Miracle-dz/UniFAR-FTUs huggingface dataset:
Digital Image Analysis of BAP-1 Accurately Predicts Uveal Melanoma Metastasis

Purpose Reduced nuclear expression of BRCA1 associated protein 1 (BAP-1) is associated with a high risk for metastasis in uveal melanoma. Manual assessment of the expression level may face issues with interobserver reproducibility. This could be improved with digital image analysis (DIA). Methods Thirty enucleated eyes with uveal melanoma from the Emory Eye Center (Atlanta, GA; years 2009–2017) were included and stained with BAP-1. Retrospective data on patient and tumor characteristics were retrieved. Patients were randomized to a training or validation cohort. Their tumor sections were digitally scanned and scored for percentage of BAP-1–positive cells with the QuPath Bioimage analysis software. Results Interobserver concordance was 75% (Cohen's κ 0.52) with manual BAP-1 scoring and 88% to 94% with DIA (Cohen's κ 0.75–0.88). Positive and negative predictive values for metastasis were 90% and 100% with DIA, 80% and 86% with manual scoring, and 78% and 88% with gene expression class 2. In binary logistic regression, manual and DIA of BAP-1 and gene expression class 2 were associated with metastasis, but none retained significance in multiple regression. Metastasis-free survival was significantly shorter with low BAP-1 expression as defined by DIA (log-rank P = 0.02), but not with manual scoring (log-rank P = 0.36) or with gene expression class 2 (log-rank P = 0.17). Conclusions DIA of BAP-1 is a competitive alternative to manual assessment as well as gene expression profiling in prognostication of enucleated specimens with uveal melanoma. Translational Relevance The emerging scope for automatization of qualified diagnostic tasks is applied to uveal melanoma.
On-mouse projector: peephole interaction using a mouse with a projector

In this paper, we propose a system that combines a mouse with a projector and that allows users to perform peephole interaction, which enables stable operation in a wide workspace. In our prototype system, a mobile projector is attached above a mouse and projects part of the workspace on the plane in front of the mouse. The user can change the area he/she wishes to see by moving the mouse and can perform operations in a virtually extended workspace. We conducted an experiment to compare the methods of changing the displayed region and the cursor position when the mouse moves. Our results show that the method with the highest ratio of view transition to mouse movement, in which the workspace is not fixed to the real space, outperformed the other methods and was also highly evaluated by participants. Furthermore, the task completion time decreased with repeating trials with fixed target positions, which suggests that spatial memory is helpful even when the workspace is not fixed to the real space.
Cost Management in the Public Sector: Legitimation Behaviour and Relevant Decision Making

This paper presents a case study where a cost management project was implemented using action research methodology at two Finnish organizations working in a purchaser–provider relationship. While the study demonstrates the efficiency-seeking motive behind the implementation of the management accounting tool, subsequent investigation found that tool remained partly unused despite showing its potential relevance for practice through user involvement. However, this does not necessarily signal legitimation-seeking behaviour. Reasons for not using some parts of the tool point to an overestimation of the functionality and an underestimation of implementation problems during the design process. The case also highlights the relationship between relevance and decision making.
Advances in Human B19 Erythrovirus Biology

ABSTRACT Since its discovery, human parvovirus B19 (B19V), now termed erythrovirus, has been associated with many clinical situations (neurological and myocardium infections, persistent B19V DNAemia) in addition to the prototype clinical manifestations, i.e., erythema infectiosum and erythroblastopenia crisis. In 2002, the use of new molecular tools led to the characterization of three different genotypes of human B19 erythrovirus. Although the genomic organization is conserved, the geographic distribution of the different genotypes varies worldwide, and the nucleotidic divergences can impact the molecular diagnosis of B19 virus infection. The cell cycle of the virus remains partially unresolved; however, recent studies have shed light on the mechanism of cell entry and the interactions of B19V proteins with apoptosis pathways.
Effects of Nucleus Basalis Lesions on the Muscarinic and Nicotinic Modulation of [3H] Acetylcholine Release in the Rat Cerebral Cortex

