Miracle-dz/UniFAR-FTUs huggingface dataset:
A Tablet-Based Retinal Function Test in Neovascular Age-Related Macular Degeneration Eyes and At-Risk Fellow Eye

Purpose To determine the feasibility of a tablet-based application to detect changes in retinal sensitivity and correlations with underlying pathology in neovascular age-related macular degeneration (nAMD) eyes undergoing treatment and in at-risk fellow eyes. Method Participants with nAMD in at least one eye were recruited, examined, and imaged using spectral-domain optical coherence tomography (SD-OCT). Retinal sensitivity was measured within the central 5° at 12 locations using a customized test delivered on an iPad. Test points were superimposed on SD-OCT locations to investigate structure/function relationships. Results Included in the study were 53 nAMD eyes and 21 at-risk fellow eyes. In nAMD eyes, the mean retinal sensitivity was 24.1 ± 1.8 dB with reduced retinal sensitivity associated with the presence of atrophy (P < 0.01), retinal pigment epithelium (RPE) disruption (P < 0.01), and absent ellipsoid zone (EZ) (P < 0.01), but not with the presence of subretinal fluid (P = 0.94) nor intraretinal fluid (P = 0.52). In at-risk eyes, the average retinal sensitivity was 28.8 ± 0.6 dB, with reduced sensitivity significantly associated with the presence of drusen, atrophy, RPE disruption, and absent EZ (P < 0.01). Conclusion The tablet-based test of retinal sensitivity was able to be performed by an elderly cohort with nAMD. The ability to correlate differences in sensitivity with pathology is encouraging when considering using the tablet devices as a home monitoring tool with remote surveillance. Dual pathology often present with retinal fluid confounded our ability to correlate fluid with sensitivity. Translational Relevance These findings highlight the potential of tablet-based devices in performing visual function measures as a home monitoring tool with remote surveillance for the earlier detection of nAMD.
Attempts to grow human noroviruses, a sapovirus, and a bovine norovirus in vitro

Noroviruses (NoVs) and Sapoviruses (SaVs) are enteric caliciviruses that have been detected in multiple mammalian species, including humans. Currently, efficient cell culture systems have been established only for murine NoVs and porcine SaV Cowden strain. Establishment of an efficient in vitro cell culture system for other NoVs and SaVs remains challenging; however, human NoV (HuNoV) replication in 3D cultured Caco-2 cells and a clone of Caco-2 cells, C2BBe1, human enteroids and in human B cells has been reported. In this study, we tested various cells and culture conditions to grow HuNoVs and a human SaV (HuSaV) to test the possibility of the propagation in different cells and culture conditions. We also attempted to grow a bovine NoV (BoNoV) in ex vivo organ cultures. We did not observe significant RNA level increases for HuSaV and BoNoV under our test conditions. HuNoV RNA levels increased to a maximum of ~600-fold in long-term Caco-2 cells that were cultured for 1–2 months in multi-well plates and inoculated with HuNoV-positive and bacteria-free human stool suspensions using serum-free medium supplemented with the bile acid, GCDCA. However, this positive result was inconsistent. Our results demonstrated that HuNoVs, BoNoV and HuSaV largely failed to grow in vitro under our test conditions. Our purpose is to share our findings with other researchers with the goal to develop efficient, reproducible simplified and cost-effective culture systems for human and animal NoVs and SaVs in the future.
Decreased miR-320a promotes invasion and metastasis of tumor budding cells in tongue squamous cell carcinoma

We aimed to determine the specific miRNA profile of tumor budding cells and investigate the potential role of miR-320a in invasion and metastasis of tongue squamous cell carcinoma (TSCC). We collected tumor budding cells and paired central tumor samples from five TSCC specimens with laser capture microdissection and examined the specimens using a miRNA microarray. The specific miRNA signature of tumor budding cells was identified. We found that miR-320a was dramatically decreased in tumor budding cells. Knockdown of miR-320a significantly enhanced migration and invasion of TSCC cell lines. Suz12 was shown to be a direct target of miR-320a. Similar results were also observed in nude mouse models. Multivariate analysis indicated that miR-320a was an independent prognostic factor. Kaplan–Meier analysis demonstrated that decreased miR-320a and high intensity of tumor budding were correlated with poor survival rate, especially in the subgroup with high-intensity tumor budding and low expression of miR-320a. We concluded that decreased expression of miR-320a could promote invasion and metastasis of tumor budding cells by targeting Suz12 in TSCC. A combination of tumor budding and miR-320a may serve as an index to identify an aggressive sub-population of TSCC cells with high metastatic potential.
Mitochondrial flashes regulate ATP homeostasis in the heart

