSn analysis identified a flavonoid, hesperidin, abundantly present in all the afore-mentioned Citrus extracts. Importantly, docking studies suggested that hesperidin interacts with active site residues, and acts as a potent inhibitor of NS3 protease, exhibiting an IC50 value of 11.34 ± 3.83 µg/mL.

Conclusions
A FRET assay was developed using NS3-NS4A protease, which was successfully utilized for the evaluation of Citrus fruit extracts. Hesperidin, a compound present in the Citrus extracts, was identified as the main flavonoid, which can serve as a cost-effective potent inhibitor of NS3 protease, and could be developed as a drug for antiviral therapy against HCV genotype 3a.
Factors influencing measurement for improvement skills in healthcare staff: trainee, and trainer perspectives
Authors: Khurshid Zuneera , De Brún Aoife , McAuliffe Eilish 
Published: April 2022

Abstract
Background
Measurement for improvement is an integral component of quality improvement (QI) trainings and demonstrates whether a change resulted in an improvement. Despite its critical role, the development of measurement for improvement skills for QI is relatively under-explored.

Purpose
To explore the training, curricular and contextual factors that influence the development of measurement for improvement skills in healthcare professionals.

Methods
This is a retrospective, qualitative, multiple case study design, based on two QI collaboratives. Trainees and trainers from these programmes participated in semi-structured interviews. A framework drawing on the Kirkpatrick’s evaluation model and the Model for Understanding Success in Quality (MUSIQ) model was developed. The interviews were analysed based on a three-step qualitative thematic analysis method.

Results
A total of 21 participants were interviewed (15 trainees and 6 trainers). Six themes emerged in the analysis of trainee interviewees: impact of differences in job role and hierarchical levels, narrow conception of QI, knowledge disparity between trained and untrained staff, balancing the benefits and burdens of measurement, early adopters of QI driving change and supportive and engaged leadership. Themes in trainer perspectives were knowledge and understanding of measurement, application of PDSA approach to programme design, balancing consistency with adaptation to context, and attributes of sites receptive to change as predictors of development of measurement for improvement skills in staff.

Conclusion
Training alone does not determine the development, sustainability and spread of measurement and QI skills. Instead, it is influenced by a combination of curricular, training, and contextual support structures. Training programmes should be aware of the impact of job role and hierarchy, increased knowledge disparity between trained and untrained staff and trainees equating QI to bundle implementation while designing programmes. Similarly, organisational support through leaders, encouraging staff who have an interest in measurement and a culture receptive to QI also supports development of measurement skills. The study highlights the need for trainees, trainers, and organisations to work together in balancing the benefits and burdens of measurement, leading to sustainable skill development in line with international best practices.
Mobile device: a useful tool to teach inhaler devices to healthcare professionals
Authors: Puah Ser Hon , Goh Chee Yen , Chan Chung Leung , Teoh Amy Kui Jie , Zhang Hao , Shen Zhiqi , Neo Lay Ping 
Published: April 2022

Abstract
Background
Proper inhaler device usage is paramount for control of underlying obstructive airway disease. Hence, education to healthcare professionals who will eventually educate patients need to be done effectively. We developed an application for mobile devices for education on six medical inhaler devices, the metered-dose inhaler (MDI), Turbuhaler, Accuhaler, Breezhaler, Ellipta and Respimat, and studied if there were any difference between the application and the manufacturer’s instructions on inhaler technique. The aim of this study is to see if inhaler education via a mobile phone app is comparable to manual instruction for health care professions.

Methods
Participants, who were nursing students, were randomized to learn the inhaler devices via the manufacturer’s instruction guide or a mobile device app designed specifically for education on inhaler devices.

Results
There were 45 participants in each group. 78% of them were females with a median age of 21 (IQR 3). 67% used an Apple mobile device and the remainder used an Android device. The mobile device showed better total improvement points for the Turbuhaler device (262 vs 287 points; P = 0.02). Participants learning from the manufacturer’s guide had a significantly higher total improvement points in the Breezhaler (370 vs 327 points; P < 0.01) and Ellipta (214 vs 174 points; P < 0.01) device. Both interventions showed improvement in total scores for demonstrating the correct usage of all inhaler devices. MDI has the least number of correct steps for both interventions. The participants’ reported their mean (SD) self-rated knowledge was significantly higher for those using the app for all devices as compared to those that did not (4.33 (0.68) vs 4.73 (0.42); P = < 0.01). Self-reported confidence level was found to be higher in the mobile app group, but this was not statistically significant. The app was well received and scored of 4.42 of 5 with regards to its quality.

