bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementation of the Family HELP Protocol: A Feasibility Project for a West Texas ICU
Authors: McClay Rebecca
Published: February 2021

The purpose of this project was to determine if bedside intensive care unit (ICU) nurse buy-in to the Family Hospital Elder Life Program (HELP) protocol was sufficient to make implementation feasible at one county hospital in West Texas. Surveys were anonymous with ballot box collection being available to the bedside ICU nurses for one week each. Questions were based on literature findings of expected outcomes, identified barriers and facilitators, Calgary Family Intervention Method framework domains, and the Centers for Disease Control and Prevention Framework for program evaluation. Outcome measures were taken from the stated aims of the project and evaluated from paired baseline and summative survey questions. Survey participation was approximately half of nurses employed in the studied ICU. Analysis of the surveys showed a positive perception of family presence decreasing patient delirium symptoms, and a positive perception of the Family HELP protocol. The results described a high perception of family members as partners in care and high intention to implement the Family HELP protocol, indicating strong support of a full implementation of the protocol. The high level of bedside nurse buy-in present in this study has large implications for successful implementation of the Family HELP protocol in the near future, with sustainability and continued use supported by potential inclusion of the task in the electronic health record charting.
A Systematic Review on Bleeding Risk Scores’ Accuracy after Percutaneous Coronary Interventions in Acute and Elective Settings
Authors: Brinza Crischentian , Burlacu Alexandru , Tinica Grigore , Covic Adrian , Macovei Liviu
Published: February 2021

Dual antiplatelet therapy (DAT) is recommended for all patients undergoing percutaneous coronary intervention (PCI), as it significantly reduces the ischemic risk at the cost of increasing the incidence of bleeding events. Several clinical predictive models were developed to better stratify the bleeding risk associated with DAT. This systematic review aims to perform a literature survey of both standard and emerging bleeding risk scores and report their performance on predicting hemorrhagic events, especially in the era of second-generation drug-eluting stents and more potent P2Y12 inhibitors. We searched PubMed, ScienceDirect, and Cochrane databases for full-text studies that developed or validated bleeding risk scores in adult patients undergoing PCI with subsequent DAT. The risk of bias for each study was assessed using the prediction model risk of bias assessment tool (PROBAST). Eighteen studies were included in the present systematic review. Bleeding risk scores showed a modest to good discriminatory power with c-statistic ranging from 0.49 (95% CI, 0.45–0.53) to 0.82 (95% CI, 0.80–0.85). Clinical models that predict in-hospital bleeding events had a relatively good predictive performance, with c-statistic ranging from 0.70 (95% CI, 0.67–0.72) to 0.80 (95% CI, 0.73–0.87), depending on the risk scores and major hemorrhagic event definition used. The knowledge and utilization of the current bleeding risk scores in appropriate clinical contexts could improve the prediction of bleeding events.
Estimation of Reference Evapotranspiration Using Spatial and Temporal Machine Learning Approaches
Authors: Rashid Niaghi Ali , Hassanijalilian Oveis , Shiri Jalal
Published: February 2021

Evapotranspiration (ET) is widely employed to measure amounts of total water loss between land and atmosphere due to its major contribution to water balance on both regional and global scales. Considering challenges to quantifying nonlinear ET processes, machine learning (ML) techniques have been increasingly utilized to estimate ET due to their powerful advantage of capturing complex nonlinear structures and characteristics. However, limited studies have been conducted in subhumid climates to simulate local and spatial ETo using common ML methods. The current study aims to present a methodology that exempts local data in ETo simulation. The present study, therefore, seeks to estimate and compare reference ET (ETo) using four common ML methods with local and spatial approaches based on continuous 17-year daily climate data from six weather stations across the Red River Valley with subhumid climate. The four ML models have included Gene Expression Programming (GEP), Support Vector Machine (SVM), Multiple Linear Regression (LR), and Random Forest (RF) with three input combinations of maximum and minimum air temperature-based (Tmax, Tmin), mass transfer-based (Tmax, Tmin, U: wind speed), and radiation-based (Rs: solar radiation, Tmax, Tmin) measurements. The estimates yielded by the four ML models were compared against each other by considering spatial and local approaches and four statistical indicators; namely, the root means square error (RMSE), the mean absolute error (MAE), correlation coefficient (r2), and scatter index (SI), which were used to assess the ML model’s performance. The comparison between combinations showed the lowest SI and RMSE values for the RF model with the radiation-based combination. Furthermore, the RF model showed the best performance for all combinations among the four defined models either spatially or locally. In general, the LR, GEP, and SVM models were improved when a local approach was used. The results showed the best performance for the radiation-based combination and the RF model with higher accuracy for all stations either locally or spatially, and the spatial SVM and GEP illustrated the lowest performance among the models and approaches.
IgM and IgG Profiles Reveal Peculiar Features of Humoral Immunity Response to SARS-CoV-2 Infection
Authors: De Donno Antonella , Lobreglio Giambattista , Panico Alessandra , Grassi Tiziana , Bagordo Francesco , Bozzetti Maria Pia , Massari Serafina , Siculella Luisa , Damiano Fabrizio , Guerra Francesco , Greco Marilena , Chicone Michele , Lazzari Roberta , Alifano Pietro
Published: February 2021

