bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induction of peroxisome proliferator activated receptor γ (PPARγ) mediated gene expression and inhibition of induced nitric oxide production by Maerua subcordata (Gilg) DeWolf
Authors: Hiben Mebrahtom Gebrelibanos , de Haan Laura , Spenkelink Bert , Wesseling Sebastiaan , Vervoort Jacques , Rietjens Ivonne M. C. M. 
Published: March 2020

Abstract
Background
The health benefits of botanicals is linked to their phytochemicals that often exert pleiotropic effects via targeting multiple molecular signaling pathways such as the peroxisome proliferator-activated receptors (PPARs) and the nuclear factor kappaB (NFκB). The PPARs are transcription factors that control metabolic homeostasis and inflammation while the NF-κB is a master regulator of inflammatory genes such as the inducible nitric-oxide synthase that result in nitric oxide (NO) overproduction.

Methods
Extracts of Maerua subcordata (MS) and selected candidate constituents thereof, identified by liquid chromatography coupled to mass spectroscopy, were tested for their ability to induce PPARγ mediated gene expression in U2OS-PPARγ cells using luciferase reporter gene assay and also for their ability to inhibit lipopolysaccharide (LPS) induced NO production in RAW264.7 macrophages. While measuring the effect of test samples on PPARγ mediated gene expression, a counter assay that used U2OS-Cytotox cells was performed to monitor cytotoxicity or any non-specific changes in luciferase activity.

Results
The results revealed that the fruit, root, and seed extracts were non-cytotoxic up to a concentration of 30 g dry weight per litre (gDW/L) and induced PPARγ mediated gene expression but the leaf extract showed some cytotoxicity and exhibited minimal induction. Instead, all extracts showed concentration (1–15 gDW/L) dependent inhibition of LPS induced NO production. The root extract showed weaker inhibition. Among the candidate constituents, agmatine, stachydrine, trigonelline, indole-3-carboxyaldehyde, plus ethyl-, isobutyl-, isopropyl, and methyl-isothiocyanates showed similar inhibition, and most showed increased inhibition with increasing concentration (1–100 μM) although to a lesser potency than the positive control, aminoguanidine.

Conclusion
The present study demonstrated for the first time the induction of PPARγ mediated gene expression by MS fruit, root, and seed extracts and the inhibition of LPS induced NO production by MS fruit, leaf, root, and seed extracts and some candidate constituents thereof.
Evaluating the effectiveness and feasibility of nurse-led distant and face-to-face interviews programs for promoting behavioral change and disease management in patients with diabetic nephropathy: a triangulation approach
Authors: Kazawa Kana , Osaki Kanae , Rahman Md Moshiur , Moriyama Michiko 
Published: March 2020

Abstract
Background
We examined whether telecommunication-device-based distance interviews are inferior to face-to-face interviews in terms of facilitating behavioral changes and disease management in patients with diabetic nephropathy. We also examined the feasibility of a newly designed six-month telenursing program.

Methods
This study represents a post-hoc analysis of data from a randomized controlled trial, in which we compared the efficacy of remote self-management education with that of direct education for patients with diabetic nephropathy. The participants were 40 company employees, who were randomly divided into two groups. Over 6 months, the intervention group (n = 21) received three distance interviews using a tablet computer. Meanwhile, the control group (n = 19) received three face-to-face interviews. In addition, both groups received biweekly nine telephone calls. A triangulation approach was used. We first compared the two groups in inferiority tests. Then, we analyzed data from semi-structured interviews with all participants and nurses, examining whether trusting relationships and motivation were developed, and the accuracy of the information exchanges. Further, for the intervention group, we also enquired about the overall operability of the telenursing device.

Results
The completion rates for the program were 81.0 and 78.9% for the participants in the intervention and control groups, respectively. Both groups showed similar behavioral changes, and the participants verified the feasibility of the distance interviews. The participants in the intervention group felt that they understood the severity of their diseases and the necessity of self-management, and felt confidence in the nurses. On the other hand, their degree of behavioral change regarding self-monitoring was lower than that shown by the control group.