Conclusion
Using a mobile inhaler app is just as effective to teach inhaler device techniques to healthcare professionals and is likely a more convenient, versatile and important adjunct to learning.

Trial registration
National Healthcare Group Ethics Board (2018/00960).
Translation and cultural adaptation of the Integrated Palliative care Outcome Scale for Dementia (IPOS-Dem) to Swedish
Authors: Martinsson Lisa , Sahlén Klas-Göran 
Published: April 2022

Abstract
Introduction
Systematic assessment tools are helpful for improving and maintaining quality of care. The Integrated Palliative care Outcome Scale (IPOS) was developed for systematic assessment of persons receiving palliative care in a patient-centred way. A version of this tool, the Integrated Palliative care Outcome Scale for Dementia (IPOS-Dem), has been developed for patients with dementia.
The aim of this study was to develop a version of the IPOS-Dem translated into Swedish and culturally adapted to a Swedish care setting.

Methods
Forward and backward translations from English into Swedish were performed to develop a first Swedish version. This version was modified for clarity and cultural adaptation based on 13 interviews with nurses and assistant nurses working in geriatrics and dementia care homes.

Results
The interview process revealed several issues with the first version that emerged from the translation process. This was changed and further tested to work well, resulting in the final version of the Swedish IPOS-Dem. The tool was perceived as clinically useful but somewhat overlapping with already implemented tools for assessing behavioural and psychological symptoms in dementia.

Conclusion
The Swedish version of the IPOS-Dem can now be used as a tool for assessing palliative care related problems and concerns for persons with advanced dementia. Future studies can focus on implementation as well as examining validity and reliability of this tool in a Swedish context.
The associations between intestinal bacteria of Eospalax cansus and soil bacteria of its habitat
Authors: Zou Yao , Han Chongxuan , Zhang Xuxin , Nan Xiaoning 
Published: April 2022

Abstract
Background
Intestinal bacteria of mammal can be influenced by many factors, environmental bacteria is an important factor. However, there are few studies on the interactions between environmental bacteria and intestinal bacteria in wild mammals. To explore the associations between the intestinal bacteriome and the related environmental bacteriome, the intestinal bacterial communities of Eospalax cansus at three different sites and the bacterial communities of the surrounding soil (outside and inside the cave) at each site were investigated by 16S rRNA sequencing.

Results
The composition and structure between zokor intestinal bacteria and related soil bacteria were distinct, and the soil of zokor habitat harbored significantly higher diversity than that of zokor intestinal bacteria. We have found that host factors may be more important than environmental factors in shaping intestinal bacteriome. In addition, it was found that the relative abundances of shared OTUs between zokors and related soil were significantly negatively related. These shared OTUs were present in the soil at relatively low abundance. However, these shared OTUs between zokors and soil were affiliated with diverse bacterial taxa, and they were related to the degradation of complex carbohydrates.

Conclusions
These results suggested that the zokor gut may mainly select for low-abundance but diverse soil bacteria, which may be a host- specific choice for zokor to meet the needs of its phytophagous dietary.
NADH oxidase of Mycoplasma hyopneumoniae functions as a potential mediator of virulence
Authors: Hao Fei , Xie Xing , Feng Zhixin , Chen Rong , Wei Yanna , Liu Jin , Xiong Qiyan , Shao Guoqing , Lin Johnson 
Published: April 2022

Abstract
Background
Mycoplasma hyopneumoniae (M. hyopneumoniae) is the etiological agent of enzootic pneumonia, a highly infectious swine respiratory disease that distributed worldwide. The pathogenesis and virulence factors of M. hyopneumoniae are not fully clarified. As an important virulence factor of bacteria, nicotinamide adenine dinucleotide (NADH) oxidase (NOX) participates in host-pathogen interaction, however, the function of NOX involved in the pathogenesis of M. hyopneumoniae is not clear.

Results
In this study, significant differences in NOX transcription expression levels among different strains of M. hyopneumoniae differed in virulence were identified, suggesting that NOX may be correlated with M. hyopneumoniae virulence. The nox gene of M. hyopneumoniae was cloned and expressed in Escherichia coli, and polyclonal antibodies against recombinant NOX (rNOX) were prepared. We confirmed the enzymatic activity of rNOX based on its capacity to oxidize NADH to NAD+. Flow cytometry analysis demonstrated the surface localization of NOX, and subcellular localization analysis further demonstrated that NOX exists in both the cytoplasm and cell membrane. rNOX was depicted to mediate adhesion to immortalized porcine bronchial epithelial cells (hTERT-PBECs). Pre-neutralizing M. hyopneumoniae with anti-rNOX antibody resulted in a more than 55% reduction in the adhesion rate of high- and low-virulence M. hyopneumoniae strains to hTERT-PBECs. Moreover, a significant difference appeared in the decline in CCU50 titer between virulent (168) and virulence-attenuated (168L) strains. NOX not only recognized and interacted with host fibronectin but also induced cellular oxidative stress and apoptosis in hTERT-PBECs. The release of lactate dehydrogenase by NOX in hTERT-PBECs was positively correlated with the virulence of M. hyopneumoniae strains.

