Miracle-dz/UniFAR-FTUs huggingface dataset:
ASSOCIATIONS BETWEEN VITAMIN D AND MICROVASCULAR COMPLICATIONS IN MIDDLE-AGED AND ELDERLY DIABETIC PATIENTS.

Objective: The objective of the cross-sectional study was to investigate the association of serum 25-hydroxyvitamin D [25(OH)D] levels with estimated glomerular filtration rate (eGFR), albuminuria/creatinine ratio (ACR) and the prevalence of diabetic retinopathy (DR) in Chinese diabetic adults. Methods: 4,767 diabetic participants were enrolled from seven communities in Shanghai, China in 2018. Participants underwent several checkups, which included the measurement of anthropometric parameters, blood pressure, glucose, lipid profiles, 25(OH)D and ACR. DR was detected by high-quality fundus photographs and was remotely read by ophthalmologists. Results: Compared with the first 25(OH)D quartile, participants in the fourth quartile had a lower prevalence of high ACR (OR 0.77, 95% CI 0.61, 0.96) (P for trend <0.01). No association was found between 25(OH)D levels and eGFR. For DR, OR (95% CI) of DR ranging from 0 to 4 in ordinal logistic regression associated with 25(OH)D was 0.62 (0.47, 0.82) for the fourth 25(OH)D quartile (P for trend <0.01) compared with the first quartile. These associations were all fully adjusted for confounding factors. Conclusions: Lower serum 25(OH)D concentration is significantly associated with increased ACR and higher prevalence of DR in middle-aged and elderly diabetic adults. However, the possibility of a causal relationship between 25(OH)D deficiency and diabetic microvascular complications remains to be demonstrated. Abbreviations: 25(OH)D = 25-hydroxyvitamin D; DKD = diabetic kidney disease; DR = diabetic retinopathy; ACR = albuminuria/creatinine ratio; T2DM = Type 2 diabetes mellitus; NHANES = national health and nutrition examination survey; eGFR = estimated glomerular filtration rate; BMI = body mass index; FPG = fasting plasma glucose; HbA1c = glycated hemoglobin; HDL = high-density lipoprotein; LDL = low-density lipoprotein; SD = standard deviation, OR = odds ratios; CI = confidence intervals; ADA = American Diabetes Association.
Rare cancers in childhood and adolescence in Brazil: First report of data from 19 population‐based cancer registries

Rare childhood cancer is challenging to define. The Italian Pediatric Rare Tumor (TREP) Study considers rare tumors to include solid malignancies characterized by an annual incidence rate of <2 cases per 1 million and not enrolled in clinical trials. The objective of the current study was to analyze the population incidence rate of rare tumors among children and adolescents (those aged birth‐19 years) in Brazil.
Priming Dental Pulp Stem Cells from Human Exfoliated Deciduous Teeth with Fibroblast Growth Factor‐2 Enhances Mineralization Within Tissue‐Engineered Constructs Implanted in Craniofacial Bone Defects

The craniofacial area is prone to trauma or pathologies often resulting in large bone damages. One potential treatment option is the grafting of a tissue‐engineered construct seeded with adult mesenchymal stem cells (MSCs). The dental pulp appears as a relevant source of MSCs, as dental pulp stem cells display strong osteogenic properties and are efficient at bone formation and repair. Fibroblast growth factor‐2 (FGF‐2) and/or hypoxia primings were shown to boost the angiogenesis potential of dental pulp stem cells from human exfoliated deciduous teeth (SHED). Based on these findings, we hypothesized here that these primings would also improve bone formation in the context of craniofacial bone repair. We found that both hypoxic and FGF‐2 primings enhanced SHED proliferation and osteogenic differentiation into plastically compressed collagen hydrogels, with a much stronger effect observed with the FGF‐2 priming. After implantation in immunodeficient mice, the tissue‐engineered constructs seeded with FGF‐2 primed SHED mediated faster intramembranous bone formation into critical size calvarial defects than the other groups (no priming and hypoxia priming). The results of this study highlight the interest of FGF‐2 priming in tissue engineering for craniofacial bone repair. Stem Cells Translational Medicine 2019;8:844&857
Cellular/molecular Ca 2ϩ Current versus Ca Channel Cooperativity of Exocytosis

