Miracle-dz/UniFAR-FTUs huggingface dataset:
siRNA Screen for Genes That Affect Junín Virus Entry Uncovers Voltage-Gated Calcium Channels as a Therapeutic Target

Voltage-gated calcium channel blockers may prevent fusion and cell entry of New World arenaviruses. Reduce, Reuse, Recycle Drug repurposing is becoming the focus of an increasingly large body of biomedical research. A drug that has already achieved regulatory approval is less likely to have unexpected toxicity, paving the way for approval against previously unthought-of diseases. Now, Lavanya et al. report that drugs that target voltage-gated calcium channels (VGCCs) may be a new area of therapy against New World arenavirus infection. Although human diseases caused by arenaviruses range in severity, the most severe, such as Junín viruses, may cause hemorrhagic fever. The authors used a high-throughput small interfering RNA screening approach to identify VGCCs as a putative target for Junín virus infection. Either knocking down VGCCs or blocking them with channel blockers decreased viral fusion and subsequent cell entry and infection. What’s more, gabapentin, a Food and Drug Administration–approved drug that targets VGCCs, inhibited Junín virus infection in a mouse model. If these data hold true in humans, VGCC blockers may be a new therapeutic avenue for Junín virus infection. New World hemorrhagic fever arenavirus infection results in 15 to 30% mortality in humans. We performed a high-throughput small interfering RNA screen with Junín virus glycoprotein-pseudotyped viruses to find potential host therapeutic targets. Voltage-gated calcium channel (VGCC) subunits, for which there are Food and Drug Administration (FDA)–approved drugs, were identified in the screen. Knockdown of VGCC subunits or treatment with channel blockers diminished Junín virus–cell fusion and entry into cells and thereby decreased infection. Gabapentin, an FDA-approved drug used to treat neuropathic pain that targets the α2δ2 subunit, inhibited infection of mice by the Candid 1 vaccine strain of the virus. These findings demonstrate that VGCCs play a role in virus infection and have the potential to lead to therapeutic intervention of New World arenavirus infection.
Making sense of it: intensive care patients' phenomenological accounts of story construction.

BACKGROUND Patients entering intensive care encounter physical and psychological stress that may lead to psychological morbidity such as depression, anxiety and post-traumatic stress. It has been suggested that constructing a story may assist psychological recovery. However, this has been minimally investigated in intensive care patients. AIM The aim of this article is to examine the process of story construction in people's phenomenological accounts of being a patient in the technological environment of intensive care. STUDY DESIGN The study design was informed by Heideggerian phenomenology. METHODS Semi-structured interviews were conducted with 19 patients who had been in intensive care for at least 4 days. Interviews were digitally recorded, transcribed and analysed utilizing Van Manen's framework for thematic analysis. FINDINGS Making sense of their experiences in an intensive care unit appeared to be fundamental to story construction. Themes that arose were 'why am I here? ', 'filling in the gaps', 'sorting the real from the unreal' and 'searching for familiarity'. These themes describe how participants sought temporal and causal coherence in order to construct their integrated and understandable story. Families appeared to play a critical role in helping participants fill in the gaps, sorting the real from the unreal and their subsequent psychological recovery. CONCLUSIONS AND RELEVANCE TO CLINICAL PRACTICE The importance of early support from health care professionals to facilitate patients' story construction is highlighted. The study also emphasizes the role families play in supporting patients while they make sense of their experiences and the associated psychological recovery process. Further research to evaluate methods of facilitating story construction, such as nurse-led debriefing and patient diaries, is recommended. In addition, an investigation of families' perceptions of their role in assisting patients construct their story may facilitate the development of strategies by health care professionals to effectively support families in their role.
The Effect of Visual Impairment on the Strength of Children's Hip and Knee Extensors

A test of the strength of children's hip and knee extensors found that children who were congenitally blind or had low vision had weaker knee extensors than did sighted children, but that after the correction for lean body weight (LBW), these differences were not significant. The children who were blind or had low vision also had weaker hip extensors, but after LBW correction, only the blind children's hip extensors were weaker than those of the children with normal vision. The findings indicate that congenitally blind children may be prone to develop weak leg extensors because of poor body build or the constraints of blindness and that they require extensive physical intervention during infancy.
Beyond Point Clouds: Scene Understanding by Reasoning Geometry and Physics

