bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intellectual capital-based performance improvement: a study in healthcare sector
Authors: Alfiero Simona , Brescia Valerio , Bert Fabrizio 
Published: January 2021

Abstract
Background
Knowledge resources are in most productive sectors distinctive in terms of competitiveness. Still, in the health sector, they can have an impact on the health of the population, help make the organisations more efficient and can help improve decision-making processes. The purpose of this paper is to investigate the Intellectual Capital impact on healthcare organization’ performance in the Italian healthcare system.

Methods
The theoretical framework linked to intellectual Capital in the health sector and the performance evaluation related to efficiency supports the analysis carried out in two stages to determine the right placement of resources and the exogenous variables that influence performance level. The evaluation of the impact of the ICs on performance is determined through the Data envelopment analysis. The incidence of the exogenous variables has been established through linear regression.

Results
Empirical results in Italy show some IC components influence organization ‘performance (Essential Levels of Assistance) and could be used for defining the policy of allocation of resources in healthcare sector. The efficiency of 16 regions considered in 2016 based on Slack-Based-Model constant returns-to-scale (SBM-CRS) and Slack-Based-Model variable returns-to-scale (SBM-VRS) identifies a different ability to balance IC and performance. Current healthcare expenditure and the number of residents is correlated with the identified efficiency and performance levels.

Conclusions
This paper embeds an innovative link between healthcare performance, in term of efficiency and IC which aligns resource management with future strategy. The study provides a new decision-making approach.
The use of dried tube specimens of Plasmodium falciparum in an external quality assessment programme to evaluate health worker performance for malaria rapid diagnostic testing in healthcare centres in Togo
Authors: Dorkenoo Ameyo M. , Kouassi Kafui Codjo , Koura Adjane K. , Adams Martin L. , Gbada Komivi , Katawa Gnatoulma , Yakpa Kossi , Charlebois Remi , Milgotina Ekaterina , Merkel Michele O. , Aidoo Michael 
Published: January 2021

Abstract
Background
The use of rapid diagnostic tests (RDTs) to diagnose malaria is common in sub-Saharan African laboratories, remote primary health facilities and in the community. Currently, there is a lack of reliable methods to ascertain health worker competency to accurately use RDTs in the testing and diagnosis of malaria. Dried tube specimens (DTS) have been shown to be a consistent and useful method for quality control of malaria RDTs; however, its application in National Quality Management programmes has been limited.

Methods
A Plasmodium falciparum strain was grown in culture and harvested to create DTS of varying parasite density (0, 100, 200, 500 and 1000 parasites/µL). Using the dried tube specimens as quality control material, a proficiency testing (PT) programme was carried out in 80 representative health centres in Togo. Health worker competency for performing malaria RDTs was assessed using five blinded DTS samples, and the DTS were tested in the same manner as a patient sample would be tested by multiple testers per health centre.

Results
All the DTS with 100 parasites/µl and 50% of DTS with 200 parasites/µl were classified as non-reactive during the pre-PT quality control step. Therefore, data from these parasite densities were not analysed as part of the PT dataset. PT scores across all 80 facilities and 235 testers was 100% for 0 parasites/µl, 63% for 500 parasites/µl and 93% for 1000 parasites/µl. Overall, 59% of the 80 healthcare centres that participated in the PT programme received a score of 80% or higher on a set of 0, 500 and 1000 parasites/ µl DTS samples. Sixty percent of health workers at these centres recorded correct test results for all three samples.

Conclusions
The use of DTS for a malaria PT programme was the first of its kind ever conducted in Togo. The ease of use and stability of the DTS illustrates that this type of samples can be considered for the assessment of staff competency. The implementation of quality management systems, refresher training and expanded PT at remote testing facilities are essential elements to improve the quality of malaria diagnosis.
Urban poverty and nutrition challenges associated with accessibility to a healthy diet: a global systematic literature review
Authors: Vilar-Compte Mireya , Burrola-Méndez Soraya , Lozano-Marrufo Annel , Ferré-Eguiluz Isabel , Flores Diana , Gaitán-Rossi Pablo , Teruel Graciela , Pérez-Escamilla Rafael 
Published: January 2021

Abstract
Background
There is an increasing global trend towards urbanization. In general, there are less food access issues in urban than rural areas, but this “urban advantage” does not benefit the poorest who face disproportionate barriers to accessing healthy food and have an increased risk of malnutrition.