Recently there has been significant interest and progress in the study of spatiotemporal dynamics of Ca 2ϩ that triggers exocytosis at a fast chemical synapse, which requires understanding the contribution of individual calcium channels to the release of a single vesicle. Experimental protocols provide insight into this question by probing the sensitivity of exocytosis to Ca 2ϩ influx. While varying extra-cellular or intracellular Ca 2ϩ concentration assesses the intrinsic biochemical Ca 2ϩ cooperativity of neurotransmitter release, varying the number of open Ca 2ϩ channels using pharmacological channel block or the tail current titration probes the cooperativity between individual Ca 2ϩ channels in triggering exocytosis. Despite the wide use of these Ca 2ϩ sensitivity measurements, their interpretation often relies on heuristic arguments. Here we provide a detailed analysis of the Ca 2ϩ sensitivity measures probed by these experimental protocols, present simple expressions for special cases, and demonstrate the distinction between the Ca 2ϩ current cooperativity, defined by the relationship between exocytosis rate and the whole-terminal Ca 2ϩ current magnitude, and the underlying Ca 2ϩ channel cooper-ativity, defined as the average number of channels involved in the release of a single vesicle. We find simple algebraic expressions that show that the two are different but linearly related. Further, we use three-dimensional computational modeling of buffered Ca 2ϩ diffusion to analyze these distinct Ca 2ϩ cooperativity measures, and demonstrate the role of endogenous Ca 2ϩ buffers on such measures. We show that buffers can either increase or decrease the Ca 2ϩ current cooperativity of exocytosis, depending on their concentration and the single-channel Ca 2ϩ current.
Effect of UDP‐glucuronosyltransferase 1A1 activity on risk for developing Gilbert's syndrome

Variations at the six nucleotides −3279 (T > G), −53 (A[TA]6TAA > A[TA]7TAA), 211 (G > A), 686 (C > A), 1091 (C > T), and 1456 (T > G) in the UDP‐glucuronosyltransferase 1A1 (UGT1A1) gene were determined in 178 Taiwanese patients with Gilbert's syndrome and in 200 healthy adults. Every subject was classified as a genotype depending on variation status of the six nucleotides in the UGT1A1 gene. The UGT1A1 activity for each genotype was calculated and then those genotypes were divided into 10 subgroups (Q1~Q10) according to their UGT1A1 activities, by using 10% as an interval. There were 24 genotypes observed, with UGT1A1 activity ranged 9%~100% of normal. There were two and six subjects with Gilbert's syndrome and none of healthy controls carrying genotypes in the Q1 and Q2 subgroups, respectively. The odds of developing Gilbert's syndrome were significantly higher for subjects carrying genotypes in the Q3, Q4, and Q5 subgroups than for those with genotype in the Q10 subgroup (odds ratios: 240.22, 59.80, and 14.67, respectively, P < .001 for each). Among the 178 patients of Gilbert's syndrome, serum bilirubin value was inversely correlated with UGT1A1 activity (r = −.306, P < .001). The sensitivity was 72.0% and the specificity was 90.5% by using UGT1A1 activity ≦40% of normal as the cut‐off point to distinguish between healthy subjects and patients of Gilbert's syndrome. Our results demonstrate that UGT1A1 activity is certainly a determinate for serum bilirubin value and UGT1A1 activity ≦40% of normal is a proper risk factor for the development of Gilbert's syndrome.
A Mobile Device App to Reduce Time to Drug Delivery and Medication Errors During Simulated Pediatric Cardiopulmonary Resuscitation: A Randomized Controlled Trial