The maintenance of a constant ATP level (‘set-point’) is a vital homeostatic function shared by eukaryotic cells. In particular, mammalian myocardium exquisitely safeguards its ATP set-point despite 10-fold fluctuations in cardiac workload. However, the exact mechanisms underlying this regulation of ATP homeostasis remain elusive. Here we show mitochondrial flashes (mitoflashes), recently discovered dynamic activity of mitochondria, play an essential role for the auto-regulation of ATP set-point in the heart. Specifically, mitoflashes negatively regulate ATP production in isolated respiring mitochondria and, their activity waxes and wanes to counteract the ATP supply-demand imbalance caused by superfluous substrate and altered workload in cardiomyocytes. Moreover, manipulating mitoflash activity is sufficient to inversely shift the otherwise stable ATP set-point. Mechanistically, the Bcl-xL-regulated proton leakage through F1Fo-ATP synthase appears to mediate the coupling between mitoflash production and ATP set-point regulation. These findings indicate mitoflashes appear to constitute a digital auto-regulator for ATP homeostasis in the heart. DOI: http://dx.doi. org/10.7554/eLife.23908. 001
Chromosomal Rearrangements between Serotype A and D Strains in Cryptococcus neoformans

Cryptococcus neoformans is a major human pathogenic fungus that can cause meningoencephalitis in immunocompromised hosts. It contains two divergent varieties, var. grubii (serotype A) and var. neoformans (serotype D), as well as hybrids (serotype AD) between these two varieties. In this study, we investigated the extent of chromosomal rearrangements between the two varieties, estimated the effects of chromosomal rearrangements on recombination frequencies, and surveyed the potential polymorphisms of the rearrangements among natural strains of the three serotypes. Through the analyses of two sequenced genomes from strains H99 (representing var. grubii) and JEC21 (representing var. neoformans), we revealed a total of 32 unambiguous chromosome rearrangements, including five translocations, nine simple inversions, and 18 complex rearrangements. Our analyses identified that overall, rearranged regions had recombination frequencies about half of those around syntenic regions. Using a direct PCR screening strategy, we examined the potential polymorphisms of 11 rearrangements among 64 natural C. neoformans strains from five countries. We found no polymorphism within var. neoformans and very limited polymorphism within var. grubii. However, strains of serotype AD showed significant polymorphism, consistent with their hybrid origins coupled with differential loss of heterozygosity. We discuss the implications of these results on the genome structure, ecology, and evolution of C. neoformans.
Genetic Determinants of Antibody Levels in Cerebrospinal Fluid in Multiple Sclerosis: Possible Links to Endogenous Retroviruses

The pathogenesis of multiple sclerosis (MS) has not been clarified. In addition to environmental factors; genetic determinants have been implicated in the pathogenesis of MS. Furthermore, endogenous retroviruses (ERV) might play a role in MS. The presence of oligoclonal immunoglobulin in cerebrospinal fluid (CSF) is a typical feature of MS. Recently, genetic polymorphisms in loci on human chromosomes 6, 14 and 18 have been identified as major determinants of CSF antibody levels in MS. The functional relevance of these single nucleotide polymorphisms (SNPs) remains unclear and none of them is located in an open reading frame. In previous studies, we identified ERV sequences in the vicinity of MS associated SNPs. Here, we describe the identification of ERV sequences in the neighborhood of SNPs associated with CSF antibody levels. All of the identified SNPs are located in the vicinity of ERV sequences. One of these sequences has very high homology to a sequence derived from the so-called MS-associated retrovirus (MSRV). Another cluster of three ERV sequences from the immunoglobulin heavy chain locus has retained the typical organization of retroviral genomes. These observations might shed new light on a possible association between ERVs and MS pathogenesis.
Flexible Piezoelectric Sensor-Based Gait Recognition

Most motion recognition research has required tight-fitting suits for precise sensing. However, tight-suit systems have difficulty adapting to real applications, because people normally wear loose clothes. In this paper, we propose a gait recognition system with flexible piezoelectric sensors in loose clothing. The gait recognition system does not directly sense lower-body angles. It does, however, detect the transition between standing and walking. Specifically, we use the signals from the flexible sensors attached to the knee and hip parts on loose pants. We detect the periodic motion component using the discrete time Fourier series from the signal during walking. We adapt the gait detection method to a real-time patient motion and posture monitoring system. In the monitoring system, the gait recognition operates well. Finally, we test the gait recognition system with 10 subjects, for which the proposed system successfully detects walking with a success rate over 93%.
Mesenchymal stromal SB623 cell implantation mitigates nigrostriatal dopaminergic damage in a mouse model of Parkinson's disease