Conclusion
Our findings show that both interview methods are effective for encouraging the adoption of self-management; further, in terms of taking medication and improving the main clinical indicators, we found that the distance method is not inferior to the direct face-to-face method. However, when considering long-term effects, based on the respective degrees of improvement in behavioral change, the direct method seems to be more effective.

Trial registration
The trial was registered with the University Hospital Medical Information Network clinical trial registry (No. UMIN000026568) on March 15, 2017, retrospectively.
School health in Europe: a review of workforce expenditure across five countries
Authors: van der Pol Simon , Postma Maarten J. , Jansen Danielle E. M. C. 
Published: March 2020

Abstract
Background
Most European countries have implemented a form of school health services (SHS) to provide young children and adolescents with various types of healthcare. No estimations on SHS expenditure for European countries have been published until now. We estimated SHS workforce expenditure in Europe, expected to serve as the main driver of school healthcare costs.

Methods
Using two networks of experts on healthcare provision for children we contacted various country representatives to provide data on the number of professionals working in SHS and salaries. These data were used, together with publicly available data, to estimate annual SHS workforce expenditure on the national level.

Results
We received sufficient data for five European countries, and estimated the SHS workforce expenditure. Nurses were the most widely reported professionals working in this field, followed by doctors and psychologists. Our SHS expenditure estimations ranged from €43,000 for Estonia to €195,300 in Norway (per 1000 pupils). For Norway, Estonia, Finland and Iceland, school nurses were the main drivers of SHS expenditure, mainly due to their large numbers, while in Austria, school doctors played the largest role in SHS expenditure.

Conclusions
We estimated the spending on SHS workforce for five European countries, which comprises relatively minor parts of total healthcare spending (0.16 to 0.69%). Many questions regarding SHS spending in Europe remain, due to a general lack of data on national levels.
A discrete choice experiment to identify the most efficient quality indicators for the supervision of psychiatric hospitals
Authors: van Dijk Pieter , Schellings Ron , Essers Brigitte A. B. , Kessels Alfons G. , Leistikow Ian , Zeegers Maurice P. 
Published: March 2020

Abstract
Background
In the Netherlands, health care is regulated by the Health and Youth Care Inspectorate. Forty-six indicators are used to prioritize supervision of psychiatric hospitals. The objective of this study is to define a smaller set of weighted indicators which reflects a consensus among inspectors about which aspects are most important for risk assessment.

Methods
The set of 46 indicators, complemented with missing information, was reduced to six indicators by means of interviews, group discussions and ranking among the inspectors. These indicators were used as attributes in a discrete choice experiment (DCE) to define their weights.

Results
Twenty-six inspectors defined the top four indicators suitable for the risk assessment of psychiatric hospitals. These are: the policy on prevention of compulsory treatment; the policy on dysfunctional professionals; the quality of internal research after a serious incident; and the implementation of multidisciplinary guidelines on suicidal behaviour. These indicators share the same importance with regard to risk assessment. The screening of somatic symptoms and the policy on integrated care are important indicators too, but less relevant.

Conclusion
Through a DCE, we reduced the amount of information for risk assessment of psychiatric hospitals to six weighted indicators. Inspectors can use these indicators to prioritize their inspections.
Volunteering, health and the homeless – the cost of establishing a student-run primary healthcare clinic serving the inner-city homeless in South Africa
Authors: Johnston Deanne , McInerney Patricia , Miot Jacqui 
Published: March 2020

Abstract
Background
Those who are homeless are more prone to communicable, respiratory and cardiovascular diseases and are less likely to access healthcare services. In South Africa there are no specific public healthcare services tailored to the needs of these communities, particularly if they are immigrants. Trinity Health Services is a student-run inner-city clinic providing free healthcare to the homeless of Johannesburg, South Africa. The clinic operates two nights per month and provides treatment for mainly acute conditions. The purpose of this study was to determine the costs of establishing and operating a student-run clinic for an indigent population.

