Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic modifiers of long‐term survival in sickle cell anemia

Abstract Background Sickle cell anemia (SCA) is a clinically heterogeneous, monogenic disorder. Medical care has less‐than‐optimal impact on clinical outcomes in SCA in Africa due to several factors, including patient accessibility, poor access to resources, and non‐availability of specific effective interventions for SCA. Methods Against this background, we investigated 192 African participants who underwent whole exome sequencing. Participants included 105 SCA patients spanning variable clinical expression: a “long survivor” group (age over 40 years), a “stroke” group (at least one episode of overt stroke), and a “random” group (patients younger than 40 years without overt cerebrovascular disease). Fifty‐eight ethnically matched homozygous hemoglobin A controls were also studied. Findings were validated in an independently recruited sample of 29 SCA patients. Statistical significance of the mutational burden of deleterious and loss‐of‐function variants per gene against a null model was estimated for each group, and gene‐set association tests were conducted to test differences between groups. Results In the “long survivor” group, deleterious/loss‐of‐function variants were enriched in genes including CLCN6 (a voltage‐dependent chloride channel for which rare deleterious variants have been associated with lower blood pressure) and OGHDL (important in arginine metabolism, which is a therapeutic target in SCA). In the “stroke” group, significant genes implicated were associated with increased activity of the blood coagulation cascade and increased complement activation, for example, SERPINC1, which encodes antithrombin. Oxidative stress and glutamate biosynthesis pathways were enriched in “long survivors” group. Published transcriptomic evidence provides functional support for the role of the identified pathways. Conclusions This study provides new gene sets that contribute to variability in clinical expression of SCA. Identified genes and pathways suggest new avenues for other interventions.
Three-dimensional imaging in myotonic dystrophy type 1

Objective We aimed to determine whether 3D imaging reconstruction allows identifying molecular:clinical associations in myotonic dystrophy type 1 (DM1). Methods We obtained myoblasts from 6 patients with DM1 and 6 controls. We measured cytosine-thymine-guanine (CTG) expansion and detected RNA foci and muscleblind like 1 (MBNL1) through 3D reconstruction. We studied dystrophia myotonica protein kinase (DMPK) expression and splicing alterations of MBNL1, insulin receptor, and sarcoplasmic reticulum Ca(2+)-ATPase 1. Results Three-dimensional analysis showed that RNA foci (nuclear and/or cytoplasmic) were present in 45%–100% of DM1-derived myoblasts we studied (range: 0–6 foci per cell). RNA foci represented <0.6% of the total myoblast nuclear volume. CTG expansion size was associated with the number of RNA foci per myoblast (r = 0.876 [95% confidence interval 0.222–0.986]) as well as with the number of cytoplasmic RNA foci (r = 0.943 [0.559–0.994]). Although MBNL1 colocalized with RNA foci in all DM1 myoblast cell lines, colocalization only accounted for 1% of total MBNL1 expression, with the absence of DM1 alternative splicing patterns. The number of RNA foci was associated with DMPK expression (r = 0.967 [0.079–0.999]). On the other hand, the number of cytoplasmic RNA foci was correlated with the age at disease onset (r = −0.818 [−0.979 to 0.019]). Conclusions CTG expansion size modulates RNA foci number in myoblasts derived from patients with DM1. MBNL1 sequestration plays only a minor role in the pathobiology of the disease in these cells. Higher number of cytoplasmic RNA foci is related to an early onset of the disease, a finding that should be corroborated in future studies.
Diagnostic and Predictive Values of 18F-FDG PET/CT Metabolic Parameters in EGFR-Mutated Advanced Lung Adenocarcinoma

