Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparing the Efficiency of Three Protocols in Isolation of Cell Free Fetal DNA From Maternal Blood

Objective: Recent advances in non-invasive prenatal diagnosis (NIPD) through cell free fetal DNA (cffDNA) has highlighted cffDNA purification as a critical initial step. Herein, we aimed to compare the efficiency of one proposed protocol with two commercial kits for isolation of cffDNA. Materials and methods: cffDNA was isolated from whole blood of 50 normal pregnancies using one proposed manual protocol compared with QIAamp DNA Blood Mini and Bioneer Kits. Methylated DNA immunoprecipitation real time polymerase chain reaction (MeDIP-Real time PCR) was performed to quantify three fetal specific sequences. Results: Maximum cffDNA quantity was obtained by suggested protocol (248.79 ± 14.07 ng/µl) and the best quality was achieved by Bioneer Kit (OD ratio: 260/280 nm/nm: 1.69 ± 0.09, 260/230 nm/nm: 1.15 ± 0.13) (p < 0.001). Enrichment of fetal specific sequences was significantly higher when proposed protocol was used to isolate cffDNA (p = 0.01). Conclusion: Inhibitory effect of NaI on nucleases and double digestion of DNA associated proteins may be the main reasons behind the superiority of suggested protocol. Significantly higher amplification of fetal specific sequences in suggested protocol would be a strong evidence on recovery of small fetal fragments as demonstrated with its maximum total DNA quantity and amplification in different PCR reactions.
Adaptive Neural Trees

Deep neural networks and decision trees operate on largely separate paradigms; typically, the former performs representation learning with pre-specified architectures, while the latter is characterised by learning hierarchies over pre-specified features with data-driven architectures. We unite the two via adaptive neural trees (ANTs) that incorporates representation learning into edges, routing functions and leaf nodes of a decision tree, along with a backpropagation-based training algorithm that adaptively grows the architecture from primitive modules (e.g., convolutional layers). We demonstrate that, whilst achieving competitive performance on classification and regression datasets, ANTs benefit from (i) lightweight inference via conditional computation, (ii) hierarchical separation of features useful to the task e.g. learning meaningful class associations, such as separating natural vs. man-made objects, and (iii) a mechanism to adapt the architecture to the size and complexity of the training dataset.
Forward Attention in Sequence- To-Sequence Acoustic Modeling for Speech Synthesis

This paper proposes a forward attention method for the sequence-to-sequence acoustic modeling of speech synthesis. This method is motivated by the nature of the monotonic alignment from phone sequences to acoustic sequences. Only the alignment paths that satisfy the monotonic condition are taken into consideration at each decoder timestep. The modified attention probabilities at each timestep are computed recursively using a forward algorithm. A transition agent for forward attention is further proposed, which helps the attention mechanism to make decisions whether to move forward or stay at each decoder timestep. Experimental results show that the proposed forward attention method achieves faster convergence speed and higher stability than the baseline attention method. Besides, the method of forward attention with transition agent can also help improve the naturalness of synthetic speech and control the speed of synthetic speech effectively.
Genetic flow among olive populations within the Mediterranean basin

Background The olive tree is a typical crop of the Mediterranean basin where it shows a wide diversity, accounting for more than 2,600 cultivars. The ability to discriminate olive cultivars and determine their genetic variability is pivotal for an optimal exploitation of olive genetic resources. Methods We investigated the genetic diversity within 128 olive accessions belonging to four countries in the Mediterranean Basin (Italy, Algeria, Syria, and Malta), with the purpose of better understanding the origin and spread of the olive genotypes across Mediterranean Basin countries. Eleven highly polymorphic simple sequence repeat (SSR) markers were used and proved to be very informative, producing a total of 179 alleles. Results Cluster analysis distinguished three main groups according to their geographical origin, with the current sample of Maltese accessions included in the Italian group. Phylogenetic analysis further differentiated Italian and Maltese olive accessions, clarifying the intermediate position of Maltese accessions along the x/y-axes of principal coordinate analysis (PCoA). Model-based and neighbor clustering, PCoA, and migration analysis suggested the existence of two different gene pools (Algerian and Syrian) and that the genetic exchange occurred between the Syrian, Italian and Maltese populations. Discussion The close relationship between Syrian and Italian and Maltese olives was consistent with the historical domestication and migration of olive tree from the North Levant to eastern Mediterranean basin. This study lays the foundations for a better understanding of olive genetic diversity in the Mediterranean basin and represents a step toward an optimal conservation and exploitation of olive genetic resources.
Cardiomyogenic Heterogeneity of Clonal Subpopulations of Human Bone Marrow Mesenchymal Stem Cells