The emergence of coronavirus disease 2019 (COVID-19) is globally a major healthcare threat. There is little information regarding the mechanisms and roles of the humoral response in SARS-CoV-2 infection. The aim of this study was to analyze the antibody levels (IgM and IgG) by chemiluminescence immunoassay in 54 subjects positive to SARS-CoV-2 swab test in relation to their clinical status (whether asymptomatic, pauci-symptomatic or with mild, sever or critical symptoms), the time from the symptom onset, sex, age, and comorbidities. Overall, the presence of comorbidities and the age of subjects were associated with their clinical status. The IgG concentrations were significantly higher in patients who developed critical and severe symptoms and seemed to be independent from age, sex and comorbidities. IgG titers peaked around day 60, and then began gradually to drop, decreasing by approximately 50% on the 180th day, while the IgM titers progressively decreased as early as the tenth day, but they could be detected even at later time points. Despite the small number of individuals, some peculiar characteristics of the humoral response in COVID-19 emerged. We observed a high inter-individual variability, an ephemeral IgG half-life in several patients, and a persistence of IgM in others.
A Clinical-Epidemiological and Geospatial Study of Tuberculosis in a Neglected Area in the Amazonian Region Highlights the Urgent Need for Control Measures
Authors: Mesquita Cristal Ribeiro , Conceição Emilyn Costa , Monteiro Lúcia Helena Martins Tavares , da Silva Odinea Maria , Lima Luana Nepomuceno Gondim Costa , de Oliveira Rafael Aleixo Coelho , de Brito Artemir Coelho , Guimarães Ricardo José de Paula Souza e , Lima Karla Valéria Batista
Published: February 2021

Tuberculosis (TB) is an infectious communicable disease, which despite global efforts, still needs special attention in regions with difficult access. This study aims to describe the spatial and epidemiological trends of TB incidences from 2013 to 2018 in Marajó Island, the Amazonian region, Pará, Brazil. We have obtained secondary data from the Brazilian TB databases and performed geospatial and statistical analyses on the data for new TB cases, relapses, and re-admissions. From 2013 to 2018, 749 new cases were reported, in which the diagnostics (culture) was not performed for 652 (87.2%) patient samples, the drug resistance test (DST) was performed for nine (1.2%) samples, and one (0.13%) was multidrug-resistant TB (MDR-TB). The rapid molecular testing (RMT) was performed on 40 (5.3%) patient samples, with results indicating that eight (20%) were susceptible to rifampicin and two (5%) were rifampicin resistant. Overall, the cure rate was 449 (66.7%), while relapses and re-admissions were 41 and 44, respectively. On the geospatial distribution, the municipality of Soure stands out with a high number of incidences, relapses, and re-admissions. Spatially, the eight MDR cases were randomly distributed. Our data highlight the urgent need for TB control measures in this region, by introducing the Xpert-Ultra® MTB/RIF (Cepheid, Sunnyvale, CA, USA) and Ogawa-Kudoh.
Holiday Club Programmes in Northern Ireland: The Voices of Children and Young People
Authors: Shinwell Jackie , Finlay Ellen , Allen Caitlin , Defeyter Margaret Anne
Published: February 2021

In Northern Ireland, nearly 30% of children are thought to be at risk of going hungry in the summer holidays when they are unable to access free school meals. Community groups, voluntary groups, local authorities, and faith groups have responded to this concern by developing and delivering holiday programmes that enable children from low-income families to take part in activities and access food. The current study used purposive sampling to investigate children’s and young people’s views of holiday provision, from across three holiday clubs, in Northern Ireland. Both primary school children (n = 34; aged 4–11) and secondary school children (n = 31; aged 12–17) showed high levels of awareness of poverty and food insecurity and associated pressures and stresses on households. Importantly, children and young people did not feel stigmatised about attending holiday provision, suggesting a positive and inclusive culture towards holiday club attendance. Children reported that they enjoyed the range of activities provided at holiday clubs and reported that attendance improved their self-confidence, especially for some older children, who acted as peer mentors to younger attendees, helped them to develop new skills, and provided them with opportunities to socialise with peers in a safe environment, out with their normal social groupings in school. Older children showed a high level of shrewdness and knowledge of sectarian divides in communities but spoke positively about how different religious or cultural backgrounds did not matter in terms of meeting and making new friends in holiday club settings. In terms of food provision, the findings of this study suggest that further work needs to be done to support children to access and eat healthy, nutritious food.
Development of a Conceptual Framework for Occupational Safety and Health in Palestinian Manufacturing Industries
Authors: Tuhul Hanan S. , El-Hamouz Amer , Hasan A. Rasem , Jafar Hanan A.
Published: February 2021