Methods
This costing analysis used a mixed-methods approach combining an ingredients-based and top-down methodology. The costs, capital and recurrent, pertaining to the establishment and operating of the clinic as well as the cost of treatment per patient were identified and quantified from 1st January 2016 – 31st December 2017.

Results
The capital costs incurred in establishing the clinic were calculated to be £10,968.57 (ZAR 214157.08) and included building alterations, equipment purchased, installations, furniture, application for a pharmacy license, consumables and medications. The recurrent costs per annum were estimated at £17,730.72 (ZAR 346185.54) and comprised of overheads and maintenance, rental, personnel, pharmacy license, consumables and medication. The cost of treatment per patient, included medication dispensed and consumables used in the consultation, was estimated at £3.54 (ZAR 69.05) per visit.

Conclusions
This study summarised the costs of establishing and operating a student-run clinic providing pertinent information essential to the sustainability of the service. It also provides a model for costs associated with free clinics in faith-based and university settings.
The challenge of safe anesthesia in developing countries: defining the problems in a medical center in Cambodia
Authors: Tao Kun-ming , Sokha Sann , Yuan Hong-bin 
Published: March 2020

Abstract
Background
The International Standards for a Safe Practice of Anesthesia (ISSPA) were developed on behalf of the World Federation of Societies of Anaesthesiologists and the World Health Organization. It has been recommend as an assessment tool that allows anesthetic providers in developing countries to assess their compliance and needs. This study was performed to describe the anesthesia service in one main public hospital during an 8-month medical mission in Cambodia and evaluate its anesthetic safety issues according to the ISSPA.

Methods
We conduct a retrospective study involving 1953 patients at the Preah Ket Mealea hospital. Patient demographics, anesthetic techniques, and complications were reviewed according to the registers of the anesthetic services and questionnaires. The inadequacies in personnel, facilities, equipment, medications, and conduct of anesthesia drugs were recorded using a checklist based on the ISSPA.

Results
A total of 1792 patients received general and regional anesthesia in the operating room, while 161 patients receiving sedation for gastroscopy. The patients’ mean age was 45.0 ± 16.6 years (range, 17–87 years). The three most common surgical procedures were abdominal (52.0%; confidence interval [CI], 49.3–54.7), orthopedic (27.6%; CI, 25.2–29.9), and urological surgery (14.7%; CI, 12.8–16.6). General anesthesia, spinal anesthesia, and brachial plexus block were performed in 54.3% (CI, 51.7–56.8), 28.2% (CI, 25.9–30.5), and 9.4% (CI, 7.9–10.9) of patients, respectively. One death occurred. Twenty-six items related to professional aspects, monitoring, and conduct of anesthesia did not meet the ISSPA-recommended standards. A lack of commonly used drugs and monitoring equipment was noted, posing major threats to the safety of anesthesia practice, especially in emergency situations.

Conclusions
This study adds to the scarce literature on anesthesia practice in low- and middle-income countries such as Cambodia. Future medical assistance should help to strengthen these countries’ inadequacies, allowing for the adoption of international standards for the safe practice of anesthesia.
Linked-read sequencing identifies abundant microinversions and introgression in the arboviral vector Aedes aegypti
Authors: Redmond Seth N. , Sharma Atashi , Sharakhov Igor , Tu Zhijian , Sharakhova Maria , Neafsey Daniel E. 
Published: March 2020