We have evaluated the cardiomyogenic potential of clonal populations of human bone marrow mesenchymal stem cells (BM-MSC). Four rapidly proliferating clones of BM-MSC were obtained from the BM of a healthy donor which were then treated with 5-azacytidine and evaluated for the expression of GATA-4, NKx-2.5, FOG-2, TDGF-1, β-MHC, MEF2D and NPPA genes and cTnT, Desmin and β-MHC proteins. Of the four clones (i) Clone-1 had high expression of GATA-4 (1.89 fold (p<0.05), Nkx2.5 (2.29 fold; p<0.05), FOG2 (2.76 fold; p<0.05), TDGF1 (6.97 fold, p<0.005), βMHC (10.22 fold; p<0.005), MEF-2D (1.91 fold; p<0.005) and NPPA (1.65 fold; p<0.005); (ii) clone-2 had up-regulation of Nkx2.5 (1.98 fold; p<0.05) but down-regulation of rest of the genes; (iii) clone-3 had up-regulation of Nkx2.5 (2.11 fold; p<0.05), TDGF1 (1.88 fold; p<0.05), MEF-2D (1.30 fold; p<0.05) and NPPA (1.21 fold; p<0.05), down regulation of GATA-4 and Fog-2 but no change in βMHC gene; and (iv) clone-4 had up-regulation of MEF-2D (1.17 fold; p<0.05) and down regulation of GATA-4, Nkx2.5 but no change in other genes compared to untreated cells of the clones. At the protein level, clone-1 expressed cTnT, Desmin, and βMHC; clone-2 Desmin only while clones-3 and 4 each expressed cTnT, Desmin, and βMHC. Our data shows that BM-MSC are a heterogenous population of stem cells with sub-populations exhibiting a marked difference in the expression of cardiac markers both at gene and protein levels. This highlights that administering selected sub-populations of BM-MSC with a cardiomyogenic potential may be more efficacious than whole population of cells for cardiac regeneration.
Large-Scale Multi-Domain Belief Tracking with Knowledge Sharing

Robust dialogue belief tracking is a key component in maintaining good quality dialogue systems. The tasks that dialogue systems are trying to solve are becoming increasingly complex, requiring scalability to multi-domain, semantically rich dialogues. However, most current approaches have difficulty scaling up with domains because of the dependency of the model parameters on the dialogue ontology. In this paper, a novel approach is introduced that fully utilizes semantic similarity between dialogue utterances and the ontology terms, allowing the information to be shared across domains. The evaluation is performed on a recently collected multi-domain dialogues dataset, one order of magnitude larger than currently available corpora. Our model demonstrates great capability in handling multi-domain dialogues, simultaneously outperforming existing state-of-the-art models in single-domain dialogue tracking tasks.
Efficacy and safety of dabigatran versus warfarin from the RE-LY trial