Presynaptic muscarinic and nicotinic receptors in the cerebral cortex reportedly inhibit and increase acetyl‐choline (ACh) release, respectively. In this study, we investigated whether these receptors reside on cholinergic nerve terminals projecting to the cerebral cortex from the nucleus basalis magnocellularis (nbm). Adult male rats received unilateral infusions of ibotenic acid (5 μg/1 μl) in the nbm. Two weeks later, cerebral cortical cholinergic markers (choline acetyltransferase activity, high‐affinity choline uptake, and coupled ACh synthesis) were significantly reduced in synaptosomes prepared from the lesioned hemispheres compared to contralateral controls. The depolarization‐induced release of [3H]ACh from these synaptosomes was also reduced in the lesioned hemispheres, reflecting the reduced synthesis of transmitter. However, the nbm lesions had no effect on the inhibition of release induced by 100 μM oxotremorine. Synaptosomal [3H]ACh release was not altered by nicotine or the nicotinic agonists anabaseine and 2‐(3‐pyridyl)‐l, 4, 5, 6‐tetrahydropyrimdine. Nicotine (10–100 μM) did increase [3H]ACh release in control and lesioned hemispheres in cortical minces, but to a similar extent. These results suggest that neither muscarinic nor nicotinic receptors modulating ACh release reside on nbm‐cholinergic terminals.
Naturally Occurring Resistance-Associated Variants to Hepatitis C Virus Direct-Acting Antiviral Agents in Treatment-Naive HCV Genotype 6a-Infected Patients

Background and Objective The direct-acting antiviral agents (DAAs) antiviral therapy has drastically improved the prognosis of hepatitis C virus (HCV) patients. However, the viral drug resistance-associated variants (RAVs) can limit the efficacy of DAAs. For the HCV-6a is not the predominant prevalent genotype; the data on the prevalence of naturally occurring RAVs in it is scarce. Our study aims to assess the prevalence of RAVs in treatment-naive HCV-6a patients. Methods Nested PCR assays were performed on 95 HCV-6a patients to amplify HCV viral regions of NS3, NS5A, and NS5B. Results In NS3/4A region, we detected Q80K in 95.5% isolates (84/88) and D168E in 2.3% isolates (2/88). In NS5A region, we detected Q30R in 93.2% isolates (82/88), L31M in 4.6% isolates (4/88), and H58P in 6.8% isolates (6/88). In NS5B region, we detected A15G in 2.3% isolates (2/88), S96T in 1.1% isolates (1/88), and S282T in 20.7% isolates (17/88) and we detected I482L in 100% isolates (4/4), V494A in 50% isolates (2/4), and V499A in 100% isolates (4/4). Conclusions RAVs to DAAs preexist in treatment-naive HCV-6a patients. Further studies should address the issue of the impact of RAVs in response to DAA therapies for HCV-6a patients.
Stereoselective uptake of atenolol into storage granules isolated from PC12 cells.

Atenolol has been shown to be stored and secreted from PC12 cells by calcium-dependent and stereoselective mechanisms. The present study was designed to determine if the cytoplasmic amine storage granule was the site for storage and release of atenolol and if the drug was, in fact, an enantiomeric selective substrate for the vesicular amine transport protein. Uptake of racemic [3H]atenolol and (-)-[3H]norepinephrine was studied in a vesicular preparation of storage granules isolated from PC12 cells. Uptake of both molecules was found to be ATP-dependent (80%) and to reach steady state in approximately 10 to 15 min. Uptake and storage was inhibited (95%) by either reserpine, an inhibitor of the vesicular amine carrier, or by nigericin which dissipates the proton gradient across the membrane. Uptake of neither compound was inhibited by desipramine, an inhibitor of uptake 1, or oligomycin, an inhibitor of mitochondrial adenosine triphosphatase. Furthermore, uptake of the (-)-enantiomer of atenolol was found to be approximately 5-fold greater than the (+)-enantiomer. Kinetic studies revealed a Km of 184 microM for (+/-)-atenolol and 79 microM for (-)-norepinephrine and Vmax values of 750 and 503 pmol/min/mg of protein for atenolol and norepinephrine, respectively. The interaction of the two compounds with the transport process was found to be kinetically competitive. In separate experiments, atenolol was also found to be transported stereoselectively into bovine adrenal chromaffin granule ghosts and to be ATP dependent (85%) and reserpine sensitive (44%). (ABSTRACT TRUNCATED AT 250 WORDS)
Signal processing transmitter for wireless implantable neural recording systems

