Miracle-dz/UniFAR-FTUs huggingface dataset:
Can radiologists improve their breast cancer detection in mammography when using a deep learning based computer system as decision support?

For more than a decade, radiologists have used traditional computer aided detection systems to read mammograms, but mainly because of a low computer specificity may not improve their screening performance, according to several studies. The breakthrough in deep learning techniques has boosted the performance of machine learning algorithms, also for breast cancer detection in mammography. The objective of this study was to determine whether radiologists improve their breast cancer detection performance when they concurrently use a deep learningbased computer system for decision support, compared to when they read mammography unaided. A retrospective, fully-crossed, multi-reader multi-case (MRMC) study was designed to compare this. The employed decision support system was Transpara™ (Screenpoint Medical, Nijmegen, the Netherlands). Radiologists interact by clicking an area on the mammogram, for which the computer system displays its cancer likelihood score (1-100). In total, 240 cases (100 cancers, 40 false positive recalls, 100 normals) acquired with two different mammography systems were retrospectively collected. Seven radiologists scored each case once with, and once without the use of decision support, providing a forced BI-RADS® score and a level of suspiciousness (1-100). MRMC analysis of variance of the area under the receiver operating characteristic curves (AUC), and specificity and sensitivity were computed. When using decision support, the AUC increased from 0.87 to 0.89 (P=0.043) and specificity increased from 73% to 78% (P=0.030), while sensitivity did not significantly increment (84% to 87%, P=0.180). In conclusion, radiologists significantly improved their performance when using a deep learningbased computer system as decision support.
Thrombogenicity assessment of Pipeline Flex, Pipeline Shield, and FRED flow diverters in an in vitro human blood physiological flow loop model

Abstract Endovascular treatment of intracranial aneurysms with endoluminal flow diverters (single or multiple) has proven to be clinically safe and effective, but is associated with a risk of thromboembolic complications. Recently, a novel biomimetic surface modification with covalently bound phosphorylcholine (Shield Technology™) has shown to reduce the material thrombogenicity of the Pipeline flow diverter. Thrombogenicity of Pipeline Flex, Pipeline Shield, and Flow Redirection Endoluminal Device (FRED) in the presence of human blood under physiological flow conditions—in addition to relative increase in thrombogenicity with multiple devices—remains unknown and was investigated here. Thrombin generation (mean ± SD; μg/mL; thrombin–antithrombin complex or TAT) was measured as FRED (30.3 ± 2.9), Pipeline (13.9 ± 4.4), Pipeline Shield (0.4 ± 0.3), and negative control (no device; 0.1 ± 0.0). Platelet activation (mean ± SD; IU/μL; beta‐thromboglobulin or βTG) was measured as FRED (148 ± 45), Pipeline (92.8 ± 41), Pipeline Shield (16.2 ± 3.5), and negative control (2.70 ± 0.16). FRED was significantly more thrombogenic than Pipeline and Pipeline Shield (p < 0.05) for TAT. Additionally, Pipeline Shield had significantly lower TAT and βTG than the other devices tested (p < 0.05) and these were comparable to the negative control (p > 0.05). TAT and βTG scaled proportionately with multiple Pipeline devices (N = 6) but was unaffected by multiple Pipeline Shield (N = 6) devices—the latter being statistically similar to negative control (p > 0.05). © 2018 The Authors. Journal Of Biomedical Materials Research Part A Published By Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3195–3202, 2018.
Disease and economic burden for rare diseases in Taiwan: A longitudinal study using Taiwan’s National Health Insurance Research Database