Background Current data for atrial fibrillation (AF) and stroke are predominantly derived from North American and European patients. Although the burden of AF is high in Latin America (LA), little is known about current management of AF in the region. Methods We aimed to assess the consistency of efficacy and safety outcomes associated with dabigatran etexilate (DE) versus warfarin in patients with AF in LA from the RE-LY (Randomised Evaluation of Long-Term Anticoagulant Therapy) trial. Data from 956 LA patients and 17 157 non-LA patients were included in this analysis. χ2 test and Cox proportional regression analysis were performed. The primary efficacy outcome included all strokes or systemic embolism (SE). Main safety outcome was major bleeding. Results LA patients were more often female, had higher proportion of permanent AF and lower creatinine clearance, among other characteristics. Vitamin K antagonist use at randomisation and time in therapeutic range were lower in LA than in non-LA patients (44% vs 63%, p<0.001; and 61.3±22.6% vs 64.6±19.6%, p=0.015, respectively). Efficacy endpoints were 0.91% versus 1.68% for DE 150 mg twice daily versus warfarin, respectively. Stroke/SE risk was lower in LA patients treated with DE 150 mg twice daily compared with warfarin, although not significant (HR 0.54; 95% CI 0.18 to 1.62). The annual stroke/SE rates for DE 110 mg twice daily versus warfarin were 1.82 versus 1.68, also not significantly different (HR 1.09; CI 0.44 to 2.67). There were no treatment-by-region interactions for either dose of DE on efficacy and safety outcomes. Conclusion Despite differences in the clinical profile and AF management, the efficacy and safety benefits of dabigatran over warfarin in LA patients relative to non-LA patients are consistent with those observed in the main RE-LY trial.
Exploring the Clinical and Genetic Spectrum of Steroid Resistant Nephrotic Syndrome: The PodoNet Registry

Background: Steroid resistant nephrotic syndrome (SRNS) is a rare condition, accounting for 10–15% of all children with idiopathic nephrotic syndrome. SRNS can be caused by genetic abnormalities or immune system dysfunction. The prognosis of SRNS varies from permanent remission to progression to end-stage kidney disease, and post-transplant recurrence is common. Objectives: The PodoNet registry project aims to explore the demographics and phenotypes of immune-mediated and genetic forms of childhood SRNS, to assess genotype-phenotype correlations, to evaluate clinical management and long-term outcomes, and to search for novel genetic entities and diagnostic and prognostic biomarkers in SRNS. Methods: In 2009, an international registry for SRNS was established to collect retro- and prospective information on renal and extrarenal disease manifestations, histopathological and genetic findings and information on family history, pharmacotherapy responsiveness and long-term outcomes. To date, more than 2,000 patients have been enrolled at 72 pediatric nephrology centers, constituting the largest pediatric SRNS cohort assembled to date. Results: In the course of the project, traditional Sanger sequencing was replaced by NGS-based gene panel screening covering over 30 podocyte-related genes complemented by whole exome sequencing. These approaches allowed to establish genetic diagnoses in 24% of the patients screened, widened the spectrum of genetic disease entities presenting with SRNS phenotype (COL4A3-5, CLCN5), and contributed to the discovery of new disease causing genes (MYOE1, PTPRO). Forty two percent of patients responded to intensified immunosuppression with complete or partial remission of proteinuria, whereas 58% turned out multi-drug resistant. Medication responsiveness was highly predictive of a favorable long-term outcome, whereas the diagnosis of genetic disease was associated with a high risk to develop end-stage renal disease during childhood. Genetic SRNS forms were generally resistant to immunosuppressive treatment, justifying to avoid such pharmacotherapies altogether once a genetic diagnosis is established. Even symptomatic anti-proteinuric treatment with RAS antagonists seems to be challenging and of limited efficacy in genetic forms of SRNS. The risk of post-transplant disease recurrence was around 30% in non-genetic SRNS whereas it is negligible in genetic cases. Conclusion: In summary, the PodoNet Registry has collected detailed clinical and genetic information in a large SRNS cohort and continues to generate fundamental insights regarding demographic and etiological disease aspects, genotype-phenotype associations, the efficacy of therapeutic strategies, and long-term patient and renal outcomes including post-transplant disease recurrence.
Evaluating Characteristics of Electrostatic Discharge (ESD) Events in Wearable Medical Devices: Comparison With the IEC 61000-4-2 Standard