Background During pediatric cardiopulmonary resuscitation (CPR), vasoactive drug preparation for continuous infusion is both complex and time-consuming, placing children at higher risk than adults for medication errors. Following an evidence-based ergonomic-driven approach, we developed a mobile device app called Pediatric Accurate Medication in Emergency Situations (PedAMINES), intended to guide caregivers step-by-step from preparation to delivery of drugs requiring continuous infusion. Objective The aim of our study was to determine whether the use of PedAMINES reduces drug preparation time (TDP) and time to delivery (TDD; primary outcome), as well as medication errors (secondary outcomes) when compared with conventional preparation methods. Methods The study was a randomized controlled crossover trial with 2 parallel groups comparing PedAMINES with a conventional and internationally used drugs infusion rate table in the preparation of continuous drug infusion. We used a simulation-based pediatric CPR cardiac arrest scenario with a high-fidelity manikin in the shock room of a tertiary care pediatric emergency department. After epinephrine-induced return of spontaneous circulation, pediatric emergency nurses were first asked to prepare a continuous infusion of dopamine, using either PedAMINES (intervention group) or the infusion table (control group), and second, a continuous infusion of norepinephrine by crossing the procedure. The primary outcome was the elapsed time in seconds, in each allocation group, from the oral prescription by the physician to TDD by the nurse. TDD included TDP. The secondary outcome was the medication dosage error rate during the sequence from drug preparation to drug injection. Results A total of 20 nurses were randomized into 2 groups. During the first study period, mean TDP while using PedAMINES and conventional preparation methods was 128.1 s (95% CI 102-154) and 308.1 s (95% CI 216-400), respectively (180 s reduction, P=.002). Mean TDD was 214 s (95% CI 171-256) and 391 s (95% CI 298-483), respectively (177.3 s reduction, P=.002). Medication errors were reduced from 70% to 0% (P<.001) by using PedAMINES when compared with conventional methods. Conclusions In this simulation-based study, PedAMINES dramatically reduced TDP, to delivery and the rate of medication errors.
Key Factors of Joint-liability Loan Contracts an Empirical Analysis

This paper provides an empirical analysis of joint-liability micro-lending contracts. Using our data set from Constanta (a Georgian micro-lender), we examine the efficacy of various incentives set by this contract such as joint-liability between groups of borrowers or group access to future and to larger loans. As proposed by theory, we find that joint liability induces a group formation where better-risk borrowers team up with better-risk borrowers before the loan contract is concluded. After the loan disbursement, parts of the incentive system lead to peer monitoring, peer support and peer pressure between the borrowers, thus helping the lending institution to address the moral hazard and enforcement problem. This paper also demonstrates that the mechanism realizes repayment rates of nearly 100%, if the loan officers fulfill their complementary duties in the screening and enforcement process. Finally, we make clear that dynamic incentives, in contrast to theory, have to be restricted if the two long-term problems of the joint-liability lending mechanism, i.e. its mismatching problem and the domino effect, are to be tackled notably. 1 We are very grateful for the comments and suggestions of and two anonymous referees, as well as of the Seminar participants in Athens, Berlin, Frankfurt (Main), Frankfurt (Oder), Leipzig and of the Sozialwissenschaftlicher Ausschuss des Vereins für Socialpolitik in Koblenz. We would also like to thank Giorgi Nadareishvili for the support in the field as well as the team and the borrowers of Constanta who agreed to participate in the questionnaire and who were helpful in many ways, when we designed and conducted the empirical research. Vigenina also thanks for the financial support of Deutsche Bank Stiftung.
A Multi-Institutional International Analysis of Textbook Outcomes Among Patients Undergoing Curative-Intent Resection of Intrahepatic Cholangiocarcinoma.