Thanks to the fast growth of the technological sector and more precisely of the biomedical electronics, a total improvement of the living conditions of the human being and an appreciable increase of its longevity were carried out. This development allows creating implantable electronic devices for recording neural signals. This paper lies within the scope of acquisition and wireless transmission of these signals. We have developed a multichannel wireless implantable transmitter for digital neural signal processing after simultaneous recording through 16 channels. The simulation results attained are sufficient in terms of integrated design, low power consumption, low noise and high speed. These results confirm that this system is functional and has the aptitude to be extended to 32 channels and even 64.
Phenotypic and Genotypic Characterization of Pyrazinamide Resistance among Multidrug-Resistant Mycobacterium tuberculosis Isolates in Zhejiang, China

ABSTRACT To explore the phenotypic and genotypic characterization of pyrazinamide (PZA) resistance among multidrug-resistant Mycobacterium tuberculosis (MDR-TB) isolates in Zhejiang province, a total of 274 MDR-TB isolates were collected. Drug susceptibility testing and spoligotyping were performed on all clinical isolates. In addition, the mutated features of PZA-resistant loci, including pncA and rpsA, were also analyzed by DNA sequencing. Our results showed that the prevalence of PZA resistance among MDR-TB strains in Zhejiang province was 43.07% and that PZA resistance was associated with concomitant resistance to streptomycin. The majority of PZA-resistant MDR-TB isolates belonged to the Beijing family. Mutations within pncA, not rpsA, constituted the primary mechanism of PZA resistance. Among 118 PZA-resistant isolates, 53 different mutations were observed in pncA, and most of them were point mutations. Compared with the phenotypic data, DNA sequencing of pncA has sensitivity and specificity of 77.97% and 96.79%, respectively. Analysis of pncA provided a robust tool for rapid detection of PZA drug resistance.
Music emotion recognition based on two-level support vector classification

Music emotion recognition (MER) detects the inherently emotional expression of people for a music clip. MER is helpful in music understanding, music retrieval, and other music-related applications. As volume of online musical contents expands rapidly in recent years, demands for retrieval by emotion have been emerging lately. Determining the emotional content of music computationally is an interdisciplinary research involving not only signal processing and machine learning, but the understanding of auditory perception, psychology, cognitive science, and musicology. One of the challenges in evaluating automatic music emotion detection is that there is currently no well-developed emotion model for music emotion description. Moreover, owing to the low transparency of the acoustic feature based music emotion recognizer, it is difficult to interpret data generated by this mechanism. In this study, a two-level classification system based on both music genre and music feature pre-described by the domain knowledge is proposed. This framework has the advantage of utilizing the most suitable acoustic information. Experiments will be conducted via the measure of the correlation between diverse emotional expressions and various musical cues. To verify the performance of overall system, the proposal model will also be evaluated based on the consistency between music features and ground-truth emotions.
UBE2L6/UBCH8 and ISG15 attenuate autophagy in esophageal cancer cells

Esophageal cancer remains a poor prognosis cancer due to advanced stage of presentation and drug resistant disease. To understand the molecular mechanisms influencing response to chemotherapy, we examined genes that are differentially expressed between drug sensitive, apoptosis competent esophageal cancer cells (OE21, OE33, FLO-1) and those which are more resistant and do not exhibit apoptosis (KYSE450 and OE19). Members of the ISG15 (ubiquitin-like) protein modification pathway, including UBE2L6 and ISG15, were found to be more highly expressed in the drug sensitive cell lines. In this study, we evaluated the contribution of these proteins to the response of drug sensitive cells. Depletion of UBE2L6 or ISG15 with siRNA did not influence caspase-3 activation or nuclear fragmentation following treatment with 5-fluorouracil (5-FU). We assessed autophagy by analysis of LC3II expression and Cyto-ID staining. Depletion of either ISG15 or UBE2L6 resulted in enhanced endogenous autophagic flux. An increase in autophagic flux was also observed following treatment with cytotoxic drugs (5-FU, rapamycin). In ISG15 depleted cells, this increase in autophagy was associated with improved recovery of drug treated cells. In contrast, UBE2L6 depleted cells, did not show enhanced recovery. UBE2L6 may therefore influence additional targets that limit the pro-survival effect of ISG15 depletion. These data identify UBE2L6 and ISG15 as novel inhibitors of autophagy, with the potential to influence chemosensitivity in esophageal cancer cells.
Lactic acidosis following convulsions