The annual increase in the number of occupational accidents and diseases in the Palestinian manufacturing industries confirms a serious problem that threatens the Occupational Safety and Health (OSH) in such industries, with negative consequences in the society and economy. As the Palestinian OSH data are insufficient, tightwad, and with discrepancies in published data by different agencies, this study aimed to investigate the OSH status in the Palestinian manufacturing industries and determine the Palestinian OSH trends rates based on international practice in the EU and USA. Also, to shed light on the OSH situation in the manufacturing sector and warrant the inspection and monitoring of industries by the respective officials. The OSH data of 175 industrial establishments and 199 industrial employees was collected by meetings, interviews, and structured questionnaires for the period 2009–2016. The US and EU OSHA (Occupational Safety and Health Administration) formulas were used to calculate the OSH rates. The analysis showed that 32.30% of the industrial employees suffered from occupational injuries. The average injury rate was 7566 per 100,000 workers, indicating a low OSH level in the Palestinian manufacturing industries. The leather industry was found as the most dangerous in terms of OSH, with an average safety performance factor (SPF) of 145.6 off days/accident. Pearson’s chi-square test (χ2) revealed a correlation between occupational accidents and injuries and the employees’ commitment and lost working days. An OSH framework was developed based on safety and sustainable development pillars to assure effective enforcement of the OSH law and prevent future occupational accidents and diseases.
Evaluation of Find Your Fuel: A Point-of-Service Labelling Campaign in a Military Dining Facility
Authors: Carins Julia , Casado Francisco Crespo , Rundle-Thiele Sharyn , Kitunen Anna
Published: February 2021

Nutrition plays a critical role in health and job performance in physically demanding roles. Studies have shown Australian military personnel do not consume diets suited to their roles. A range of foods are provided in military dining facilities; however, personnel still need to make appropriate choices for healthier eating and to optimise performance. This study explored the effect of a labelling scheme based on military-specific nutrition guidance, over a one-month period. Food choices were evaluated in a pre-post design using plate photography (pre n = 190; post n = 159 plates); with satisfaction and behavioural influences assessed through a survey (pre n = 79; post n = 67). The results indicate the scheme had a small effect on food choice—potato and hot vegetable choices increased post-campaign for the dinner meal. On average, choices were heathier at lunch post-campaign, and less healthy at dinner. Satisfaction with the meal experience was higher after the campaign, and no difference was observed in behavioural influences (e.g., self-efficacy and other perceptions). These results are in alignment with other point-of-service labelling studies showing the limited capacity labelling schemes have on guiding consumer choices. Rather than using point-of-service labelling in isolation, additional individual and/or environmental strategies may be needed to more effectively encourage nutritious food choices by personnel.
The Contribution Ratio of Autotrophic and Heterotrophic Metabolism during a Mixotrophic Culture of Chlorella sorokiniana
Authors: Park Jeong-Eun , Zhang Shan , Han Thi Hiep , Hwang Sun-Jin
Published: February 2021

The contribution ratio of autotrophic and heterotrophic metabolism in the mixotrophic culture of Chlorella sorokiniana (C. sorokiniana) was investigated. At the early stage of mixotrophic growth (day 0–1), autotrophy contributed over 70% of the total metabolism; however, heterotrophy contributed more than autotrophy after day 1 due to the rapid increase in cell density, which had a shading effect in the photo-bioreactor. Heterotrophy continued to have a higher contribution until the available organic carbon was depleted at which point autotrophy became dominant again. Overall, the increase in algal biomass and light conditions in the photo-bioreactor are important factors in determining the contribution of autotrophy and heterotrophy during a mixotrophic culture.
The Relationship of Race, Psychosocial Stress and Resiliency Indicators to Neurocognitive Impairment among Older Americans Enrolled in the Health and Retirement Survey: A Cross-Sectional Study
Authors: Nkwata Allan K. , Zhang Ming , Song Xiao , Giordani Bruno , Ezeamama Amara E.
Published: February 2021

Background: Race/ethnicity, toxic stress (TS), resilience-promoting factors (RPFs), and their interactions were investigated in relationship to neurocognitive impairment (NI) in a nationally representative sample of adult Americans ≥50 years enrolled in the Health and Retirement Study (HRS) between 2012 and 2014. Methods: NI was defined as physician diagnosis of Alzheimer’s disease/dementia or HRS total cognition score ≤ 10. Race/ethnicity (i.e., African American, White, or Other), TS (i.e., everyday discrimination and chronic stressors), and mastery (as indicator of RPF) were self-reported. Multivariable logistic regression models estimated race-, TS-, RPF-associated odds ratios (ORs), and 95% confidence intervals (CI) for NI adjusting for socio-demographic confounders. Results: 6317 respondents interviewed between the years 2012 and 2014, age range 55–104 years old, 83% White, 13% Black and 4% Other race were included in the study. Chronic stress (OR = 1.88, 95% CI: 1.42–2.48), discrimination (OR = 3.31, 95% CI: 2.12–5.19) and low mastery (OR = 1.85, 95% CI: 1.38–2.48) were each associated with higher NI risk while low mastery was associated with higher NI risk in discrimination and race/ethnicity dependent manner. Specifically, low mastery-associated risk for NI was evident among adults that denied experiencing discrimination (OR = 2.01, 95% CI: 1.51–2.68), but absent among those that experienced discrimination (OR = 0.72, 95% CI: 0.32–1.62). Further, AA race was associated with NI risk but only among adults with high mastery (OR = 2.00, 95% CI: 1.20–3.35). Conclusions: Discrimination, chronic stress, and low mastery were associated with worse cognition. Persisting cognitive disadvantage for AA vs. White/Other race only among high mastery adults suggests that adverse social experiences may counteract mastery-associated cognitive benefits among AA population. TS reduction through policies that promote equal treatment by race/ethnicity in social life, health, justice, and economic systems may promote successful cognitive aging.
Machine Learning Approaches to Bike-Sharing Systems: A Systematic Literature Review
Authors: Albuquerque Vitória , Sales Dias Miguel , Bacao Fernando
Published: February 2021