Electrostatic discharge (ESD) malfunctions in wearable medical devices have resulted in injuries and deaths. The U.S. Food and Drug Administration (FDA) recommends medical device manufacturers to qualify the electromagnetic compatibility of their products according to the IEC 60601-1-2 collateral standard, within which the IEC 61000-4-2 standard is the recommended ESD immunity test method. This paper shows that the IEC 61000-4-2 standard does not provide adequate immunity for wearable medical devices, due to the differences between the test setup and the real usage. The peak and maximum time derivative of the ESD current and transient magnetic fields were measured during realistic discharge scenarios, where a metal piece, in lieu of a wearable device, was worn around human hand or waist. At five voltage levels from 2 to 10 kV, the peak currents and their maximum time derivatives for realistic discharge scenarios were larger than the most severe discharges obtained from the IEC 61000-4-2 test configuration. This discrepancy between the current results from the IEC 61000-4-2 standard setup and the realistic discharge scenarios indicates that the ESD immunity standard for wearable devices needs to be changed with realistic test configurations, to prevent device malfunctions that can subsequently jeopardize patient safety.
Osteoconductive Microarchitecture of Bone Substitutes for Bone Regeneration Revisited

In the last three decades, all efforts in bone tissue engineering were driven by the dogma that the ideal pore size in bone substitutes lies between 0.3 and 0.5 mm in diameter. Newly developed additive manufacturing methodologies for ceramics facilitate the total control over pore size, pore distribution, bottleneck size, and bottleneck distribution. Therefore, this appears to be the method of choice with which to test the aforementioned characteristics of an ideal bone substitute. To this end, we produced a library of 15 scaffolds with diverse defined pore/bottleneck dimensions and distributions, tested them in vivo in a calvarial bone defect model in rabbits, and assessed the clinically most relevant parameters: defect bridging and bony regenerated area. Our in vivo data revealed that the ideal pore/bottleneck dimension for bone substitutes is in the range of 0.7–1.2 mm, and appears therefore to be twofold to fourfold more extended than previously thought. Pore/bottleneck dimensions of 1.5 and 1.7 mm perform significantly worse and appear unsuitable in bone substitutes. Thus, our results set the ideal range of pore/bottleneck dimensions and are likely to have a significant impact on the microarchitectural design of future bone substitutes for use in orthopedic, trauma, cranio-maxillofacial and oral surgery.
Automated Treatment Planning in Radiation Therapy using Generative Adversarial Networks

Knowledge-based planning (KBP) is an automated approach to radiation therapy treatment planning that involves predicting desirable treatment plans before they are then corrected to deliverable ones. We propose a generative adversarial network (GAN) approach for predicting desirable 3D dose distributions that eschews the previous paradigms of site-specific feature engineering and predicting low-dimensional representations of the plan. Experiments on a dataset of oropharyngeal cancer patients show that our approach significantly outperforms previous methods on several clinical satisfaction criteria and similarity metrics.
Prevalence and burden of overuse injuries in elite junior handball

Aim To record overuse injuries among male junior handball players throughout a handball season. Design Prospective cohort study. Methods Ten Norwegian junior male handball teams (145 players aged 16–18 years) were followed for one 10-month season. All players were sent the Oslo Sports Trauma Research Center Overuse Injury Questionaire every second week to record overuse injuries located in the shoulder, elbow, lower back and knee. The relative burden of overuse injuries was calculated in each anatomical area represented, defined as the proportion of the total cumulative severity score. Results The average prevalence of all overuse injury problems was 39% (95% CI 29% to 49%) across all anatomical areas. The average prevalence of substantial overuse injury problems, defined as those leading to moderate or large reductions in training volume or sports performance, or to complete inability to participate, was 15% (95% CI 13% to 17%). Over the duration of the study, the cumulative incidence of overuse injury problems was 91% (133 players). Shoulder problems were the most prevalent (average prevalence 17%, 95% CI 16% to 19%), whereas knee problems had the greatest relative burden. Conclusion Overuse injuries, particularly in the shoulder and knee, have a substantial impact on junior handball players’ training participation and performance. Interventions to prevent overuse injuries among male junior handball players should focus on these areas.
Recovery characteristics of total intravenous anesthesia with propofol versus sevoflurane anesthesia: a prospective randomized clinical trial

