Miracle-dz/UniFAR-FTUs huggingface dataset:
Inflammatory demyelination induces ependymal modifications concomitant to activation of adult (SVZ) stem cell proliferation

Ependymal cells (E1/E2) and ciliated B1cells confer a unique pinwheel architecture to the ventricular surface of the subventricular zone (SVZ), and their cilia act as sensors to ventricular changes during development and aging. While several studies showed that forebrain demyelination reactivates the SVZ triggering proliferation, ectopic migration, and oligodendrogenesis for myelin repair, the potential role of ciliated cells in this process was not investigated. Using conventional and lateral wall whole mount preparation immunohistochemistry in addition to electron microscopy in a forebrain‐targeted model of experimental autoimmune encephalomyelitis (tEAE), we show an early decrease in numbers of pinwheels, B1 cells, and E2 cells. These changes were transient and simultaneous to tEAE‐induced SVZ stem cell proliferation. The early drop in B1/E2 cell numbers was followed by B1/E2 cell recovery. While E1 cell division and ependymal ribbon disruption were never observed, E1 cells showed important morphological modifications reflected by their enlargement, extended cytoskeleton, and reinforced cell–cell junction complexes overtime, possibly reflecting protective mechanisms against ventricular insults. Finally, tEAE disrupted motile cilia planar cell polarity and cilia orientation in ependymal cells. Therefore, significant ventricular modifications in ciliated cells occur early in response to tEAE suggesting a role for these cells in SVZ stem cell signalling not only during development/aging but also during inflammatory demyelination. These observations may have major implications for understanding pathophysiology of and designing therapeutic approaches for inflammatory demyelinating diseases such as MS.
Examining Incentives to Promote Physical Activity Maintenance Among Hospital Employees Not Achieving 10,000 Daily Steps: A Web-Based Randomized Controlled Trial Protocol

Background The economic burden of physical inactivity in Canada is estimated at Can $6.8 billion (US $5 billion) per year. Employers bear a substantial proportion of the economic costs, as they pay more for inactive workers in health care and other organizational costs. In response, many Canadian employers offer wellness programs, though these are often underutilized. While financial health incentives have been proposed as one way of increasing participation, their longer term effects (ie postintervention effects) are not clear. Objective The objective of this paper is to outline the methodology for a randomized control trial (RCT) examining the longer term impact of an existing physical activity promotion program that is enhanced by adding guaranteed rewards (Can $1 [US $0.74] per day step goal met) in a lower active hospital employee population (less than 10,000 steps per day). Methods A 12-week, parallel-arm RCT (with a 12-week postintervention follow-up) will be employed. Employees using Change4Life (a fully automated, incentive-based wellness program) and accumulating fewer than 10,000 steps per day at baseline (weeks 1 to 2) will be randomly allocated (1:1) to standard care (wellness program, accelerometer) or an intervention group (standard care plus guaranteed incentives). All study participants will be asked to wear the accelerometer and synchronize it to Change4Life daily, although only intervention group participants will receive guaranteed incentives for reaching tailored daily step count goals (Can $1 [US $0.74] per day; weeks 3 to 12). The primary study outcome will be mean proportion of participant-days step goal reached during the postintervention follow-up period (week 24). Mean proportion of participant-days step goal reached during the intervention period (week 12) will be a secondary outcome. Results Enrollment for the study will be completed in February 2017. Data analysis will commence in September 2017. Study results are to be published in the winter of 2018. Conclusions This protocol was designed to examine the impact of guaranteed rewards on physical activity maintenance in lower active hospital employees. ClinicalTrial ClinicalTrials.gov NCT02638675; https://clinicaltrials.gov/ct2/show/NCT0 2638675 (Archived by WebCite at http://www.webcitation.org/6g4pvZvhW)
A New Zincian Greenockite Occurrence in the Saishitang Cu Skarn Deposit, Qinghai Province, Northwest China

