Miracle-dz/UniFAR-FTUs huggingface dataset:
Tbx20 controls the expression of the KCNH2 gene and of hERG channels

Significance Tbx20 is a transcription factor whose critical role in cardiogenesis is well-established. Here we functionally analyzed the electrophysiological effects produced by a mutation (p.R311C) in Tbx20 found in some affected individuals belonging to a family with long QT syndrome (an inherited cardiac arrhythmia due to delayed ventricular repolarization). We demonstrated that Tbx20 selectively increases the expression of KCNH2, which encodes for the channel Kv11.1 (hERG) that generates the main ventricular repolarizing current. Conversely, the p.R311C mutation disables the Tbx20 protranscriptional activity over KCNH2, leading to a decrease in the hERG current and a prolongation of the action potentials recorded in human induced pluripotent stem cell-derived cardiomyocytes. Therefore, we propose that Tbx20, besides its described role, regulates KCNH2 expression. Long QT syndrome (LQTS) exhibits great phenotype variability among family members carrying the same mutation, which can be partially attributed to genetic factors. We functionally analyzed the KCNH2 (encoding for Kv11.1 or hERG channels) and TBX20 (encoding for the transcription factor Tbx20) variants found by next-generation sequencing in two siblings with LQTS in a Spanish family of African ancestry. Affected relatives harbor a heterozygous mutation in KCNH2 that encodes for p.T152HfsX180 Kv11.1 (hERG). This peptide, by itself, failed to generate any current when transfected into Chinese hamster ovary (CHO) cells but, surprisingly, exerted “chaperone-like” effects over native hERG channels in both CHO cells and mouse atrial-derived HL-1 cells. Therefore, heterozygous transfection of native (WT) and p.T152HfsX180 hERG channels generated a current that was indistinguishable from that generated by WT channels alone. Some affected relatives also harbor the p.R311C mutation in Tbx20. In human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), Tbx20 enhanced human KCNH2 gene expression and hERG currents (IhERG) and shortened action-potential duration (APD). However, Tbx20 did not modify the expression or activity of any other channel involved in ventricular repolarization. Conversely, p.R311C Tbx20 did not increase KCNH2 expression in hiPSC-CMs, which led to decreased IhERG and increased APD. Our results suggest that Tbx20 controls the expression of hERG channels responsible for the rapid component of the delayed rectifier current. On the contrary, p.R311C Tbx20 specifically disables the Tbx20 protranscriptional activity over KCNH2. Therefore, TBX20 can be considered a KCNH2-modifying gene.
Highly Coarse-Grained Representations of Transmembrane Proteins

Numerous biomolecules and biomolecular complexes, including transmembrane proteins (TMPs), are symmetric or at least have approximate symmetries. Highly coarse-grained models of such biomolecules, aiming at capturing the essential structural and dynamical properties on resolution levels coarser than the residue scale, must preserve the underlying symmetry. However, making these models obey the correct physics is in general not straightforward, especially at the highly coarse-grained resolution where multiple (∼3–30 in the current study) amino acid residues are represented by a single coarse-grained site. In this paper, we propose a simple and fast method of coarse-graining TMPs obeying this condition. The procedure involves partitioning transmembrane domains into contiguous segments of equal length along the primary sequence. For the coarsest (lowest-resolution) mappings, it turns out to be most important to satisfy the symmetry in a coarse-grained model. As the resolution is increased to capture more detail, however, it becomes gradually more important to match modular repeats in the secondary structure (such as helix-loop repeats) instead. A set of eight TMPs of various complexity, functionality, structural topology, and internal symmetry, representing different classes of TMPs (ion channels, transporters, receptors, adhesion, and invasion proteins), has been examined. The present approach can be generalized to other systems possessing exact or approximate symmetry, allowing for reliable and fast creation of multiscale, highly coarse-grained mappings of large biomolecular assemblies.
Robust Human Pose Tracking For Realistic Service Robot Applications

Robust human pose estimation and tracking plays an integral role in assistive service robot applications, as it provides information regarding the body pose and motion of the user in a scene. Even though current solutions provide high-accuracy results in controlled environments, they fail to successfully deal with problems encountered under real-life situations such as tracking initialization and failure, body part intersection, large object handling and partial-view body-part tracking. This paper presents a framework tailored for deployment under real-life situations addressing the above limitations. The framework is based on the articulated 3D-SDF data representation model, and has been extended with complementary mechanisms for addressing the above challenges. Extensive evaluation on public datasets demonstrates the framework's state-of-the-art performance, while experimental results on a challenging realistic human motion dataset exhibit its robustness in real life scenarios.
Radioguided Occult Lesion Localization: Technical Procedures and Clinical Applications

