Miracle-dz/UniFAR-FTUs huggingface dataset:
Two-Year Outcomes and Predictors of Target Lesion Revascularization for Non-Left Main Coronary Bifurcation Lesions Following Two-Stent Strategy With 2nd-Generation Drug-Eluting Stents.

BACKGROUND Data on outcomes of non-left main coronary bifurcation lesions treated with the 2-stent strategy using 2nd-generation drug-eluting stents (DES) are insufficient.Methods and Results:The 2-year outcomes and predictors of target lesion revascularization (TLR) in 356 patients with 364 non-left main coronary bifurcation lesions treated with the 2-stent strategy using 2nd-generation DES were retrospectively evaluated. The primary outcome measure was defined as TLR. The median follow-up duration was 3.6 years (interquartile range, 2.7-4.9 years). A 2-year clinical follow-up was achieved in 99.2%. The 2-year cumulative incidence of TLR was 9.2%. Multiple stents implanted in either the main branch (adjusted odds ratio [OR] 3.01; 95% confidence interval [CI]: 1.37-6.62; P=0.006) or the side branch (adjusted OR 4.55; 95% CI: 1.99-10.4; P<0.001) and the culprit in the left anterior descending artery and its diagonal branch (adjusted OR 0.33; 95% CI: 0.15-0.75: P=0.008) were independent predictors of TLR within 2 years. CONCLUSIONS The 2-year outcomes for the 2-stent strategy using 2nd-generation DES in non-left main coronary bifurcation lesions were acceptable. Coronary bifurcation location in the left anterior descending artery and its diagonal branch is protective against TLR, whereas multiple stents implanted in either the main branch or the side branch was associated with TLR.
Molecular dynamics simulation of d-Benzedrine transmitting through molecular channels within D3R

Dex-Benzedrine (known as d-Benzedrine or SAT) acts in dopamine receptors of central nerve cell system. In clinic, SAT is used to treat a variety of diseases; meanwhile, it has dependence and addiction. In order to investigate the pharmacology and addiction mechanisms of SAT as a medicine, in this paper, we have studied the structure of D3R complex protein with SAT, and based on which, using potential mean force with umbrella samplings and the simulated phospholipid bilayer membrane (or POPC bilayer membrane), the molecular dynamics simulation was performed to obtain free energy changes upon the trajectories for SAT moving along the molecular channels within D3R. The free energy change for SAT transmitting toward the outside of cell along the functional molecular channel within D3R is 83.5 kJ mol−1. The change of free energy for SAT to permeate into the POPC bilayer membrane along the protective molecular channel within D3R is 87.7 kJ mol−1. Our previous work gave that the free energy for Levo-Benzedrine (RAT) transmitting toward the outside of cell along the functional molecular channel within D3R is 91.4 kJ mol−1, while it is 117.7 kJ mol−1 for RAT to permeate into the POPC bilayer membrane along the protective molecular channel within D3R. The values of free energy suggest that SAT relatively prefers likely to pass through the functional molecular channel within D3R for increasing the release of dopamine molecules resulting in a variety of functional effects for SAT. The obtained results show that the pharmacology and addiction mechanisms of SAT as a drug are closely related to the molecular dynamics and mechanism for SAT transmitting along molecular channels within D3R.
Fine-scale biogeography : tidal elevation strongly affects population genetic structure and demographic history in intertidal fishes

Numerous studies have demonstrated population genetic structuring in marine species, yet few have investigated the effect of vertical zonation on gene flow and population structure. Here we use three sympatric, closely related clinid species, Clinus cottoides, C. superciliosus and Muraenoclinus dor- salis, to test whether zonation on South African intertidal rocky sho res affects phylogeographic patterns. We show that the high-shore restricted species has reduced gene flow and considerably higher FST val- ues (FST = 0.9) than the mid- and low-shore species (FST < 0.14). Additionally, we provide evidence for remarkably different demographic and evolutionary histories, ranging from extreme population bottle- necks to population persistence, which are probably linked to effective population size and habitat spe- cialisation. This study further highlights the need for a multispecies approach to unravel the biological and evolutionary processes that drive extant population geneti c patterns in marine species, as even closely related species with similar life histories show highly variable results.
In Situ Growth and Chemical Composition of the Giant Kelp, Macrocystis pyrifera: Response to Temporal Changes in Ambient Nutrient Availability