In this paper, we present an approach for scene understanding by reasoning physical stability of objects from point cloud. We utilize a simple observation that, by human design, objects in static scenes should be stable with respect to gravity. This assumption is applicable to all scene categories and poses useful constraints for the plausible interpretations (parses) in scene understanding. Our method consists of two major steps: 1) geometric reasoning: recovering solid 3D volumetric primitives from defective point cloud, and 2) physical reasoning: grouping the unstable primitives to physically stable objects by optimizing the stability and the scene prior. We propose to use a novel disconnectivity graph (DG) to represent the energy landscape and use a Swendsen-Wang Cut (MCMC) method for optimization. In experiments, we demonstrate that the algorithm achieves substantially better performance for i) object segmentation, ii) 3D volumetric recovery of the scene, and iii) better parsing result for scene understanding in comparison to state-of-the-art methods in both public dataset and our own new dataset.
Exploration of Work and Health Disparities among Black Women Employed in Poultry Processing in the Rural South

We describe an ongoing collaboration that developed as academic investigators responded to a specific request from community members to document health effects on black women of employment in poultry-processing plants in rural North Carolina. Primary outcomes of interest are upper extremity musculoskeletal disorders and function as well as quality of life. Because of concerns of community women and the history of poor labor relations, we decided to conduct this longitudinal study in a manner that did not require involvement of the employer. To provide more detailed insights into the effects of this type of employment, the epidemiologic analyses are supplemented by ethnographic interviews. The resulting approach requires community collaboration. Community-based staff, as paid members of the research team, manage the local project office, recruit and retain participants, conduct interviews, coordinate physical assessments, and participate in outreach. Other community members assisted in the design of the data collection tools and the recruitment of longitudinal study participants and took part in the ethnographic component of the study. This presentation provides an example of one model through which academic researchers and community members can work together productively under challenging circumstances. Notable accomplishments include the recruitment and retention of a cohort of low-income rural black women, often considered hard to reach in research studies. This community-based project includes a number of elements associated with community-based participatory research.
Fuzzy Consensus and Synchronization: Theory and Application to Critical Infrastructure Protection Problems

In this paper the Distributed Consensus and Synchronization problems with fuzzy-valued initial conditions are introduced, in order to obtain a shared estimation of the state of a system based on partial and distributed observations, in the case where such a state is affected by ambiguity and/or vagueness. The Discrete-Time Fuzzy Systems (DFS) are introduced as an extension of scalar fuzzy difference equations and some conditions for their stability and representation are provided. The proposed framework is then applied in the field of Critical Infrastructures; the consensus framework is used to represent a scenario where human operators, each able to observe directly the state of a given infrastructure (or of a given area considering vast and geographically dispersed infrastructures), reach an agreement on the overall situation, whose severity is expressed in a linguistic, fuzzy way; conversely synchronization is used to provide a distributed interdependency estimation system, where an array of interdependency models is synchronized via partial observation.
Confocal Comparison of Corneal Reinnervation after Small Incision Lenticule Extraction (SMILE) and Femtosecond Laser In Situ Keratomileusis (FS-LASIK)

Purpose To evaluate corneal reinnervation, and the corresponding corneal sensitivity and keratocyte density after small incision lenticule extraction (SMILE) and femtosecond laser in situ keratomileusis (FS-LASIK). Methods In this prospective, non-randomized observational study, 18 patients (32 eyes) received SMILE surgery, and 22 patients (42 eyes) received FS-LASIK surgery to correct myopia. The corneal subbasal nerve density and microscopic morphological changes in corneal architecture were evaluated by confocal microscopy prior to surgery and at 1 week, 1 month, 3 months, and 6 months after surgery. A correlation analysis was performed between subbasal corneal nerve density and the corresponding keratocyte density and corneal sensitivity. Results The decrease in subbasal nerve density was less severe in SMILE-treated eyes than in FS-LASIK-treated eyes at 1 week (P = 0.0147), 1 month (P = 0.0243), and 3 months (P = 0.0498), but no difference was detected at the 6-month visit (P = 0.5277). The subbasal nerve density correlated positively with central corneal sensitivity in both groups (r = 0.416, P<0.0001, and r = 0.2567, P = 0.0038 for SMILE group and FS-LASIK group, respectively). The SMILE-treated eyes have a lower risk of developing peripheral empty space with epithelial cells filling in (P = 0.0005). Conclusions The decrease in subbasal nerve fiber density was less severe in the SMILE group than the FS-LASIK group in the first 3 months following the surgeries. The subbasal nerve density was correlated with central corneal sensitivity.
Monitoring of Physiological Parameters to Predict Exacerbations of Chronic Obstructive Pulmonary Disease (COPD): A Systematic Review

