bluuebunny/crossref_metadata_2025_split huggingface dataset:
The iSEARCH Trials of oral Sildenafil in labour: Protocol for a randomised trial in 3,200 Australian women and Rationale for an Individual Participant Data Prospective Meta-Analysis of trials in 14,000 women in high-income countries and a mega-trial of 50,000 women in low or middle-income countries.
Authors: Kumar Sailesh , Tarnow-Mordi William , Mol Ben , Flenady Vicki , Liley Helen , Badawi Nadia , Colditz Paul , Walker Susan , Hyett Jonathan , Seidler Anna Lene , Callander Emily , Bora Samudragupta , O’Connell Rachel 
Published: February 2022

Abstract
IntroductionWe showed in a Phase 2 RCT that oral Sildenafil during term labour halves the need for operative birth for suspected fetal distress. To assess if Sildenafil reduces adverse perinatal outcomes, we describe a Phase 3 RCT (iSEARCH) and the rationale for an individual participant data prospective meta-analysis (IPD PMA) of RCTs in high-income countries and a mega-trial in low- and middle-income countries.Methods and analysisiSEARCH will enrol 3200 women in term labour, yielding >80% power to determine whether oral administration of up to three 50 mg doses of Sildenafil versus placebo reduces the relative risk of intrapartum hypoxia, determined as a primary composite endpoint of ten perinatal outcomes, by 35% (from 7% to 4.55%). We also outline the rationale for (i) an IPD PMA of RCTs in about 14,000 women in Australia and other countries with low perinatal mortality rates which would yield 90% power to test if oral Sildenafil achieves a more moderate and realistic reduction of 20% in the relative risk of this composite endpoint and (ii) a mega-trial in about 50,000 women in countries with moderate or high perinatal mortality rates to test if oral Sildenafil achieves a similarly moderate and realistic 20% reduction in the relative risk of a composite endpoint comprising intrapartum stillbirth or 7-day neonatal mortality. Secondary aims will be to evaluate the rate of operative birth for fetal distress, its cost-effectiveness, and developmental and educational outcomes.
Transport of ammonia nitrogen for groundwater pollution control in an informal low-permeability landfill site
Authors: Niu Juanting , Hu Litang , Zhang Menglin 
Published: February 2022

Abstract
In informal landfills, leachate leaked into the underlying soil and groundwater has been gaining increasing attention. Recently, an informal low-permeability landfill site in northern China was investigated in detail, and it was found that the groundwater was contaminated by leachate. A groundwater flow and contamination transport model was developed using FEFLOW to forecast contaminant transport and evaluate feasible pollutant control schemes. In this model, good matches between the simulated and observed groundwater level and good matches between the simulated and observed concentration of ammonia nitrogen show that the established model can reproduce the process of groundwater movement effectively. Three kinds of schemes, including natural conditions, pollution source removal, and pump and treatment, were simulated, and the results were compared. The results showed that, under natural conditions, the pollution does not travel far horizontally and vertically. Removal of pollution sources has little effect on the concentration of ammonia nitrogen in groundwater over a period of 100 years. The pump and treatment system can effectively remove high concentrations of ammonia nitrogen in the groundwater of the landfill site, with a maximum decline of over 90%. Therefore, the pump and treatment method may be valid for short-term soil and groundwater remediation.
Comparative analysis of molecular and conventional methods for bacteriological water quality assessment in drinking water resources around Chennai
Authors: Dinakaran Divakar Raj , Shanmugam Hemaiswarya , Nambi Indumathi M. , Doble Mukesh 
Published: February 2022

