bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study protocol: a randomised, controlled trial of a nurse navigator program for the management of hepatitis C virus in patients with severe mental disorder
Authors: Quemada-González Casta , Morales-Asencio José Miguel , Hurtado María M. , Martí-García Celia 
Published: April 2022

Abstract
Background
To evaluate the impact of a nurse navigation program on treatment adherence and resolution of hepatitis C infection in patients with severe mental disorder.

Methods
An open, randomized, controlled trial with blinded outcome assessment. The intervention group will engage in a nurse navigation program designed by mental health nurses. The program involves active screening for patients with severe mental disorder. The patients and caregivers included in the program will receive information, training, support and guidance throughout the treatment and recovery process, which involves different healthcare professionals and units. The control group will receive the standard of care, which includes follow-up by a family physician, referral to the hepatologist, serological testing, new referral to the hepatologist, onset of treatment, and follow-up. Multidisciplinary care will be provided along a coordinated and seamless clinical pathway led by a nurse navigator.
The primary endpoints are total recovery (hepatitis C cure) and treatment adherence. Occurrence of symptoms of schizophrenia and health-related quality of life will be also recorded. Follow-up of patients will be performed three and six months after the administration of antiviral treatment.
The study was authorised by the Ethics Committee of Malaga in December 2021. Funding was approved in March 2021.

Discussion
If this intervention is proven to be effective in improving treatment access and adherence, it will represent a step forward in addressing a chronic health issue that is 16 times more prevalent in the population with severe mental disease. Finally, this intervention may lead to the detection of undertreated HCV infection in this population of patients.

Trial registration
This protocol has been registered in ClinicalTrials.gov with identifier code NCT04891445 on May 18, 2021.
Determination and pharmacokinetics study of UK-5099 in mouse plasma by LC–MS/MS
Authors: Zeng Qingyuan , Si Hongfei , Lv Kun , Mo Jiao , Wang Xinnian , Yan Biqing , Zhang Jili 
Published: April 2022

Abstract
Background
UK-5099 is a potent mitochondrial acetone carrier inhibitor, that exhibits anticancer activity. Recently, the anti-Toxoplasma gondii activity of UK-5099 was proposed, and in vivo studies of its pharmacokinetics in BALB/c mice are necessary to further evaluate the clinical effect of UK-5099.

Methods and results
A simple and fast high-performance liquid chromatography-tandem mass spectrometry (HPLC–MS/MS) analysis method was established and verified in terms of its linearity, matrix effect, accuracy, precision, recovery and stability. The analytes were separated by an Agilent ZORBAX XDB-C18 column (2.1 × 50 mm, 3.5 μm) at 30 °C. A gradient mobile phase consisting of water with 0.1% formic acid (FA) (phase A) and acetonitrile (ACN) (phase B) was delivered at a flow rate of 0.40 mL·min−1 with an injection volume of 5 μL. A good linear response was obtained in a concentration range of 5–5000 ng·mL−1 (r2 = 0.9947). The lower limit of quantification (LLOQ) was 5 ng·mL−1. The extraction recovery of UK-5099 was greater than 95%. The inter- and intra-day accuracy and precision of the method showed relative standard deviations (RSDs) of less than 15%. This method has been successfully applied to the pharmacokinetic evaluation of UK-5099 in mouse plasma. In health mice, the main pharmacokinetic parameters of UK-5099 after intraperitoneal administration were measured using a noncompartmental model, in which the AUC0-t was 42,103 ± 12,072 ng·h·mL−1 and the MRT0-t was 0.857 ± 0.143 h. The peak concentration (Cmax) was 82,500 ± 20,745 ng·h·mL−1, which occurred at a peak time (Tmax) = 0.250 ± 0.000 h.