Regenerative medicine for the treatment of motor features in Parkinson's disease (PD) is a promising therapeutic option. Donor cells can simultaneously address multiple pathological mechanisms while responding to the needs of the host tissue. Previous studies have demonstrated that mesenchymal stromal cells (MSCs) promote recovery using various animal models of PD. SanBio Inc. has developed a novel cell type designated SB623, which are adult bone marrow‐derived MSCs transfected with Notch intracellular domain. In this preclinical study, SB623 cells protected against 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced nigrostriatal injury when transplanted unilaterally into C57BL/6 mouse striatum 3 days prior to toxin exposure. Specifically, mice with the SB623 cell transplants revealed significantly higher levels of striatal dopamine, tyrosine hydroxylase immunoreactivity and stereological nigral cell counts in the ipsilateral hemisphere vs vehicle‐treated mice following MPTP administration. Interestingly, improvement in markers of striatal dopaminergic integrity was also noted in the contralateral hemisphere. These data indicate that MSCs transplantation, specifically SB623 cells, may represent a novel therapeutic option to ameliorate damage related to PD, not only at the level of striatal terminals (i.e. the site of implantation) but also at the level of the nigral cell body. Copyright © 2015 John Wiley & Sons, Ltd.
Sibling Competition and Conspicuousness of Nestling Gapes in Altricial Birds: A Comparative Study

Background Nestlings of altricial birds capture parents' attention through conspicuous visual displays, including exposure of their gape coloration which informs parents about their level of need, competitive ability or health; information that parents use for deciding food allocation among their offspring. Thus, because nestlings compete with nest mates for parental care, nestling conspicuousness is expected to increase with level of sibling competition along bird phylogeny. Methodology/Principal Findings We test this prediction by jointly using information of brood reduction, clutch size and duration of nestling period as proxies for intensity of sibling competition, and visual models that assess detectability of nestlings by adult birds. As predicted, we found a positive association between nestling conspicuousness and intensity of brood reduction, while clutch size and duration of nestling period did not enter in the best models. Level of brood reduction was positively related with the achromatic component of nestling conspicuousness and body mass was negatively related with the chromatic component. Conclusions These associations are in agreement with the hypothesis that sibling competition for parental attention has driven the evolution of visual nestling conspicuousness in a context of parent-offspring communication in altricial birds.
Microstructure Stability and Creep Behaviour of a Cu-0.2wt.%Zr Alloy Processed by Equal-Channel Angular Pressing

A dispersion-strengthened Cu-0.2 wt. % Zr alloy was subjected to equal-channel angular pressing (ECAP) at room temperature for up to 12 passes through route BC using a die having a channel angle of 90°. The microstructural investigations were performed using both transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Tensile creep tests were conducted at temperature 673 K and at the applied stress in the range from 80 to 180 MPa. The migration of boundaries and subsequent grain growth were restricted by Cu9Zr2 precipitates. The study was performed in order to evaluate the effects of severe plastic deformation and precipitation on creep behaviour and microstructure of the pressed alloy. It was found that creep behaviour is strongly dependent on number of ECAP passes. The pressed alloy after up to 4 ECAP passes exhibited a considerable improvement in creep properties in comparison with the unpressed alloy.
Influences of organic montmorillonite on the combustion behaviors and thermal stability of polyamide 6/polystyrene blends

The nanocomposites of polyamide 6/polystyrene (PA6/PS) with different contents of organic montmorillonite (OMMT) have been obtained by melt blending. The combustion behaviors, morphology of char residues, and thermal stability of nanocomposites have been characterized by cone calorimeter tests (CCT), electron probe microanalysis, scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). The CCT results indicated that the OMMT was an efficient flame retardant (FR) in the FR-PA6/PS blends. The heat release rates, the total heat release, and carbon monoxide and carbon dioxide production of the FR nanocomposites decreased in comparison with PA6/PS blends. The SEM photographs showed that the “spongy” structure on the surface of char residues increased. In addition, the thickness and strength of char residues enhanced with the increase of OMMT content. The tight multilayer carbon silicate layer structure was formed which was conducive to FR. The TGA data indicated that OMMT greatly enhanced the thermal stability, and char residues of PA6/PS/OMMT nanocomposites gradually increased with increasing the OMMT content.
Learning to live with nephrotic syndrome: experiences of adult patients and parents of children with nephrotic syndrome.

Background People living with nephrotic syndrome (NS) need to develop an in-depth understanding of their condition in order to participate in treatment decisions, develop self-management skills and integrate illness into daily life. However, the learning needs of adult patients and parents of children with NS are unknown. We therefore explored patient and parent perspectives on learning needs related to NS as part of a larger study to develop a shared learning tool for NS. Methods Qualitative data were collected using semistructured focus groups and individual interviews with adult patients (n = 22) and parents of children with NS (n = 25). Results The complexity of NS and its treatment made decision making challenging, as patients/parents often had to assimilate information about a condition that is poorly understood. Specific informational needs related to understanding the diagnosis and treatment approaches as well as learning to manage NS were identified. Difficulty in getting accurate information often made learning challenging. The importance of learning to monitor their condition, including understanding triggers that might precipitate a relapse, was highlighted, underscoring the need for individualized approaches to ensure unique learning needs are addressed. Conclusions Our findings reveal some of the unique concerns of people with NS given its uncertain course and the limited information available specific to NS. These results suggest the need for shared communication between the patient/parents and providers to elicit the patient's/parents' understanding of NS and to support them in meeting their unique learning needs.
Effectiveness of a mobile cooperation intervention during the clinical practicum of nursing students: a parallel group randomized controlled trial protocol

