Miracle-dz/UniFAR-FTUs huggingface dataset:
Tacrolimus rescues the signaling and gene expression signature of endothelial ALK1 loss-of-function and improves HHT vascular pathology

Hereditary hemorrhagic telangiectasia (HHT) is a highly debilitating and life-threatening genetic vascular disorder arising from endothelial cell (EC) proliferation and hypervascularization, for which no cure exists. Because HHT is caused by loss-of-function mutations in bone morphogenetic protein 9 (BMP9)-ALK1-Smad1/5/8 signaling, interventions aimed at activating this pathway are of therapeutic value. We interrogated the whole-transcriptome in human umbilical vein ECs (HUVECs) and found that ALK1 signaling inhibition was associated with a specific pro-angiogenic gene expression signature, which included a significant elevation of DLL4 expression. By screening the NIH clinical collections of FDA-approved drugs, we identified tacrolimus (FK-506) as the most potent activator of ALK1 signaling in BMP9-challenged C2C12 reporter cells. In HUVECs, tacrolimus activated Smad1/5/8 and opposed the pro-angiogenic gene expression signature associated with ALK1 loss-of-function, by notably reducing Dll4 expression. In these cells, tacrolimus also inhibited Akt and p38 stimulation by vascular endothelial growth factor, a major driver of angiogenesis. In the BMP9/10-immunodepleted postnatal retina-a mouse model of HHT vascular pathology-tacrolimus activated endothelial Smad1/5/8 and prevented the Dll4 overexpression and hypervascularization associated with this model. Finally, tacrolimus stimulated Smad1/5/8 signaling in C2C12 cells expressing BMP9-unresponsive ALK1 HHT mutants and in HHT patient blood outgrowth ECs. Tacrolimus repurposing has therefore therapeutic potential in HHT.
Doppelganger Mining for Face Representation Learning

In this paper we present Doppelganger mining - a method to learn better face representations. The main idea of this method is to maintain a list with the most similar identities for each identity in the training set. This list is used to generate better mini-batches by sampling pairs of similar-looking identities ("doppelgangers") together. It is especially useful for methods, based on exemplar-based supervision. Usually hard example mining comes with a price of necessity to use large mini-batches or substantial extra computation and memory cost, particularly for datasets with large numbers of identities. Our method needs only a negligible extra computation and memory. In our experiments on a benchmark dataset with 21,000 persons we show that Doppelganger mining, being inserted in the face representation learning process with joint prototype-based and exemplar-based supervision, significantly improves the discriminative power of learned face representations.
Early clinical and echocardiographic outcomes after SAPIEN 3 transcatheter aortic valve replacement in inoperable, high-risk and intermediate-risk patients with aortic stenosis.

AIMS Based on randomized trials using first-generation devices, transcatheter aortic valve replacement (TAVR) is well established in the treatment of high-risk (HR) patients with severe aortic stenosis (AS). To date, there is a paucity of adjudicated, prospective data evaluating outcomes with newer generation devices and in lower risk patients. We report early outcomes of a large, multicentre registry of inoperable, HR, and intermediate-risk (IR) patients undergoing treatment with the next-generation SAPIEN 3 transcatheter heart valve (THV). METHODS AND RESULTS Patients with severe, symptomatic AS (583 high surgical risk or inoperable and 1078 IR) were enrolled in a multicentre, non-randomized registry at 57 sites in the USA and Canada. All patients received TAVR with the SAPIEN 3 system via transfemoral (n = 1443, 86.9%) and transapical or transaortic (n = 218, 13.1%) access routes. The rate of 30-day all-cause mortality was 2.2% in HR/inoperable patients [mean Society of Thoracic Surgeons (STS) score 8.7%] and 1.1% in IR patients (mean STS score 5.3%); cardiovascular mortality was 1.4 and 0.9%, respectively. In HR/inoperable patients, the 30-day rate of major/disabling stroke was 0.9%, major bleeding 14.0%, major vascular complications 5.1%, and requirement for permanent pacemaker 13.3%. In IR patients, the 30-day rate of major/disabling stroke was 1.0%, major bleeding 10.6%, major vascular complications 6.1%, and requirement for permanent pacemaker 10.1%. Mean overall Kansas City Cardiomyopathy Questionnaire score increased from 47.8 to 67.8 (HR/inoperable, P < 0.0001) and 54.7 to 74.0 (IR, P < 0.0001). Overall, paravalvular regurgitation at 30 days was none/trace in 55.9% of patients, mild in 40.7%, moderate in 3.4%, and severe in 0.0%. Mean gradients among patients with paired baseline and 30-day or discharge echocardiograms decreased from 45.8 mmHg at baseline to 11.4 mmHg at 30 days, while aortic valve area increased from 0.69 to 1.67 cm(2). CONCLUSIONS The SAPIEN 3 THV system was associated with low rates of 30-day mortality and major/disabling stroke as well as low rates of moderate or severe paravalvular regurgitation. TRIAL REGISTRATION ClinicalTrials.gov #NCT01314313.
Text Detection Based on MSER and CNN Features