Lactic acidosis is a common cause of metabolic acidosis and is usually connected with high mortality. However, changes in the level of lactate and pH can also be seen after generalized epileptic attacks, due to local muscle hypoxia during the seizures. Although these changes can be quite marked, the condition is self‐limiting and usually does not call for any specific treatment. We report five cases of lactic acidosis following convulsions from our centre.
An Investigation into Performance Rankings of the Omega Ratio vs the Sharpe Ratio Applied to South African General Equity Unit Trusts

Abstract The Omega function is a relatively newly developed performance measure, falling in the class of downside risk measures. This measure does not make any assumptions regarding the return distributions evaluated, but incorporates the actual return distribution in the calculation. The sensitivity of this measure to simulated changes within the class of stable distributions was investigated, within a range of parameters that was representative of the South African investment environment. The Omega and Sharpe ratios calculated for these distributions were ranked and compared. Even though the rankings were largely similar, discrepancies did occur. On investigation it was found that these discrepancies were caused by the inability of the Sharpe measure to differentiate between increased volatility caused by higher probability weighted gains (or positive skewness) and losses, as the Sharpe ratio penalises funds for volatility. The simulated tests were extended to various distributions, which have different risk profiles and distribution shapes, and ranked. A higher incidence of ranking differences occurred due to the inability of the Sharpe ratio to differentiate between gains and losses, or to correctly account for the risk of positively skewed distributions. Negative Sharpe ratios, caused by the average realized returns being exceeded by the threshold (target) rate, resulted in incorrect rankings. Normally, practical performance evaluation is not initiated with a detailed analysis of the return distributions in order to determine which performance measure is more appropriate. The Omega measure, however, incorporates the distribution into the calculation, which is not the case with the Sharpe measure. If the distributions are normal, the Omega measure gives exactly the same result as the Sharpe measure. However, where return distributions diverge from normality, the Omega measure will incorporate the divergence, whilst the Sharpe measure fails in this regard. The result is a ranking of performance that is more relevant to investor decision-making.
Modeling large-scale dynamic processes in the cell: polarization, waves, and division

Abstract The past decade has witnessed significant developments in molecular biology techniques, fluorescent labeling, and super-resolution microscopy, and together these advances have vastly increased our quantitative understanding of the cell. This detailed knowledge has concomitantly opened the door for biophysical modeling on a cellular scale. There have been comprehensive models produced describing many processes such as motility, transport, gene regulation, and chemotaxis. However, in this review we focus on a specific set of phenomena, namely cell polarization, F-actin waves, and cytokinesis. In each case, we compare and contrast various published models, highlight the relevant aspects of the biology, and provide a sense of the direction in which the field is moving.
Test execution checkpointing for web applications

Test isolation is a prerequisite for the correct execution of test suites on web applications. We present Test Execution Checkpointing, a method for efficient test isolation. Our method instruments web applications to support checkpointing and exploits this support to isolate and optimize tests. We have implemented and evaluated this method on five popular PHP web applications. The results show that our method not only provides test isolation essentially for free, it also reduces testing time by 44% on average.
Chrono and clinical pharmacokinetic study of tacrolimus in continuous intravenous administration

Abstract Background: The circadian variation of clinical pharmacokinetics of tacrolimus in kidney transplant recipients receiving continuous intravenous administration has not been clarified. The aim of this study was to evaluate the circadian variation of this drug in continuous intravenous administration, with regard to the dosing scheme for conversion from intravenous to oral therapy.
Disparate survival and risk of secondary non-Hodgkin lymphoma in histologic subtypes of Hodgkin lymphoma: a population-based study