Zn-Cd-S series minerals not only comprise industrial resources for Zn and Cd, but are also significant mineralogical indicators for hydrothermal ore-forming processes. Due to its unique formation conditions and rare occurrence, our understanding of the formation of zincian greenockite in natural systems is limited. Zincian greenockite was discovered during mineralogical studies in the Saishitang Cu skarn deposit, Qinghai Province, Northwest China. This provided an ideal opportunity to assess the occurrence and formation of zincian greenockite in skarn-type deposits. Ore minerals were observed using reflected-light microscopy, and the zincian greenockite was further analyzed using electron-probe microanalysis (EPMA) and X-ray diffraction (XRD). The zincian greenockite occurs in the bornite–chalcopyrite ores and is composed of subhedral to anhedral grains approximately 50 × 150 μm2 to 200 × 300 μm2 in size, replaces the bornite, and is replaced by native silver. Two phases (I and II) were identified based on back-scattered electron images, X-ray element-distributions maps, and EPMA data. The textural relationship indicated that Phase I was replaced by Phase II. Phase I contained high Zn (14.6 to 21.7 mol % ZnS) and low Cd (72.4 to 82.2 mol % CdS), while Phase II contained low Zn (5.6 to 9.1 mol % ZnS) and high Cd (85.4 to 89.9 mol % CdS). The zincian greenockite was formed at temperature of 300~270 °C during the transformation from a reducing environment to an oxidizing one in the late stage of the mineralization process in the Saishitang deposit.
Degraded perceptual and affective processing of racial out-groups: An electrophysiological approach

ABSTRACT Human beings process perceptual and affective information of racial out-groups in a degraded manner. Relative to racial in-group members, we lack perceptual individuation of racial out-group members and empathize their pain to a less degree. To date, however, the relationship between the deficiency of individuation and the impairment of empathy in responding to racial out-groups remains elusive. By recording event-related brain potentials in response to racial in-group and out-group faces portraying pain and neutral expressions, we simultaneously measured neural activity that underpinned individuation and empathy. Deficiency in individuating members of racial out-groups, manifesting as reduced reactivity of face-sensitive N170 in the occipitotemporal region of the brain, predicted attenuation of fronto-central empathic response to the suffering of racial out-groups. Further, the individuation bias mediated the influence of racial prejudice on racial in-group bias in empathic neural responses. These findings suggest an interplay between degraded perceptual and affective processing of racial out-groups.
Ebastine in the light of CONGA recommendations for the development of third-generation antihistamines

In 2003 a consensus group on new-generation antihistamines (CONGA) defined the characteristics required for a third-generation H1 antihistamine as there had been much controversy about this issue since the early 1990s. One of the antihistamines that had been claimed to belong to such a group is the second-generation antihistamine, ebastine. The objective of this review is to analyze the pharmacology of ebastine, in light of the CONGA recommendations for the development of new-generation antihistamines: (1) anti-inflammatory properties, (2) potency, efficacy and effectiveness, (3) lack of cardiotoxicity, (4) lack of drug interactions, (5) lack of CNS effects, and (6) pharmacological approach. Ebastine seems to have anti-inflammatory properties that help to ameliorate nasal congestion, though this has not yet been conclusively demonstrated. Its pharmacological–therapeutic profile does not differ greatly from that of other second-generation antihistamines. Its cardiac safety has been widely assessed and no cardiac toxicity has been found at therapeutic doses despite initial concerns. The risk of potentially relevant drug interactions has been investigated and ruled out. Ebastine does not produce sedation at therapeutic doses and drug interaction studies with classical CNS depressants have not demonstrated a synergistic effect. Pharmacologically, ebastine is an H1 inverse agonist. Perhaps the answer to the quest for new-generation antihistamines lies not only in H1 but in a combined approach with other histamine receptors.
Machine learning attacks on 65nm Arbiter PUFs: Accurate modeling poses strict bounds on usability

Arbiter Physically Unclonable Functions (PUFs) have been proposed as efficient hardware security primitives for generating device-unique authentication responses and cryptographic keys. However, the assumed possibility of modeling their underlying challenge-response behavior causes uncertainty about their actual applicability. In this work, we apply well-known machine learning techniques on challenge-response pairs (CRPs) from 64-stage Arbiter PUFs realized in 65nm CMOS, in order to evaluate the effectiveness of such modeling attacks on a modern silicon implementation. We show that a 90%-accurate model can be built from a training set of merely 500 CRPs, and that 5000 CRPs are sufficient to perfectly model the PUFs. To study the implications of these attacks, there is need for a new methodology to assess the security of PUFs suffering from modeling. We propose such a methodology and apply it to our machine learning results, yielding strict bounds on the usability of Arbiter PUFs. We conclude that plain 64-stage Arbiter PUFs are not secure for challenge-response authentication, and the number of extractable secret key bits is limited to at most 600.
Prognostic value of transglutaminase 2 in non-small cell lung cancer patients