Cities are moving towards new mobility strategies to tackle smart cities’ challenges such as carbon emission reduction, urban transport multimodality and mitigation of pandemic hazards, emphasising on the implementation of shared modes, such as bike-sharing systems. This paper poses a research question and introduces a corresponding systematic literature review, focusing on machine learning techniques’ contributions applied to bike-sharing systems to improve cities’ mobility. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) method was adopted to identify specific factors that influence bike-sharing systems, resulting in an analysis of 35 papers published between 2015 and 2019, creating an outline for future research. By means of systematic literature review and bibliometric analysis, machine learning algorithms were identified in two groups: classification and prediction.
Peripheral Blood miRome Identified miR-155 as Potential Biomarker of MetS and Cardiometabolic Risk in Obese Patients
Authors: Cerda Alvaro , Amaral Adonai Aralim , de Oliveira Raquel , Moraes Tamiris Invencioni , Braga Aécio Assunção , Graciano-Saldarriaga Magda Elizabeth , Fajardo Cristina Moreno , Hirata Thiago Dominguez Crespo , Bonezi Vivian , Campos-Salazar Antony Brayan , Dorea Egidio Lima , Bernik Marcia Martins Silveira , Hirata Mario Hiroyuki , Hirata Rosario Dominguez Crespo
Published: February 2021

This study explored circulating miRNAs and target genes associated with metabolic syndrome (MetS) and cardiometabolic risk in obese patients. Small-RNA sequencing was used to assess the peripheral blood miRNome of 12 obese subjects (6 MetS and 6 non-MetS). Differentially expressed miRNAs and target genes were further analyzed by qPCR in a larger sample of obese patients (48 MetS and 32 non-MetS). miRNA:mRNA interactions were studied using in silico tools. miRNome analysis identified 10 downregulated miRNAs in MetS compared to non-Met patients (p < 0.05). In silico studies revealed three miRNAs (miR-155, miR-181a, and let-7a) and their predictive targets (CCAAT/enhancer-binding protein beta—CEBPB, KRAS proto-oncogene, GTPase—KRAS and suppressor of cytokine signaling 1—SOCS1) with a potential role in the insulin receptor signaling pathway. miR-155 expression was reduced and CEBPB mRNA levels were increased in MetS patients (p < 0.05), and these effects were correlated with the number of MetS diagnostic criteria (p < 0.05). Increased HOMA-IR (>7.6) was associated with low miR-155 levels, high CEBPB expression, and serum hsCRP (p < 0.05). miR-155 was negatively correlated with CEBPB, HOMA-IR, and plasma fibrinogen, and positively correlated with serum adiponectin (p < 0.05). Downregulation of circulating miR-155 is associated with insulin resistance, poor glycemic control, and increased MetS-related cardiometabolic risk, and these effects are potentially mediated by interaction with CEBPB.
Biosensor-Based Directed Evolution of Methanol Dehydrogenase from Lysinibacillus xylanilyticus
Authors: Le Thien-Kim , Ju Su-Bin , Lee Hyewon , Lee Jin-Young , Oh So-Hyung , Kwon Kil-Koang , Sung Bong-Hyun , Lee Seung-Goo , Yeom Soo-Jin
Published: February 2021

Methanol dehydrogenase (Mdh), is a crucial enzyme for utilizing methane and methanol as carbon and energy sources in methylotrophy and synthetic methylotrophy. Engineering of Mdh, especially NAD-dependent Mdh, has thus been actively investigated to enhance methanol conversion. However, its poor catalytic activity and low methanol affinity limit its wider application. In this study, we applied a transcriptional factor-based biosensor for the direct evolution of Mdh from Lysinibacillus xylanilyticus (Lxmdh), which has a relatively high turnover rate and low KM value compared to other wild-type NAD-dependent Mdhs. A random mutant library of Lxmdh was constructed in Escherichia coli and was screened using formaldehyde-detectable biosensors by incubation with low methanol concentrations. Positive clones showing higher fluorescence were selected by fluorescence-activated cell sorting (FACS) system, and their catalytic activities toward methanol were evaluated. The successfully isolated mutants E396V, K318N, and K46E showed high activity, particularly at very low methanol concentrations. In kinetic analysis, mutant E396V, K318N, and K46E had superior methanol conversion efficiency, with 79-, 23-, and 3-fold improvements compared to the wild-type, respectively. These mutant enzymes could thus be useful for engineering synthetic methylotrophy and for enhancing methanol conversion to various useful products.
Expression Pattern of iNOS, BCL-2 and MMP-9 in the Hip Synovium Tissue of Patients with Osteoarthritis
Authors: Caric Davor , Zekic Tomas Sandra , Filipovic Natalija , Soljic Violeta , Benzon Benjamin , Glumac Sandro , Rakovac Ivan , Vukojevic Katarina
Published: February 2021