Background High-cost orphan drugs are becoming increasingly available to treat rare diseases that affect a relatively small population. Little attention has been given to the prevalence of rare diseases and their health-related economic burden in Taiwan. Objectives This study examined the national trends in the prevalence of rare diseases and their health-related economic burden (including medication costs) in Taiwan. Methods Rare disease-related claims data from 2003–2014 (12 years) from the National Health Insurance Research Database were used in this study. We used a time series analysis to assess trends in the yearly rates of treated patients with rare diseases, overall healthcare use, and expenditures, including drugs. Results During the 12-year study period, the estimated prevalence of rare diseases increased from 10.57 to 33.21 per 100,000 population, an average rate of a 19.46% increase per year. Total health expenditures for treatment of rare diseases increased from US$18.65 million to US$137.44 million between 2003 and 2014, accounting for 0.68% of the total national health expenditures in 2014. Drug expenditures for treatment of rare diseases increased from US$13.24 million to US$121.98 million between 2003 and 2014, which accounted for 71.00% and 88.75% of the health expenditures for patients with rare diseases in 2003 and 2014, respectively. In 2014, we found a 20.43-fold difference in average health expenditures and a 69.46-fold difference in average drug expenditures between patients with rare diseases and the overall population. Conclusions The prevalence of rare diseases and the related economic burden have grown substantially in Taiwan over the past 12 years, and these trends are likely to continue. Drug expenditures accounted for almost 90% of health expenditures for rare diseases. Further analyses are underway to examine the economic burden of individual rare diseases.
Natural history and molecular evolution of demersal Mediterranean sharks and skates inferred by comparative phylogeographic and demographic analyses

Background The unique and complex paleoclimatic and paleogeographic events which affected the Mediterranean Sea since late Miocene deeply influenced the distribution and evolution of marine organisms and shaped their genetic structure. Following the Messinian salinity crisis and the sea-level fluctuations during the Pleistocene, several Mediterranean marine species developed deep genetic differentiation, and some underwent rapid radiation. Here, we consider two of the most prioritized groups for conservation in the light of their evolutionary history: sharks and rays (elasmobranchs). This paper deals with a comparative multispecies analysis of phylogeographic structure and historical demography in two pairs of sympatric, phylogenetically- and ecologically-related elasmobranchs, two scyliorhinid catsharks (Galeus melastomus, Scyliorhinus canicula) and two rajid skates (Raja clavata, Raja miraletus). Sampling and experimental analyses were designed to primarily test if the Sicilian Channel can be considered as effective eco-physiological barrier for Mediterranean demersal sympatric elasmobranchs. Methods The phylogeography and the historical demography of target species were inferred by analysing the nucleotide variation of three mitochondrial DNA markers (i.e., partial sequence of COI, NADH2 and CR) obtained from a total of 248 individuals sampled in the Western and Eastern Mediterranean Sea as well as in the adjacent northeastern Atlantic Ocean. Phylogeographic analysis was performed by haplotype networking and testing spatial genetic differentiation of samples (i.e., analysis of molecular variance and of principal components). Demographic history of Mediterranean populations was reconstructed using mismatch distribution and Bayesian Skyline Plot analyses. Results No spatial genetic differentiation was identified in either catshark species, while phylogeographic structure of lineages was identified in both skates, with R. miraletus more structured than R. clavata. However, such structuring of skate lineages was not consistent with the separation between Western and Eastern Mediterranean. Sudden demographic expansions occurred synchronously during the upper Pleistocene (40,000–60,000 years ago) in both skates and G. melastomus, likely related to optimal environmental conditions. In contrast, S. canicula experienced a slow and constant increase in population size over the last 350,000 years. Discussion The comparative analysis of phylogeographic and historical demographic patterns for the Mediterranean populations of these elasmobranchs reveals that historical phylogeographic breaks have not had a large impact on their microevolution. We hypothesize that interactions between environmental and ecological/physiological traits may have been the driving force in the microevolution of these demersal elasmobranch species in the Mediterranean rather than oceanographic barriers.
Avocado Seed: A Comparative Study of Antioxidant Content and Capacity in Protecting Oil Models from Oxidation