Transglutaminase 2 (TG2) plays important roles in cell survival and cancer progression. In this study, we examined TG2 expression in specimen of 194 patients diagnosed with non-small cell lung cancer (NSCLC), and found that the TG2 gene expression was significantly higher in lung cancer tissues as compared to paired incisal marginal tissues or normal tissues. Our data revealed that patients with lower level of TG2 expression detected in cancer tissues had longer disease free survival and overall survival as compared to the patients with higher TG2 expression. We also found that TG2 expression level correlated to NSCLC recurrence. These results suggest a potential prognosis impact of TG2 for NSCLC patients.
Comparative Effectiveness and Safety of Standard-, Medium-, and High-Dose Daptomycin Strategies for the Treatment of Vancomycin-Resistant Enterococcal Bacteremia Among Veterans Affairs Patients

Background Vancomycin-resistant Enterococcus bloodstream infections (VRE-BSIs) are associated with significant mortality. Daptomycin exhibits concentration-dependent activity vs VRE in vitro, yet the clinical impact of higher-dose strategies remains unclear. Methods We performed a national retrospective cohort study of hospitalized Veterans Affairs patients treated with standard-dose (6 mg/kg total body weight), medium-dose (8 mg/kg total body weight), or high-dose (≥10 mg/kg total body weight) daptomycin for VRE-BSI. Patient-related, microbiological, and outcomes data were abstracted from clinical databases. The primary outcome was overall survival, evaluated by Cox regression. Secondary outcomes included 30-day mortality, time to microbiological clearance, and creatine phosphokinase (CPK) elevation. Results A total of 911 patients were included (standard dose, n = 709; medium dose, n = 142; high dose, n = 60). Compared to high-dose daptomycin, both standard-dose (hazard ratio [HR], 2.68; 95% confidence interval; [CI], 1.33-3.06; P = .002) and medium-dose (HR, 2.66; 95% CI, 1.33-3.92; P = .003) daptomycin were associated with poorer survival. After adjusting for confounders, the relationship between poorer survival and standard-dose (adjusted HR [aHR], 2.58; 95% CI, 1.27-4.88; P = .004) and medium-dose (aHR, 2.52; 95% CI, 1.27-5.00; P = .008) daptomycin persisted. Thirty-day mortality was significantly lower among high-dose daptomycin-treated patients compared with other dosing strategies (risk ratio, 0.83; 95% CI, .74-.94; P = .015). Compared with standard-dose daptomycin, both medium-dose (HR, 0.78; 95% CI, .55-.90; P = .012) and high-dose daptomycin (HR, 0.70; 95% CI, .41-.84; P = .006) were associated with significantly improved microbiological clearance. No difference in the risk of CPK elevation was observed between the treatment groups (P = .504). Conclusions High-dose daptomycin was associated with improved survival and microbiological clearance in VRE-BSI.
Standing Balance and Spatiotemporal Aspects of Gait Are Impaired Upon Nocturnal Awakening in Healthy Late Middle-Aged and Older Adults.

STUDY OBJECTIVES Nocturnal awakenings may constitute a unique risk for falls among older adults. We describe differences in gait and balance between presleep and midsleep testing, and whether changes in the lighting environment during the midsleep testing further affect gait and balance. METHODS Twenty-one healthy, late middle-aged and older (64.7 ± 8.0 y) adults participated in this repeated-measures design consisting of four overnight laboratory stays. Each night, participants completed baseline visual acuity, gait, and balance testing. After a 2-h sleep opportunity, they were awakened for 13 min into one of four lighting conditions: very dim white light (< 0.5 lux); dim white light (∼28.0 lux); dim orange light (∼28.0 lux); and white room-level light (∼200 lux). During this awakening, participants completed the same sequence of testing as at baseline. RESULTS Low-contrast visual acuity significantly decreased with decreasing illuminance conditions (F(3,45) = 98.26, p < 0.001). Our a priori hypothesis was confirmed in that variation in stride velocity and center of pressure path length were significantly worse during the mid-sleep awakening compared to presleep baseline. Lighting conditions during the awakening, however, did not influence these parameters. In exploratory analyses, we found that over one-third of the tested gait and balance parameters were significantly worse at the midsleep awakening as compared to baseline (p < 0.05), and nearly one-quarter had medium to large effect sizes (Cohen d ≥ 0.5; r ≥ 0.3). CONCLUSIONS Balance and gait are impaired during midsleep awakenings among healthy, late middle-aged and older adults. This impairment is not ameliorated by exposure to room lighting, when compared to dim lights.
Optimal Grasp Distance and Muscle Loads for People With Rheumatoid Arthritis Using Carpometacarpal and Metacarpophalangeal Immobilization Orthoses

