Miracle-dz/UniFAR-FTUs huggingface dataset:
Three-dimensional holographic visualization of high-resolution myocardial scar on HoloLens

Visualization of the complex 3D architecture of myocardial scar could improve guidance of radio-frequency ablation in the treatment of ventricular tachycardia (VT). In this study, we sought to develop a framework for 3D holographic visualization of myocardial scar, imaged using late gadolinium enhancement (LGE), on the augmented reality HoloLens. 3D holographic LGE model was built using the high-resolution 3D LGE image. Smooth endo/epicardial surface meshes were generated using Poisson surface reconstruction. For voxel-wise 3D scar model, every scarred voxel was rendered into a cube which carries the actual resolution of the LGE sequence. For surface scar model, scar information was projected on the endocardial surface mesh. Rendered layers were blended with different transparency and color, and visualized on HoloLens. A pilot animal study was performed where 3D holographic visualization of the scar was performed in 5 swines who underwent controlled infarction and electroanatomic mapping to identify VT substrate. 3D holographic visualization enabled assessment of the complex 3D scar architecture with touchless interaction in a sterile environment. Endoscopic view allowed visualization of scar from the ventricular chambers. Upon completion of the animal study, operator and mapping specialist independently completed the perceived usefulness questionnaire in the six-item usefulness scale. Operator and mapping specialist found it useful (usefulness rating: operator, 5.8; mapping specialist, 5.5; 1–7 scale) to have scar information during the intervention. HoloLens 3D LGE provides a true 3D perception of the complex scar architecture with immersive experience to visualize scar in an interactive and interpretable 3D approach, which may facilitate MR-guided VT ablation.
Speech-driven mobile games for speech therapy: User experiences and feasibility

Abstract Purpose: To assist in remote treatment, speech-language pathologists (SLPs) rely on mobile games, which though entertaining, lack feedback mechanisms. Games integrated with automatic speech recognition (ASR) offer a solution where speech productions control gameplay. We therefore performed a feasibility study to assess children’s and SLPs’ experiences towards speech-controlled games, game feature preferences and ASR accuracy. Method: Ten children with childhood apraxia of speech (CAS), six typically developing (TD) children and seven SLPs trialled five games and answered questionnaires. Researchers also compared the results of ASR to perceptual judgment. Result: Children and SLPs found speech-controlled games interesting and fun, despite ASR–human disagreements. They preferred games with rewards, challenge and multiple difficulty levels. Automatic speech recognition–human agreement was higher for SLPs than children, similar between TD and CAS and unaffected by CAS severity (77% TD, 75% CAS – incorrect; 51% TD, 47% CAS, 71% SLP – correct). Manual stop recording yielded higher agreement than automatic. Word length did not influence agreement. Conclusion: Children’s and SLPs’ positive responses towards speech-controlled games suggest that they can engage children in higher intensity practice. Our findings can guide future improvements to the ASR, recording methods and game features to improve the user experience and therapy adherence.
The histone deacetylase inhibitor LBH589 inhibits undifferentiated pleomorphic sarcoma growth via downregulation of FOS‐like antigen 1

Undifferentiated pleomorphic sarcoma (UPS) is the second most frequent soft tissue sarcoma. Because of its resistance to chemotherapy, UPS patients are treated with surgical resection and complementary radiotherapy. However, since standard chemotherapy has not been established, unresectable or metastatic cases result in a poor prognosis. Therefore, the identification of a more effective therapy for UPS patients is needed. The development and progression of malignant tumors involve epigenetic alterations, and histone deacetylases (HDAC) have become a promising chemotherapeutic target. In this study, we investigated the potential effects and mechanisms of an HDAC inhibitor, LBH589, in UPS cells. We confirmed that LBH589 exhibits potent antitumor activities in four human UPS cell lines (GBS‐1, TNMY‐1, Nara‐F, and Nara‐H) and IC50 values ranged from 7 to 13 nM. A mouse xenograft model showed that LBH589 treatment effectively suppressed tumor growth. FACS analysis showed that LBH589 induced apoptosis and G2/M cell cycle arrest. Among apoptosis‐related proteins, the expressions of Bcl‐2 and Bcl‐xL were decreased and the expression of Bak and Bim increased. Among cell cycle‐related proteins, reductions of CDK1, p‐CDK1, cyclin B1, Aurora A, and Aurora B were observed after LBH589 treatment. RNA microarray identified the FOS‐like antigen 1 (FOSL1) gene as a downregulated gene in response to LBH589 in UPS cells. While knockdown of FOSL1 decreased UPS cell proliferation, overexpression induced cell proliferation. Our results show that LBH589 could be a promising chemotherapeutic agent in the treatment of UPS and downregulation of the FOSL1 gene could be the new molecular target of UPS treatment.
TM9SF4 levels determine sorting of transmembrane domains in the early secretory pathway