Conclusions
A fast and sensitive HPLC–MS/MS method was developed, validated and successfully used for the determination of UK-5099 levels in mice after intraperitoneal administration. This study was the first report of the pharmacokinetic parameters of UK-5099 in mice, which will help to further study the administration of UK-5099 in animals and humans.
Determination of the regulatory network and function of the lysR-type transcriptional regulator of Lactiplantibacillus plantarum, LpLttR
Authors: Liu Xin-Xin , Liu Lei , Song Xin , Wang Guang-Qiang , Xiong Zhi-Qiang , Xia Yong-Jun , Ai Lian-Zhong 
Published: April 2022

Abstract
Background
Lactiplantibacillus plantarum has various healthcare functions including the regulation of immunity and inflammation, reduction of serum cholesterol levels, anti-tumor activity, and maintenance of the balance of intestinal flora. However, the underlying metabolic and regulatory mechanisms of these processes remain unclear. Our previous studies have shown that the LysR type transcriptional regulator of L. plantarum (LpLttR) regulates the biotransformation of conjugated linoleic acids (CLAs) through the transcriptional activation of cla-dh (coding gene for CLA short-chain dehydrogenase) and cla-dc (coding gene for CLA acetoacetate decarboxylase). However, the regulatory network and function of LpLttR have not yet been characterized in L. plantarum.

Results
In this study, the regulatory role of LpLttR in various cellular processes was assessed using transcriptome analysis. The deletion of LpLttR had no evident influence on the bacterial growth. The transcriptome data showed that the expression of nine genes were positively regulated by LpLttR, and the expression of only two genes were negatively regulated. Through binding motif analysis and molecular interaction, we demonstrated that the regulatory region of the directly regulated genes contained a highly conserved sequence, consisting of a 15-base long box and rich in AT.

Conclusion
This study revealed that LpLttR of L. plantarum did not play a global regulatory role similar to that of the other transcriptional regulators in this family. This study broadens our knowledge of LpLttR and provides a theoretical basis for the utilization of L. plantarum.
Win or loss? Combination therapy does improve the oncolytic virus therapy to pancreatic cancer
Authors: Luo Wenhao , Wang Yawen , Zhang Taiping 
Published: April 2022

AbstractPancreatic cancer (PC) is a growing global burden, remaining one of the most lethal cancers of the gastrointestinal tract. Moreover, PC is resistant to various treatments such as chemotherapy, radiotherapy, and immunotherapy. New therapies are urgently needed to improve the prognosis of PC. Oncolytic virus (OV) therapy is a promising new treatment option. OV is a genetically modified virus that selectively replicates in tumor cells. It can kill tumor cells without harming normal cells. The activation of tumor-specific T-cells is a unique feature of OV-mediated therapy. However, OV-mediated mono-therapeutic efficacy remains controversial, especially for metastatic or advanced patients who require systemically deliverable therapies. Hence, combination therapies will be critical to improve the therapeutic efficacy of OV-mediated therapy and prevent tumor recurrence. This review aims to investigate novel combinatorial treatments with OV therapy and explore the inner mechanism of those combined therapies, hopefully providing a new direction for a better prognosis of PC.
Delta-5® oil, containing the anti-inflammatory fatty acid sciadonic acid, improves skin barrier function in a skin irritation model in healthy female subjects
Authors: Berger Alvin 
Published: April 2022

Abstract
Background
Sciadonic acid (SA) is an anti-inflammatory fatty acid displacing arachidonic acid (ARA) from specific phospholipid pools, thus modulating downstream pro-inflammatory lipid mediators. Its novel anti-inflammatory actions have been studied in vitro, in pre-clinical models, and stemming from testimonials, after topical- and oral application. It has not been tested in a formal clinical study for topical benefits previously. Skin barrier layer was our focus as it has a critically important role in maintaining skin moisture balance.

Methods
Herein, forearm skin was left undamaged; or barrier layer was chemically-damaged with 2% sodium lauryl sulfate (SLS) for 24 h. SLS-damaged skin was left untreated or treated with Delta-5® oil containing 24% SA twice daily for 27 days. Barrier function was assessed by open chamber transepidermal water loss (TEWL) and skin surface impedance on days 0 (clear skin), -1 (1-day post-SLS), -2 (2-days post-SLS, 1-day post-Delta-5), -3, -7, and − 28.