Purpose The clinical implications of the metabolic parameters of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) in epidermal growth factor receptor (EGFR)-mutated lung cancer are not fully understood. The aim of this study was to evaluate the diagnostic and prognostic utility of the parameters in EGFR-mutated lung cancer patients. Patients and Methods We retrospectively enrolled 134 patients with advanced lung adenocarcinoma (72 EGFR-negative and 62 EGFR-positive). We evaluated the correlation between EGFR mutational status and the maximum standardized uptake value (SUVmax), as well as the associations between treatment outcomes in EGFR-mutated patients and various metabolic parameters of primary tumors. For the best predictive parameters, we calculated the metabolic tumor volume (MTV) and total lesion glycolysis (TLG) using two SUV cutoffs: 1.5 (MTV1.5, TLG1.5) and 2.5 (MTV2.5, TLG2.5). Results Mean SUVmax was lower for EGFR-mutated tumors compared with EGFR wild-type (6.11 vs 10.41, p < 0.001) tumors. Low SUVmax was significantly associated with positive EGFR mutation (odds ratio = 1.74). Multivariate analysis for survival demonstrated that high MTV1.5, TLG1.5, MTV2.5, and TLG2.5 were independently associated with shorter progression-free survival (PFS) and overall survival (OS), and the highest hazard ratios were found in TLG1.5 (3.26 for PFS and 4.62 for OS). Conclusion SUVmax may be predictive for EGFR mutational status, and MTV and TLG of primary tumors may be promising prognostic parameters; 18F-FDG PET/CT has potential utility for the risk stratification of EGFR-mutated patients treated with targeted therapy.
Automatic 3D reconstruction of structured indoor environments

Creating high-level structured 3D models of real-world indoor scenes from captured data is a fundamental task which has important applications in many fields. Given the complexity and variability of interior environments and the need to cope with noisy and partial captured data, many open research problems remain, despite the substantial progress made in the past decade. In this tutorial, we provide an up-to-date integrative view of the field, bridging complementary views coming from computer graphics and computer vision. After providing a characterization of input sources, we define the structure of output models and the priors exploited to bridge the gap between imperfect sources and desired output. We then identify and discuss the main components of a structured reconstruction pipeline, and review how they are combined in scalable solutions working at the building level. We finally point out relevant research issues and analyze research trends.
Motivation to Follow a Career in Dentistry of Students in Three South-East European Countries

Objective To investigate and compare the factors that motivated students to study dentistry in countries with similar background (Albania, Croatia and the Republic of Northern Macedonia) and to assess whether or not their motivation changed during time. Material and methods In 2014/2015, cross-sectional studies were conducted in state funded dental schools in Tirana (Albania), Zagreb (Croatia) and Skopje (Macedonia) to assess student views on their career motivation. All dental students from the first, third and final years of study were invited to participate. The participation was voluntary and anonymous. A five-item questionnaire was translated into languages of the participating countries. Ethics approval was granted by the Ethics Committee of the University of Saints Cyril and Methodius, Skopje. The Chi square test was used to test if there were statistically significant differences in answers between students in 3 countries, furthermore between years of the study. Results The total number of respondents was 739 (319 in Tirana, 211 in Zagreb and 208 in Skopje) The differences in the answers between the first-year students from all three countries were statistically significant (χ2=82.65; p<.01). The most striking answer was to the question on parents' pressure to study dentistry, which was far more frequent in Tirana (up to 27.7%). A "positive image" was the most frequent response from students from Zagreb (up to 79.7%), but it declined from the first to the final year in Skopje. There were also significant differences between the schools within the 3rdand final years of study. Conclusions A positive image of dental profession was the main reason for students studying dentistry at all three schools; as many as 97% of the students of the final year in Croatia, a member of the European Union (EU). In the two non-EU countries (Albania, Macedonia) it seemed that dental profession does not have such good status and student expectations are not being fulfilled, especially in Skopje (up to 33.9% willing to change their vocation and up to 64.5% lost their motivation to study) One of the strategies to improve the situation could be to include more clinical practice and to better organize the study.
Leadership and Management Competencies for Hospital Managers: A Systematic Review and Best-Fit Framework Synthesis