ABSTRACT Previous studies have shown that TM9SF4 interacts with glycine-rich transmembrane domains (TMDs) and promotes their surface localization, presumably by escorting them along the secretory pathway. Here, we delineated the role of TM9 proteins in the sorting of TMDs. Our results indicate that TM9SF4 interacts with and sorts a variety of TMDs. In human embryonic kidney (HEK) cells, a TMD carrying a positively charged residue (T-R1) or a negatively charged residue (T-D1) was localized to the endoplasmic reticulum (ER), but partially relocated to the Golgi complex upon overexpression of TM9SF4. These results show that TM9SF4 controls the sorting of TMDs at the ER-Golgi interface. Remarkably, sorting of T-R1 in HCT116 cells was different from that in HEK cells: in HCT116 cells, a substantial fraction of T-R1 was localized to the Golgi complex, and it was relocated to the ER by genetic ablation of TM9SF4. This observation indicates that TM9SF4 sorting activity differs in HEK and HCT116 cells, resulting in different sorting of TMDs in these two cell types. Although TM9SF1 associated with several TMDs, it did not visibly alter their intracellular transport in the secretory pathway and may function in other intracellular transport pathways. Summary: TM9SF4 interacts with a variety of transmembrane domains (TMDs) and facilitates their transport from the endoplasmic reticulum to the Golgi complex. TM9SF4 levels modulate transport of TMDs in the early secretory pathway in different cell types.
The Hippocampal Film Editor: Sensitivity and Specificity to Event Boundaries in Continuous Experience

The function of the human hippocampus is normally investigated by experimental manipulation of discrete events. Less is known about what triggers hippocampal activity during more naturalistic, continuous experience. We hypothesized that the hippocampus would be sensitive to the occurrence of event boundaries, that is, moments in time identified by observers as a transition between events. To address this, we analyzed functional MRI data from two groups: one (n = 253, 131 female) who viewed an 8.5 min film and another (n = 15, 6 female) who viewed a 120 min film. We observed a strong hippocampal response at boundaries defined by independent observers, which was modulated by boundary salience (the number of observers that identified each boundary). In the longer film, there were sufficient boundaries to show that this modulation remained after covarying out a large number of perceptual factors. This hypothesis-driven approach was complemented by a data-driven approach, in which we identified hippocampal events as moments in time with the strongest hippocampal activity. The correspondence between these hippocampal events and event boundaries was highly significant, revealing that the hippocampal response is not only sensitive, but also specific to event boundaries. We conclude that event boundaries play a key role in shaping hippocampal activity during encoding of naturalistic events. SIGNIFICANCE STATEMENT Recent years have seen the field of human neuroscience research transitioning from experiments with simple stimuli to the study of more complex and naturalistic experience. Nonetheless, our understanding of the function of many brain regions, such as the hippocampus, is based primarily on the study of brief, discrete events. As a result, we know little of what triggers hippocampal activity in real-life settings when we are exposed to a continuous stream of information. When does the hippocampus “decide” to respond during the encoding of naturalistic experience? We reveal here that hippocampal activity measured by fMRI during film watching is both sensitive and specific to event boundaries, identifying a potential mechanism whereby event boundaries shape experience by modulation of hippocampal activity.
Current Understanding of the Role of Nesfatin-1