Purpose Regarding radioguided surgery, the concept of “radioguided occult lesion localization” (ROLL) is based on both preoperative interventional imaging and intraoperative radioguided detection of a clinically occult neoplastic lesion. Methods This methodology consists in the direct administration into the lesion of 99mTc–macroaggregated human albumin formed by relatively large particles retained at the injection site, which direct radioguided excisional biopsy. Results This modality has expanded from the classic application of ROLL for nonpalpable breast lesions to other tumors, such as solitary pulmonary nodules or recurrences from differentiated thyroid carcinoma. In 2011, in order to improve the classification of different radioguided surgical procedures, ROLL applications were included in the more complete concept of GOSTT (Guided intraOperative Scintigraphic Tumor Targeting). This concept was introduced to include the entire range of basic and advanced radioguided procedures necessary to supply a “road map” for the surgeon. Conclusions The terms ROLL and GOSTT have further developed by incorporating novel modalities such as hybrid tracers for simultaneous fluorescence and radioactive signal detection and innovative navigation systems based on mixed-reality protocols.
Multistatic micro-Doppler radar feature extraction for classification of unloaded/loaded micro-drones

This study presents the use of micro-Doppler signatures collected by a multistatic radar to detect and discriminate between micro-drones hovering and flying while carrying different payloads, which may be an indication of unusual or potentially hostile activities. Different features have been extracted and tested, namely features related to the radar cross-section of the micro-drones, as well as the singular value decomposition and centroid of the micro-Doppler signatures. In particular, the added benefit of using multistatic information in comparison with conventional radar is quantified. Classification performance when identifying the weight of the payload that the drone was carrying while hovering was found to be consistently above 96% using the centroid-based features and multistatic information. For the non-hovering scenarios, classification results with accuracy above 95% were also demonstrated in preliminary tests in discriminating between three different payload weights.
Automatic Salient Object Detection for Panoramic Images Using Region Growing and Fixation Prediction Model

Almost all previous works on saliency detection have been dedicated to conventional images, however, with the outbreak of panoramic images due to the rapid development of VR or AR technology, it is becoming more challenging, meanwhile valuable for extracting salient contents in panoramic images. In this paper, we propose a novel bottom-up salient object detection framework for panoramic images. First, we employ a spatial density estimation method to roughly extract object proposal regions, with the help of region growing algorithm. Meanwhile, an eye fixation model is utilized to predict visually attractive parts in the image from the perspective of the human visual search mechanism. Then, the previous results are combined by the maxima normalization to get the coarse saliency map. Finally, a refinement step based on geodesic distance is utilized for post-processing to derive the final saliency map. To fairly evaluate the performance of the proposed approach, we propose a high-quality dataset of panoramic images (SalPan). Extensive evaluations demonstrate the effectiveness of our proposed method on panoramic images and the superiority of the proposed method against other methods.
Detection of the European epidemic strain of Trichomonas gallinae in finches, but not other non-columbiformes, in the absence of macroscopic disease

SUMMARY Finch trichomonosis is an emerging infectious disease affecting European passerines caused by a clonal strain of Trichomonas gallinae. Migrating chaffinches (Fringilla coelebs) were proposed as the likely vector of parasite spread from Great Britain to Fennoscandia. To test for such parasite carriage, we screened samples of oesophagus/crop from 275 Apodiform, Passeriform and Piciform birds (40 species) which had no macroscopic evidence of trichomonosis (i.e. necrotic ingluvitis). These birds were found dead following the emergence of trichomonosis in Great Britain, 2009–2012, and were examined post-mortem. Polymerase chain reactions were used to detect (ITS1/5·8S rRNA/ITS2 region and single subunit rRNA gene) and to subtype (Fe-hydrogenase gene) T. gallinae. Trichomonas gallinae was detected in six finches [three chaffinches, two greenfinches (Chloris chloris) and a bullfinch (Pyrrhula pyrrhula)]. Sequence data had 100% identity to the European finch epidemic A1 strain for each species. While these results are consistent with finches being vectors of T. gallinae, alternative explanations include the presence of incubating or resolved T. gallinae infections. The inclusion of histopathological examination would help elucidate the significance of T. gallinae infection in the absence of macroscopic lesions.
Barriers to Patient-Centered Human Immunodeficiency Virus (Hiv) Care with African American Patients who Use Drugs: Social Construction of the Typical and Ideal Care Visit