Abstract
Coliforms and Escherichia coli represent the fecal contamination in drinking water and hence its potability. The present study estimates uidA and lacZ genes as distinctive biomarkers for rapid and efficient detection of contaminated water resources. In total, 39 environmental water samples were collected in and around the metropolitan city of Chennai, India. The results were compared with culture-based method using selective medium. The study shows that the performance and amplification efficiency of uidA and lacZ are 99.6% and 103.4% respectively. The sensitivity of the qPCR method in selectively identifying E. coli was 71.4% in a total of 92.3% coliform contamination. The conventional method showed that 10 samples were positive for E. coli and 12 samples positive for coliforms from a total of 39 samples. A lower positive predictive value of the biomarkers observed is due to the insignificant association between the two methods and is determined to be 59.0% and 66.6% for E. coli and coliforms respectively. The study reports 50 and 70% of the overhead tank (OHT) samples were contaminated with E. coli and coliform respectively, which indicates sanitation measures through these water supplies are not adequately taken care of. High throughput molecular detection technique is reported here, which can be used for monitoring environmental samples more quickly.
Pristine and activated bentonite for toxic metal removal from wastewater
Authors: Ibigbami Tope B. , Adeola Adedapo O. , Olawade David B. , Ore Odunayo T. , Isaac Babatunde O. , Sunkanmi Alabi A. 
Published: February 2022

AbstractNatural bentonite clay (NBC) was activated using nitric acid (HNO3). Characterization techniques including FTIR, SEM, XRD and BET were employed to examine the morphology of NBC and ABC (activated bentonite clay) sorbents. Comparative application of ABC and NBC to remove heavy metals (Fe2+, Zn2+, Ni2+) from pharmaceutical effluents was investigated under various experimental conditions. The maximum proportional removal by ABC was 88.90, 81.80 and 75.50% at pH 8, and 63.90, 59.60, 58.70% at pH 10 for NBC, both for Zn2+, Fe2+ and Ni2+ respectively. The Freundlich multilayer adsorption model and pseudo-second-order kinetics best fit the experimental data, suggesting the formation of multiple adsorption layers via strong ionic and electrostatic interactions. Heavy metals adsorption is more favorable with ABC than NBC, due to the availability of more sorption sites and a larger specific surface. The thermodynamic parameters (ΔH°, ΔS°, and ΔG°) revealed that the adsorption is endothermic and spontaneous in nature for both ABC and NBC.
Chemical Advances in Therapeutic Application of Exosomes and Liposomes
Authors: Chew Boon Cheng , Liew Fong Fong , Tan Hsiao Wei , Chung Ivy 
Published: February 2022

Abstract:
Exosomes and liposomes are vesicular nanoparticles that can encapsulate functional cargo. The chemical similarities between naturally occurring exosomes and synthetic liposomes have accelerated the development of exosome mimetics as a therapeutic drug delivery platform under physiological and pathological environments. To maximise the applications of exosomes and liposomes in the clinical setting, it is essential to look into their basic chemical properties and utilise these characteristics to optimise the preparation, loading, modification and hybridisation. This review summarises the chemical and biological properties of both exosomal and liposomal systems as well as some of the challenges related to their production and application. This article concludes with a discussion on potential perspectives for the integration of exosomal and liposomal technologies in mapping better approaches for their biomedical use, especially in therapeutics.
Investigating the Mechanism of Shengmaiyin (Codonopsis pilosula) in the
Treatment of Heart Failure Based on Network Pharmacology
Authors: Kan Mo , Wang Jifeng , Ming Sitong , Sui Xin , Zhang Zhuang , Yang Qing , Liu Xiaoran , Lin Jianan , Zhang Yanhong , Pang Qihang , Liu Yaxin , Li Zhen , Li Na , Lin Zhe 
Published: February 2022

Background and Objective:
To explore the molecular mechanism by which Shengmaiyin
(Codonopsis pilosula) (SMY) improves isoproterenol (ISO)-induced heart failure (HF) in rats
via a traditional Chinese medicine (TCM) integrated pharmacology research platform, The Chinese
Medicine Integrated Pharmacology Platform (TCMIP V2.0).

Method::
The chemical constituents and drug targets of SMY medicines were identified through
TCMIP, and HF disease target information was collected. A prescription Chinese medicinecomponent-
core target network was constructed through the TCM network mining module, and biological
process and pathway enrichment analyses of core targets were conducted. In vivo experiments
in rats were performed to verify the pathway targets. Hematoxylin and eosin staining was
used to observe myocardial tissue morphology. ELISA kits were used to detect cAMP content, and
Western blotting was used to detect the expression levels of signaling pathway-related proteins.