Hip osteoarthritis (HOA) is characterized by degradation of the cartilage and synovitis. However, the pathohistological effects of synovial tissue inflammation on HOA are not clear. The aim of this study was to evaluate the expression of iNOS, BCL-2 and MMP-9 markers in different synovial cell populations. A total of 32 patients were evaluated retrospectively. Age, sex, height, weight, body mass index were recorded and lymphocyte, fibrocytes and macrophages were analysed in tissue sections. Osteoarthritis cartilage histopathology assessment system (OARSI), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Krenn score, Harris Hip Score (HHS) and Kellgren–Lawrence (K-L) grading of the hip joints were performed. Total hip arthroplasty was performed on 32 patients and controls. Patients were divided into two groups according to their disease severity. The tissues were immunohistochemically analysed. K-L grade and Krenn score differ between all three groups, but also between moderate and severe OA. Synovial lining cell layer, resident cells in stroma and especially inflammatory infiltration were increasing with severity of OA. iNOS expression in both intima and subintima was positively correlated with Krenn score in moderate and severe osteoarthritis (OA) groups. Expression of BCL-2 in intima of severe OA patients was positively correlated with Krenn score. In conclusion, iNOS, BCL-2 and MMP-9 are involved in the regulation of HOA. Our study indicates a relationship between the pathohistological features, the synovial inflammation and the cartilage condition at the time of hip replacement due to OA or femoral neck fracture.
Melatonin: From Pharmacokinetics to Clinical Use in Autism Spectrum Disorder
Authors: Lalanne Sébastien , Fougerou-Leurent Claire , Anderson George M. , Schroder Carmen M. , Nir Tali , Chokron Sylvie , Delorme Richard , Claustrat Bruno , Bellissant Eric , Kermarrec Solenn , Franco Patricia , Denis Laure , Tordjman Sylvie
Published: February 2021

The role of melatonin has been extensively investigated in pathophysiological conditions, including autism spectrum disorder (ASD). Reduced melatonin secretion has been reported in ASD and led to many clinical trials using immediate-release and prolonged-release oral formulations of melatonin. However, melatonin’s effects in ASD and the choice of formulation type require further study. Therapeutic benefits of melatonin on sleep disorders in ASD were observed, notably on sleep latency and sleep quality. Importantly, melatonin may also have a role in improving autistic behavioral impairments. The objective of this article is to review factors influencing treatment response and possible side effects following melatonin administration. It appears that the effects of exposure to exogenous melatonin are dependent on age, sex, route and time of administration, formulation type, dose, and association with several substances (such as tobacco or contraceptive pills). In addition, no major melatonin-related adverse effect was described in typical development and ASD. In conclusion, melatonin represents currently a well-validated and tolerated treatment for sleep disorders in children and adolescents with ASD. A more thorough consideration of factors influencing melatonin pharmacokinetics could illuminate the best use of melatonin in this population. Future studies are required in ASD to explore further dose-effect relationships of melatonin on sleep problems and autistic behavioral impairments.
Potential Effects of Nonadherent on Adherent Human Umbilical Venous Endothelial Cells in Cell Culture
Authors: Schulz Christian , Krüger-Genge Anne , Lendlein Andreas , Küpper Jan-Heiner , Jung Friedrich
Published: February 2021

The adherence and shear-resistance of human umbilical venous endothelial cells (HUVEC) on polymers is determined in vitro in order to qualify cardiovascular implant materials. In these tests, variable fractions of HUVEC do not adhere to the material but remain suspended in the culture medium. Nonadherent HUVEC usually stop growing, rapidly lose their viability and can release mediators able to influence the growth and function of the adherent HUVEC. The aim of this study was the investigation of the time dependent behaviour of HUVEC under controlled nonadherent conditions, in order to gain insights into potential influences of these cells on their surrounding environment in particular adherent HUVEC in the context of in vitro biofunctionality assessment of cardiovascular implant materials. Data from adherent or nonadherent HUVEC growing on polystyrene-based cell adhesive tissue culture plates (TCP) or nonadhesive low attachment plates (LAP) allow to calculate the number of mediators released into the culture medium either from adherent or nonadherent cells. Thus, the source of the inflammatory mediators can be identified. For nonadherent HUVEC, a time-dependent aggregation without further proliferation was observed. The rate of apoptotic/dead HUVEC progressively increased over 90% within two days. Concomitant with distinct blebbing and loss of membrane integrity over time, augmented releases of prostacyclin (PGI2, up to 2.91 ± 0.62 fg/cell) and platelet-derived growth factor BB (PDGF-BB, up to 1.46 ± 0.42 fg/cell) were detected. The study revealed that nonadherent, dying HUVEC released mediators, which can influence the surrounding microenvironment and thereby the results of in vitro biofunctionality assessment of cardiovascular implant materials. Neglecting nonadherent HUVEC bears the risk for under- or overestimation of the materials endothelialization potential, which could lead to the loss of relevant candidates or to uncertainty with regard to their suitability for cardiac applications. One approach to minimize the influence from nonadherent endothelial cells could be their removal shortly after observing initial cell adhesion. However, this would require an individual adaptation of the study design, depending on the properties of the biomaterial used.
Comparative Analysis Identifies Similarities between the Human and Murine Microglial Sensomes
Authors: Abels Erik R. , Nieland Lisa , Hickman Suzanne , Broekman Marike L. D. , El Khoury Joseph , Maas Sybren L. N.
Published: February 2021