Abstract We compared survival outcomes and rates of secondary non-Hodgkin lymphoma (NHL) in 28 323 patients with nodular lymphocyte predominant (NLPHL) and classical Hodgkin lymphoma (HL) from the Surveillance, Epidemiology and End Results database, diagnosed between 1995 and 2010. In a multivariate analysis NLPHL demonstrated a significantly better relative survival (5-year risk of lymphoma-related death 5.7%, hazard ratio [HR] 0.46, p < 0.0001) than the reference nodular sclerosis (NSHL) subtype (5-year risk 12.7%). Lymphocyte-rich classical HL had outcomes comparable to NSHL (5-year risk 14.3%, HR 0.84, p = 0.11). Exceptionally poor outcomes were observed in lymphocyte depleted HL (5-year risk 48.8%, HR 2.26, p < 0.0001). The risk of secondary NHL was increased in NLPHL (HR 2.81, p < 0.001) and lymphocyte-rich classical HL (HR 2.27, p = 0.002), but not in other subtypes compared with NSHL. In conclusion, the histologic classification retains a significant prognostic value in HL and the disparities between the subtypes warrant customized treatment and surveillance strategies.
Progressive dysfunction of the retinal pigment epithelium and retina due to increased VEGF‐A levels

Patients with nonexudative (“dry”) age‐related macular degeneration (AMD) frequently also develop neovascular (“wet”) AMD, suggesting a common pathomechanism. Increased vascular endothelial growth factor A (VEGF‐A) has been implicated in the pathogenesis of choroidal neovascularization (CNV) in neovascular AMD, while its role in nonexudative AMD that manifests with progressive retinal pigment epithelium (RPE) and photoreceptor degeneration is not well defined. Mice with overall increased VEGF‐A levels develop progressive morphological features of both forms of AMD, suggesting that an increase in VEGF‐A has a direct age‐dependent adverse effect on RPE and photoreceptor function independently of its CNV‐promoting proangiogenic effect. Here we provide evidence for this hypothesis and show that morphological RPE abnormalities and retinal thinning in mice with increased VEGF‐A levels correlate with progressive age‐dependent attenuation of visual function with abnormal electroretinograms and reduced retinal rhodopsin levels. Retinoid profiling revealed a progressive reduction of 11‐cis and all‐trans retinal in the retinas of these mice, consistent with an impaired retinoid transport between the RPE and photoreceptors. These findings suggest that increased VEGF‐A leads to an age‐dependent RPE and retinal dysfunction that occurs also at sites where no CNV lesions form. The data support a central role of increased VEGF‐A not only in the pathogenesis of neovascular but also of nonexudative AMD. —Ablonczy, Z. , Dahrouj, M. , Marneros, A. G. Progressive dysfunction of the retinal pigment epithelium and retina due to increased VEGF‐A levels. FASEB J. 28, 2369–2379 (2014). www.fasebj. org
Heatwave Early Warning Systems and Adaptation Advice to Reduce Human Health Consequences of Heatwaves

Introduction: With climate change, there has been an increase in the frequency, intensity and duration of heatwave events. In response to the devastating mortality and morbidity of recent heatwave events, many countries have introduced heatwave early warning systems (HEWS). HEWS are designed to reduce the avoidable human health consequences of heatwaves through timely notification of prevention measures to vulnerable populations. Objective: To identify the key characteristics of HEWS in European countries to help inform modification of current, and development of, new systems and plans. Methods: We searched the internet to identify HEWS policy or government documents for 33 European countries and requested information from relevant organizations. We translated the HEWS documents and extracted details on the trigger indicators, thresholds for action, notification strategies, message intermediaries, communication and dissemination strategies, prevention strategies recommended and specified target audiences. Findings and Conclusions: Twelve European countries have HEWS. Although there are many similarities among the HEWS, there also are differences in key characteristics that could inform improvements in heatwave early warning plans.