Objectives
This systematic literature review aimed to assess urban poverty as a determinant of access to a healthy diet, and to examine the contribution of urban poverty to the nutritional status of individuals.

Methods
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) methodology, our review included quantitative and qualitative studies published in English or in Spanish between 2000 and 2019. The articles were eligible if they focused on nutrition access (i.e. access to a healthy diet) or nutrition outcomes (i.e., anemia, overweight and obesity, micronutrient deficiency, micronutrient malnutrition) among urban poor populations. Articles were excluded if they did not meet pre-established criteria. The quality of the quantitative studies was assessed by applying Khan et al.’s methodology. Similarly, we assessed the quality of qualitative articles through an adapted version of the National Institute for Health and Care Excellence (NICE) methodology checklist. Finally, we systematically analyzed all papers that met the inclusion criteria based on a qualitative content and thematic analysis.

Results
Of the 68 papers included in the systematic review, 55 used quantitative and 13 used qualitative methods. Through the analysis of the literature we found four key themes: (i) elements that affect access to healthy eating in individuals in urban poverty, (ii) food insecurity and urban poverty, (iii) risk factors for the nutritional status of urban poor and (iv) coping strategies to limited access to food. Based on the systematization of the literature on these themes, we then proposed a conceptual framework of urban poverty and nutrition.

Conclusions
This systematic review identified distinct barriers posed by urban poverty in accessing healthy diets and its association with poorer nutrition outcomes, hence, questioning the “urban advantage”. A conceptual framework emerging from the existing literature is proposed to guide future studies and policies.

Systematic review registration
PROSPERO Registration number: CRD42018089788.
A multicentric quality-control study of exercise Doppler echocardiography of the right heart and the pulmonary circulation. The RIGHT Heart International NETwork (RIGHT-NET)
Authors:   On behalf of the RIGHT Heart International NETwork (RIGHT-NET) Investigators, Ferrara Francesco , Gargani Luna , Contaldi Carla , Agoston Gergely , Argiento Paola , Armstrong William F. , Bandera Francesco , Cademartiri Filippo , Citro Rodolfo , Cittadini Antonio , Cocchia Rosangela , D’Alto Michele , D’Andrea Antonello , Douschan Philipp , Ghio Stefano , Grünig Ekkehard , Guazzi Marco , Guida Stefania , Kasprzak Jaroslaw D. , Kolias Theodore John , Limongelli Giuseppe , Marra Alberto Maria , Mazzola Matteo , Mauro Ciro , Moreo Antonella , Pieri Francesco , Pratali Lorenza , Pugliese Nicola Riccardo , Raciti Mauro , Ranieri Brigida , Rudski Lawrence , Saggar Rajan , Salzano Andrea , Serra Walter , Stanziola Anna Agnese , Vannan Mani , Voilliot Damien , Vriz Olga , Wierzbowska-Drabik Karina , Naeije Robert , Bossone Eduardo 
Published: January 2021

AbstractPurposeThis study was a quality-control study of resting and exercise Doppler echocardiography (EDE) variables measured by 19 echocardiography laboratories with proven experience participating in the RIGHT Heart International NETwork.MethodsAll participating investigators reported the requested variables from ten randomly selected exercise stress tests. Intraclass correlation coefficients (ICC) were calculated to evaluate the inter-observer agreement with the core laboratory. Inter-observer variability of resting and peak exercise tricuspid regurgitation velocity (TRV), right ventricular outflow tract acceleration time (RVOT Act), tricuspid annular plane systolic excursion (TAPSE), tissue Doppler tricuspid lateral annular systolic velocity (S’), right ventricular fractional area change (RV FAC), left ventricular outflow tract velocity time integral (LVOT VTI), mitral inflow pulsed wave Doppler velocity (E), diastolic mitral annular velocity by TDI (e’) and left ventricular ejection fraction (LVEF) were measured.ResultsThe accuracy of 19 investigators for all variables ranged from 99.7 to 100%. ICC was > 0.90 for all observers. Inter-observer variability for resting and exercise variables was for TRV = 3.8 to 2.4%, E = 5.7 to 8.3%, e’ = 6 to 6.5%, RVOT Act = 9.7 to 12, LVOT VTI = 7.4 to 9.6%, S’ = 2.9 to 2.9% and TAPSE = 5.3 to 8%. Moderate inter-observer variability was found for resting and peak exercise RV FAC (15 to 16%). LVEF revealed lower resting and peak exercise variability of 7.6 and 9%.ConclusionsWhen performed in expert centers EDE is a reproducible tool for the assessment of the right heart and the pulmonary circulation.
Reduction of miR-744 delivered by NSCLC cell-derived extracellular vesicles upregulates SUV39H1 to promote NSCLC progression via activation of the Smad9/BMP9 axis
Authors: Gao Liming , Tian Qi , Wu Tong , Shi Shanshan , Yin Xiaobo , Liu Lijie , Zheng Lei , Wang Ping , Tian Yaling , Xu Shufeng 
Published: January 2021