Objective Competent managers are vital to the productivity and service quality of healthcare organizations and the sustainability of the healthcare system. To improve their management competence, understanding of management competency requirements is important. The purpose of this study was to synthesize the evidence related to the leadership and management competencies in healthcare organizations through the best-fit method. Methods A systematic review of literature published between 2000 and 2020 was performed to identify studies focusing on confirming and/or identifying the competency requirements of hospital managers. The best-fit framework synthesis method was used to map the identified competencies and associated behavioral items against the validated management competency assessment program (MCAP) management competency framework. Results Twelve studies were identified for inclusion in the review. The mapping of the identified competencies and behavioral items generated a competency model for hospital managers that can apply for different healthcare context. The new competency model includes the following seven core leadership and management competencies: evidence-informed decision-making, operations, administration and resource management, knowledge of healthcare environment and the organization, interpersonal, communication qualities and relationship management, leading people and organisation, enabling and managing change, and professionalism. Conclusion This review and the mapping of the competencies identified in previous studies against the validated MCAP framework has resulted in the recommendation for an extended leadership and management competency framework for health service managers. It provides guidance for the formulation of training and development directions for the health service management workforce in a different healthcare context.
Natriuretic Peptides, Cognitive Impairment and Dementia: An Intriguing Pathogenic Link with Implications in Hypertension

The natriuretic peptides (NPs) belong to a family of cardiac hormones that exert relevant protective functions within the cardiovascular system. An increase of both brain and atrial natriuretic peptide levels, particularly of the amino-terminal peptides (NT-proBNP and NT-proANP), represents a marker of cardiovascular damage. A link between increased NP levels and cognitive decline and dementia has been reported in several human studies performed both in general populations and in cohorts of patients affected by cardiovascular diseases (CVDs). In particular, it was reported that the elevation of NP levels in dementia can be both dependent and independent from CVD risk factors. In the first case, it may be expected that, by counteracting early on the cardiovascular risk factor load and the pathological processes leading to increased aminoterminal natriuretic peptide (NT-proNP) level, the risk of dementia could be significantly reduced. In case of a link independent from CVD risk factors, an increased NP level should be considered as a direct marker of neuronal damage. In the context of hypertension, elevated NT-proBNP and mid-regional (MR)-proANP levels behave as markers of brain microcirculatory damage and dysfunction. The available evidence suggests that they could help in identifying those subjects who would benefit most from a timely antihypertensive therapy.
An Improved Real-Time R-Wave Detection Efficient Algorithm in Exercise ECG Signal Analysis

R-wave detection is a prerequisite for the extraction and recognition of ECG signal feature parameters. In the analysis and diagnosis of exercise electrocardiograms, accurate and real-time detection of QRS complexes is very important for the prevention and monitoring of heart disease. This paper proposes a lightweight R-wave real-time detection method for exercise ECG signals. After real-time denoising of the exercise ECG signal, the median line is used to correct the baseline, and the first-order difference processing is performed on the differential square signal. Max-Min Threshold (MMT) is used to realize real-time R-wave detection of the exercise ECG signal. The abovementioned method was verified by using the measured data in the MIT-BIH ECG database of the Massachusetts Institute of Technology and the exercise plate experiment. The R-wave detection rates were 99.93% and 99.98%, respectively. Experimental results show that this method has high accuracy and low computational complexity and is suitable for wearable devices and motion process monitoring.
Sphingolipid Analysis Indicate Lactosylceramide as a Potential Biomarker of Inflammatory Bowel Disease in Children