Abstract Nesfatin-1 was discovered in 2006 and implicated in the regulation of food intake. Subsequently, its widespread central and peripheral distribution gave rise to additional effects. Indeed, a multitude of actions were described, including modulation of gastrointestinal functions, glucose and lipid metabolism, thermogenesis, mediation of anxiety and depression, as well as cardiovascular and reproductive functions. Recent years have witnessed a great increase in our knowledge of these effects and their underlying mechanisms, which will be discussed in the present review. Lastly, gaps in knowledge will be highlighted to foster further studies.
Mechanobiology of Periodontal Ligament Stem Cells in Orthodontic Tooth Movement

Periodontal ligament stem cells (PDLSCs) possess self-renewal, multilineage differentiation, and immunomodulatory properties. They play a crucial role in maintaining periodontal homeostasis and also participated in orthodontic tooth movement (OTM). Various studies have applied controlled mechanical stimulation to PDLSCs and investigated the effects of orthodontic force on PDLSCs. Physical stimuli can regulate the proliferation and differentiation of PDLSCs. During the past decade, a variety of studies has demonstrated that applied forces can activate different signaling pathways in PDLSCs, including MAPK, TGF-β/Smad, and Wnt/β-catenin pathways. Besides, recent advances have highlighted the critical role of orthodontic force in PDLSC fate through mediators, such as IL-11, CTHRC1, miR-21, and H2S. This perspective review critically discusses the PDLSC fate to physical force in vitro and orthodontic force in vivo, as well as the underlying molecular mechanism involved in OTM.
Use of fungal alpha amylase and ascorbic acid in the optimisation of grain amaranth–wheat flour blended bread

Grain amaranth–wheat flour bread was optimised using ascorbic acid (0.03% dry weight basis) and fungal α-amylase (10 ppm) to investigate their effects on sensory properties of the breads. Six formulations were used in the ratios of 5:95, 10:90, 15:85, 20:80 and 25:75 grain amaranth to wheat flour compositions, while the control bread had 100% wheat flour. Consumer acceptability and preference ranking tests were conducted to describe and evaluate preference and acceptability of the breads. Analysis of consumer acceptability data revealed that there were significant differences (p < 0.05) for all the samples in all the attributes tested. Overall consumer acceptability results showed no difference at 25% for all improvers. Principal component analysis for descriptive tests performed by a trained panel demonstrated variations among the breads in graininess, elasticity, crumb colour, stickiness and crumb moistness regardless of the improvers used. The study concludes that using improvers to optimise grain amaranth–wheat flour bread can help improve both the nutritional and organoleptic properties of bread.
Learning One-hidden-layer Neural Networks under General Input Distributions

Significant advances have been made recently on training neural networks, where the main challenge is in solving an optimization problem with abundant critical points. However, existing approaches to address this issue crucially rely on a restrictive assumption: the training data is drawn from a Gaussian distribution. In this paper, we provide a novel unified framework to design loss functions with desirable landscape properties for a wide range of general input distributions. On these loss functions, remarkably, stochastic gradient descent theoretically recovers the true parameters with global initializations and empirically outperforms the existing approaches. Our loss function design bridges the notion of score functions with the topic of neural network optimization. Central to our approach is the task of estimating the score function from samples, which is of basic and independent interest to theoretical statistics. Traditional estimation methods (example: kernel based) fail right at the outset; we bring statistical methods of local likelihood to design a novel estimator of score functions, that provably adapts to the local geometry of the unknown density.
Clinical manifestations and basic mechanisms of myocardial ischemia/reperfusion injury