Results
Relative to day 1, Delta-5 oil statistically significantly decreased TEWL vs. untreated damaged sites, on days 3 (125% more reduced), -7 (74% more reduced), and − 28 (69% more reduced). Decreases in TEWL following chemical damage indicates improved skin barrier repair and healing. Similar patterns were quantified for skin impedance. There was also reduced redness observed on days 3 and − 7 with Delta-5 oil vs. untreated SLS-damaged skin.

Conclusions
Delta-5 oil thus has anti-inflammatory potential in human skin, under controlled clinical conditions, to accelerate irritant-induced healing, and improve skin barrier function. Improvement in barrier function would benefit dermatitis, acne, eczema, and skin scarring. In normal skin, Delta-5 oil has potential to promote healthy, moisturized skin; and improve skin structure, elasticity, and firmness.
Photogenerated reactive oxygen species and hyperthermia by Cu3SnS4 nanoflakes for advanced photocatalytic and photothermal antibacterial therapy
Authors: Yang Yangzi , Wang Chengwei , Wang Ning , Li Jiaxin , Zhu Yingchun , Zai Jiantao , Fu Jingke , Hao Yongqiang 
Published: April 2022

AbstractBackgroundThe rapid spread of infectious bacteria has brought great challenges to public health. It is imperative to explore effective and environment-friendly antibacterial modality to defeat antibiotic-resistant bacteria with high biosafety and broad-spectrum antibacterial property.ResultsHerein, biocompatible Cu3SnS4nanoflakes (NFs) were prepared by a facile and low-cost fabrication procedure. These Cu3SnS4NFs could be activated by visible light, leading to visible light-mediated photocatalytic generation of a myriad of reactive oxygen species (ROS). Besides, the plasmonic Cu3SnS4NFs exhibit strong near infrared (NIR) absorption and a high photothermal conversion efficiency of 55.7%. The ROS mediated cellular oxidative damage and the NIR mediated photothermal disruption of bacterial membranes collaboratively contributed to the advanced antibacterial therapy, which has been validated by the efficient eradication of both Gram-negativeEscherichia coliand Gram-positive methicillin-resistantStaphylococcus aureusstrains in vitro and in vivo. Meanwhile, the exogenous copper ions metabolism from the Cu3SnS4NFs facilitated the endothelial cell angiogenesis and collagen deposition, thus expediting the wound healing. Importantly, the inherent localized surface plasmon resonance effect of Cu3SnS4NFs empowered them as an active substrate for surface-enhanced Raman scattering (SERS) imaging and SERS-labeled bacteria detection.ConclusionsThe low cost and biocompatibility together with the solar-driven broad-spectrum photocatalytic/photothermal antibacterial property of Cu3SnS4NFs make them a candidate for sensitive bacteria detection and effective antibacterial treatment.Graphical Abstract
Building evidence into youth health policy: a case study of the Access 3 knowledge translation forum
Authors: Waller Daniel , Robards Fiona , Schneider Carmen Huckel , Sanci Lena , Steinbeck Katharine , Gibson Sally , Usherwood Tim , Hawke Catherine , Jan Stephen , Kong Marlene , Kang Melissa 
Published: April 2022

Abstract
Background
Effective integration of evidence and youth perspectives into policy is crucial for supporting the future health and well-being of young people. The aim of this project was to translate evidence from the Access 3 project to support development of a new state policy on youth health and well-being within New South Wales (NSW), Australia. Ensuring the active contribution of young people within policy development was a key objective of the knowledge translation (KT) process.

Methods
The KT activity consisted of a 1-day facilitated forum with 64 purposively sampled stakeholders. Participants included eight young people, 14 policy-makers, 15 academics, 22 clinicians or managers from NSW health services, four general practitioners and one mental health service worker. Research to be translated came from the synthesized findings of the NSW Access 3 project. The design of the forum included stakeholder presentations and group workshops, guided by the 2003 Lavis et al. KT framework that was improved by the Grimshaw et al. KT framework in 2012. Members of the Access 3 research team took on the role of knowledge brokers throughout the KT process. Participant satisfaction with the workshop was evaluated using a brief self-report survey. Policy uptake was determined through examination of the subsequent NSW Youth Health Framework 2017–2024.