Text detection in natural scenes holds great importance in the field of research and still remains a challenge and an important task because of size, various fonts, line orientation, different illumination conditions, weak characters and complex backgrounds in image. The contribution of our proposed method is to filtering out complex backgrounds by combining three strategies. These are enhancing the edge candidate detection in HSV space color using the fractal dimension (FD) to transform the image intensities, then using MSER candidate detection to get different masks applied in HSV space color as well as gray color. After that, we opt for the Stroke Width Transform (SWT) and heuristic filtering. Such strategies are followed so as to maximize the capacity of zones text pixels candidates and distinguish between text boxes and the rest of the image. The components selected non text are filtered by classifying the characters candidates using Support Vector Machines (SVM) exploring Convolutional Neural Networks (CNN) features and Histogram of Oriented Gradients (HOG) vector features. We use the technique of word grouping who the boundary box localization select different words in the image where false positives text blocks are eliminated by geometrical properties. The evaluation of the proposed method demonstrate the effectiveness of our method for complex foreground through the experimental results tested on three benchmarks ICDAR2013, ICDAR2015 and MSRA-TD500.
Scalable and Reliable Key Management for Secure Deduplication in Cloud Storage

Secure deduplication using convergent encryption eliminates duplicate data and stores only one copy to save storage costs while preserving the security of the outsourced data. However, convergent encryption produces a number of encryption keys, of which size is linear to the number of different data. Although a deduplication scheme has been proposed for efficient convergent key management recently, it has drawbacks in terms of scalability and key management security. In order to solve these problems, we propose a novel secure deduplication scheme with scalable and reliable key management based on paring-based cryptography. The proposed scheme does not require additional secure channels to distribute key components while still guaranteeing secure key management as opposed to the previous schemes.
Comparison of two methods for determination of intestinal villus to crypt ratios and documentation of early age‐associated ratio changes in broiler chickens1,2,3

&NA; The determination of intestinal villus to crypt ratios (VCR) is a common method utilized to evaluate effects of various diet regimens on gut microanatomy and for the histologic quantification of intestinal responses to disease processes. Two methods for the determination of small intestinal VCR were compared in early age chickens. A standard method for VCR determination based on 10 villus and crypt length measurements in the jejunal region of the small intestine was employed for the calculation of villus to crypt length ratio (VCLR). That method was compared to a new approach based on a single histomorphometric determination of the crypt and total mucosal areas using image analysis software. Subtraction of the crypt area from the total area provided the villus area and allowed for the subsequent calculation of villus to crypt area ratio (VCAR). At 4 and 18 h posthatch, VCLR was higher than that of VCAR, but there was no significant difference between VCLR and VCAR at 0 h (hatch) and at 168 h (d 7) posthatch. Nevertheless, the pattern of age‐associated changes for VCLR and VCAR were comparable throughout the early posthatch period. Furthermore, the new method used in determining VCAR is subject to less human error, allows for an appreciable reduction in the number of measurements required, and facilitates a larger intestinal segment evaluation. Standard linear measurements require the selection of variable numbers of villi and crypts, whereas the area method only requires selection of a single region that incorporates numerous villi and crypts of variable sizes in providing a less subjective approach. This is particularly advantageous in studies on intestinal disease conditions resulting in marked multifocal variation in villus stature. This study further documented age‐associated changes occurring in the VCR of the small intestine during the early posthatch period. Across the 2 methods used for VCR determination, a major and highly significant reduction in the VCR was observed to occur between 18 h and 168 h posthatch.
The effect of a practical nutrition education programme on feeding skills of caregivers of children with cerebral palsy at Muhimbili National Hospital, in Tanzania