Acute myocardial ischemia/reperfusion (I/R) injury is a significant, unsolved clinical puzzle. In the disease context of acute myocardial infarction, reperfusion remains the only effective strategy to salvage ischemic myocardium, but it also causes additional damage. Myocardial I/R injury is composed of four types of damage, and these events attenuate the benefits of reperfusion therapy. Thus, inventing new strategies to conquer I/R injury is an unmet clinical need. A variety of pathological processes and mediators, including changes in the pH, generation of reactive oxygen radicals, and intracellular calcium overload, are proposed to be crucial in I/R-related cell injury. Among the intracellular events that occur during I/R, we stress the importance of protein phosphorylation signaling and elaborate its regulation. A variety of protein kinase pathways could be activated in I/R, including reperfusion injury salvage kinase and survivor-activating factor enhancement pathways, which are critical to cardiomyocyte survival. In addition to serine/threonine phosphorylation signaling, protein tyrosine phosphorylation is also critical in multiple cell functions and survival. However, the roles of protein kinases and phosphatases in I/R have not been extensively studied yet. By better understanding the mechanisms of I/R injury, we may have a better chance to develop new strategies for I/R injury and apply them in the clinical patient care.
Calories in Context: Conceptual Metaphors and Consumers’ Perception and Use of Calorie Information

The U.S. Food and Drug Administration (FDA) recently made changes to the nutrition facts label so that calories will be emphasized over all other nutrient information (U.S. Food and Drug Administration (FDA), 2016a, August 3). In light of calories’ increased visibility, strategic health communicators need to understand both how individuals perceive calorie information and how calories influence consumption decisions. Therefore, a qualitative study was conducted to analyze the metaphors that structure consumers’ thoughts about calorie information and food choices. In-depth interviews were conducted with 34 women from diverse racial/ethnic and socioeconomic backgrounds. Through the interviews and subsequent thematic analysis, metaphors were gathered that explained perceptions of different kinds of calories and how calories function in the diet. Five conceptual metaphors were uncovered. The metaphors individuals used varied based on their eating paradigms, and the metaphors were related to different approaches to consumption decisions. The implications of using these different calorie metaphors for translational communication interventions are further discussed.
Investigation of structural stability and functionality of homodimeric gramicidin towards peptide‐based drug: a molecular simulation approach

Increasing death rates due to antibiotic resistance deteriorate the existing treatment measures. Antimicrobial peptides have turned into the emerging cure for multidrug resistance. However, the stability and functionality determine an antimicrobial peptide as a drug. Analyses of the homodimeric β‐helical peptide, gramicidin have suggested the significant role of gramicidin‐A, gramicidin‐B, and gramicidin‐C as antimicrobial compounds, but the structural basis for understanding the stability and functionality is insufficient to resolve multidrug resistance. To identify the best template among gramicidin types as a therapeutic product, we combined a detailed comparative static analysis and dynamic analysis along with conformational free energy and secondary structure prediction. We observed that the high intramolecular interactions and the geometrical features favored gramicidin‐A among other types of gramicidin. Our analyses further revealed that the secondary structure of gramicidin‐A showed β sheets with coils along the conformations without any disruption, thereby enhanced its membrane interactions in terms of binding free energy. In conclusion, gramicidin‐A has definitely showed enhanced structural stability and functionality; this could be considered the best template for a potential therapeutic product.
Factors underlying suboptimal diagnostic performance in physicians under time pressure

Time pressure has been implicated in the suboptimal diagnostic performance of doctors and in increases in diagnostic errors. However, the reasons underlying these effects are not clear. The aim of this study was to investigate the influence of time pressure on physicians’ diagnostic accuracy and to explore the mediating effects of perceived stress (emotional pathway) and number of plausible diagnostic hypotheses (cognitive pathway) on the proposed relationship.
Assessment of Diagnostic Reference Level in Radiography of Neonatal Chest Anteroposterior Examination: A Hospital-based Study