Results
A total of 25 policy recommendations were established through the workshop, and these were grouped into six themes that broadly aligned with the synthesized findings from the Access 3 project. The six policy themes were (1) technology solutions, (2) integrated care and investment to build capacity, (3) adolescent health checks, (4) workforce, (5) youth participation and (6) youth health indicators. Forum members were asked to vote on the importance of individual recommendations. These policy recommendations were subsequently presented to the NSW Ministry of Health, with some evidence of policy uptake identified. The majority of participants rated the forum positively.

Conclusions
The utilization of KT theories and active youth engagement led to the successful translation of research evidence and youth perspectives into NSW youth health policy. Future research should examine the implementation of policy arising from these KT efforts.
Intestinal parasitic infections and associated factors among people living with HIV attending Dessie Referral Hospital, Dessie town, North-east Ethiopia: a cross-sectional study
Authors: Feleke Daniel Getacher , Ali Abdurahaman , Bisetegn Habtye , Andualem Mengaye 
Published: April 2022

Abstract
Introduction
Intestinal parasites and HIV/AIDS co-infection become a major public health concern in Africa. The management and care of HIV/AIDS patients is being complicated by intestinal parasitic infections. Therefore, this study aimed to determine the prevalence and associated factors of intestinal parasitic infections among people living with HIV at Dessie Referral Hospital, North-east Ethiopia.

Methods
This cross sectional study was conducted from March to May 2019. Systematic simple random sampling technique was used to recruit study participants. Stool specimen was collected and examined microscopically using wet mount, formol-ether concentration technique and modified Zeihl–Neelsen methods. Socio-demographic characteristics and associated factors were collected using structured questionnaire. The recent CD4 cell count was obtained from patients ART follow-up record. Data were analysed using SPSS version 20 software. Bivariate and multivariate logistic regression was done to investigate the association between independent and dependent variables.

Results
Of the total of 223 study participants 120 (53.8%) were females and 162 (72.6%) were urban resident. The overall prevalence of intestinal parasites was 47 (21.1%). Eleven different intestinal parasites species were detected. The dominant intestinal parasite species was Entameobahistolytica 14 (6.3%) followed by Enterobius vermicularis 5 (2.2%). Multivariate logistic regression analysis showed that individuals who had a habit of hand washing after latrine were less likely to be infected with intestinal parasitic infection (AOR 0.15, 95% CI 0.05–0.412). On the other hand individuals who had CD4 cell count of < 200 cells/ml3 were 45.53 times more likely infected with intestinal parasites.

Conclusion
The prevalence of intestinal parasite was higher than previous report from the same study area almost a decade ago. There was statistical significant association between hand washing habit after latrine, habit of eating raw vegetables and CD4 cell count less than 200 cells/ml3 and intestinal parasitic infections. Health education program interrupted in Dessie referral hospital should be continued to reduce the prevalence of intestinal parasites. Utilization of water treatment, washing hand after latrine and eating cooked or appropriately washed vegetables should also be promoted. Moreover, periodic laboratory stool specimen examination and prompt treatment are necessary.
Socioeconomic and demographic correlates of child nutritional status in Nepal: an investigation of heterogeneous effects using quantile regression
Authors: Bhusal Umesh Prasad , Sapkota Vishnu Prasad 
Published: April 2022

Abstract
Background
Child undernutrition continues to be a major public health problem in many countries, including Nepal. The repercussions of undernutrition are not only limited to the affected children and families but also transcend to the national and global economy. Earlier studies from Nepal have predominantly used either ordinary least squares (OLS) regression or binary regression to analyse the socioeconomic and demographic correlates of the nutritional outcome. In this study, quantile regression was used to understand a complete and more precise estimate of the effects of the covariates on the child nutritional status.

Methods
This study was based on the most recent nationally representative Nepal Multiple Indicator Cluster Survey (MICS) 2019. Height-for-age z scores (HAZ) were used as an indicator for assessing the nutritional status of under-five children. Quantile regression was used to examine the heterogeneous association of covariates with conditional HAZ distribution across the different quantiles (0.10, 0.30, 0.50, 0.85). As a comparison, the effects of covariates at conditional mean of HAZ using OLS regression was also analysed. The graphs were plotted to visualize the changes in the coefficients for each regressor across the entire conditional HAZ distribution.