BACKGROUND Feeding children with cerebral palsy (CP) is challenging and can lead to poor health outcomes. Using a facility-based intervention, we assessed the effect of a practical nutrition programme on feeding skills in caregivers of children with CP attending a pediatric clinic in urban Tanzania. METHODS A randomized-controlled intervention study, involving 2-block stratified sample of under-5 CP children attending a specialized pediatric clinic at the Muhimbili National Hospital was done. One hundred ten moderate-to-severe, new and follow-up cases of children with CP were randomly allocated to the intervention (N = 63) and control groups (N = 47). A short nutrition education on feeding and positioning skills was provided to caregivers and occupational therapy sessions to CP children. Bivariate and multivariable logistic regression analyses of collected data were done. Statistical significance was assessed at p < . 05. FINDINGS The intervention significantly improved feeding skills of caregiver in the select indicators assessed. More caregivers appropriately positioned the children (AOR = 5.29; 95% CI: 2.00-13.96), fed children slowly (AOR: 5.17, 95% CI: 1.99-13.44), and involved the child during the feeding process (AOR = 3.46; 95% CI: 1.42-8.44). During feeding, caregiver's reported being less stressed (AOR = 2.53, 95% CI: 1.04-6.13) and the child's mood was more likely to be reported as improved (AOR = 3.15, 95% CI: 1.33-7.474). Although changes were observed in oral motor feeding skills (AOR = 1.67; 95% CI: 0.72-3.91) and functional feeding skills (AOR = 2.28; 95% CI: 0.86-6.06), they did not reach statistical significance in the multivariable models. CONCLUSION Strengthening nutrition education and services for caregivers of children with CP has great value in the care of children with special needs and may improve the health outcomes of children as well as reduce stress among parents/caregivers.
Electrocardiogram interpretation skills among ambulance nurses

Background: To describe ambulance nurses’ practical electrocardiogram (ECG) interpretation skills and to measure the correlation between these skills and factors that may impact on the level of knowledge. Methods: This study was conducted using a prospective quantitative survey with questionnaires and a knowledge test. A convenience sample collection was conducted among ambulance nurses in three different districts in western Sweden. The knowledge test consisted of nine different ECGs. The score of the ECG test were correlated against the questions in the questionnaire regarding both general ECG interpretation skill and ability to identify acute myocardial infarction using Mann–Whitney U test, Kruskal–Wallis test and Spearman’s rank correlation. Results: On average, the respondents had 54% correct answers on the test and identified 46% of the ECGs indicating acute myocardial infarction. The median total score was 9 of 16 (interquartile range 7–11) and 1 of 3 (IQR 1–2) in infarction points. No correlation between ECG interpretation skill and factors such as education and professional experience was found, except that coronary care unit experience was associated with better results on the ECG test. Conclusions: Ambulance nurses have deficiencies in their ECG interpretation skills. This also applies to conditions where the ambulance crew has great potential to improve the outcome of the patient’s health, such as myocardial infarction and cardiac arrest. Neither education, extensive experience in ambulance service nor in nursing contributed to an improved result. The only factor of importance for higher ECG interpretation knowledge was prior experience of working in a coronary care unit.
A non‐canonical tumor suppressive role for the long non‐coding RNA MALAT1 in colon and breast cancers