An altered ceramide composition in patients with inflammatory bowel disease (IBD) has been reported recently. The aim of this study was to evaluate the concentrations of sphingolipids in the serum of treatment-naive children with newly diagnosed IBD and to determine the diagnostic value of the tested lipids in pediatric IBD. The concentrations of sphingolipids in serum samples were evaluated using a quantitative method, an ultra-high-performance liquid chromatography-tandem mass spectrometry in children with Crohn’s disease (CD) (n=34), ulcerative colitis (UC) (n = 39), and controls (Ctr) (n = 24). Among the study groups, the most significant differences in concentrations were noted for C16:0-LacCer, especially in children with CD compared to Ctr or even to UC. Additionally, the relevant increase in C20:0-Cer and C18:1-Cer concentrations were detected in both IBD groups compared to Ctr. The enhanced C24:0-Cer level was observed only in UC, while C18:0-Cer only in the CD group. The highest area under the curve (AUC), specificity, and sensitivity were determined for C16:0-LacCer in CD diagnosis. Our results suggest that the serum LacC16-Cer may be a potential biomarker that distinguishes children with IBD from healthy controls and differentiates IBD subtypes. In addition, C20:0-Cer and C18:0-Cer levels also seem to be closely connected with IBD.
T-Cell Immunodeficiencies With Congenital Alterations of Thymic Development: Genes Implicated and Differential Immunological and Clinical Features

Combined Immunodeficiencies (CID) are rare congenital disorders characterized by defective T-cell development that may be associated with B- and NK-cell deficiency. They are usually due to alterations in genes expressed in hematopoietic precursors but in few cases, they are caused by impaired thymic development. Athymia was classically associated with DiGeorge Syndrome due to TBX1 gene haploinsufficiency. Other genes, implicated in thymic organogenesis include FOXN1, associated with Nude SCID syndrome, PAX1, associated with Otofaciocervical Syndrome type 2, and CHD7, one of the genes implicated in CHARGE syndrome. More recently, chromosome 2p11.2 microdeletion, causing FOXI3 haploinsufficiency, has been identified in 5 families with impaired thymus development. In this review, we will summarize the main genetic, clinical, and immunological features related to the abovementioned gene mutations. We will also focus on different therapeutic approaches to treat SCID in these patients.
The effect of breeding systems and pollination vectors on the genetic variation of small plant populations within an agricultural landscape

Within an agricultural landscape (approximately 8 km2) the genetic structures of the herbs Festuca ovina, Lychnis viscaria and Arabis thaliana were examined using isoenzymes. The species have different breeding systems and pollination vectors, and occur in small populations in remnant patches of semi-natural habitats throughout the landscape. There was no or only a weak correlation between population size and genetic diversity. The wind-pollinated, outcrossing species F. ovina had the highest levels of genetic variation, intermediate levels were found in the largely outcrossing and insect pollinated L. viscaria, while lowest levels of variation were found in the inbreeding A. thaliana. Relative to their breeding systems and the small geographical scale of the study all species exhibited remarkably high levels of total genetic variation. In the outbreeding species most of the genetic variation was found within populations (F. ovina: FST = 0.059 and L. viscaria: FST = 0.092). No geographic pattern was found between populations in the outbreeding species, indicating high levels of gene flow. The cereal fields separating the populations may function as conduits rather than barriers to pollen dispersed by wind, and pollinating insects (bumblebees and butterflies) may have no problems moving between patches at this scale, thus alleviating the danger of genetic erosion associated with small population size. In contrast, the fields appear to be efficient barriers to gene flow by seed dispersal. In the inbreeding Arabis thaliana a geographic pattern was evident. Most of the variation in this species was found between populations (FST = 0.722) indicating low levels of gene flow; single populations exhibited large variation in the number of
Explorative and Exploitative Learning in Teams: Unpacking the Antecedents and Consequences

Many organizations adopt team-based structures to better survive in the highly competitive environment. To achieve this goal, teams not only need to develop new ideas to adapt to the changing situations, but also follow standardized procedures to complete tasks effectively, suggesting the importance of ambidextrous capacity on addressing the paradoxical demands. However, we have little knowledge about both of how to respectively facilitate team ambidextrous learning (i.e., team explorative and exploitative learning) and how team the two learning activities contributes to team effectiveness. Using the multi-time and multi-source data gathered from 140 teams in 6 Chinese companies, we found that team leader’s power sharing and management control behaviors (i.e., ambidextrous leader behaviors) specifically enhanced team explorative and exploitative learning. In addition, our results showed that team explorative and exploitative learning drove overall team performance via the mechanisms of team creativity and task completion respectively. The theoretical and practical implications, limitations, and future research directions are discussed as well.
Blood Biomarkers of Glioma in Response Assessment Including Pseudoprogression and Other Treatment Effects: A Systematic Review

