Neonatal diabetes mellitus due to a new KCNJ11 mutation - 10 years of the patient`s follow-up.

BACKGROUND: Mutations in the KCNJ11 gene, which encodes the Kir6.2 subunit of the ATP-sensitive potassium channel, often result in neonatal diabetes. CASE: In this report, we describe a 10-year-old girl who is heterozygous for a new missense mutation in the KCNJ11 gene and whose treatment was successfully switched from insulin to sulfonylurea (glibenclamide) therapy when she was one month old. 10-year data on a low-dose of glibenclamide monotherapy showed excellent glycaemic control with no reports of severe hypoglycaemia and microvascular complications. CONCLUSION: An early genetic diagnosis of neonatal diabetes mellitus is highly beneficial because early switch from insulin to sulfonylurea is safe, avoids unnecessary insulin therapy and promotes sustained improvement of glycaemic control on long-term follow-up.

Lung Nodule Segmentation with a Region-Based Fast Marching Method.

When dealing with computed tomography volume data, the accurate segmentation of lung nodules is of great importance to lung cancer analysis and diagnosis, being a vital part of computer-aided diagnosis systems. However, due to the variety of lung nodules and the similarity of visual characteristics for nodules and their surroundings, robust segmentation of nodules becomes a challenging problem. A segmentation algorithm based on the fast marching method is proposed that separates the image into regions with similar features, which are then merged by combining regions growing with k-means. An evaluation was performed with two distinct methods (objective and subjective) that were applied on two different datasets, containing simulation data generated for this study and real patient data, respectively. The objective experimental results show that the proposed technique can accurately segment nodules, especially in solid cases, given the mean Dice scores of 0.933 and 0.901 for round and irregular nodules. For non-solid and cavitary nodules the performance dropped-0.799 and 0.614 mean Dice scores, respectively. The proposed method was compared to active contour models and to two modern deep learning networks. It reached better overall accuracy than active contour models, having comparable results to DBResNet but lesser accuracy than 3D-UNet. The results show promise for the proposed method in computer-aided diagnosis applications.

Factors Influencing Utilization of Preventive Health Services in Primary Health Care in the Republic of Serbia.

The use of preventive health services is a long-term health investment due to its potential to help individuals to take care of their health. This study aimed to explore the availability and performance of health services in primary health care (PHC) in the domain of general practice (GP), pediatrics, and gynecology, as well as to analyze the influence of sociodemographic and health determinants on the utilization of preventive health services. This descriptive study used data from the National Health Insurance Fund and the Statistical Office of the Republic of Serbia for 2015 and included 149 independent PHC units. The relationship between the utilization of preventive services and sociodemographic and health characteristics of the population was analyzed by bivariate and multivariate linear regression models. The higher health expenditure per capita and noncommunicable diseases mortality rate were, the more preventive health services were provided by a chosen GP. Children with a higher completion rate of primary school (p = 0.024), higher health expenditure (p = 0.017), and higher life expectancy at birth (p = 0.041) had more preventive health services. The fertility rate was positively associated with the number of preventive health services per 1000 women (p = 0.033). Our findings should serve as a starting point for where efforts should be made to achieve better health outcomes.

How accurate are citations of frequently cited papers in biomedical literature?

Citations are an important, but often overlooked, part of every scientific paper. They allow the reader to trace the flow of evidence, serving as a gateway to relevant literature. Most scientists are aware of citations' errors, but few appreciate the prevalence of these problems. The purpose of the present study was to examine how often frequently cited papers in biomedical scientific literature are cited inaccurately. The study included an active participation of the first authors of included papers; to first-hand verify the citations accuracy. Findings from feasibility study, where we reviewed 1540 articles containing 2526 citations of 14 most cited articles in which the authors were affiliated with the Faculty of Medicine University of Belgrade, were further evaluated for external confirmation in an independent verification set of articles. Verification set included 4912 citations identified in 2995 articles that cited 13 most cited articles published by authors affiliated with the Mayo Clinic Division of Nephrology and Hypertension. A citation was defined as being accurate if the cited article supported or was in accordance with the statement by citing authors. At least one inaccurate citation was found in 11 and 15% of articles in the feasibility study and verification set, respectively, suggesting that inaccurate citations are common in biomedical literature. The most common problem was the citation of nonexistent findings (38.4%), followed by an incorrect interpretation of findings (15.4%). One-fifth of inaccurate citations were due to chains of inaccurate citations. Based on these findings, several actions to reduce citation inaccuracies have been proposed.