Importance Composite measures may be superior to individual measures for the analysis of hospital performance and quality of surgical care. Objective To determine the incidence of a so-called textbook outcome, a composite measure of the quality of surgical care, among patients undergoing curative-intent resection of intrahepatic cholangiocarcinoma. Design, Setting, and Participants This cohort study involved an analysis of a multinational, multi-institutional cohort of patient from 15 major hepatobiliary centers in North America, Europe, Australia, and Asia who underwent curative-intent resection of intrahepatic cholangiocarcinoma between 1993 and 2015. Data analysis was conducted from April 2018 to May 2018. Main Outcomes and Measures Hospital variation in the composite end point of textbook outcome, defined as negative margins, no perioperative transfusion, no postoperative surgical complications, no prolonged length of stay, no 30-day readmissions, and no 30-day mortality. Secondary end points were factors associated with achieving textbook outcomes. Results Among 687 patients (of whom 370 [53.9%] were men; median patient age, 61 [range, 18-86] years) undergoing curative-intent resection of intrahepatic cholangiocarcinoma, a textbook outcome was achieved in 175 patients (25.5%). Being 60 years or younger (odds ratio [OR], 1.61 [95% CI, 1.04-2.49]; P = .03), absence of preoperative jaundice (OR, 4.40 [95% CI, 1.28-15.15]; P = .02), no neoadjuvant chemotherapy (OR, 2.57 [95% CI, 1.05-6.29]; P = .04), T1a/T1b-stage disease (OR, 1.58 [95% CI, 1.01-2.49]; P = .049), N0 status (OR, 3.89 [95% CI, 1.77-8.54]; P = .001), and no bile duct resection (OR, 2.46 [95% CI, 1.25-4.84]; P = .009) were independently associated with achieving a textbook outcome after resection. A prolonged length of stay had the greatest negative association with a textbook outcome. A nomogram to assess the probability of textbook outcome was developed and had good accuracy in both the training data set (area under the curve, 0.755) and validation data set (area under the curve, 0.763). Conclusions and Relevance In this study, while hepatic resection for intrahepatic cholangiocarcinoma was performed with less than 5% mortality in specialized centers, a textbook outcome was achieved in only approximately 26% of patients. A textbook outcome may be useful for the reporting of patient-level hospital performance and hospital variation, leading to quality improvement efforts after resection of intrahepatic cholangiocarcinoma.
Individual differences in general and specific cognitive precursors in early mathematical learning

Background: The acquisition of mathematical abilities is associated not only with several academic aptitudes but also with the development of particular cognitive skills. This study analysed the role of the general and specific domain precursors of informal mathematical thinking. Method: A total of 109 4‐year‐old children (M = 59.30 months; SD = 3.56) participated in the study, in which the participants' informal math and cognitive variables were assessed. A stepwise regression model was calculated. Results: The complex inferential model evidenced the role of the three general‐domain variables analysed, in addition to numerical estimation as a specific‐domain variable. 48.5% of participants' variability in informal mathematical thinking, evaluated with the TEMA‐3 test, was explained by three of the general domain precursors: working memory, processing speed and receptive vocabulary; as well as by estimation, a specific‐domain precursor. The model showed a higher explanatory statistical weight for boys (48.9%) than girls (37.5%). Conclusions: The model indicated that working memory and processing speed were the main predictors of informal mathematical thinking at the age of four. A joint remedial or preventative intervention, taking into account predictors of the specific and general domains, could be the optimal option to improve achievement in mathematics. &NA; Diferencias individuales en los precursores cognitivos generales y específicos del aprendizaje matemático temprano. Antecedentes: la adquisición de habilidades matemáticas está asociada no solo con aptitudes académicas, sino también con el desarrollo de habilidades cognitivas específicas. Este estudio analizó el papel de los precursores del dominio general y específico en el pensamiento matemático informal. Método: un total de 109 niños de 4 años participaron en el estudio (M= 59.30; SD= 3.56). Se evaluaron el pensamiento matemático informal con la prueba TEMA‐3, y diferentes variables cognitivas. Resultados: tras la realización de un análisis de regresión por pasos, el modelo inferencial evidenció que el 48,5% de la variabilidad de los participantes en el pensamiento matemático informal fue explicado por la memoria de trabajo, velocidad de procesamiento y vocabulario receptivo, así como por la estimación. El modelo indicó que la memoria de trabajo y la velocidad de procesamiento fueron los principales predictores del pensamiento matemático informal a la edad de cuatro años. Mostró también un mayor peso estadístico explicativo para los niños (48,9%) que para las niñas (37,5%). Conclusiones: los datos sugieren que una intervención conjunta correctiva o preventiva, teniendo en cuenta los factores predictivos de los dominios específicos y generales, podría ser la opción óptima para mejorar el rendimiento en matemáticas en niños en riesgo de tener dificultades en esta materia.
Vaccine literacy is undervalued