Imaging-based monitoring of disease burden in glioma patients is frequently confounded by treatment effects. Circulating biomarkers could theoretically augment imaging-based response monitoring. This systematic review aimed to present and evaluate evidence for differential expression and diagnostic accuracy of circulating biomarkers with respect to outcomes of tumor response, progression, stable disease, and treatment effects (pseudoprogression, radionecrosis, pseudoresponse, and pseudolesions) in patients undergoing treatment for World Health Organization grades II–IV diffuse astrocytic and oligodendroglial tumors. MEDLINE, EMBASE, Web Of Science, and SCOPUS databases were searched until August 18, 2019, for observational or diagnostic studies on multiple circulating biomarker types: extracellular vesicles, circulating nucleic acids, circulating tumor cells, circulating proteins, and metabolites, angiogenesis related cells, immune cells, and other cell lines. Methodological quality of included studies was assessed using an adapted Quality Assessment of Diagnostic Accuracy Studies-2 tool, and level of evidence (IA–IVD) for individual biomarkers was evaluated using an adapted framework from the National Comprehensive Cancer Network guidelines on evaluating tumor marker utility. Of 13,202 unique records, 58 studies met the inclusion criteria. One hundred thirty-three distinct biomarkers were identified in a total of 1,853 patients across various treatment modalities. Fifteen markers for response, progression, or stable disease and five markers for pseudoprogression or radionecrosis reached level IB. No biomarkers reached level IA. Only five studies contained data for diagnostic accuracy measures. Overall methodological quality of included studies was low. While extensive data on biomarker dysregulation in varying response categories were reported, no biomarkers ready for clinical application were identified. Further assay refinement and evaluation in larger cohorts with diagnostic accuracy study designs are required. PROSPERO Registration: CRD42018110658.
Grazing Allometry: Anatomy, Movement, and Foraging Behavior of Three Cattle Breeds of Different Productivity

Modern breeding has formed a multitude of cattle breeds ranging from undemanding, low-productive breeds to high-productive, specialized dairy, or beef cattle. The choice of breed has important implications for farm management, but its impact on pasture vegetation is underestimated. We hypothesized (i) that anatomy, movement, and foraging behavior of cattle are allometrically related on the individual level, (ii) that differences among cattle are not explained by individual variation alone but also by breed, and (iii) that anatomy, movement, and foraging behavior of a cattle breed is related to its productivity. In order to test these hypotheses, we conducted a controlled grazing experiment in which three cattle breeds simultaneously grazed three types of heterogenous, alpine pastures: low-productive Highland cattle (average weight: 358 kg); local, dual-purpose Original Braunvieh (582 kg); and high-productive Angus × Holstein crossbreed (679 kg). We measured body weight and claw base of nine cows per breed after 10 weeks of grazing alpine pastures. Over a period of 9 days, we recorded the step frequency and lying time by pedometer and space use by GPS. Moreover, we visually observed foraging behavior on three occasions per cow. Forage selectivity and quality were calculated for every cow's diet. Allometric relationships were analyzed on the individual level by fitting standardized major axes. For most parameters measured, we detected strong allometric relationships and clear differences among breeds that depended on the level of productivity. The claws of Highland cattle were relatively large compared to their body weight and thus they exerted less static pressure than other breeds. Moreover, the more productive a breed was, the higher its selectivity and step frequency were. For example, Highland cattle foraged shrubs and thistles more frequently than high-productive Angus × Holstein. The latter walked longer distances to select higher-quality forage, while Highland cattle used the space more evenly, visited steeper slopes, and moved further away from water points. Irrespective of breed, vegetation composition influenced cattle behavior: On pastures of low forage quality, animals walked more, foraged more selectively, and used space less evenly. In conclusion, the observed breed-specific differences can be used to improve pasture management and grassland conservation.