One of the essential functions of microglia is to continuously sense changes in their environment and adapt to those changes. For this purpose, they use a set of genes termed the sensome. This sensome is comprised of the most abundantly expressed receptors on the surface of microglia. In this study, we updated previously identified mouse microglial sensome by incorporating an additional published RNAseq dataset into the data-analysis pipeline. We also identified members of the human microglial sensome using two independent human microglia RNAseq data sources. Using both the mouse and human microglia sensomes, we identified a key set of genes conserved between the mouse and human microglial sensomes as well as some differences between the species. We found a key set of 57 genes to be conserved in both mouse and human microglial sensomes. We define these genes as the “microglia core sensome”. We then analyzed expression of genes in this core sensome in five different datasets from two neurodegenerative disease models at various stages of the diseases and found that, overall, changes in the level of expression of microglial sensome genes are specific to the disease or condition studied. Our results highlight the relevance of data generated in mice for understanding the biology of human microglia, but also stress the importance of species-specific gene sets for the investigation of diseases involving microglia. Defining this microglial specific core sensome may help identify pathological changes in microglia in humans and mouse models of human disease.
Does C-C Motif Chemokine Ligand 2 (CCL2) Link Obesity to a Pro-Inflammatory State?
Authors: Dommel Sebastian , Blüher Matthias
Published: February 2021

The mechanisms of how obesity contributes to the development of cardio-metabolic diseases are not entirely understood. Obesity is frequently associated with adipose tissue dysfunction, characterized by, e.g., adipocyte hypertrophy, ectopic fat accumulation, immune cell infiltration, and the altered secretion of adipokines. Factors secreted from adipose tissue may induce and/or maintain a local and systemic low-grade activation of the innate immune system. Attraction of macrophages into adipose tissue and altered crosstalk between macrophages, adipocytes, and other cells of adipose tissue are symptoms of metabolic inflammation. Among several secreted factors attracting immune cells to adipose tissue, chemotactic C-C motif chemokine ligand 2 (CCL2) (also described as monocyte chemoattractant protein-1 (MCP-1)) has been shown to play a crucial role in adipose tissue macrophage infiltration. In this review, we aimed to summarize and discuss the current knowledge on CCL2 with a focus on its role in linking obesity to cardio-metabolic diseases.
Impact of the 25-Hydroxycholecalciferol Concentration and Vitamin D Deficiency Treatment on Changes in the Bone Level at the Implant Site during the Process of Osseointegration: A Prospective, Randomized, Controlled Clinical Trial
Authors: Kwiatek Jakub , Jaroń Aleksandra , Trybek Grzegorz
Published: February 2021

Introduction: The most important factor which is responsible for the positive course of implant treatment is the process of osseointegration between the implant structure and the host’s bone tissue. The aim of this study was to assess what effect the 25-hydroxycholecalciferol concentration and vitamin D deficiency treatment have on changes in the bone level at the implant site during the process of osseointegration in the mandible. Materials and Methods: The study was with 122 people qualified for implant surgery, who were assigned to three research groups (A, B, and C). Laboratory, clinical, and radiological tests were performed on the day of surgery, and after 6 and 12 weeks. The bone level in the immediate proximity of the implant was determined by radiovisiography (RVG). Results: The bone level after 12 weeks in Groups B and C was significantly higher than after 6 weeks. The bone level in the study Group B was significantly higher than in Group A. The study showed that the higher the levels of 25-hydroxycholecalciferol were observed on the day of surgery, the higher was the level of bone surrounding the implant after 6 and 12 after surgery. Conclusion: The correct level of 25-hydroxycholecalciferol on the day of surgery and vitamin D deficiency treatment significantly increase the bone level at the implant site in the process of radiologically assessed osseointegration.
Making Sense of Intracellular Nucleic Acid Sensing in Type I Interferon Activation in Sjögren’s Syndrome
Authors: Huijser Erika , Versnel Marjan A.
Published: February 2021

Primary Sjögren’s syndrome (pSS) is a systemic autoimmune rheumatic disease characterized by dryness of the eyes and mucous membranes, which can be accompanied by various extraglandular autoimmune manifestations. The majority of patients exhibit persistent systemic activation of the type I interferon (IFN) system, a feature that is shared with other systemic autoimmune diseases. Type I IFNs are integral to anti-viral immunity and are produced in response to stimulation of pattern recognition receptors, among which nucleic acid (NA) receptors. Dysregulated detection of endogenous NAs has been widely implicated in the pathogenesis of systemic autoimmune diseases. Stimulation of endosomal Toll-like receptors by NA-containing immune complexes are considered to contribute to the systemic type I IFN activation. Accumulating evidence suggest additional roles for cytosolic NA-sensing pathways in the pathogenesis of systemic autoimmune rheumatic diseases. In this review, we will provide an overview of the functions and signaling of intracellular RNA- and DNA-sensing receptors and summarize the evidence for a potential role of these receptors in the pathogenesis of pSS and the sustained systemic type I IFN activation.
ECMO in Cardiac Arrest: A Narrative Review of the Literature
Authors: De Charrière Amandine , Assouline Benjamin , Scheen Marc , Mentha Nathalie , Banfi Carlo , Bendjelid Karim , Giraud Raphaël
Published: February 2021