Long noncoding RNAs (lncRNAs) constitute one of the largest classes of transcripts and have been widely implicated in various diseases such as cancer. Increasing evidence suggests that several lncRNAs are dysregulated and play critical roles in tumorigenesis. LncRNAs can be regulated by key oncogenes and tumor suppressors, adding complexity to the intricate crosstalk between protein coding genes and the noncoding transcriptome. In our study, we investigated the effect that dysregulation of the key tumor suppressor PTEN has on the noncoding transcriptome. We identified the lncRNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) as a target of PTEN and find that this regulation is conserved in both human and mouse as well as with both chronic and acute PTEN dysregulation. We show that this regulation is at least in part microRNA (miRNA)‐dependent, and characterize the miRNAs that may be mediating this crosstalk. In summary, we establish and characterize a non‐canonical PTEN‐microRNA‐MALAT1 axis that regulates tumorigenesis and describe for the first time that the MALAT1 lncRNA possesses novel tumor suppressive properties in colon and breast cancers.
Comparative Gait Analysis in Progressive Supranuclear Palsy and Parkinson's Disease

Background: Although changes to gait are an important clinical feature of progressive supranuclear palsy (PSP), systematic analyses have not been well examined, especially in comparison to Parkinson's disease (PD). Methods: The characteristics of gait in 20 PSP patients (14 males and 6 females) were evaluated in comparison to 124 PD patients (64 males and 60 females) and 24 controls, that is, healthy age-matched adults (5 males and 19 females). Gait in patients was recorded in a 10-m walking test at a self-selected speed. During this time, patients felt most comfortable while wearing a new portable triaxial accelerometer rhythmogram device. Gait variables among the 3 groups were compared. Results: Both PSP and PD patients shared the following similar hypokinetic gait characteristics: decreased velocity, step length, cadence and mean acceleration. Step time and variability in step time were mutually related. However, among the 3 groups, PSP patients showed characteristically low vertical displacement and a higher acceleration than PD patients at the same cadence. Conclusion: Although PSP and PD patients showed similar hypokinetic gait, a reduced vertical displacement characterized walking in PSP patients, differing substantially from the characteristics of walking displayed by PD patients.
Dynamic mechanical properties of keratin fibers during water absorption and desorption

The dynamic modulus and loss angle of keratin fibers have been measured during changes of relative humidity at a fixed fiber strain, temperature, and frequency of oscillation. From these measurements and the observation of an overshoot in loss angle in particular, certain conclusions about the structure of fibers can be made. This overshoot during absorption can be attributed to an interaction between two phases of keratin fibers. When a fiber at a fixed strain is dried from the wet state, the amount of α helices that have opened up during extension in water remains practically constant. A fiber that has been extended in the dry state contains α helices which open more rapidly than in the wet state for a given strain and rate of strain. When a wet fiber is dried and then rewetted while it is held at a fixed strain, the fiber achieves essentially the same structural state as in its original strained state.
A major trade-off between structural and photosynthetic investments operative across plant and needle ages in three Mediterranean pines