Abstract
Background
Non-small cell lung cancer (NSCLC) is a common type of lung cancer. Extracellular vehicles (EVs) are nano-sized particles containing proteins, lipids, and miRNAs secreted by various cells, which play important roles in the development of lung cancer by regulating a wide range of signaling pathways. This study focused on elucidating a potential mechanism by which EVs promote the development of NSCLC.

Methods
Expression levels of miR-744, SUV39H1, Smad9, and BMP4 in clinical tissue samples of NSCLC patients and cell lines were quantified by RT-qPCR and/or western blot analysis. The interaction between SUV39H1 and miR-744 was identified by dual-luciferase reporter assay. miR-744, SUV39H1, and BMP4 expression levels were modulated in A549 and H460 cells, in order to evaluate their effects on cell proliferation, colony formation and cell cycle. A NSCLC xenograft mouse model was used to verify the in vitro findings. NSCLC cell-derived EVs and normal bronchial epithelial cell-derived EVs were isolated and their roles in NSCLC development were evaluated in vivo and in vitro.

Results
miR-744 expression was lower in cancer cell-derived derived EVs than in normal lung epithelial cell-derived EVs. Reduced miR-744 expression in EVs upregulated SUV39H1 in NSCLC cells and further increased BMP4 levels to promote NSCLC development. BMP4 was upregulated in NSCLC cells upon suppression of Smad9 mediated by SUV39H1. Reduced miR-744 expression transferred from cancer cell-derived EVs into NSCLC cells enhanced cancer development.

Conclusion
Overall, our findings unveiled a mechanism whereby miR-744 delivered by NSCLC-derived EVs upregulated SUV39H1, activating the Smad9/BMP9 axis and thus promoted cancer development.
Peripherally misfolded proteins exacerbate ischemic stroke-induced neuroinflammation and brain injury
Authors: Liu Yanying , Subedi Kalpana , Baride Aravind , Romanova Svetlana , Callegari Eduardo , Huber Christa C. , Wang Xuejun , Wang Hongmin 
Published: January 2021

Abstract
Background
Protein aggregates can be found in peripheral organs, such as the heart, kidney, and pancreas, but little is known about the impact of peripherally misfolded proteins on neuroinflammation and brain functional recovery following ischemic stroke.

Methods
Here, we studied the ischemia/reperfusion (I/R) induced brain injury in mice with cardiomyocyte-restricted overexpression of a missense (R120G) mutant small heat shock protein, αB-crystallin (CryABR120G), by examining neuroinflammation and brain functional recovery following I/R in comparison to their non-transgenic (Ntg) littermates. To understand how peripherally misfolded proteins influence brain functionality, exosomes were isolated from CryABR120G and Ntg mouse blood and were used to treat wild-type (WT) mice and primary cortical neuron-glia mix cultures. Additionally, isolated protein aggregates from the brain following I/R were isolated and subjected to mass-spectrometric analysis to assess whether the aggregates contained the mutant protein, CryABR120G. To determine whether the CryABR120G misfolding can self-propagate, a misfolded protein seeding assay was performed in cell cultures.

Results
Our results showed that CryABR120G mice exhibited dramatically increased infarct volume, delayed brain functional recovery, and enhanced neuroinflammation and protein aggregation in the brain following I/R when compared to the Ntg mice. Intriguingly, mass-spectrometric analysis of the protein aggregates isolated from CryABR120G mouse brains confirmed presence of the mutant CryABR120G protein in the brain. Importantly, intravenous administration of WT mice with the exosomes isolated from CryABR120G mouse blood exacerbated I/R-induced cerebral injury in WT mice. Moreover, incubation of the CryABR120G mouse exosomes with primary neuronal cultures induced pronounced protein aggregation. Transduction of CryABR120G aggregate seeds into cell cultures caused normal CryAB proteins to undergo dramatic aggregation and form large aggregates, suggesting self-propagation of CryABR120G misfolding in cells.