Background: A successful patient-provider relationship ensures that patients are treated as individuals and receive appropriate care for their unique circumstances. For this to occur, the relationship needs open communication and trust. African American persons who inject drugs (PWIDs) and who smoke crack cocaine are at elevated risks of poor health outcomes and are often lost to care. In addition, providers often experience difficulty serving this population. Although some barriers are documented in the peer-reviewed literature, this study sought to provide in-depth context to the relationship and how it is constructed. Methods: Individual, semistructured interviews were conducted with human immunodeficiency virus (HIV) care providers and their patients, specifically PWIDs and persons who smoke crack cocaine, in publicly funded HIV clinics in low-resource urban communities. n = 31 patients and n = 7 providers were interviewed about their perceptions of the other and the relationship. Interview transcripts were coded and analyzed for common themes, which were used to generate a conceptual, constructionist model of the HIV care visit. Results: Common patient themes included the tendency to describe providers in familial terms, match between their current provider and ideal provider, concern about stigma related to their use, and expression of unmet needs. Provider themes revealed less match with their ideal patient—preferring patients who were both abstinent and adherent, and expressing frustration with patient refusal to change. Conclusions: Thematic results were used to create a visual and conceptual model for the HIV care visit. The model demonstrates both the positive and negative perceptions that inform the visit, and the barriers that impede a more fruitful patient-provider dynamic with a shared power structure. Provider training in communication and other identified topics may begin to lay the foundation for a shift in this structure.
Association Between Early-Life Antibiotic Use and the Risk of Islet or Celiac Disease Autoimmunity

Importance Evidence is lacking regarding the consequences of antibiotic use in early life and the risk of certain autoimmune diseases. Objective To test the association between early-life antibiotic use and islet or celiac disease (CD) autoimmunity in genetically at-risk children prospectively followed up for type 1 diabetes (T1D) or CD. Design, Setting, and Participants HLA-genotyped newborns from Finland, Germany, Sweden, and the United States were enrolled in the prospective birth cohort of The Environmental Determinants of Diabetes in the Young (TEDDY) study between November 20, 2004, and July 8, 2010. The dates of analysis were November 20, 2004, to August 31, 2014. Individuals from the general population and those having a first-degree relative with T1D were enrolled if they had 1 of 9 HLA genotypes associated with a risk for T1D. Exposures Parental reports of the most common antibiotics (cephalosporins, penicillins, and macrolides) used between age 3 months and age 4 years were recorded prospectively. Main Outcomes and Measures Islet autoimmunity and CD autoimmunity were defined as being positive for islet or tissue transglutaminase autoantibodies at 2 consecutive clinic visits at least 3 months apart. Hazard ratios and 95% CIs calculated from Cox proportional hazards regression models were used to assess the relationship between antibiotic use in early life before seroconversion and the development of autoimmunity. Results Participants were 8495 children (49.0% female) and 6558 children (48.7% female) enrolled in the TEDDY study who were tested for islet and tissue transglutaminase autoantibodies, respectively. Exposure to and frequency of use of any antibiotic assessed in this study in early life or before seroconversion did not influence the risk of developing islet autoimmunity or CD autoimmunity. Cumulative use of any antibiotic during the first 4 years of life was not associated with the appearance of any autoantibody (hazard ratio [HR], 0.98; 95% CI, 0.95-1.01), multiple islet autoantibodies (HR, 0.99; 95% CI, 0.95-1.03), or the transglutaminase autoantibody (HR, 1.00; 95% CI, 0.98-1.02). Conclusions and Relevance The use of the most prescribed antibiotics during the first 4 years of life, regardless of geographic region, was not associated with the development of autoimmunity for T1D or CD. These results suggest that a risk of islet or tissue transglutaminase autoimmunity need not influence the recommendations for clinical use of antibiotics in young children at risk for T1D or CD.
Fecal microbiota transplantation–early steps on a long journey ahead

“In the early days of oral antibiotics we were plagued by frequent diarrhea in our patients due presumably to killing off intestinal bacteria. I was Chief of Surgery at the VA and simplistically considered merely reintroducing normal organisms to counter such absence. Those were days when if one had an idea, we simply tried. It seemed to work and I wrote it up. It made a small splash.Best Wishes. ” Ben Eiseman. Emeritus Professor of Surgery. (E-mail, September 20, 2011)
Plasma Membrane Repair Is Regulated Extracellularly by Proteases Released from Lysosomes