Temporal variations in growth of the giant kelp Macrocystis pyrifera were examined in relation to ambient nutrient availability and chemical composition of mature blades, the primary site of nutrient and carbohydrate storage in M. pyrifera. The effect of nutrient availability on growth was well approximated by a Monod rectangular hyperbola, with growth saturating at ambient nitrate concentrations between 1 and 2 FM. M. pyrlfera was unable to generate nutrient reserves that would last beyond 30 d. Nitrogen reserves were stored as free amino acids, and generally constituted about 10 % of total tissue nitrogen. Total nitrogen content was never more than 2 . 5% of dry weight. There was no significant corrc.lation between growth and tissue nitrogen. In contrast, carbohydrate levels were negatively correlated with growth rates, tissue nitrogen content, and ambient nutrient availability. Although concentrations of nitrogen and carbohydrate reserves showed familiar variations described for other kelps, the physical environment in southern California is probably not amenable to M. pyrifera making strategic use of these reserves. Nutrient availability appears to be too low to permit accumulation of more than 30 d reserve of nitrogen, and light levels are probably never low enough to make stored carbohydrate reserves necessary for survival.
Intranuclear Actin Structure Modulates Mesenchymal Stem Cell Differentiation

Actin structure contributes to physiologic events within the nucleus to control mesenchymal stromal cell (MSC) differentiation. Continuous cytochalasin D (Cyto D) disruption of the MSC actin cytoskeleton leads to osteogenic or adipogenic differentiation, both requiring mass transfer of actin into the nucleus. Cyto D remains extranuclear, thus intranuclear actin polymerization is potentiated by actin transfer: we asked whether actin structure affects differentiation. We show that secondary actin filament branching via the Arp2/3 complex is required for osteogenesis and that preventing actin branching stimulates adipogenesis, as shown by expression profiling of osteogenic and adipogenic biomarkers and unbiased RNA‐seq analysis. Mechanistically, Cyto D activates osteoblast master regulators (e.g., Runx2, Sp7, Dlx5) and novel coregulated genes (e.g., Atoh8, Nr4a3, Slfn5). Formin‐induced primary actin filament formation is critical for Arp2/3 complex recruitment: osteogenesis is prevented by silencing of the formin mDia1, but not its paralog mDia2. Furthermore, while inhibition of actin, branching is a potent adipogenic stimulus, silencing of either mDia1 or mDia2 blocks adipogenic gene expression. We propose that mDia1, which localizes in the cytoplasm of multipotential MSCs and traffics into the nucleus after cytoskeletal disruption, joins intranuclear mDia2 to facilitate primary filament formation before mediating subsequent branching via Arp2/3 complex recruitment. The resulting intranuclear branched actin network specifies osteogenic differentiation, while actin polymerization in the absence of Arp2/3 complex‐mediated secondary branching causes adipogenic differentiation. Stem Cells 2017;35:1624–1635
Glaucoma A Novel Method to Detect Local Ganglion Cell Loss in Early Glaucoma Using Spectral-Domain Optical Coherence Tomography

METHODS. This study included 58 glaucomatous and 48 healthy eyes from Japanese subjects. Combined thickness of the ganglion cell layer and inner plexus layer (GCIPL) was measured on a macular cube scan in Cirrus HD-OCT. Average GCIPL thickness within a macular elliptical annulus and minimum GCIPL thickness on 360 spokes extending from the inner to the outer radius of the elliptical annulus were calculated. Area under the receiver operating characteristic curve (AROC) to discriminate between healthy eyes and early (mean deviation [MD], ‡ 6 dB)/advanced (MD, < 6 dB) glaucomatous were compared between parameters.
Incidence of Tuberculosis Among HIV-Positive Individuals Initiating Antiretroviral Treatment at Higher CD4 Counts in the HPTN 071 (PopART) Trial in South Africa