Pine (Pinus) species exhibit extensive variation in needle shape and size between juvenile (primary) and adult (secondary) needles (heteroblasty), but few studies have quantified the changes in needle morphological, anatomical and chemical traits upon juvenile-to-adult transition. Mediterranean pines keep juvenile needles longer than most other pines, implying that juvenile needles play a particularly significant role in seedling and sapling establishment in this environment. We studied needle anatomical, morphological and chemical characteristics in juvenile and different-aged adult needles in Mediterranean pines Pinus halepensis Mill. , Pinus pinea L. and Pinus nigra J. F. Arnold subsp. salzmannii (Dunal) Franco hypothesizing that needle anatomical modifications upon juvenile-to-adult transition lead to a trade-off between investments in support and photosynthetic tissues, and that analogous changes occur with needle aging albeit to a lower degree. Compared with adult needles, juvenile needles of all species were narrower with 1.6- to 2.4-fold lower leaf dry mass per unit area, and had ~1.4-fold thinner cell walls, but needle nitrogen content per dry mass was similar among plant ages. Juvenile needles also had ~1.5-fold greater mesophyll volume fraction, ~3-fold greater chloroplast volume fraction and ~1.7-fold greater chloroplast exposed to mesophyll exposed surface area ratio, suggesting overall greater photosynthetic activity. Changes in needle traits were similar in aging adult needles, but the magnitude was generally less than the changes upon juvenile to adult transition. In adult needles, the fraction in support tissues scaled positively with known ranking of species tolerance of drought (P. halepensis > P. pinea > P. nigra). Across all species, and needle and plant ages, a negative correlation between volume fractions of mesophyll and structural tissues was observed, manifesting a trade-off between biomass investments in different needle functions. These results demonstrate that within the broad trade-off, juvenile and adult needle morphophysiotypes are separated by varying investments in support and photosynthetic functions. We suggest that the ecological advantage of the juvenile morphophysiotype is maximization of carbon gain of establishing saplings, while adult needle physiognomy enhances environmental stress tolerance of established plants.
Type 1 Diabetes and Impaired Awareness of Hypoglycemia Are Associated with Reduced Brain Gray Matter Volumes

In this study, we retrospectively analyzed the anatomical MRI data acquired from 52 subjects with type 1 diabetes (26M/26F, 36 ± 11 years old, A1C = 7.2 ± 0.9%) and 50 age, sex and BMI frequency-matched non-diabetic controls (25M/25F, 36 ± 14 years old). The T1D group was further sub-divided based on whether subjects had normal, impaired, or indeterminate awareness of hypoglycemia (n = 31, 20, and 1, respectively). Our goals were to test whether the gray matter (GM) volumes of selected brain regions were associated with diabetes status as well as with the status of hypoglycemia awareness. T1D subjects were found to have slightly smaller volume of the whole cortex as compared to controls (−2.7%, p = 0.016), with the most affected brain region being the frontal lobe (−3.6%, p = 0.024). Similar differences of even larger magnitude were observed among the T1D subjects based on their hypoglycemia awareness status. Indeed, compared to the patients with normal awareness of hypoglycemia, patients with impaired awareness had smaller volume of the whole cortex (−7.9%, p = 0.0009), and in particular of the frontal lobe (−9.1%, p = 0.006), parietal lobe (−8.0%, p = 0.015) and temporal lobe (−8.2%, p = 0.009). Such differences were very similar to those observed between patients with impaired awareness and controls (−7.6%, p = 0.0002 in whole cortex, −9.1%, p = 0.0003 in frontal lobe, −7.8%, p = 0.002 in parietal lobe, and −6.4%, p = 0.019 in temporal lobe). On the other hand, patients with normal awareness did not present significant volume differences compared to controls. No group-differences were observed in the occipital lobe or in the anterior cingulate, posterior cingulate, hippocampus, and thalamus. We conclude that diabetes status is associated with a small but statistically significant reduction of the whole cortex volume, mainly in the frontal lobe. The most prominent structural effects occurred in patients with impaired awareness of hypoglycemia (IAH) as compared to those with normal awareness, perhaps due to the long-term exposure to recurrent episodes of hypoglycemia. Future studies aimed at quantifying relationships of structural outcomes with functional outcomes, with cognitive performance, as well as with parameters describing glucose variability and severity of hypoglycemia episodes, will be necessary to further understand the impact of T1D on the brain.
Towards Engaging Upper Extremity Motor Dysfunction Assessment Using Augmented Reality Games

Advances in technology offer new opportunities for a better understanding of how different disorders affect motor function. Our aim is to explore the potential of augmented reality (AR) using free hand and body tracking to develop engaging games for a uniform, cost-effective and objective evaluation of upper extremity motor dysfunction in different patient groups. Based on the insights from a study with 20 patients (10 Parkinson’s Disease patients and 10 stroke patients) who performed hand/arm movement tasks in AR, we created a set of different augmented reality games for upper extremity motor dysfunction assessment.