Conclusions
NOX is considered to be a potential virulence factor of M. hyopneumoniae and may play a significant role in mediating its pathogenesis.
Does zinc oxide nanoparticles potentiate the regenerative effect of platelet-rich fibrin in healing of critical bone defect in rabbits?
Authors: Zalama Esraa , Karrouf Gamal , Rizk Awad , Salama Basma , Samy Alaa 
Published: April 2022

Abstract
Background
Many encouraging studies confirmed the ability of Zinc Oxide Nanoparticles (ZnONPs) in accelerating bone growth and mineralization. The use of Platelet Rich-Fibrin (PRF) as a sole filling material for large segmental bone defects remains questionable. The objectives are to investigate the regenerative efficacy of autologous Platelet Rich-Fibrin (PRF) and Zinc Oxide Nanoparticles (ZnONPs) in repairing large segmental bone ulnar defects in a randomized controlled study in rabbits using computed tomographic interpretations. A 12 mm critical size defect was surgically induced in the ulna of 30 rabbits (n = 10/ group). In the control group, the defect was left empty. In the PRF group, the defect is filled with PRF. In the PRF/ZnONPs group, the defect is filled with PRF that was inoculated with 0.1 ml of 0.2% ZnONPs. Radiologic healing capacity was evaluated at the first, second, and third postoperative months.

Results
Statistical analysis showed significant differences in the radiologic healing scores between the groups (P = 0.000–0.0001) at all-time points (P = 0.000–0.047) during the study.

Conclusion
Rabbits in the PRF/ZnONPs group showed the highest appreciable bone quality and quantity followed by the PRF group with high quantity but low bone quality meanwhile, rabbits in the control group showed minimal quantity but medium bone quality. Interestingly, the addition of ZnONPs to PRF can accelerate the healing of ulnar critical-size defects in rabbits.
bZIP transcription factors PcYap1 and PcRsmA link oxidative stress response to secondary metabolism and development in Penicillium chrysogenum
Authors: Pérez-Pérez W. D. , Carrasco-Navarro U. , García‑Estrada C. , Kosalková K. , Gutiérrez-Ruíz M. C. , Barrios-González J. , Fierro F. 
Published: April 2022

Abstract
Background
Reactive oxygen species (ROS) trigger different morphogenic processes in filamentous fungi and have been shown to play a role in the regulation of the biosynthesis of some secondary metabolites. Some bZIP transcription factors, such as Yap1, AtfA and AtfB, mediate resistance to oxidative stress and have a role in secondary metabolism regulation. In this work we aimed to get insight into the molecular basis of this regulation in the industrially important fungus Penicillium chrysogenum through the characterization of the role played by two effectors that mediate the oxidative stress response in development and secondary metabolism.

Results
In P. chrysogenum, penicillin biosynthesis and conidiation are stimulated by the addition of H2O2 to the culture medium, and this effect is mediated by the bZIP transcription factors PcYap1 and PcRsmA. Silencing of expression of both proteins by RNAi resulted in similar phenotypes, characterized by increased levels of ROS in the cell, reduced conidiation, higher sensitivity of conidia to H2O2 and a decrease in penicillin production. Both PcYap1 and PcRsmA are able to sense H2O2-generated ROS in vitro and change its conformation in response to this stimulus. PcYap1 and PcRsmA positively regulate the expression of brlA, the first gene of the conidiation central regulatory pathway. PcYap1 binds in vitro to a previously identified regulatory sequence in the promoter of the penicillin gene pcbAB: TTAGTAA, and to a TTACTAA sequence in the promoter of the brlA gene, whereas PcRsmA binds to the sequences TGAGACA and TTACGTAA (CRE motif) in the promoters of the pcbAB and penDE genes, respectively.