Increasingly, consumers want products containing little or no synthetic compounds. Avocado seeds, which are a residue of the food industry, could be used to obtain extracts with high antioxidant power. In the present study, the most popular radical scavenging methods are presented, establishing a comparison between them, besides working with two different extractions: pure methanol and ethanol–water (50:50 v/v). The radical scavenging assay methods ORAC and ABTS were performed, as well as a novel method: the reaction to methoxy radical, as determined by electron paramagnetic resonance (EPR). Peroxide value and thiobarbituric acid reactive compounds (TBARs) were used to monitor the oxidation of avocado seed oil, as well as the power of the avocado seed extract (ASE) to delay oil oxidation by oxidation induction time (OIT) and measured by differential scanning calorimetry (DSC). Radical scavenging methods have values between 1310–263 µmol TE/g of mass dissolved for ORAC and ABTS, respectively. The individual contribution of each of the compounds present in the extract was analyzed. The sum of all of them contributed up to 84% of the total radical scavenging activity. The concentration of 0.75% ASE causes a delay in the oxidation that is close to 80%, as measured by OIT. This implies that avocado seed residue may have a use as a natural antioxidant source, providing added value to organic waste.
Modeling language variability with reusable language components

Proliferation of modeling languages has produced a great variety of similar languages whose individual maintenance is challenging and costly. Reusing the syntax and semantics of modeling languages and their heterogeneous constituents, however, is rarely systematic. Current research on modeling language reuse focuses on reusing abstract syntax in form of metamodel parts. Systematic reuse of static and dynamic semantics is yet to be achieved. We present an approach to compose syntax and semantics of independently developed modeling languages through language product lines and derive new stand-alone language products. Using the MontiCore language workbench, we implemented a mechanism to compose language syntaxes and the realization of their semantics in form of template-based code generators according to language product line configurations. Leveraging variability of product lines greatly facilitates reusing modeling language and alleviates their proliferation.
Macrolunula: Case Reports of Patients with Trauma-associated Enlarged Lunula and a Concise Review of this Nail Finding

The lunula refers to the visible portion of the distal nail matrix that extends beyond the proximal nail fold. Macrolunula, or enlarged lunula, is not only a physiologic variant but also has been associated with a variety of local and systemic disorders. Macrolunula has been described in congenital conditions including hereditary onycho-osteodysplasia, neoplasms such as superficial acral fibromyxoma, as well as iatrogenic causes as in the topical administration of hydrocortisone; it can also occur in systemic disorders including hyperthyroidism, ischemia, leprosy, and scleroderma. While macrolunula has been described in self-induced trauma secondary to habit-tic deformity, we observe in this case report that any mechanism of trauma to the nail unit may produce enlargement of the lunula.
Finding optimal convex gray-scale structuring elements for morphological multiscale representation

Recent papers in multiscale morphological filtering, particularly, have renovated the interest in signal representation via multiscale openings. Although most of the analysis was done with flat structuring elements, extensions to grayscale structuring elements (GSE) are certainly possible. In fact, we have shown that opening a signal with convex and symmetric GSE does not introduce additional zero-crossings as the filter moves to a coarser scales. However, the issue of finding an optimal GSE is still an open problem. In this paper, we present a procedure to find an optimal GSE under the least mean square (LMS) algorithm subject to three constraints: The GSE must be convex, symmetric, and non-negative. The use of the basis functions simplifies the problem formulation. In fact, we show that the basis functions for convex and symmetric GSE are concave and symmetric, thus alternative constraints are developed. The results of this algorithm are compared with our previous work.
Cost-effectiveness of using a rapid diagnostic test to screen for human African trypanosomiasis in the Democratic Republic of the Congo