Introduction: Antiretroviral treatment (ART) guidelines recommend life-long ART for all HIV-positive individuals. This study evaluated tuberculosis (TB) incidence on ART in a cohort of HIV-positive individuals starting ART regardless of CD4 count in a programmatic setting at 3 clinics included in the HPTN 071 (PopART) trial in South Africa. Methods: A retrospective cohort analysis of HIV-positive individuals aged ≥18 years starting ART, between January 2014 and November 2015, was conducted. Follow-up was continued until 30 May 2016 or censored on the date of (1) incident TB, (2) loss to follow-up from HIV care or death, or (3) elective transfer out; whichever occurred first. Results: The study included 2423 individuals. Median baseline CD4 count was 328 cells/&mgr;L (interquartile range 195–468); TB incidence rate was 4.41/100 person-years (95% confidence interval [CI]: 3.62 to 5.39). The adjusted hazard ratio of incident TB was 0.27 (95% CI: 0.12 to 0.62) when comparing individuals with baseline CD4 >500 and ⩽500 cells/&mgr;L. Among individuals with baseline CD4 count >500 cells/&mgr;L, there were no incident TB cases in the first 3 months of follow-up. Adjusted hazard of incident TB was also higher among men (adjusted hazard ratio 2.16; 95% CI: 1.41 to 3.30). Conclusions: TB incidence after ART initiation was significantly lower among individuals starting ART at CD4 counts above 500 cells/&mgr;L. Scale-up of ART, regardless of CD4 count, has the potential to significantly reduce TB incidence among HIV-positive individuals. However, this needs to be combined with strengthening of other TB prevention strategies that target both HIV-positive and HIV-negative individuals.
Distracting the Mind Improves Performance: An ERP Study

Background When a second target (T2) is presented in close succession of a first target (T1), people often fail to identify T2, a phenomenon known as the attentional blink (AB). However, the AB can be reduced substantially when participants are distracted during the task, for instance by a concurrent task, without a cost for T1 performance. The goal of the current study was to investigate the electrophysiological correlates of this paradoxical effect. Methodology/Principal Findings Participants successively performed three tasks, while EEG was recorded. The first task (standard AB) consisted of identifying two target letters in a sequential stream of distractor digits. The second task (grey dots task) was similar to the first task with the addition of an irrelevant grey dot moving in the periphery, concurrent with the central stimulus stream. The third task (red dot task) was similar to the second task, except that detection of an occasional brief color change in the moving grey dot was required. AB magnitude in the latter task was significantly smaller, whereas behavioral performance in the standard and grey dots tasks did not differ. Using mixed effects models, electrophysiological activity was compared during trials in the grey dots and red dot tasks that differed in task instruction but not in perceptual input. In the red dot task, both target-related parietal brain activity associated with working memory updating (P3) as well as distractor-related occipital activity was significantly reduced. Conclusions/Significance The results support the idea that the AB might (at least partly) arise from an overinvestment of attentional resources or an overexertion of attentional control, which is reduced when a distracting secondary task is carried out. The present findings bring us a step closer in understanding why and how an AB occurs, and how these temporal restrictions in selective attention can be overcome.
Energy-Aware Preferential Attachment Model for Wireless Sensor Networks with Improved Survivability

Recent years have witnessed a dramatic increase in topology research of wireless sensor networks (WSNs) where both energy consumption and survivability need careful consideration. To balance energy consumption and ensure survivability against both random failures and deliberate attacks, we resort to complex network theory and propose an energy-aware preferential attachment (EPA) model to generate a robust topology for WSNs. In the proposed model, by taking the transmission range and energy consumption of the sensor nodes into account, we combine the characters of Erdős -Renyi (ER) model and Barabasi-Albert (BA) model in this new model and introduce tunable coefficients for balancing connectivity, energy consumption, and survivability. The correctness of our theoretic analysis is verified by simulation results. We find that the topology of WSNs built by EPA model is asymptotically power-law and can have different characters in connectivity, energy consumption, and survivability by using different coefficients. This model can significantly improve energy efficiency as well as enhance network survivability by changing coefficients according to the requirement of the real environment where WSNs deployed and therefore lead to a crucial improvement of network performance.
Identifying reports of randomized controlled trials (RCTs) via a hybrid machine learning and crowdsourcing approach