OBJECTIVES. The objectives of this study were to investigate whether people with rheumatoid arthritis (RA) require greater muscle loads to equal the grip strength of healthy adults and to find the optimal grip distance for people with RA using carpometacarpal and metacarpophalangeal immobilization orthoses as measured by electromyography of the forearm muscles. METHOD. A 2 × 2 (Group × Orthosis) experiment and a 2 × 3 (Orthosis × Grasp Distance) factorial were conducted. Grip strength and muscle load were measured. RESULTS. Grip strength was significantly lower, and muscle load was greater, in 18 participants with RA than in 18 healthy adults. No effect of orthosis use on grip strength and muscle load was found. Muscle load was lower for the 42.25-mm diameter dynamometer handle than for handles with larger diameters. CONCLUSION. People with RA require more muscle load than healthy adults to produce the same exertion, and 42.25 mm is recommended for people with RA as the optimal grasp distance.
Veterinary Immunology and Immunopathology Lipopolysaccharide-induced neutrophil extracellular trap formation in canine neutrophils is dependent on histone H3 citrullination by peptidylarginine deiminase

Neutrophils release neutrophil extracellular traps (NETs), which are extracellular chromatin decorated with histones and antimicrobial proteins. Although known for antimicrobial properties, overzealous production of NETs (NETosis) may lead to cytotoxicity and multiple organ failure in sepsis. Pathogen-induced NETosis has been extensively studied in mice but its importance in dogs remains largely unknown. This study sought to characterize in vitro NETosis induced by E.coli LPS, including assessing the role of peptidylarginine deiminase (PAD) in canine NETosis. Neutrophils (1 × 10 6 cells/ml) from healthy dogs were isolated and treated with 100 μ g/ml LPS, 100 nM phorbol 12-myristate 13-acetate (PMA), or bu ﬀ er for either 90 or 180 min. NETs were assessed using ﬂ uorescence microscopy of living neutrophils and immuno ﬂ uorescent microscopy. Supernatant and cellular debris were puri ﬁ ed and cell-free DNA was quanti ﬁ ed by spectrophotometry. The role of PAD was assessed by treating LPS- and PMA-activated neutrophils with 50, 100 or 200 μ M of the PAD inhibitor, Cl-amidine. In vitro NETosis was characterized by co-localization of cell-free DNA, citrullinated histone H3, and myeloperoxidase. LPS stimulation resulted in intracellular citrullination of histone H3. Compared to PMA chemically-induced NETosis, LPS resulted in smaller NETs with less extracellular citrullinated histone H3. Cl- amidine decreased citrullination of histones and NET production in either LPS- or PMA-stimulated neutrophils demonstrating that neutrophil PAD is essential for these cellular processes.
Time Trials Versus Time-to-Exhaustion Tests: Effects on Critical Power, W', and Oxygen-Uptake Kinetics.

PURPOSE To investigate single-day time-to-exhaustion (TTE) and time-trial (TT) -based laboratory tests values of critical power (CP), W prime (W'), and respective oxygen-uptake-kinetic responses. METHODS Twelve cyclists performed a maximal ramp test followed by 3 TTE and 3 TT efforts interspersed by 60 min recovery between efforts. Oxygen uptake ( V ˙ O 2 ) was measured during all trials. The mean response time was calculated as a description of the overall [Formula: see text]-kinetic response from the onset to 2 min of exercise. RESULTS TTE-determined CP was 279 ± 52 W, and TT-determined CP was 276 ± 50 W (P = .237). Values of W' were 14.3 ± 3.4 kJ (TTE W') and 16.5 ± 4.2 kJ (TT W') (P = .028). While a high level of agreement (-12 to 17 W) and a low prediction error of 2.7% were established for CP, for W' limits of agreements were markedly lower (-8 to 3.7 kJ), with a prediction error of 18.8%. The mean standard error for TTE CP values was significantly higher than that for TT CP values (2.4% ± 1.9% vs 1.2% ± 0.7% W). The standard errors for TTE W' and TT W' were 11.2% ± 8.1% and 5.6% ± 3.6%, respectively. The [Formula: see text] response was significantly faster during TT (~22 s) than TTE (~28 s). CONCLUSIONS The TT protocol with a 60-min recovery period offers a valid, time-saving, and less error-filled alternative to conventional and more recent testing methods. Results, however, cannot be transferred to W'.
Risk for hypertension crosses generations in the community: a multi-generational cohort study