New rapid diagnostic tests (RDTs) for screening human African trypanosomiasis (HAT) have been introduced as alternatives to the card agglutination test for trypanosomiasis (CATT). One brand of RDT, the SD BIOLINE HAT RDT has been shown to have lower specificity but higher sensitivity than CATT, so to make a rational choice between screening strategies, a cost-effectiveness analysis is a key element. In this paper we estimate the relative cost-effectiveness of CATT and the RDT when implemented in the Democratic Republic of the Congo (DRC). Data on the epidemiological parameters and costs were collected as part of a larger study. These data were used to model three different diagnostic algorithms in mobile teams and fixed health facilities, and the relative cost-effectiveness was measured as the average cost per case diagnosed. In both fixed facilities and mobile teams, screening of participants using the SD BIOLINE HAT RDT followed by parasitological confirmation had a lower cost-effectiveness ratio than in algorithms using CATT. Algorithms using the RDT were cheaper by 112.54 (33.2%) and 88.54 (32.92%) US dollars per case diagnosed in mobile teams and fixed health facilities respectively, when compared with algorithms using CATT. Sensitivity analysis demonstrated that these conclusions were robust to a number of assumptions, and that the results can be scaled to smaller or larger facilities, and a range of prevalences. The RDT was the most cost-effective screening test in all realistic scenarios and detected more cases than CATT. Thus, on this basis, the SD BIOLINE HAT RDT could be considered as the most cost-effective option for use in routine screening for HAT in the DRC.
Neglected Functions of TFCP2/TFCP2L1/UBP1 Transcription Factors May Offer Valuable Insights into Their Mechanisms of Action

In recent years, the TFCP2 (transcription factor cellular promoter 2)/TFCP2L1 (TFCP2-like 1)/UBP1 (upstream binding protein 1) subfamily of transcription factors has been attracting increasing attention in the scientific community. These factors are very important in cancer, Alzheimer’s disease, and other human conditions, and they can be attractive targets for drug development. However, the interpretation of experimental results is complicated, as in principle, any of these factors could substitute for the lack of another. Thus, studying their hitherto little known functions should enhance our understanding of mechanisms of their functioning, and analogous mechanisms might govern their functioning in medically relevant contexts. For example, there are numerous parallels between placental development and cancer growth; therefore, investigating the roles of TFCP2, TFCP2L1, and UBP1 in the placenta may help us better understand their functioning in cancer, as is evidenced by the studies of various other proteins and pathways. Our review article aims to call the attention of the scientific community to these neglected functions, and encourage further research in this field. Here, we present a systematic review of current knowledge of the TFCP2/TFCP2L1/UBP1 subfamily in reproduction, embryonic development, renal function, blood-pressure regulation, brain function, and other processes, where their involvement has not been studied much until now.
Use of Deep Learning for Detailed Severity Characterization and Estimation of 5-Year Risk Among Patients With Age-Related Macular Degeneration

Importance Although deep learning (DL) can identify the intermediate or advanced stages of age-related macular degeneration (AMD) as a binary yes or no, stratified gradings using the more granular Age-Related Eye Disease Study (AREDS) 9-step detailed severity scale for AMD provide more precise estimation of 5-year progression to advanced stages. The AREDS 9-step detailed scale’s complexity and implementation solely with highly trained fundus photograph graders potentially hampered its clinical use, warranting development and use of an alternate AREDS simple scale, which although valuable, has less predictive ability. Objective To describe DL techniques for the AREDS 9-step detailed severity scale for AMD to estimate 5-year risk probability with reasonable accuracy. Design, Setting, and Participants This study used data collected from November 13, 1992, to November 30, 2005, from 4613 study participants of the AREDS data set to develop deep convolutional neural networks that were trained to provide detailed automated AMD grading on several AMD severity classification scales, using a multiclass classification setting. Two AMD severity classification problems using criteria based on 4-step (AMD-1, AMD-2, AMD-3, and AMD-4 from classifications developed for AREDS eligibility criteria) and 9-step (from AREDS detailed severity scale) AMD severity scales were investigated. The performance of these algorithms was compared with a contemporary human grader and against a criterion standard (fundus photograph reading center graders) used at the time of AREDS enrollment and follow-up. Three methods for estimating 5-year risk were developed, including one based on DL regression. Data were analyzed from December 1, 2017, through April 15, 2018. Main Outcomes and Measures Weighted &kgr; scores and mean unsigned errors for estimating 5-year risk probability of progression to advanced AMD. Results This study used 67 401 color fundus images from the 4613 study participants. The weighted &kgr; scores were 0.77 for the 4-step and 0.74 for the 9-step AMD severity scales. The overall mean estimation error for the 5-year risk ranged from 3.5% to 5.3%. Conclusions and Relevance These findings suggest that DL AMD grading has, for the 4-step classification evaluation, performance comparable with that of humans and achieves promising results for providing AMD detailed severity grading (9-step classification), which normally requires highly trained graders, and for estimating 5-year risk of progression to advanced AMD. Use of DL has the potential to assist physicians in longitudinal care for individualized, detailed risk assessment as well as clinical studies of disease progression during treatment or as public screening or monitoring worldwide.
The neural oscillatory markers of phonetic convergence during verbal interaction