Results:
The TCMIP analysis indicated that SMY treatment of HF activates the GS-β-adrenergic
receptor (βAR)-cAMP-protein kinase A (PKA) signaling pathway. The in vivo experimental results
confirmed this finding. High-dose SMY significantly improved the morphology of ISO-injured
myocardium. The levels of G-protein-coupled receptor (GPCR), adenylate cyclase (AC), βAR, and
PKA proteins in myocardial tissue were significantly increased in the SMY group. In addition, the
content of cAMP in myocardial tissue was increased, and the content of cAMP in serum was decreased.

Conclusion:
Based on the analysis of TCMIP, SMY treatment of HF may activate the GS-βARcAMP-
PKA signaling pathway. The findings provide a theoretical basis for further research on the
anti-HF mechanism of SMY.
A Study on Immune Cell Infiltration in Lung Adenocarcinoma
Authors: Zhao Hongwen , Sun Bingqing 
Published: February 2022

Background:
As a vital part of the tumor environment, immune cells affect the progression
of tumors, and their composition and role vary in different types of tumors and influence
prognosis. These immune cells have the potential to be beneficially targeted for immunotherapy,
or, conversely, they may react negatively, even leading to drug resistance. For these reasons, probing
into the composition and possible effects of immune cells in lung cancer is conducive to discovering
valuable therapeutic targets.

Materials and Methods:
The lung adenocarcinoma gene expression data were downloaded from
the TCGA database (https://cancergenome.nih.gov/; https://portal.gdc.cancer.gov/), and the lung
adenocarcinoma gene expression matrix was converted into an immune cell-matrix using CIBERSORT
software (https://cibersort.stanford.edu/), followed by an analysis of immune cells in lung
adenocarcinoma tissues.

Results:
The results showed that among all immune cells in lung adenocarcinoma tissues, macrophages
(Mφ) had the highest number, followed by T cells. The number of plasma cells in lung adenocarcinoma
tissues was higher than in adjacent normal tissues. Compared with those in adjacent
normal tissues, the number of resting memory clusters of differentiation 4 (CD4)+ T cells was lower,
whereas active memory CD4+ T cells were higher in lung adenocarcinoma tissues. In addition,
the number of CD8+ T cells was negatively related to that of resting memory CD4+ T cells, with a
correlation coefficient of -0.44, whereas it showed a positive association with the number of active
memory CD4+ T cells, with a correlation coefficient of 0.47. It was found that among various immune
cells infiltrating lung adenocarcinoma tissues, unstimulated Mφ (M0), alternatively activated
Mφ (M2), and resting memory CD4+ T cells accounted for the largest proportions. However, these
three types of immune cells were found to be lower in lung adenocarcinoma tissues than in adjacent
normal tissues.

Conclusion:
Immune cells infiltrating lung adenocarcinoma tissues are complex, which affect the
development and progression of the tumor and may also be a significant cause of drug resistance.
Studying the changes in immune cell infiltration during the development of specific types of tumors
contributes to disease progression interpretation, prognosis assessment, and potential solutions
to the existing drug resistance issue. In this paper, the status of immune cells in lung adenocarcinoma
tissues was preliminarily discussed based on the database mining, but more experimental
studies and in-depth discussions are needed in the future.
Therapeutic Potential of Silybum marianum and Pergularia tomentosa
Extracts from Jordanian Origin in Diabetes Mellitus
Authors: Sweidan Nuha I. , Abu Khalaf Reema A. , Shatat Alaa' M. , Hammad Wa'ed A. 
Published: February 2022

Background:
Jordan is a country well-known for its diversity in wild plants, and for
many decades, folk medicines have represented part of its cultural heritage. In the present study,
investigations have been focused on the therapeutic potential of Silybum marianum and Pergularia
tomentosa on type 2 diabetes mellitus. In type 2 diabetes, which is considered a global health problem,
the body cannot respond to or produce insulin hormonem, which raises the blood glucose
level, resulting in mortality, morbidity, healthcare expenses, and reduced life quality. Dipeptidyl
peptidase-IV (DPP-IV) enzyme, a serine protease, is responsible for deactivating incretin hormones
that promote insulin secretion. Accordingly, the DPP-IV inhibitory activity of these plant
extracts that prolong the hypoglycemic effect of incretins was evaluated.