Preeclamptic Women Have Disrupted Placental microRNA Expression at the Time of Preeclampsia Diagnosis: Meta-Analysis.

Introduction: Preeclampsia (PE) is a pregnancy-associated, multi-organ, life-threatening disease that appears after the 20th week of gestation. The aim of this study was to perform a systematic review and meta-analysis to determine whether women with PE have disrupted miRNA expression compared to women who do not have PE. Methods: We conducted a systematic review and meta-analysis of studies that reported miRNAs expression levels in placenta or peripheral blood of pregnant women with vs. without PE. Studies published before October 29, 2021 were identified through PubMed, EMBASE and Web of Science. Two reviewers used predefined forms and protocols to evaluate independently the eligibility of studies based on titles and abstracts and to perform full-text screening, data abstraction and quality assessment. Standardized mean difference (SMD) was used as a measure of effect size. Results: 229 publications were included in the systematic review and 53 in the meta-analysis. The expression levels in placenta were significantly higher in women with PE compared to women without PE for miRNA-16 (SMD = 1.51,95%CI = 0.55-2.46), miRNA-20b (SMD = 0.89, 95%CI = 0.33-1.45), miRNA-23a (SMD = 2.02, 95%CI = 1.25-2.78), miRNA-29b (SMD = 1.37, 95%CI = 0.36-2.37), miRNA-155 (SMD = 2.99, 95%CI = 0.83-5.14) and miRNA-210 (SMD = 1.63, 95%CI = 0.69-2.58), and significantly lower for miRNA-376c (SMD = -4.86, 95%CI = -9.51 to -0.20). An increased level of miRNK-155 expression was found in peripheral blood of women with PE (SMD = 2.06, 95%CI = 0.35-3.76), while the expression level of miRNA-16 was significantly lower in peripheral blood of PE women (SMD = -0.47, 95%CI = -0.91 to -0.03). The functional roles of the presented miRNAs include control of trophoblast proliferation, migration, invasion, apoptosis, differentiation, cellular metabolism and angiogenesis. Conclusion: miRNAs play an important role in the pathophysiology of PE. The identification of differentially expressed miRNAs in maternal blood creates an opportunity to define an easily accessible biomarker of PE.

Introducing Clinical Informatics Course in Medical School Curricula: Lessons Learned from Medical Faculty University of Belgrade.

The healthcare environment in Serbia has changed dramatically over a last two decades, pointing out the necessity of clinical informatics (CI) education for future MDs. Total of 77 students were enrolled and 72 (93.5%) have successfully finished this course during 4 academic years. Mean total score for all students was 83.4 Âs 9.0 points, without difference between genders. We presented blended learning module as an effective way of gaining competences in CI and recommend this course to be required for future MDs.

Reveal, Don't Conceal: Transforming Data Visualization to Improve Transparency.

Reports highlighting the problems with the standard practice of using bar graphs to show continuous data have prompted many journals to adopt new visualization policies. These policies encourage authors to avoid bar graphs and use graphics that show the data distribution; however, they provide little guidance on how to effectively display data. We conducted a systematic review of studies published in top peripheral vascular disease journals to determine what types of figures are used, and to assess the prevalence of suboptimal data visualization practices. Among papers with data figures, 47.7% of papers used bar graphs to present continuous data. This primer provides a detailed overview of strategies for addressing this issue by (1) outlining strategies for selecting the correct type of figure depending on the study design, sample size, and the type of variable; (2) examining techniques for making effective dot plots, box plots, and violin plots; and (3) illustrating how to avoid sending mixed messages by aligning the figure structure with the study design and statistical analysis. We also present solutions to other common problems identified in the systematic review. Resources include a list of free tools and templates that authors can use to create more informative figures and an online simulator that illustrates why summary statistics are meaningful only when there are enough data to summarize. Last, we consider steps that investigators can take to improve figures in the scientific literature.