Conclusions
These results suggest that peripherally misfolded proteins in the heart remotely enhance neuroinflammation and exacerbate brain injury following I/R likely through exosomes, which may represent an underappreciated mechanism underlying heart-brain crosstalk.
Molecular characterization of a complex small supernumerary marker chromosome derived from chromosome 18p: an addition to the literature
Authors: Marchina Eleonora , Forti Michela , Tonelli Mariella , Maccarini Stefania , Malvestiti Francesca , Piantoni Chiara , Filippini Elena , Fazzi Elisa , Borsani Giuseppe 
Published: January 2021

Abstract
Background
Small supernumerary marker chromosomes (sSMC) are a heterogeneous group of structurally abnormal chromosomes, with an incidence of 0,044% in newborns that increases up to almost 7 times in developmentally retarded patients. sSMC from all 24 chromosome have been described, most of them originate from the group of the acrocentric, with around half deriving from the chromosome 15. Non-acrocentric sSMC are less common and, in the 30 percent of the cases, are associated with phenotypic effect. Complex sSMC consist of chromosomal material derived from more than one chromosome. Genotype–phenotype correlations in patients with sSMC are difficult to assess. Clinical features depend on factors such as its size, genetic content, the involvement of imprinted genes which may be influenced by uniparental disomy and the level of mosaicism. Trisomy of the short arm of chromosome 18 (18p) is an infrequent finding and does not appear to be associated with a specific syndrome. However, mild intellectual disability with or without other anomalies is reported in almost one-third of the patients.

Case presentation
Here we present clinical and molecular characterization of a new case of de novo complex sSMC consisting of the entire short arm of chromosome 18p associated with a centromere of either chromosome 13 or 21, evidenced in a 5-year-old boy during diagnostic workup for moderate intellectual disability and dysmorphisms. To date, only seven cases of isolated trisomy 18p due to a sSMC have been reported, three of which have been characterized by array CGH. In two of them the breakpoints and the size of the duplication have been described. In the manuscript we also reviewed cases reported in the DECIPHER database carrying similar duplication and also considered smaller duplications within the region of interest, in order to evaluate the presence of critical regions implicated in the pathological phenotype.

Conclusions
Our case provides additional information about phenotypic effects of pure trisomy 18p, confirms chromosomal microarray analysis as gold standard to characterize complex sSMC, and supplies additional elements for genetic counselling.
Identification of a small molecule as inducer of ferroptosis and apoptosis through ubiquitination of GPX4 in triple negative breast cancer cells
Authors: Ding Yahui , Chen Xiaoping , Liu Can , Ge Weizhi , Wang Qin , Hao Xin , Wang Mengmeng , Chen Yue , Zhang Quan 
Published: January 2021

Abstract
Background
TNBC is the most aggressive breast cancer with higher recurrence and mortality rate than other types of breast cancer. There is an urgent need for identification of therapeutic agents with unique mode of action for overcoming current challenges in TNBC treatment.

Methods
Different inhibitors were used to study the cell death manner of DMOCPTL. RNA silencing was used to evaluate the functions of GPX4 in ferroptosis and apoptosis of TNBC cells and functions of EGR1 in apoptosis. Immunohistochemical assay of tissue microarray were used for investigating correlation of GPX4 and EGR1 with TNBC. Computer-aided docking and small molecule probe were used for study the binding of DMOCPTL with GPX4.

Results
DMOCPTL, a derivative of natural product parthenolide, exhibited about 15-fold improvement comparing to that of the parent compound PTL for TNBC cells. The cell death manner assay showed that the anti-TNBC effect of DMOCPTL mainly by inducing ferroptosis and apoptosis through ubiquitination of GPX4. The probe of DMOCPTL assay indicated that DMOCPTL induced GPX4 ubiquitination by directly binding to GPX4 protein. To the best of our knowledge, this is the first report of inducing ferroptosis through ubiquitination of GPX4. Moreover, the mechanism of GPX4 regulation of apoptosis is still obscure. Here, we firstly reveal that GPX4 regulated mitochondria-mediated apoptosis through regulation of EGR1 in TNBC cells. Compound 13, the prodrug of DMOCPTL, effectively inhibited the growth of breast tumor and prolonged the lifespan of mice in vivo, and no obvious toxicity was observed.