Cardiac arrest (CA) is a frequent cause of death and a major public health issue. To date, conventional cardiopulmonary resuscitation (CPR) is the only efficient method of resuscitation available that positively impacts prognosis. Extracorporeal membrane oxygenation (ECMO) is a complex and costly technique that requires technical expertise. It is not considered standard of care in all hospitals and should be applied only in high-volume facilities. ECMO combined with CPR is known as ECPR (extracorporeal cardiopulmonary resuscitation) and permits hemodynamic and respiratory stabilization of patients with CA refractory to conventional CPR. This technique allows the parallel treatment of the underlying etiology of CA while maintaining organ perfusion. However, current evidence does not support the routine use of ECPR in all patients with refractory CA. Therefore, an appropriate selection of patients who may benefit from this procedure is key. Reducing the duration of low blood flow by means of performing high-quality CPR and promoting access to ECPR, may improve the survival rate of the patients presenting with refractory CA. Indeed, patients who benefit from ECPR seem to carry better neurological outcomes. The aim of this present narrative review is to present the most recent literature available on ECPR and to clarify its potential therapeutic role, as well as to provide an in-depth explanation of equipment and its set up, the patient selection process, and the patient management post-ECPR.
Thrombotic Thrombocytopenic Purpura: Pathophysiology, Diagnosis, and Management
Authors: Sukumar Senthil , Lämmle Bernhard , Cataland Spero R.
Published: February 2021

Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, severe thrombocytopenia, and ischemic end organ injury due to microvascular platelet-rich thrombi. TTP results from a severe deficiency of the specific von Willebrand factor (VWF)-cleaving protease, ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13). ADAMTS13 deficiency is most commonly acquired due to anti-ADAMTS13 autoantibodies. It can also be inherited in the congenital form as a result of biallelic mutations in the ADAMTS13 gene. In adults, the condition is most often immune-mediated (iTTP) whereas congenital TTP (cTTP) is often detected in childhood or during pregnancy. iTTP occurs more often in women and is potentially lethal without prompt recognition and treatment. Front-line therapy includes daily plasma exchange with fresh frozen plasma replacement and immunosuppression with corticosteroids. Immunosuppression targeting ADAMTS13 autoantibodies with the humanized anti-CD20 monoclonal antibody rituximab is frequently added to the initial therapy. If available, anti-VWF therapy with caplacizumab is also added to the front-line setting. While it is hypothesized that refractory TTP will be less common in the era of caplacizumab, in relapsed or refractory cases cyclosporine A, N-acetylcysteine, bortezomib, cyclophosphamide, vincristine, or splenectomy can be considered. Novel agents, such as recombinant ADAMTS13, are also currently under investigation and show promise for the treatment of TTP. Long-term follow-up after the acute episode is critical to monitor for relapse and to diagnose and manage chronic sequelae of this disease.
Vitamin D Concentrations at Term Do Not Differ in Newborns and Their Mothers with and without Polycystic Ovary Syndrome
Authors: Kollmann Martina , Obermayer-Pietsch Barbara , Lerchbaum Elisabeth , Feigl Sarah , Hochstätter Rüdiger , Pregartner Gudrun , Trummer Christian , Klaritsch Philipp
Published: February 2021

Studies suggest that non-pregnant women with polycystic ovary syndrome (PCOS) may be at elevated risk of 25 hydroxyvitamin D (25(OH)D) deficiency. Furthermore, there is evidence suggesting that 25(OH)D may also play an important role during pregnancy. Data regarding 25(OH)D deficiency during pregnancy in PCOS patients and its association with perinatal outcome is scarce. The aim of the study was to investigate whether mothers with and without PCOS have different 25(OH)D levels at term, how maternal 25(OH)D levels are reflected in their offspring, and if 25(OH)D levels are associated with an adverse perinatal outcome. Therefore, we performed a cross-sectional observational study and included 79 women with PCOS according to the ESHRE/ASRM 2003 definition and 354 women without PCOS and an ongoing pregnancy ≥ 37 + 0 weeks of gestation who gave birth in our institution between March 2013 and December 2015. Maternal serum and cord blood 25(OH)D levels were analyzed at the day of delivery. Maternal 25(OH)D levels did not differ significantly in women with PCOS and without PCOS (p = 0.998), nor did the 25(OH)D levels of their respective offspring (p = 0.692). 25(OH)D deficiency (<20 ng/mL) was found in 26.9% and 22.5% of women with and without PCOS (p = 0.430). There was a strong positive correlation between maternal and neonatal 25(OH)D levels in both investigated groups (r ≥ 0.79, p < 0.001). Linear regression estimates of cord blood 25(OH)D levels are about 77% of serum 25(OH)D concentrations of the mother. Compared to healthy controls, the risk for maternal complications was increased in PCOS women (48% vs. 65%; p = 0.009), while there was no significant difference in neonatal complications (22% and 22%; p = 1.0). However, 25(OH)D levels were similar between mothers and infants with and without perinatal complications. Although the share of women and infants with 25(OH)D deficiency was high in women with PCOS and without PCOS, it seems that the incidence of adverse perinatal outcome was not affected. The long-term consequences for mothers and infants with a 25(OH)D deficiency have to be investigated in future studies.
An MRI-Based Radiomic Prognostic Index Predicts Poor Outcome and Specific Genetic Alterations in Endometrial Cancer
Authors: Jacob Havjin , Dybvik Julie A. , Ytre-Hauge Sigmund , Fasmer Kristine E. , Hoivik Erling A. , Trovik Jone , Krakstad Camilla , Haldorsen Ingfrid S.
Published: February 2021