Introduction: The value of monitoring physiological parameters to predict chronic obstructive pulmonary disease (COPD) exacerbations is controversial. A few studies have suggested benefit from domiciliary monitoring of vital signs, and/or lung function but there is no existing systematic review. Objectives: To conduct a systematic review of the effectiveness of monitoring physiological parameters to predict COPD exacerbation. Methods: An electronic systematic search compliant with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted. The search was updated to April 6, 2016. Five databases were examined: Medical Literature Analysis and Retrieval System Online, or MEDLARS Online (Medline), Excerpta Medica dataBASE (Embase), Allied and Complementary Medicine Database (AMED), Cumulative Index of Nursing and Allied Health Literature (CINAHL) and the Cochrane clinical trials database. Results: Sixteen articles met the pre-specified inclusion criteria. Fifteen of these articules reported positive results in predicting COPD exacerbation via monitoring of physiological parameters. Nine studies showed a reduction in peripheral oxygen saturation (SpO2%) prior to exacerbation onset. Three studies for peak flow, and two studies for respiratory rate reported a significant variation prior to or at exacerbation onset. A particular challenge is accounting for baseline heterogeneity in parameters between patients. Conclusion: There is currently insufficient information on how physiological parameters vary prior to exacerbation to support routine domiciliary monitoring for the prediction of exacerbations in COPD. However, the method remains promising.
Optimal Time and Efficient Space Free Scheduling For Nested Loops

The most important issue when parallelizing sequential programs is the efficient assignment of computations into different processing elements. The most extensive, in terms of time execution, part of a program is the nested loops. Too many approaches have been devoted in parallelizing nested loops, and assigning the concurrent partitions of such a loop into different processors. In the past, all methods have been focused upon linear schedules produced by manipulating the reduced dependence graph, which in some cases achieve near optimal solutions. This paper presents a new method of free scheduling loop computations into time, based on task graph scheduling techniques. It will be shown that this schedule is optimal in terms of time, outperforming all linear schedules. Furthermore, in terms of total number of processors, the presented method includes a heuristic refinement of the free schedule which 'shuffles' computations into time, without loss of the optimal time performance, to augment the mean processor utilization. In all cases, the proposed method uses less number of processors, while preserving the optimal total execution time. The 'shuffling' of computations is based on graph theory approaches, and uses PERT problem techniques. Such scheduling is convenient for parallelizing tools (such as compilers), but has practical interest for shared memory multiprocessor systems, where the communication delay imposed by such non-regular scheduling is of no interest.
Skin glands, poison and mimicry in dendrobatid and leptodactylid amphibians

In amphibians, secretions of toxins from specialized skin poison glands play a central role in defense against predators. The production of toxic secretions is often associated with conspicuous color patterns that warn potential predators, as it is the case of many dendrobatid frogs, including Ameerega picta. This species resembles the presumably nontoxic Leptodactylus lineatus. This study tests for mimicry by studying the morphology and distribution of skin glands, components of skin secretion, and defensive behavior. Dorsal skin was studied histologically and histochemically, and skin secretions were submitted to sodium dodecyl sulfate polyacrylamide gel electrophoresis, reversed phase high performance liquid chromatography and assays for proteolytic activity. We found that poison glands in A. picta are filled with nonprotein granules that are rich in carbohydrates, while L. lineatus glands present protein granules. Accordingly, great amounts of proteins, at least some of them enzymes, were found in the poison of L. lineatus but not in that of A. picta. Both species differ greatly on profiles of gland distribution: In L. lineatus, poison glands are organized in clusters whose position coincides with colored elements of the dorsum. These regions are evidenced through a set of displays, suggesting that poison location is announced to predators through skin colors. In contrast, A. picta presents lower densities of glands, distributed homogeneously. This simpler profile suggests a rather qualitative than quantitative investment in chemical defense, in agreement with the high toxicity attributed to dendrobatids in general. Our data suggest that both species are toxic or unpalatable and transmit common warning signals to predators, which represents a case of Müllerian mimicry. J. Morphol. 2012. © 2011 Wiley Periodicals, Inc.
Bisphenol-A-induced inactivation of the p53 axis underlying deregulation of proliferation kinetics, and cell death in non-malignant human breast epithelial cells