Radiological imaging is an important modality of today's overall practicum. Imaging can begin as early as the 1st day of life. Neonates are 3–4 times more sensitive to radiation than adults. The purpose of the work was to assess the diagnostic reference level (DRL), the radiation organ dose, and effective organ dose for both sexes from chest anteroposterior radiograph, which is the most common radiographic examination performed at the Neonatal Intensive Care Unit (NICU). The entrance air kerma was measured using a solid-state PIN type detector, and the value was used as the input factor to PCXMC-2.0 software to calculate the entrance surface air kerma (ESAK), patient-specific organ dose, and effective dose originated from chest anteroposterior examinations of neonates at NICU. The mean value of ESAK is taken as a diagnostic reference level (DRL) for neonates (both male and female). The mean ESAK value of male neonates is (79.6 ± 1.4) μGy and for female is (79.9 ± 1.9) μGy, and the institutional diagnostic reference level (DRL) is 80.35 μGy for male and 81.2 μGy for female (i.e., third quartile value). A statistical dependency (correlation) between neonates body mass index (BMI) and ESAK was defined for both the sexes. Significant positive correlation was found between ESAK per patient with respect to BMI of both male (R = 0.83, P = 0.00001) and female (R = 0.72, P = 0.00055) neonates. The results for neonatal dose in NICU were compatible with the literature. The result presented will serve as baseline data for the selection of technical parameters in neonatal chest anteroposterior X-ray examination.
The Challenge of Implementing the Marine Ecosystem Service Concept

The concept of ecosystem services has gained traction as a means of linking societal benefits to the underlying ecology and functioning of ecosystems, and is now frequently included in decision-making and legislation. Moving the ecosystem service concept from theory into practice is now crucial. However, advancements in this area of research differ by ecosystem type, and marine systems lag significantly behind terrestrial counterparts in terms of understanding, implementation and number of studies. In this paper we explore several reasons why ecosystem service research has been limited in marine systems and we outline the challenges that hinder progress. Marine systems suffer from a scarcity of spatial data relative to terrestrial counterparts. In terrestrial systems the spatial patterns of land-use/land-cover (LULC) are relatively straightforward to access via satellite and have been used as proxy indicators of service provisions. In contrast, remote sensing tools used to study the surface of the Earth are much less effective at capturing images of the seabed, and by extension marine habitats. Marine waters and their constituents are also frequently driven great distances by winds, tides and currents. This creates a challenge for management as the identification and protection of areas where ecosystem services are exploited is not necessarily sufficient to ensure sustained service delivery. Further complications arise from the three-dimensional uses of marine systems, incorporating activities that use the sea surface, the water column and the benthic habitats below. Progress is being made as technological advancements are resulting in the acquisition of spatial data at faster rates and higher resolutions than previously possible. There is a growing capacity to map, model and value an increasing number of services with initiatives such as InVEST or principle-based modelling. We suggest that awareness is needed around the limited progress in marine systems as this could affect the way we value the biosphere and the relative proportion between biomes.
Conventional and quantitative MRI in a novel feline model of demyelination and endogenous remyelination

The feeding of irradiated food to healthy adult cats results in widespread, noninflammatory demyelination of the central nervous system (CNS); a return to a normal diet results in endogenous remyelination with functional recovery. This recently discovered, reversible disease might provide a compelling clinical neuroimaging model system for the development and testing of myelin‐directed MRI methods as well as future remyelination therapies.
Context-enriched interactome powered by proteomics helps the identification of novel regulators of macrophage activation

The role of pro-inflammatory macrophage activation in cardiovascular disease (CVD) is a complex one amenable to network approaches. While an indispensible tool for elucidating the molecular underpinnings of complex diseases including CVD, the interactome is limited in its utility as it is not specific to any cell type, experimental condition or disease state. We introduced context-specificity to the interactome by combining it with co-abundance networks derived from unbiased proteomics measurements from activated macrophage-like cells. Each macrophage phenotype contributed to certain regions of the interactome. Using a network proximity-based prioritization method on the combined network, we predicted potential regulators of macrophage activation. Prediction performance significantly increased with the addition of co-abundance edges, and the prioritized candidates captured inflammation, immunity and CVD signatures. Integrating the novel network topology with transcriptomics and proteomics revealed top candidate drivers of inflammation. In vitro loss-of-function experiments demonstrated the regulatory role of these proteins in pro-inflammatory signaling.