Long Term Outcomes of The Off-Pump and On-Pump Coronary Artery Bypass Grafting In A High-Volume Center.

Coronary artery bypass grafting (CABG) remains the most frequent surgery in the practice of an adult cardiac surgeon and the most frequently performed cardiac surgical procedure worldwide. Despite the ongoing debates regarding the superiority or inferiority of off-pump coronary artery bypass grafting, it still comprises 15-30% of all CABG cases varying in different national registries. We performed a propensity matched study of 302 consecutive CABG patients,143 off -pump cases performed by the four experienced off-pump surgeons and the on-pump CABG cases performed by those surgeons and four other experienced coronary surgeons. The five year follow up was performed and data collected comprised of mortality, rehospitalization due to cardiac origin, repeated revascularization, myocardial infarction and cerebrovascular accident. Overall, the off-pump group of patients had a higher risk profile than the patients in the on-pump group. After matching, fewer differences were found between the groups. Propensity score matching analysis showed no difference in long-term survival as well as MACCE and repeated revascularization. The higher risk profile of the patients subjected to OPCAB and the comparable survival to lower risk CPB patients in this series indicate that in experienced hands, OPCAB is a valuable option in this important subgroup of patients.

Electronic Algorithm Is Superior to Hospital Discharge Codes for Diagnoses of Hypertensive Disorders of Pregnancy in Historical Cohorts.

OBJECTIVES: To develop and validate criteria for the retrospective diagnoses of hypertensive disorders of pregnancy that would be amenable to the development of an electronic algorithm, and to compare the accuracy of diagnoses based on both the algorithm and diagnostic codes with the gold standard, of physician-made diagnoses based on a detailed review of medical records using accepted clinical criteria. PATIENTS AND METHODS: An algorithm for hypertensive disorders of pregnancy was developed by first defining a set of criteria for retrospective diagnoses, which included relevant clinical variables and diagnosis of hypertension that required blood pressure elevations in greater than 50% of readings ("the 50% rule"). The algorithm was validated using the Rochester Epidemiology Project (Rochester, Minnesota). A stratified random sample of pregnancies and deliveries between January 1, 1976, and December 31, 1982, with the algorithm-based diagnoses was generated for review and physician-made diagnoses (normotensive, gestational hypertension, and preeclampsia), which served as the gold standard; the targeted cohort size for analysis was 25 per diagnosis category according to the gold standard. Agreements between (1) algorithm-based diagnoses and (2) diagnostic codes and the gold standard were analyzed. RESULTS: Sensitivities of the algorithm for 25 normotensive pregnancies, 25 with gestational hypertension, and 25 with preeclampsia were 100%, 88%, and 100%, respectively, and specificities were 94%, 100%, and 100%, respectively. Diagnostic code sensitivities were 96% for normotensive pregnancies, 32% for gestational hypertension, and 96% for preeclampsia, and specificities were 78%, 96%, and 88%, respectively. CONCLUSION: The electronic diagnostic algorithm was highly sensitive and specific in identifying and classifying hypertensive disorders of pregnancy and was superior to diagnostic codes.

Bridging the gap between informatics and medicine upon medical school entry: Implementing a course on the Applicative Use of ICT.