Results
Age of children, sex of children, province and wealth had a consistent and statistically significant association with HAZ in both OLS and quantile regression. Improved toilet facility was positively correlated with HAZ at the lower tails (tenth and thirtieth percentiles). Ethnicity (Janajati and Newer) was positively correlated with HAZ at the lower tail (thirtieth percentile) and mean (OLS regression). Maternal education was a significant predictor of improved height-for-age across conditional quantiles, except at the tenth percentile. Maternal age, number of under-five children in household, number of household members, and improved source of drinking water showed heterogeneous effects across different quantiles of conditional HAZ distribution.

Conclusion
Use of quantile regression approach showed that the effect of different factors differed across the conditional distribution of HAZ. Policymakers should consider the heterogeneous effect of different factors on HAZ so that the targeted intervention could be implemented to maximize the nutritional benefits to children.
Asclepion of Epidaurus: the application of a historical perspective in medical education
Authors: Papageorgiou Charalabos , Konstantinou Gerasimos , Lambrinoudakis Vassilis , Papageorgiou Christos , Yiannopoulou Konstantina G. 
Published: April 2022

Abstract
Background
The Asclepion of Epidaurus is one of the first healing environments in the world. Descendants of Asclepius, specifically medical students, have been singularly deprived of any information concerning this legacy. This article illuminates the role of Asclepion of Epidaurus and examines the view of medical students upon the subject and the possible benefits of this knowledge in their medical education.

Methods
The participants were 105 senior-year students from the Athens Medical School, who attended a multi-media assisted lecture related to the structure and the role of the Asclepion of Epidaurus. Afterwards, they answered anonymously a questionnaire of 12 pairs of opposite adjectives in order to describe their view regarding the meaning of Asclepion. The method used in the evaluation of their answers was that of semantic differential.

Results
The attitude of the students towards the meaning of Asclepion was positive, showing interest and excitement about a powerful, though unfamiliar piece of knowledge.

Conclusion
Today’s novice doctors have welcomed the concept of Asclepion as essential knowledge for the service they will be called to fulfill. The potential benefits of the Asclepian ideals in medical education and ethos are thoroughly discussed.
One- and 2-year flare rates after treat-to-target and tight-control therapy of gout: results from the NOR-Gout study
Authors: Uhlig Till , Karoliussen Lars F. , Sexton Joe , Kvien Tore K. , Haavardsholm Espen A. , Perez-Ruiz Fernando , Hammer Hilde Berner 
Published: April 2022

AbstractObjectivesTo explore the frequency and predictors of flares over 2 years during a treat-to-target strategy with urate-lowering therapy (ULT) in patients with gout.MethodsIn the treat-to-target, tight control NOR-Gout study patients started ULT with escalating doses of allopurinol. Flares were recorded over 2 years. Baseline predictors of flares during months 9–12 in year 1 and during year 2 were analyzed by multivariable logistic regression.ResultsOf 211 patients included (mean age 56.4 years, disease duration 7.8 years, 95% males), 81% (150/186) of patients experienced at least one gout flare during the first year and 26% (45/173) during the second year. The highest frequency of flares in the first year was seen during months 3–6 (46.8% of patients).Baseline crystal depositions detected by ultrasound and by dual-energy computed tomography (DECT) were the only variables which predicted flares both during the first period of interest at months 9–12 (OR 1.033; 95% CI 1.010–1.057, and OR 1.056; 95% CI 1.007–1.108) and also in year 2. Baseline subcutaneous tophi (OR 2.42, 95% CI 1.50–5.59) and prior use of colchicine at baseline (OR 2.48, 95% CI 1.28-4.79) were independent predictors of flares during months 9–12, whereas self-efficacy for pain was a protective predictor (OR 0.98 per unit, 95% CI 0.964–0.996).ConclusionsIn patients with gout, flares remain frequent during the first year of a treat-to-target ULT strategy, especially during months 3–6, but are much less frequent during year 2. Baseline crystal depositions predict flares over 2 years, supporting ULT early during disease course.Trial registrationACTRN12618001372279