During a conversation, the neural processes supporting speech production and perception overlap in time and, based on context, expectations and the dynamics of interaction, they are also continuously modulated in real time. Recently, the growing interest in the neural dynamics underlying interactive tasks, in particular in the language domain, has mainly tackled the temporal aspects of turn‐taking in dialogs. Besides temporal coordination, an under‐investigated phenomenon is the implicit convergence of the speakers toward a shared phonetic space. Here, we used dual electroencephalography (dual‐EEG) to record brain signals from subjects involved in a relatively constrained interactive task where they were asked to take turns in chaining words according to a phonetic rhyming rule. We quantified participants' initial phonetic fingerprints and tracked their phonetic convergence during the interaction via a robust and automatic speaker verification technique. Results show that phonetic convergence is associated to left frontal alpha/low‐beta desynchronization during speech preparation and by high‐beta suppression before and during listening to speech in right centro‐parietal and left frontal sectors, respectively. By this work, we provide evidence that mutual adaptation of speech phonetic targets, correlates with specific alpha and beta oscillatory dynamics. Alpha and beta oscillatory dynamics may index the coordination of the “when” as well as the “how” speech interaction takes place, reinforcing the suggestion that perception and production processes are highly interdependent and co‐constructed during a conversation.
A temporal transcriptome and methylome in human embryonic stem cell-derived cardiomyocytes identifies novel regulators of early cardiac development

ABSTRACT Stem cell-based cardiogenesis has become a powerful tool to enhance our understanding of cardiac development and test novel therapeutics for cardiovascular diseases. However, transcriptional and epigenetic regulation of multiple transitional stages from pluripotent cells to committed cardiomyocytes has not yet been fully characterized. To characterize how transcription factors, lincRNAs and DNA methylation change at temporal developmental stages, and identify potential novel regulators during cardiogenesis. We utilized a previously reported protocol that yields human cardiomyocytes (hCM) with more than 90% purity from human Embryonic Stem Cells (hESC). Leveraging the purity of cells resulting from this protocol, we systematically examined how gene expression and DNA methylation programs change at temporal developmental stages during cardiogenesis. Our results provide a comprehensive view of expression changes during cardiogenesis that extend previous studies, allowing us to identify key transcription factors as well as lincRNAs that are strongly associated with cardiac differentiation. Moreover, we incorporated a simple but powerful method to screen for novel regulators of cardiogenesis solely based on expression changes and found four novel cardiac-related transcription factors, i.e., SORBS2, MITF, DPF3, and ZNF436, which have no or few prior literature reports and we were able to validate using siRNA. Our strategy of identifying novel regulators of cardiogenesis can also be easily implemented in other stem cell-based systems. Our results provide a valuable resource for understanding cardiogenesis that extends previous findings by leveraging the purity of our cell lines, which allowed us to identify four novel cardiac-related regulators.
ICT for Development in a Post-2015 World: How to Conceptualise ICT4D in the Context of the Sustainable Development Goals

The understanding of the notion of ICT4D (ICT for Development), strongly depends on what is understood by development itself. Hence, this article argues that the introduction of the Sustainable Development Goals (SDGs) in 2015 must be understood as a caesura not only for conceptualising development, but, in turn, for conceptualising ICT4D, as well. On the basis of literature review, this paper analyses the SDG framework and applies it to theories of ICT4D, outlining the implications of transitioning to the post-2015 concept of sustainable development, beyond the cosmetic reflex of adding an ‘S’ to the acronym. In doing so, this article aims to sensitise the reader towards the challenges and potential dilemmas emerging from this transition, which go far beyond the Agenda’s new topical areas, and to spark debate on how to conceptualise ICT4D in response.