Eukaryotic cells repair wounds on their plasma‐membrane (PM) within a few seconds in a process that involves at least three steps: Ca2+ influx, lysosomal exocytosis and lesion endocytosis. Previous work from our laboratory showed that lysosomal secretion of acid sphingomyelinase (ASM) promotes PM repair by triggering endocytosis of lesions. However, the role of other lysosomal enzymes such as proteases remained unknown. We present evidence for a role of secreted lysosomal proteases in PM repair. We show that HeLa and NRK cells permeabilized with the cytolysin streptolysin‐O (SLO) in the presence of Ca2+ release cathepsins B, L and D into the extracellular medium, with a fast kinetics consistent with the time frame of PM repair. Dequenching of fluorescent DQ‐BSA was detected extracellularly in the first seconds of repair, showing that proteolysis occurs during the process. PM repair, analyzed by flow cytometry and live microscopy after SLO injury, was enhanced by pre‐treating cells with proteinase K and inhibited by the broad‐specificity protease inhibitor alpha‐2‐macroglobulin. These results show, for the first time, that extracellular proteolytic events are involved in PM repair. Specific protease inhibitors and siRNA silencing for cathepsin B, L and D showed a role for these proteases during PM repair, including the resealing of mechanical wounds. Interestingly, ASM activity and subsequent PM repair were promoted by cysteine proteases and inhibited by aspartyl proteases, whereas serine proteases did not seem to be involved. Taken together, our data suggests that at least one of the mechanisms by whichlysosomal proteases regulate PM repair is through extracellular regulation of the lysosomal enzyme ASM.
Early education and counselling of patients with acute coronary syndrome. A pilot study for a randomized controlled trial

Background: At time of discharge, patients with acute coronary syndrome often have a knowledge deficit regarding their disease, further treatment and necessary behavioural changes. It is well known that self-efficacy as a prerequisite for behavioural changes can be influenced by patient education. This study investigated whether an individualized education programme starting early in the cardiac care unit enhanced self-efficacy and rehabilitation programme attendance, and was feasible and satisfying for patients. Methods and design: In a pilot randomized controlled trial, 40 patients with acute coronary syndrome were enrolled. The intervention group received in addition to standard care an early individual needs-oriented educational session in the cardiac care unit and subsequently one on the ward addressing risk factors, medication and self-management as well as referral to a rehabilitation programme by a nurse. Self-efficacy was assessed twice, at attendance in a rehabilitation programme six weeks after discharge. The participants’ satisfaction with the intervention was assessed qualitatively. Results: When controlling for anxiety and depression, the intervention group showed significant better self-efficacy scores on the ability to control the symptoms (p=0.034). When controlling additionally for age, no significant differences could be detected. The attendance of a rehabilitation programme was higher in the intervention group. The participants in the intervention group reported high satisfaction with the early education. Conclusion: Early education seems to benefit patients with acute coronary syndrome. In light of increased confidence to control one’s symptoms and the higher attendance in rehabilitation programmes, as well as a high satisfaction with the intervention, a full powered study will be pursued.
Research in Acute Lung Injury and Pulmonary Fibrosis (cid:2) -Nitrostyrene derivatives attenuate LPS-mediated acute lung injury via the inhibition of neutrophil-platelet interactions and NET release

Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) are high-mortality and life-threatening diseases that are associated with neutrophil activation and accumulation within lung tissue. indicates that neutrophil-platelet aggregates (NPAs) at sites of injury increase acute inﬂammation and contribute to the development of ALI. Although numerous studies our understanding of the pathophysiology of ALI, there is still a lack of innovative and useful treatments that reduce mortality, that there is an urgent need for novel treatment strategies. In this study, a new series of small compounds of (cid:2) -nitrostyrene derivatives (BNSDs) were synthesized, and their anti-inﬂammatory bioactivities on neutrophils and platelets were evaluated. The new small compound C7 modulates neutrophil function by inhibiting superoxide generation and elastase release. Compound C7 elicits protective effects on LPS-induced paw edema and acute lung injury via the inhibition of neutrophil accumulation, proinﬂammatory mediator release, platelet aggregation, myeloperoxidase activity, and neutrophil extracellular trap (NET) release. was identiﬁed as the bridge for the critical interactions between neutrophils and platelets by confocal microscopy and ﬂow cytometry. This research provides new insights for elucidating the complicated regulation of neutrophils and platelets in ALI on future drug development strategies for ALI/ARDS and acute inﬂammatory diseases. measure elastase release. The are as the of elastase release compared with the control group. dehydrogenase Cytotoxicity as LDH release as a of total LDH release then as a for total LDH.
An Innovative Salient Object Detection Using Center-Dark Channel Prior

Saliency detection aims to detect the most attractive objects in images, which has been widely used as a foundation for various multimedia applications. In this paper, we propose a novel salient object detection algorithm for RGB-D images using center-dark channel prior. First, we generate an initial saliency map based on a color saliency map and a depth saliency map of a given RGB-D image. Then, we generate a center-dark channel map based on a center saliency prior and a dark channel prior. Finally, we fuse the initial saliency map with the center dark channel map to generate the final saliency map. The proposed algorithm is evaluated on two public RGB-D datasets, and the experimental results show that our method outperforms the state-of-the-art methods.