Method:
The aerial parts of S. marianum and P. tomentosa were dried, ground, and extracted with
ethanol. The ethanol extract was dried under reduced pressure and was partitioned by methanol,
butanol, and hexane according to a systematic procedure. The inhibition of the DPP-IV enzyme by
the different extracts was studied (at 10.0 mg/mL concentration). Sitagliptin was used as the positive
control.

Results:
Fortunately, most of the plant extracts have noticeable inhibitory activity against the DPPIV
enzyme. It was found that the tested methanol extract of S. marianum has an inhibitory activity
of 75.6% and the butanol extract of P. tomentosa has an inhibitory activity of 73.6%, which are
analogous to DPP-IV inhibition of sitagliptin (78.5%), the used positive inhibitor. A superior inhibition
of 98.1% was displayed for the butanol extract of S. marianum at 10.0 mg/ mL concentration.

Conclusion:
The revealed DPP-IV inhibitory activity of tested extracts advocates that their active
constituents, particularly flavonoids, are capable of binding to the enzyme’s active cleft.
Transdermal Patches Approach Towards Self-Nano-Emulsifying Drug Delivery System (SNEDDS) Using Essential Oil as Penetration Enhancer
Authors: Farooqui Heena , Upadhyay Sukirti , Upadhyay Prashant 
Published: February 2022

Abstract:
A transdermal patch is a topically applied adhesive patch that delivers a medication dose directly
into the blood. The patch allows for the safe delivery of a drug to the targeted site, ideally by a
permeable layer covering a reservoir of the drug by melting small patches of drug embedded in the adhesive,
which is one benefit of transdermal drug delivery over most types of pharmaceutical deliveries,
including oral, topical, intramuscular, intravenous, and several others. This can also help heal a damaged
body part, improving patient compliance, treatment efficacy, and dose frequency while minimizing
the side effects. This review covers the production, methods of evaluation, quality, use of penetration
enhancers, and pros and downsides of transdermal patches, as well as the benefits of essential oil
as a penetration enhancer. Compared to chemical enhancers, essential oils have shown the ability to
break down the stratum corneum layer, allowing drugs to penetrate deeper into the skin. Essential oils
are excellent penetration enhancers for the skin. These penetration enhancers are cost-effective, biocompatible,
readily available, non-toxic, chemically modifiable, and possibly biodegradable. In this
review, attention has been paid to the formulation and evaluation of transdermal patches with the help
of SNEDDS (self-nano-emulsifying drug delivery systems) using essential oil as a penetration enhancer,
and their future prospects.
Squeeze-Film Damping of Microbeam and Microplate Resonators in the Free Molecular Regime
Authors: Wang Zhaodong , Li Pu , Sun Beibei 
Published: February 2022

Background:
Correct modeling of squeeze-film damping (SFD) is an important consideration in the design of high-Q microresonators. In 2002, using the molecular dynamics (MD) approach, Bao et al. developed an analytical MD model for the evaluation of the SFD of a parallel-plate device in the free molecular regime. Their model was based on the energy exchange between the oscillating plate and gas molecules. Bao’s model is now widely used in microsystem design. However, Bao’s model cannot reduce to the air damping model in free space and is unsuitable for flexible microbeams.

Objective:
This paper first presents a more accurate analytical model for the evaluation of the SFD of the parallel plate. Then the present analytical model is extended to model the SFD of flexible microbeams with deformed shapes.

Methods:
This paper is based on the momentum transfer between the vibration plate and gas molecules.
Results: The analytical results of the present model have shown a good agreement with the available experimental results.

Conclusion:
The limitations in the previous model are overcome.
Analysis and Evaluation of Fatigue Strength for Engine Bracket Considering Load Characteristics
Authors: Li Qiang , Wu Que , Wang Shuci , Liu Xintian 
Published: February 2022

Background:
To obtain the load characteristics and fatigue characteristics of the engine
bracket during the working process, the automobile engine bracket is taken as the research object, and
the force characteristics are analyzed.

Objective:
This paper provides a theoretical basis for engine bracket design that improves the reliability
and durability of the engine bracket.