Conclusions
These findings firstly revealed novel manner to induce ferroptosis through ubiquitination of GPX4 and provided mechanism for GPX4 inducing mitochondria-mediated apoptosis through up-regulation of EGR1 in TNBC cells. Moreover, compound 13 deserves further studies as a lead compound with novel mode of action for ultimate discovery of effective anti-TNBC drug.
Lnc-GULP1–2:1 affects granulosa cell proliferation by regulating COL3A1 expression and localization
Authors: Yao Guidong , Kong Yue , Yang Guang , Kong Deqi , Xu Yijiang , He Jiahuan , Xu Ziwen , Bai Yucheng , Fan Huiying , He Qina , Sun Yingpu 
Published: January 2021

Abstract
Backgrounds
Long non-coding RNA is a novel group of non-protein coding transcripts over 200 nt in length. Recent studies have found that they are widely involved in many pathological and physiological processes. In our previous study, we found that lnc-GULP1–2:1 was significantly down-regulated in the ovarian cortical tissue of patients with primary ovarian insufficiency and predicted that lnc-GULP1–2:1 has a regulatory effect on COL3A1.

Results
In this study, we found that lnc-GULP1–2:1 was mainly localized in the cytoplasm of luteinized granulosa cells. The expression of lnc-GULP1–2:1 was lower in patients with diminished ovarian reserve but substantially elevated in patients with polycystic ovary syndrome. Overexpression of lnc-GULP1–2:1 in KGN cells significantly inhibited cell proliferation, likely through cell cycle related genes CCND2 and p16. Moreover, lnc-GULP1–2:1 expression was positively correlated with the level of COL3A in luteinized granulosa cells from patients with different ovarian functions as well as in multiple cell lines. Overexpression of lnc-GULP1–2:1 in KGN cells promoted the expression of COL3A1 and its translocation into the nucleus. Consistently, silencing COL3A1 in KGN cells also significantly inhibited cell proliferation.

Conclusions
Lnc-GULP1–2:1 affects the proliferation of granulosa cells by regulating the expression and localization of COL3A1 protein, and may participate in the regulation of ovarian follicle development. This study will provide new insight into molecular mechanisms underlying ovarian follicular development, which will help generate novel diagnostic and therapeutic strategies for diseases related to ovarian follicular development disorders.
Semi-elemental versus polymeric formula for enteral nutrition in brain-injured critically ill patients: a randomized trial
Authors: Carteron Laurent , Samain Emmanuel , Winiszewski Hadrien , Blasco Gilles , Balon Anne-Sophie , Gilli Camille , Piton Gael , Capellier Gilles , Pili-Floury Sebastien , Besch Guillaume 
Published: January 2021

Abstract
Background
The properties of semi-elemental enteral nutrition might theoretically improve gastrointestinal tolerance in brain-injured patients, known to suffer gastroparesis. The purpose of this study was to compare the efficacy and tolerance of a semi-elemental versus a polymeric formula for enteral nutrition (EN) in brain-injured critically ill patients.

Methods
Prospective, randomized study including brain-injured adult patients [Glasgow Coma Scale (GCS) ≤ 8] with an expected duration of mechanical ventilation > 48 h. Intervention: an enteral semi-elemental (SE group) or polymeric (P group) formula. EN was started within 36 h after admission to the intensive care unit and was delivered according to a standardized nurse-driven protocol. The primary endpoint was the percentage of patients who received both 60% of the daily energy goal at 3 days and 100% of the daily energy goal at 5 days after inclusion. Tolerance of EN was assessed by the rate of gastroparesis, vomiting and diarrhea.

Results
Respectively, 100 and 95 patients were analyzed in the SE and P groups: Age (57[44–65] versus 55[40–65] years) and GCS (6[3–7] versus 5[3–7]) did not differ between groups. The percentage of patients achieving the primary endpoint was similar (46% and 48%, respectively; relative risk (RR) [95% confidence interval (CI)] = 1.05 (0.78–1.42); p = 0.73). The mean daily energy intake was, respectively, 20.2 ± 6.3 versus 21.0 ± 6.5 kcal/kg/day (p = 0.42). Protein intakes were 1.3 ± 0.4 versus 1.1 ± 0.3 g/kg/day (p < 0.0001). Respectively, 18% versus 12% patients presented gastroparesis (p = 0.21), and 16% versus 8% patients suffered from diarrhea (p = 0.11). No patient presented vomiting in either group.

Conclusion
Semi-elemental compared to polymeric formula did not improve daily energy intake or gastrointestinal tolerance of enteral nutrition.

Trial registration

EudraCT/ID-RCB 2012-A00078-35 (registered January 17, 2012).