AbstractBackgroundAedes aegyptiis the principal mosquito vector of Zika, dengue, and yellow fever viruses. Two subspecies ofAe. aegyptiexhibit phenotypic divergence with regard to habitat, host preference, and vectorial capacity. Chromosomal inversions have been shown to play a major role in adaptation and speciation in dipteran insects and would be of great utility for studies ofAe. aegypti.However, the large and highly repetitive genome ofAe. aegyptimakes it difficult to detect inversions with paired-end short-read sequencing data, and polytene chromosome analysis does not provide sufficient resolution to detect chromosome banding patterns indicative of inversions.ResultsTo characterize chromosomal diversity in this species, we have carried out deep Illumina sequencing of linked-read (10X Genomics) libraries in order to discover inversion loci as well as SNPs. We analyzed individuals from colonies representing the geographic limits of each subspecies, one contact zone between subspecies, and a closely related sister species. Despite genome-wide SNP divergence and abundant microinversions, we do not find any inversions occurring as fixed differences between subspecies. Many microinversions are found in regions that have introgressed and have captured genes that could impact behavior, such as a cluster of odorant-binding proteins that may play a role in host feeding preference.ConclusionsOur study shows that inversions are abundant and widely shared among subspecies ofAedes aegyptiand that introgression has occurred in regions of secondary contact. This library of 32 novel chromosomal inversions demonstrates the capacity for linked-read sequencing to identify previously intractable genomic rearrangements and provides a foundation for future population genetics studies in this species.
Design and rationale of a multi-center, pragmatic, open-label randomized trial of antimicrobial therapy – the study of clinical efficacy of antimicrobial therapy strategy using pragmatic design in Idiopathic Pulmonary Fibrosis (CleanUP-IPF) clinical trial
Authors:   For the CleanUP-IPF Study Team, Anstrom Kevin J. , Noth Imre , Flaherty Kevin R. , Edwards Rex H. , Albright Joan , Baucom Amanda , Brooks Maria , Clark Allan B. , Clausen Emily S. , Durheim Michael T. , Kim Dong-Yun , Kirchner Jerry , Oldham Justin M. , Snyder Laurie D. , Wilson Andrew M. , Wisniewski Stephen R. , Yow Eric , Martinez Fernando J. 
Published: March 2020

Abstract
Compelling data have linked disease progression in patients with idiopathic pulmonary fibrosis (IPF) with lung dysbiosis and the resulting dysregulated local and systemic immune response. Moreover, prior therapeutic trials have suggested improved outcomes in these patients treated with either sulfamethoxazole/ trimethoprim or doxycycline. These trials have been limited by methodological concerns. This trial addresses the primary hypothesis that long-term treatment with antimicrobial therapy increases the time-to-event endpoint of respiratory hospitalization or all-cause mortality compared to usual care treatment in patients with IPF. We invoke numerous innovative features to achieve this goal, including: 1) utilizing a pragmatic randomized trial design; 2) collecting targeted biological samples to allow future exploration of ‘personalized’ therapy; and 3) developing a strong partnership between the NHLBI, a broad range of investigators, industry, and philanthropic organizations. The trial will randomize approximately 500 individuals in a 1:1 ratio to either antimicrobial therapy or usual care. The site principal investigator will declare their preferred initial antimicrobial treatment strategy (trimethoprim 160 mg/ sulfamethoxazole 800 mg twice a day plus folic acid 5 mg daily or doxycycline 100 mg once daily if body weight is < 50 kg or 100 mg twice daily if ≥50 kg) for the participant prior to randomization. Participants randomized to antimicrobial therapy will receive a voucher to help cover the additional prescription drug costs. Additionally, those participants will have 4–5 scheduled blood draws over the initial 24 months of therapy for safety monitoring. Blood sampling for DNA sequencing and genome wide transcriptomics will be collected before therapy. Blood sampling for transcriptomics and oral and fecal swabs for determination of the microbiome communities will be collected before and after study completion. As a pragmatic study, participants in both treatment arms will have limited in-person visits with the enrolling clinical center. Visits are limited to assessments of lung function and other clinical parameters at time points prior to randomization and at months 12, 24, and 36. All participants will be followed until the study completion for the assessment of clinical endpoints related to hospitalization and mortality events.