Widespread distribution of bisphenol-A (BPA) complicates epidemiological studies of possible carcinogenic effects on the breast because there are few unexposed controls. To address this challenge, we previously developed non-cancerous human high-risk donor breast epithelial cell (HRBEC) cultures, wherein BPA exposure could be controlled experimentally. BPA consistently induced activation of the mammalian target of rapamycin (mTOR) pathway—accompanied by dose-dependent evasion of apoptosis and increased proliferation—in HRBECs from multiple donors. Here, we demonstrate key molecular changes underlying BPA-induced cellular reprogramming. In 3/3 BPA-exposed HRBEC cell lines, and in T47D breast cancer cells, proapoptotic negative regulators of the cell cycle (p53, p21WAF1 and BAX) were markedly reduced, with concomitant increases in proliferation-initiating gene products (proliferating cell nuclear antigen, cyclins, CDKs and phosphorylated pRb). However, simultaneous exposure to BPA and the polyphenol, curcumin, partially or fully reduced the spectrum of effects associated with BPA alone, including mTOR pathway proteins (AKT1, RPS6, pRPS6 and 4EBP1). BPA exposure induced an increase in the ERα (Estrogen Receptor): ERβ ratio—an effect also reversed by curcumin (analysis of variance, P < 0.02 for all test proteins). At the functional level, concurrent curcumin exposure reduced BPA-induced apoptosis evasion and rapid growth kinetics in all cell lines to varying degrees. Moreover, BPA extended the proliferation potential of 6/6 primary finite-life HRBEC cultures—another effect reduced by curcumin. Even after removal of BPA, 1/6 samples maintained continuous growth—a hallmark of cancer. We show that BPA exposure induces aberrant expression of multiple checkpoints that regulate cell survival, proliferation and apoptosis and that such changes can be effectively ameliorated.
Comparison of Clustering Methods for High-Dimensional Single-Cell Flow and Mass Cytometry Data

Recent technological developments in high-dimensional flow cytometry and mass cytometry (CyTOF) have made it possible to detect expression levels of dozens of protein markers in thousands of cells per second, allowing cell populations to be characterized in unprecedented detail. Traditional data analysis by “manual gating” can be inefficient and unreliable in these high-dimensional settings, which has led to the development of a large number of automated analysis methods. Methods designed for unsupervised analysis use specialized clustering algorithms to detect and define cell populations for further downstream analysis. Here, we have performed an up-to-date, extensible performance comparison of clustering methods for high-dimensional flow and mass cytometry data. We evaluated methods using several publicly available data sets from experiments in immunology, containing both major and rare cell populations, with cell population identities from expert manual gating as the reference standard. Several methods performed well, including FlowSOM, X-shift, PhenoGraph, Rclusterpp, and flowMeans. Among these, FlowSOM had extremely fast runtimes, making this method well-suited for interactive, exploratory analysis of large, high-dimensional data sets on a standard laptop or desktop computer. These results extend previously published comparisons by focusing on high-dimensional data and including new methods developed for CyTOF data. R scripts to reproduce all analyses are available from GitHub (https://github.com/lmweber/cytometry-clustering-comparison), and pre-processed data files are available from FlowRepository (FR-FCM-ZZPH), allowing our comparisons to be extended to include new clustering methods and reference data sets.
A novel role for VEGF in endocardial cushion formation and its potential contribution to congenital heart defects.

Normal cardiovascular development is exquisitely dependent on the correct dosage of the angiogenic growth factor and vascular morphogen vascular endothelial growth factor (VEGF). However, cardiac expression of VEGF is also robustly augmented during hypoxic insults, potentially mediating the well-established teratogenic effects of hypoxia on heart development. We report that during normal heart morphogenesis VEGF is specifically upregulated in the atrioventricular (AV) field of the heart tube soon after the onset of endocardial cushion formation (i.e. the endocardium-derived structures that build the heart septa and valves). To model hypoxia-dependent induction of VEGF in vivo, we conditionally induced VEGF expression in the myocardium using a tetracycline-regulated transgenic system. Premature induction of myocardial VEGF in E9.5 embryos to levels comparable with those induced by hypoxia prevented formation of endocardial cushions. When added to explanted embryonic AV tissue, VEGF fully inhibited endocardial-to-mesenchymal transformation. Transformation was also abrogated in AV explants subjected to experimental hypoxia but fully restored in the presence of an inhibitory soluble VEGF receptor 1 chimeric protein. Together, these results suggest a novel developmental role for VEGF as a negative regulator of endocardial-to-mesenchymal transformation that underlies the formation of endocardial cushions. Moreover, ischemia-induced VEGF may be the molecular link between hypoxia and congenital defects in heart septation.
Natural Selection in Financial Markets: Does it Work?

Can investors with incorrect beliefs survive in financial markets and have a significant impact on asset prices? My paper addresses this issue by analyzing a dynamic general equilibrium model where some investors have rational expectations, whereas others have incorrect beliefs concerning the mean growth rate of the economy. The main result is that an investor can survive if and only if he has the lowest survival index, which is a function of his belief accuracy, patience parameter, and relative risk aversion coefficient. If preferences are held constant across all investors, then those with incorrect beliefs cannot survive in the limit, although calibrations reveal that the selection process is excessively slow. However, if preferences vary across investors, even slightly, it becomes possible for an irrational investor to dominate the market even if his beliefs persistently and substantially deviate from the truth.