ABSTRACT Despite weak health literacy is considered a concause of vaccine hesitancy, it is rarely taken into account when discussing about this subject. The association between health literacy skills and vaccine acceptance has been shown to be uneven when using general measures, also depending on the population settings and type of vaccine considered. Vaccine literacy has been built on the same idea of health literacy, but very few specific measuring tools have been developed until now. It is desirable that more of these instruments are validated and extensively used with the objective of assessing peoples’ vaccine literacy skills and defining interventions aimed at their improvement.
Synthesis of a Fluorous-Tagged Hexasaccharide and Interaction with Growth Factors Using Sugar-Coated Microplates

Here, we report the synthesis of a sulfated, fully protected hexasaccharide as a glycosaminoglycan mimetic and the study of its interactions with different growth factors: midkine, basic fibroblast growth factor (FGF-2) and nerve growth factor (NGF). Following a fluorous-assisted approach, monosaccharide building blocks were successfully assembled and the target oligosaccharide was prepared in excellent yield. The use of more acid stable 4,6-O-silylidene protected glucosamine units was crucial for the efficiency of this strategy because harsh reaction conditions were needed in the glycosylations to avoid the formation of orthoester side products. Fluorescence polarization experiments demonstrated the strong interactions between the synthesized hexamer, and midkine and FGF-2. In addition, we have developed an alternative assay to analyse these molecular recognition events. The prepared oligosaccharide was non-covalently attached to a fluorous-functionalized microplate and the direct binding of the protein to the sugar-immobilized surface was measured, affording the corresponding KD,surf value.
Evaluation of the Submicron Particles Distribution Between Mountain and Urban Site: Contribution of the Transportation for Defining Environmental and Human Health Issues

Transportation is one of the main causes of atmospheric pollution, especially in downtown big cities. Researchers usually point their attention to gaseous and/or particulate matter pollutants. This paper investigated the role of submicron particles, particularly the fraction ranging between 5–560 nm, in aerosol chemistry for identifying the contribution of autovehicular traffic and investigating the doses deposited in the human respiratory tract. Measurements carried out by two Fast Mobility Particle Sizer (FMPS, TSI) analyzers were simultaneously performed at two different sampling sites (an urban and a mountain site) during workdays and weekends in July. The total particle number (2–2.5 times higher in the urban site), the aerosol size distribution (different modes during the day), and the ultrafine/non-ultrafine particle ratios (ranging between 2–4 times between two sites) were investigated and discussed in relationship to the high autovehicular traffic in Rome and the almost null anthropogenic emissions at the mountain site, as well as the differing contributions of both to the “fresh nucleation” and to “aged aerosol”. Furthermore, the regional cumulative number doses deposited in the human respiratory tract were studied for both sites: The difference between the urban/mountain site was very high (up to 15 fold), confirming the pollutant role of transportation.
Comparison of Radiological and Histological Findings of Lung Parenchyma in Patients with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis

Purpose The present study investigated chest computed tomography (CT) patterns and lung histological features, as well as the consistency between radiological and histological features among patients with microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic GPA (EGPA). Materials and Methods The medical records of 74 antineutrophil cytoplasmic antibody-associated vasculitis (AAV) patients with radiological lung parenchymal lesions were reviewed along with the histological results for 28 of them. Chest CT patterns were divided according 12 items mostly suggested by radiologists and histological features were divided according to necrotising granuloma, necrotising vasculitis, eosinophilic infiltration, and hemosiderin laden macrophages as defined by a pathologist. Results The mean age was 57.1 years (22 men). The most common clinical manifestation other than lung manifestation was renal manifestation (62.2%), and the most common chest CT pattern was lung involvement of vasculitis (35.1%). In MPA patients, the major histological features were hemosiderin-laden macrophages in the alveolar space and vasculitis. In GPA patients, the major histological features were necrotizing vasculitis and necrotizing granuloma, while in EGPA patients, the major histological feature was only necrotising vasculitis. The consistency rate in GPA patients was the highest (100%), followed by that in MPA patients (66.7%) and EGPA patients (50.0%). Conclusion When lung involvement of AAV is suspected on chest CT, lung biopsy should be recommended for the proper classification of AAV, due to the discordance rate between radiological and histological findings in MPA and EGPA patients, but not GPA patients.