Trial Registration
ClinicalTrials.gov identifier NCT02759120.
RETRACTED ARTICLE: MicroRNA-93-5p promotes epithelial-mesenchymal transition in gastric cancer by repressing tumor suppressor AHNAK expression
Authors: Shen Erdong , Wang Xin , Liu Xin , Lv Mingyue , Zhang Liang , Zhu Guolian , Sun Zhe 
Published: March 2020

Abstract
Background
Gastric cancer (GC) is a common cause of cancer-related mortality worldwide, and microRNAs (miRNAs) have been shown to play an important role in GC development. This study aims to explore the effect of microRNA-93-5p (miR-93-5p) on the epithelial-mesenchymal transition (EMT) in GC, via AHNAK and the Wnt signaling pathway.

Methods
Microarray-based gene expression analysis was performed to identify GC-related differentially expressed miRNAs and genes. Then the expression of the miR-93-5p was examined in GC tissues and GC cell lines. The targeting relationship between miR-93-5p and AHNAK was verified by a dual luciferase reporter gene assay. In an attempt to ascertain the contributory role of miR-93-5p in GC, miR-93-5p mimic or inhibitor, as well as an AHNAK overexpression vector, were introduced to HGC-27 cells. HGC-27 cell migration and invasive ability, and EMT were assayed using Transwell assay and western blot analysis. Regulation of the Wnt signaling pathway was also assessed using TOP/FOP flash luciferase assay.

Results
miR-93-5p was highly expressed in GC tissue samples and cells. Notably, miR-93-5p could target and negatively regulate AHNAK. Down-regulation of miR-93-5p or overexpression of AHNAK could suppress the migration and invasion abilities, in addition to EMT in GC cells via inactivation of the Wnt signaling pathway.

Conclusion
Taken together, downregulation of miR-93-5p attenuated GC development via the Wnt signaling pathway by targeting AHNAK. These findings provide an enhanced understanding of miR-93-5p as a therapeutic target for GC treatment.
How the choice of ethnic indicator influences ethnicity-based inequities in maternal health care in four Latin American countries: who is indigenous?
Authors: Armenta-Paulino Nancy , Castelló Adela , Sandín Vázquez María , Bolúmar Francisco 
Published: March 2020

AbstractBackgroundThe current focus on monitoring health inequalities and the complexity around ethnicity requires careful consideration of how ethnic disparities are measured and presented. This paper aims to determine how inequalities in maternal healthcare by ethnicity change according to different criteria used to classify indigenous populations.MethodsNationally representative demographic surveys from Bolivia, Guatemala, Mexico, and Peru (2008–2016) were used to explore coverage gaps across maternal health care by ethnicity using different criteria. Women were classified as indigenous through self-identification (SI), spoken indigenous language (SIL), or indigenous household (IH). We compared the gaps through measuring coverage ratios (CR) with adjusted Poisson regression models.ResultsProportions of indigenous women changed significantly according to the identification criterion (Bolivia:SI-63.1%/SIL-37.7%; Guatemala:SI-49.7%/SIL-28.2%; Peru:SI-34%/SIL-6.3% & Mexico:SI-29.7%/SIL-6.9%). Indigenous in all countries, regardless of their identification, had less coverage. Gaps in care between indigenous and non-indigenous populations changed, for all indicators and countries, depending on the criterion used (e.g., Bolivia CR for contraceptive-use SI = 0.70, SIL = 0.89; Guatemala CR for skilled-birth-attendant SI = 0.77, SIL = 0.59). The heterogeneity persists when the reference groups are modified and compare just to non-indigenous (e.g., Bolivia CR for contraceptive-use under SI = 0.64, SIL = 0.70; Guatemala CR for Skilled-birth-attendant under SI = 0.77, SIL = 0.57).ConclusionsThe indigenous identification criteria could have an impact on the measurement of inequalities in the coverage of maternal health care. Given the complexity and diversity observed, it is not possible to provide a definitive direction on the best way to define indigenous populations to measure inequalities. In practice, the categorization will depend on the information available. Our results call for greater care in the analysis of ethnicity-based inequalities. A greater understanding on how the indigenous are classified when assessing inequalities by ethnicity can help stakeholders to deliver interventions responsive to the needs of these groups.