Aims Parental hypertension is known to predict high blood pressure (BP) in children. However, the extent to which risk for hypertension is conferred across multiple generations, notwithstanding the impact of environmental factors, is unclear. Our objective was therefore to evaluate the degree to which risk for hypertension extends across multiple generations of individuals in the community. Methods and results We studied three generations of Framingham Heart Study participants with standardized blood pressure measurements performed at serial examinations spanning 5 decades (1948 through 2005): First Generation (n = 1809), Second Generation (n = 2631), and Third Generation (n = 3608, mean age 39 years, 53% women). To capture a more precise estimate of conferrable risk, we defined early-onset hypertension (age <55 years) as the primary exposure. In multinomial logistic regression models adjusting for standard risk factors as well as physical activity and daily intake of dietary sodium, risk for hypertension in the Third Generation was conferred simultaneously by presence of early-onset hypertension in parents [OR 2.10 (95% CI, 1.66-2.67), P < 0.001] as well as in grandparents [OR 1.33 (95% CI, 1.12-1.58), P < 0.01]. Conclusion Early-onset hypertension in grandparents raises the risk for hypertension in grandchildren, even after adjusting for early-onset hypertension in parents and lifestyle factors. These results suggest that a substantial familial predisposition for hypertension exists, and this predisposition is not identical when assessed from one generation to the next. Additional studies are needed to elucidate the mechanisms underlying transgenerational risk for hypertension and its clinical implications.
Sever: A Robust Meta-Algorithm for Stochastic Optimization

In high dimensions, most machine learning methods are brittle to even a small fraction of structured outliers. To address this, we introduce a new meta-algorithm that can take in a base learner such as least squares or stochastic gradient descent, and harden the learner to be resistant to outliers. Our method, Sever, possesses strong theoretical guarantees yet is also highly scalable -- beyond running the base learner itself, it only requires computing the top singular vector of a certain $n \times d$ matrix. We apply Sever on a drug design dataset and a spam classification dataset, and find that in both cases it has substantially greater robustness than several baselines. On the spam dataset, with $1\%$ corruptions, we achieved $7.4\%$ test error, compared to $13.4\%-20.5\%$ for the baselines, and $3\%$ error on the uncorrupted dataset. Similarly, on the drug design dataset, with $10\%$ corruptions, we achieved $1.42$ mean-squared error test error, compared to $1.51$-$2.33$ for the baselines, and $1.23$ error on the uncorrupted dataset.
The winner takes it all: Event-related brain potentials reveal enhanced motivated attention toward athletes’ nonverbal signals of leading

ABSTRACT Observers of sports can reliably estimate who is leading or trailing based on nonverbal cues. Most likely, this is due to an adaptive mechanism of detecting motivationally relevant signals such as high status, superiority, and dominance. We reasoned that the relevance of leading athletes should lead to a sustained attentional prioritization. To test this idea, we recorded electroencephalography while 45 participants saw brief stills of athletes and estimated whether they were leading or trailing. Based on these recordings, we assessed event-related potentials and focused on the late positive complex (LPC), a well-established signature of controlled attention to motivationally relevant visual stimuli. Confirming our expectation, we found that LPC amplitude was significantly enhanced for leading as compared to trailing athletes. Moreover, this modulation was significantly related to behavioral performance on the score-estimation task. The present data suggest that subtle cues related to athletic supremacy are reliably differentiated in the human brain, involving a strong attentional orienting toward leading athletes. This mechanism might be part of an adaptive cognitive strategy that guides human social behavior.