Background Pediatric dental procedures are performed under anesthesia because children may be uncooperative in the dental clinic due to their young age. Emergence delirium (ED), which involves a variety of behavioral disturbances that are frequently observed in children following emergence from general anesthesia, remains an unclear phenomenon. The aim of this randomized controlled trial is to compare the incidence of ED in children who underwent full mouth dental rehabilitation under either sevoflurane (SEVO) anesthesia or propofol-based total intravenous anesthesia (TIVA). Patients and methods One hundred and twenty children with American Society of Anesthesiologists status I–II, aged ≥3 and ≤6 years, undergoing dental rehabilitation were assigned to receive either TIVA or SEVO. ED and postoperative pain were evaluated by a blinded investigator using the Pediatric Anesthesia Emergence Delirium scale and the Face, Legs, Activity, Cry, Consolability scale every 5 min. The recovery time, satisfaction levels of parents or guardians, extubation time, duration of the operation, and type of dental procedure were also recorded. Results Data of 116 subjects were analyzed. The incidence of ED was higher after SEVO than after TIVA (65.5 vs 3.4%, P=0.00). Greater postoperative pain was observed in the SEVO group (median 3 vs 1, P=0.000). A statistically significant, moderate correlation (rs=0.46, P<0.0001) was found between the Face, Legs, Activity, Cry, Consolability and Pediatric Anesthesia Emergence Delirium scores. A higher parental satisfaction level was observed in the TIVA group. Conclusion A lower incidence of ED and a higher parental satisfaction level were observed after TIVA. Moreover, TIVA resulted in a more comfortable postoperative period due to reduced postoperative pain, and the extubation time and recovery time were not increased.
A bidirectional relationship between sleep and oxidative stress in Drosophila

Although sleep appears to be broadly conserved in animals, the physiological functions of sleep remain unclear. In this study, we sought to identify a physiological defect common to a diverse group of short-sleeping Drosophila mutants, which might provide insight into the function and regulation of sleep. We found that these short-sleeping mutants share a common phenotype of sensitivity to acute oxidative stress, exhibiting shorter survival times than controls. We further showed that increasing sleep in wild-type flies using genetic or pharmacological approaches increases survival after oxidative challenge. Moreover, reducing oxidative stress in the neurons of wild-type flies by overexpression of antioxidant genes reduces the amount of sleep. Together, these results support the hypothesis that a key function of sleep is to defend against oxidative stress and also point to a reciprocal role for reactive oxygen species (ROS) in neurons in the regulation of sleep.
Runs of homozygosity in a selected cattle population with extremely inbred bulls: Descriptive and functional analyses revealed highly variable patterns

The analysis of runs of homozygosity (ROH), using high throughput genomic data, has become a valuable and frequently used methodology to characterize the genomic and inbreeding variation of livestock and wildlife animal populations. However, this methodology has been scarcely used in highly inbred domestic animals. Here, we analyzed and characterized the occurrence of ROH fragments in highly inbred (HI; average pedigree-based inbreeding coefficient FPED = 0.164; 0.103 to 0.306) and outbred Retinta bulls (LI; average FPED = 0.008; 0 to 0.025). We studied the length of the fragments, their abundance, and genome distribution using high-density microarray data. The number of ROH was significantly higher in the HI group, especially for long fragments (>8Mb). In the LI group, the number of ROH continuously decreased with fragment length. Genome-wide distribution of ROH was highly variable between samples. Some chromosomes presented a larger number of fragments (BTA1, BTA19, BTA29), others had longer fragments (BTA4, BTA12, BTA17), while other ones showed an increased ROH accumulation over specific loci (BTA2, BTA7, BTA23, BTA29). Similar differences were observed in the analysis of 12 individuals produced by a similar inbred event (FPED3 = 0.125). The correlation between the fraction of the genome covered by ROH (FROH) and FPED was high (0.79), suggesting that ROH-based estimations are indicative of inbreeding levels. On the other hand, the correlation between FPED and the microsatellite-based inbreeding coefficient (FMIC) was only moderate (r = 0.44), suggesting that STR-based inbreeding estimations should be avoided. Similarly, we found a very low correlation (r = -0.0132) between recombination rate and ROH abundance across the genome. Finally, we performed functional annotation analyses of genome regions with significantly enriched ROH abundance. Results revealed gene clusters related to pregnancy-associated proteins and immune reaction. The same analysis performed for regions enriched with recently formed ROH (> 8 Mb) showed gene clusters related to flagellum assembly. In both cases, the processes were related to male and female reproductive functions, which may partially explain the reduced fertility associated with inbred populations.