Methods:
Under cyclic loading, the fatigue characteristics are analyzed through the bench test. According
to the experimental results, the critical points of the engine bracket are examined.

Results:
According to the S-N curve, the estimated range of fatigue life of the engine bracket is from
34236 times to 127219 times. When the load level is low, the life span changes significantly with the
stress. As the load increases, the fatigue life is less affected and shows a slight decrease. When the stress
level is lower than the equivalent stress threshold value, the stress will not cause fatigue failure, and the
specimen has an infinite life.

Conclusion:
This paper lays a foundation for the prediction of fatigue life and the bench test of fatigue
durability of the engine bracket subjected to complex and variable random loads. The research method
can also be used to estimate the fatigue life of other bearing parts.
A Novel Approach to Transformer Fault Diagnosis Based on Transfer
Learning
Authors: Hao Bai , Chao Su , Wenquan Chen 
Published: February 2022

Background:
The condition of the power transformer directly affects the reliability and efficiency of the power system. The dissolved gas analysis (DGA) has been widely recognized as one of the effective methods in the field of transformer fault diagnosis.

Objective:
To tackle the problem of insufficient single transformer fault data and weak generalization ability of the diagnosis model, this paper proposes a transformer fault diagnosis model based on data cleaning and transfer learning.

Methods:
21 kinds of dissolved gas characteristics of the to-be-diagnosed transformer (TDT) and auxiliary transformers (ATs)are selected as fault features to detect transformer fault. The first data cleaning is used for auxiliary fault data (AFD) based on similarity analysis between target fault data (TFD) and AFD. Then the TFD and AFD are all cleaned to remove the singular edge interference data for the second cleaning. The transfer learning algorithm is applied to extract effective information from AFD and train the fault diagnosis model.

Results:
Test results show that the proposed method can improve the efficiency of fault diagnosis and the accuracy of fault identification

Conclusion:
The two data cleanings complement each other and both play a role in eliminating bad data and ensuring the accuracy of the fault diagnosis. Transfer learning can effectively extract effective information from AFD and train a better transformer fault diagnotor to improve fault diagnosis accuracy.
Embedding and Integrating a Digital Patient Management Platform Into Everyday Primary Care Routines: Qualitative Case Study
Authors: Frennert Susanne , Erlingsdóttir Gudbjörg , Muhic Mirella , Rydenfält Christofer , Milos Nymberg Veronica , Ekman Björn 
Published: February 2022

Background
Traditional primary care is characterized by patient consultations via phone and physical visits. However, the current development in Swedish primary care is to blend digital solutions with traditional solutions. This paper addresses this development by examining the normalization of embedding and integrating a digital health care platform into everyday care routines in a primary care clinic. The digital health care platform enables both synchronous (video calls) and asynchronous (chat) communication, as well as self-registration of patient data using automated questions and forms requiring the patient’s input.

Objective
This study aims to explore the work that health care professionals (HCPs) have to undertake to implement and sustain a digital health care platform as part of their everyday work practice.

Methods
HCPs were observed and interviewed to assess their individual and collective engagement and the mechanisms involved in the implementation of the digital platform and its effects on everyday work routines. The normalization process theory (NPT) was used to frame the data analysis.

Results
The analysis identified several themes related to the four NPT constructs: coherence, cognitive participation, collective action, and reflexive monitoring. The use of these constructs enabled the analysis to identify ways of supporting implementation. For example, it showed the benefits of having implementation champions and scheduling work hours for HCPs to use the platform. The analysis also revealed a theme of materiality that deviated from the NPT constructs, as NPT gives ontological priority to human actors and social structures.

Conclusions
Digital health care platform implementation is a complex process. Our findings provide insights into how individual and collective actions can be supported to embed and integrate a digital platform into everyday care routines. Primary health care organizations need to involve HCPs throughout the implementation process by reorganizing work and providing frequent feedback loops. HCPs are more likely to engage with and commit to changing practices if they perceive the digital platform to be beneficial compared with the current practice. However, they also need resources (eg, time, training, and continuous support) to put the platform into practice. Patient engagement and appraisal are important elements in implementation. Unless patients are willing to use the platform, there is no motivation for HCPs to embed the digital platform into everyday care practice.