AIM The aim of this study was to describe a study protocol for a study evaluating the effectiveness of a mobile cooperation intervention to improve students' competence level, self-efficacy in clinical performance and satisfaction with the clinical learning environment. BACKGROUND Nursing student-nurse teacher cooperation during the clinical practicum has a vital role in promoting the learning of students. Despite an increasing interest in using mobile technologies to improve the clinical practicum of students, there is limited robust evidence regarding their effectiveness. DESIGN A multicentre, parallel group, randomized, controlled, pragmatic, superiority trial. METHODS Second-year pre-registration nursing students who are beginning a clinical practicum will be recruited from one university of applied sciences. Eligible students will be randomly allocated to either a control group (engaging in standard cooperation) or an intervention group (engaging in mobile cooperation) for the 5-week the clinical practicum. The complex mobile cooperation intervention comprises of a mobile application-assisted, nursing student-nurse teacher cooperation and a training in the functions of the mobile application. The primary outcome is competence. The secondary outcomes include self-efficacy in clinical performance and satisfaction with the clinical learning environment. Moreover, a process evaluation will be undertaken. The ethical approval for this study was obtained in December 2014 and the study received funding in 2015. DISCUSSION The results of this study will provide robust evidence on mobile cooperation during the clinical practicum, a research topic that has not been consistently studied to date.
The Terneuzen Birth Cohort: BMI Changes between 2 and 6 Years Correlate Strongest with Adult Overweight

Background Complications of overweight amplify with age, and irreversible damage already exists in young persons. Identifying the most sensitive age interval(s) for adult overweight is relevant for primary prevention. The aim of the study was to assess the relative contribution of body mass index (BMI) changes between 0 and 18 years to adult overweight, and to identify the earliest critical growth period. Methods and Findings Data from 762 subjects in the Terneuzen Birth Cohort with an average of 21 growth measurements per subject from birth until 18 years were used. The main outcome measure was the BMI standard deviation score (SDS) at young adulthood. For each subject BMI SDS was fitted by a piecewise linear model at eight different ages and correlated to adult BMI SDS. The age intervals in between are considered critical according to three criteria, tested by respectively Students' t-tests, multiple linear regression analyses and Pearson's correlation tests. In the age intervals 4 months(m) -1 year(y), 2–6 y, 6–10 y and 10–18 y the BMI SDS change differs between adults with and without overweight (P≤0.001). The age intervals 2–6 y and 10–18 y also meet the second criterion, implying that the BMI change during this period has a predictive value for adult BMI SDS in addition to BMI SDS at the end of the period. The largest rise in correlation between estimated BMI SDS and measured adult BMI SDS occurs during the period 2–6 y (from 0.36 to 0.63), which results in a high sensitivity (0.6) and specificity (0.8) by the age of 6 y. Conclusions/Significance The age interval from 2 y to 6 y is the earliest and most critical growth period for adult overweight. Therefore, primary prevention of adult overweight seems most likely to be successful if targeted at this specific age interval. By identifying those with an upwards centile crossing between 2 and 6 years, the development towards adult overweight might be reversed.
Muscle Mitochondrial Uncoupling Dismantles Neuromuscular Junction and Triggers Distal Degeneration of Motor Neurons

Background Amyotrophic lateral sclerosis (ALS), the most frequent adult onset motor neuron disease, is associated with hypermetabolism linked to defects in muscle mitochondrial energy metabolism such as ATP depletion and increased oxygen consumption. It remains unknown whether muscle abnormalities in energy metabolism are causally involved in the destruction of neuromuscular junction (NMJ) and subsequent motor neuron degeneration during ALS. Methodology/Principal Findings We studied transgenic mice with muscular overexpression of uncoupling protein 1 (UCP1), a potent mitochondrial uncoupler, as a model of muscle restricted hypermetabolism. These animals displayed age-dependent deterioration of the NMJ that correlated with progressive signs of denervation and a mild late-onset motor neuron pathology. NMJ regeneration and functional recovery were profoundly delayed following injury of the sciatic nerve and muscle mitochondrial uncoupling exacerbated the pathology of an ALS animal model. Conclusions/Significance These findings provide the proof of principle that a muscle restricted mitochondrial defect is sufficient to generate motor neuron degeneration and suggest that therapeutic strategies targeted at muscle metabolism might prove useful for motor neuron diseases.