Education is undergoing profound changes due to permanent technological innovations. This paper reports the results of a pilot study aimed at developing, implementing and evaluating the course, "Applicative Use of Information and Communication Technologies (ICT) in Medicine," upon medical school entry. The Faculty of Medicine, University of Belgrade, introduced a curriculum reform in 2014 that included the implementation of the course, "Applicative Use of ICT in Medicine" for first year medical students. The course was designed using a blended learning format to introduce the concepts of Web-based learning environments. Data regarding student knowledge, use and attitudes towards ICT were prospectively collected for the classes of 2015/16 and 2016/17. The teaching approach was supported by multimedia didactic materials using Moodle LMS. The overall quality of the course was also assessed. The five level Likert scale was used to measure attitudes related to ICT. In total, 1110 students were assessed upon medical school entry. A small number of students (19%) had previous experience with e-learning. Students were largely in agreement that informatics is needed in medical education, and that it is also useful for doctors (4.1±1.0 and 4.1±0.9, respectively). Ability in informatics and use of the Internet in education in the adjusted multivariate regression model were significantly associated with positive student attitudes toward ICT. More than 80% of students stated that they had learned to evaluate medical information and would use the Internet to search medical literature as an additional source for education. The majority of students (77%) agreed that a blended learning approach facilitates access to learning materials and enables time independent learning (72%). Implementing the blended learning course, "Applicative Use of ICT in Medicine," may bridge the gap between medicine and informatics upon medical school entry. Students displayed positive attitudes towards using ICT and gained adequate skills necessary to function effectively in an information-rich environment.

Blended learning is an effective strategy for acquiring competence in public health biostatistics.

OBJECTIVES: We sought to determine whether blended learning is an effective strategy for acquiring competence in public health biostatistics. METHODS: The trial was conducted with 69 Masters' students of public health attending the School of Public Health at University of Belgrade. Students were exposed to the traditional and blended learning styles. Blended learning included a combination of face-to-face and distance learning methodologies integrated into a single course. Curriculum development was guided by competencies as suggested by the Association of Schools of Public Health in the European Region (ASPHER). Teaching methods were compared according to the final competence score. RESULTS: Forty-four students were enrolled in the traditional method of education delivery, and 25 to the blended learning format. Mean exam scores for the blended learning group were higher than for the on-site group for both the final statistics score (89.65 ± 6.93 vs. 78.21 ± 13.26; p < 0.001) and knowledge test score (35.89 ± 3.66 vs. 22.56 ± 7.12; p < 0.001), with estimated large effect size (d > 0.8). CONCLUSIONS: A blended learning approach is an attractive and effective way of acquiring biostatistics competence for Masters of Public Health (MPH) graduate students.

Data visualization, bar naked: A free tool for creating interactive graphics.

Although bar graphs are designed for categorical data, they are routinely used to present continuous data in studies that have small sample sizes. This presentation is problematic, as many data distributions can lead to the same bar graph, and the actual data may suggest different conclusions from the summary statistics. To address this problem, many journals have implemented new policies that require authors to show the data distribution. This paper introduces a free, web-based tool for creating an interactive alternative to the bar graph (http://statistika.mfub.bg.ac.rs/interactive-dotplot/). This tool allows authors with no programming expertise to create customized interactive graphics, including univariate scatterplots, box plots, and violin plots, for comparing values of a continuous variable across different study groups. Individual data points may be overlaid on the graphs. Additional features facilitate visualization of subgroups or clusters of non-independent data. A second tool enables authors to create interactive graphics from data obtained with repeated independent experiments (http://statistika.mfub.bg.ac.rs/interactive-repeated-experiments-dotplot/). These tools are designed to encourage exploration and critical evaluation of the data behind the summary statistics and may be valuable for promoting transparency, reproducibility, and open science in basic biomedical research.

The Importance of Medical Students' Attitudes Regarding Cognitive Competence for Teaching Applied Statistics: Multi-Site Study and Meta-Analysis.