Integrative tumor characterization linking radiomic profiles to corresponding gene expression profiles has the potential to identify specific genetic alterations based on non-invasive radiomic profiling in cancer. The aim of this study was to develop and validate a radiomic prognostic index (RPI) based on preoperative magnetic resonance imaging (MRI) and assess possible associations between the RPI and gene expression profiles in endometrial cancer patients. Tumor texture features were extracted from preoperative 2D MRI in 177 endometrial cancer patients. The RPI was developed using least absolute shrinkage and selection operator (LASSO) Cox regression in a study cohort (n = 95) and validated in an MRI validation cohort (n = 82). Transcriptional alterations associated with the RPI were investigated in the study cohort. Potential prognostic markers were further explored for validation in an mRNA validation cohort (n = 161). The RPI included four tumor texture features, and a high RPI was significantly associated with poor disease-specific survival in both the study cohort (p < 0.001) and the MRI validation cohort (p = 0.030). The association between RPI and gene expression profiles revealed 46 significantly differentially expressed genes in patients with a high RPI versus a low RPI (p < 0.001). The most differentially expressed genes, COMP and DMBT1, were significantly associated with disease-specific survival in both the study cohort and the mRNA validation cohort. In conclusion, a high RPI score predicts poor outcome and is associated with specific gene expression profiles in endometrial cancer patients. The promising link between radiomic tumor profiles and molecular alterations may aid in developing refined prognostication and targeted treatment strategies in endometrial cancer.
Trends and Clinical Impact of Gastrointestinal Endoscopic Procedures on Acute Heart Failure in Spain (2002–2017)
Authors: Méndez-Bailón Manuel , Jiménez-García Rodrigo , Muñoz-Rivas Nuria , Hernández-Barrera Valentín , de Miguel-Yanes José Maria , de Miguel-Díez Javier , Andrès Emmanuel , Lorenzo-Villalba Noel , López-de-Andrés Ana
Published: February 2021

Introduction: Heart failure decompensation can be triggered by many factors, including anemia. In cases of iron deficiency anemia or iron deficiency without anemia, endoscopic studies are recommended to rule out the presence of gastrointestinal neoplasms or other associated bleeding lesions. Objectives: The aims of this study were to (i) examine trends in the incidence, clinical characteristics, and in-hospital outcomes of patients hospitalized with heart failure from 2002 to 2017 who underwent esophagogastroduodenoscopy (EGD) and/or colonoscopy, and to (ii) identify factors associated with in-hospital mortality (IHM) among patients with heart failure who underwent an EGD and/or a colonoscopy. Methods: We conducted an observational retrospective epidemiological study using the Spanish National Hospital Discharge Database (SNHDD) between 2002 and 2017. We included hospitalizations of patients with a primary discharge diagnosis of heart failure. Cases were reviewed if there was an ICD-9-CM or ICD-10 procedure code for EGD or colonoscopy in any procedure field. Multivariable logistic regression models were constructed to identify predictors of IHM among HF patients who underwent an EGD or colonoscopy. Results: A total of 51,187 (1.32%) non-surgical patients hospitalized with heart failure underwent an EGD and another 72,076 (1.85%) patients had a colonoscopy during their admission. IHM was significantly higher in those who underwent an EGD than in those who underwent a red blood cell transfusion (OR 1.10; 95%CI 1.04–1.12). However, the use of colonoscopy seems to decrease the probability of IHM (OR 0.45; 95%CI 0.41–0.49). In patients who underwent a colonoscopy, older age seems to increase the probability of IHM. However, EGD was associated with a lower mortality (OR 0.60; 95% CI 0.55–0.64). Conclusion: In our study, a decrease in the number of gastroscopies was observed in relation to colonoscopy in patients with heart failure. The significant ageing of the hospitalized HF population seen over the course of the study could have contributed to this. Both procedures seemed to be associated with lower in-hospital mortality, but in the case of colonoscopy, the risk of in-hospital mortality was higher in elderly patients with heart failure and associated neoplasms. Colonoscopy and EGD seemed not to increase IHM in patients with heart failure.
Anthropogenic Impact on Beach Heterogeneity within a Littoral Cell (Northern Tuscany, Italy)
Authors: Bertoni Duccio , Bini Monica , Luppichini Marco , Cipriani Luigi Enrico , Carli Andrea , Sarti Giovanni
Published: February 2021

In this paper the evolution of the Northern Tuscany littoral cell is documented through a detailed analysis of the increasing anthropogenic pressure since the beginning of the 20th century. This sector of the Tuscany coast has been experiencing strong erosion effects that resulted in the loss of large volumes of sandy beaches. The anthropogenic impact on natural processes have been intensified by the construction of two ports in the early decades of the 20th century. Competent authorities reacted by building hard protection structures that tried to fix the position of the shoreline but offset the erosion drive downdrift. Therefore, in the last 20 years a regional Plan was undertaken to gradually replace the hard defense schemes with a softer approach, which involved a massive use of sediment redistribution activities. Many nourishments have been done ever since, using both sand and gravel. All these hard and soft protection operations have been archived in a geodatabase, and visualized in maps that clearly show the progressive change from hard to soft defense. This database may improve the approach to any future analysis of the littoral cell both in terms of research and management, while providing a practical example that may be easily replicated elsewhere.