Conclusions
bZIP transcription factors PcYap1 and PcRsmA respond to the presence of H2O2-generated ROS and regulate oxidative stress response in the cell. Both proteins mediate ROS regulation of penicillin biosynthesis and conidiation by binding to specific regulatory elements in the promoters of key genes. PcYap1 is identified as the previously proposed transcription factor PTA1 (Penicillin Transcriptional Activator 1), which binds to the regulatory sequence TTAGTAA in the pcbAB gene promoter. This is the first report of a Yap1 protein directly regulating transcription of a secondary metabolism gene. A model describing the regulatory network mediated by PcYap1 and PcRsmA is proposed.
A synthesized olean-28,13β-lactam targets YTHDF1-GLS1 axis to induce ROS-dependent metabolic crisis and cell death in pancreatic adenocarcinoma
Authors: Wu Shijia , Ai Yong , Huang Huimin , Wu Guangyu , Zhou Shipeng , Hong Weilong , Akuetteh Percy David Papa , Jin Guihua , Zhao Xingling , Zhang Yihua , Zhang Xiaolong , Lan Linhua 
Published: April 2022

Abstract
Background
Pancreatic adenocarcinoma (PAAD) is a severe malignant with a 5-year survival rate of approximately 9%. Oleanolic acid is a well-known natural triterpenoid which exhibits pharmacological activities. We previously synthesized a series of oleanolic acid derivatives and evaluated the tumor-suppressive activity of olean-28,13β-lactam (B28) in prostate cancer. However, the detailed mechanism remains to be understood.

Methods
The anti-tumor activity of B28 in PAAD was confirmed by RTCA, colony formation assay and flow cytometry. GO and KEGG enrichment analyses were performed to analyze the differentially expressed genes (DEGs) obtained by RNA sequencing. The effects of B28 on cell bioenergetics were evaluated by seahorse analyzer. Lenti-virus packaged plasmids were performed to knockdown or overexpress target genes. Alteration of mitochondrial membrane potential, ROS and GSH/GSSG were measured by corresponding detection kits according to the manufacturer's protocol.

Results
We evaluated and confirmed the promising anti-tumor activity of B28 in vitro. RNA-seq profile indicated that multiple metabolic pathways were interrupted in B28 treated PAAD cells. Next, we demonstrated that B28 induces cellular bioenergetics crisis to inhibit PAAD cells growth and induce cell death. We further validated that cell cycle arrest, inhibition of cell growth, cell apoptosis and cell bioenergetics disruption were functionally rescued by ROS scavenger NAC. Mechanistically, we found glutamine metabolism was inhibited due to B28 administration. Moreover, we validated that down-regulation of GLS1 contributes to ROS generation and bioenergetics interruption induced by B28. Furthermore, we elucidated that YTHDF1-GLS1 axis is the potential downstream target of B28 to induce PAAD cell metabolic crisis and cell death. Finally, we also confirmed the anti-tumor activity of B28 in vivo.

Conclusions
Current study demonstrates B28 disrupts YTDFH1-GLS1 axis to induce ROS-dependent cell bioenergetics crisis and cell death which finally suppress PAAD cell growth, indicating that this synthesized olean-28,13β-lactam maybe a potent agent for PAAD intervention.
A review of progress and an advanced method for shock advice algorithms in automated external defibrillators
Authors: Nguyen Minh Tuan , Nguyen Thu-Hang T. , Le Hai-Chau 
Published: April 2022

AbstractShock advice algorithm plays a vital role in the detection of sudden cardiac arrests on electrocardiogram signals and hence, brings about survival improvement by delivering prompt defibrillation. The last decade has witnessed a surge of research efforts in racing for efficient shock advice algorithms, in this context. On one hand, it has been reported that the classification performance of traditional threshold-based methods has not complied with the American Heart Association recommendations. On the other hand, the rise of machine learning and deep learning-based counterparts is paving the new ways for the development of intelligent shock advice algorithms. In this paper, we firstly provide a comprehensive survey on the development of shock advice algorithms for rhythm analysis in automated external defibrillators. Shock advice algorithms are categorized into three groups based on the classification methods in which the detection performance is significantly improved by the use of machine learning and/or deep learning techniques instead of threshold-based approaches. Indeed, in threshold-based shock advice algorithms, a parameter is calculated as a threshold to distinguish shockable rhythms from non-shockable ones. In contrast, machine learning-based methods combine multiple parameters of conventional threshold-based approaches as a set of features to recognize sudden cardiac arrest. Noticeably, those features are possibly extracted from stand-alone ECGs, alternative signals using various decomposition techniques, or fully augmented ECG segments. Moreover, these signals can be also used directly as the input channels of deep learning-based shock advice algorithm designs. Then, we propose an advanced shock advice algorithm using a support vector machine classifier and a feature set extracted from a fully augmented ECG segment with its shockable and non-shockable signals. The relatively high detection performance of the proposed shock advice algorithm implies a potential application for the automated external defibrillator in the practical clinic environment. Finally, we outline several interesting yet challenging research problems for further investigation.