BACKGROUND: The scientific community increasingly is recognizing the need to bolster standards of data analysis given the widespread concern that basic mistakes in data analysis are contributing to the irreproducibility of many published research findings. The aim of this study was to investigate students' attitudes towards statistics within a multi-site medical educational context, monitor their changes and impact on student achievement. In addition, we performed a systematic review to better support our future pedagogical decisions in teaching applied statistics to medical students. METHODS: A validated Serbian Survey of Attitudes Towards Statistics (SATS-36) questionnaire was administered to medical students attending obligatory introductory courses in biostatistics from three medical universities in the Western Balkans. A systematic review of peer-reviewed publications was performed through searches of Scopus, Web of Science, Science Direct, Medline, and APA databases through 1994. A meta-analysis was performed for the correlation coefficients between SATS component scores and statistics achievement. Pooled estimates were calculated using random effects models. RESULTS: SATS-36 was completed by 461 medical students. Most of the students held positive attitudes towards statistics. Ability in mathematics and grade point average were associated in a multivariate regression model with the Cognitive Competence score, after adjusting for age, gender and computer ability. The results of 90 paired data showed that Affect, Cognitive Competence, and Effort scores demonstrated significant positive changes. The Cognitive Competence score showed the largest increase (M = 0.48, SD = 0.95). The positive correlation found between the Cognitive Competence score and students' achievement (r = 0.41; p<0.001), was also shown in the meta-analysis (r = 0.37; 95% CI 0.32-0.41). CONCLUSION: Students' subjective attitudes regarding Cognitive Competence at the beginning of the biostatistics course, which were directly linked to mathematical knowledge, affected their attitudes at the end of the course that, in turn, influenced students' performance. This indicates the importance of positively changing not only students' cognitive competency, but also their perceptions of gained competency during the biostatistics course.

Correction: From Static to Interactive: Transforming Data Visualization to Improve Transparency.

[This corrects the article DOI: 10.1371/journal.pbio.1002484.].

From Static to Interactive: Transforming Data Visualization to Improve Transparency.

Data presentation for scientific publications in small sample size studies has not changed substantially in decades. It relies on static figures and tables that may not provide sufficient information for critical evaluation, particularly of the results from small sample size studies. Interactive graphics have the potential to transform scientific publications from static reports of experiments into interactive datasets. We designed an interactive line graph that demonstrates how dynamic alternatives to static graphics for small sample size studies allow for additional exploration of empirical datasets. This simple, free, web-based tool (http://statistika.mfub.bg.ac.rs/interactive-graph/) demonstrates the overall concept and may promote widespread use of interactive graphics.

Improving Education in Medical Statistics: Implementing a Blended Learning Model in the Existing Curriculum.

BACKGROUND: Although recent studies report on the benefits of blended learning in improving medical student education, there is still no empirical evidence on the relative effectiveness of blended over traditional learning approaches in medical statistics. We implemented blended along with on-site (i.e. face-to-face) learning to further assess the potential value of web-based learning in medical statistics. METHODS: This was a prospective study conducted with third year medical undergraduate students attending the Faculty of Medicine, University of Belgrade, who passed (440 of 545) the final exam of the obligatory introductory statistics course during 2013-14. Student statistics achievements were stratified based on the two methods of education delivery: blended learning and on-site learning. Blended learning included a combination of face-to-face and distance learning methodologies integrated into a single course. RESULTS: Mean exam scores for the blended learning student group were higher than for the on-site student group for both final statistics score (89.36±6.60 vs. 86.06±8.48; p = 0.001) and knowledge test score (7.88±1.30 vs. 7.51±1.36; p = 0.023) with a medium effect size. There were no differences in sex or study duration between the groups. Current grade point average (GPA) was higher in the blended group. In a multivariable regression model, current GPA and knowledge test scores were associated with the final statistics score after adjusting for study duration and learning modality (p<0.001). CONCLUSION: This study provides empirical evidence to support educator decisions to implement different learning environments for teaching medical statistics to undergraduate medical students. Blended and on-site training formats led to similar knowledge acquisition; however, students with higher GPA preferred the technology assisted learning format. Implementation of blended learning approaches can be considered an attractive, cost-effective, and efficient alternative to traditional classroom training in medical statistics.