Abstract Objectives Identifying all published reports of randomized controlled trials (RCTs) is an important aim, but it requires extensive manual effort to separate RCTs from non-RCTs, even using current machine learning (ML) approaches. We aimed to make this process more efficient via a hybrid approach using both crowdsourcing and ML. Methods We trained a classifier to discriminate between citations that describe RCTs and those that do not. We then adopted a simple strategy of automatically excluding citations deemed very unlikely to be RCTs by the classifier and deferring to crowdworkers otherwise. Results Combining ML and crowdsourcing provides a highly sensitive RCT identification strategy (our estimates suggest 95%–99% recall) with substantially less effort (we observed a reduction of around 60%–80%) than relying on manual screening alone. Conclusions Hybrid crowd-ML strategies warrant further exploration for biomedical curation/annotation tasks.
Cervical cancer screening in low-resource settings: a smartphone image application as an alternative to colposcopy

Background Visual inspection after application of acetic acid (VIA) and Lugol’s iodine (VILI) is a cervical cancer (CC) screening approach that has recently been adopted in low- and middle-income countries (LMIC). Innovative technologies allow the acquisition of consecutive cervical images of VIA and VILI using a smartphone application. The aim of this study was to evaluate the quality of smartphone images in order to assess the feasibility and usability of a mobile application for CC screening in LMIC. Methods Between May and November 2015, women aged 30–65 years were recruited in a CC screening campaign in Madagascar. Human papillomavirus-positive women were invited to undergo VIA/VILI assessment. Pictures of their cervix were taken using a Samsung Galaxy S5 with an application called “Exam”, which was designed to obtain high-quality images and to classify them in the following sequence: native, VIA, VILI and posttreatment. Experts in colposcopy were asked to evaluate if the quality of the pictures was sufficient to establish the diagnosis and to assess sharpness, focus and zoom. Results The application use was simple and intuitive, and 208 pictures were automatically classified and recorded in the patient’s file. The quality was judged as adequate for diagnosis in 93.3% of cases. The interobserver agreement was κ =0.45 (0.23–0.58), corresponding to a moderate agreement on the common scale of kappa values. Conclusion This smartphone application allows the acquisition of good quality images for VIA/VILI diagnosis. The classification of images in a patient database makes them accessible to on- and off-site experts, and allows continuous clinical education. Smartphone applications may offer an alternative to colposcopy for CC screening in LMIC.
Antithrombin concentrate use in disseminated intravascular coagulation of sepsis: meta‐analyses revisited

Recently, two meta‐analyses examined the effect of antithrombin on mortality in patients with sepsis and disseminated intravascular coagulation (DIC) with diverging results. In the meta‐analysis observing no significant survival effect of antithrombin, the results of a large trial were included under the assumption that all 2314 participants of the trial had sepsis and DIC, which according to post hoc analyses was not the case. To the other meta‐analysis reporting beneficial effect, the same trial contributed only those 229 patients that had confirmed sepsis‐induced DIC. Replacing the mixed sepsis patient group with and without DIC with the group of sepsis patients with confirmed DIC provides evidence for a beneficial intervention effect of antithrombin also in the meta‐analysis that reported no beneficial effect of antithrombin on mortality. This revised result does not change the overall conclusion that the quantity and quality of evidence supporting the use of antithrombin in sepsis patients with DIC is low.
Allogeneic hematopoietic stem cell transplant overcomes the adverse survival effect of very high risk and unfavorable karyotype in myelofibrosis

The prognostic importance of genetic information in primary myelofibrosis (PMF) was recently highlighted in a study of over 1000 cytogenetically‐annotated patients; 5‐year survival rates were 8% for very high risk (VHR), 27% “unfavorable” and 45% “favorable” karyotype. The current study addresses the practice‐relevant question of whether or not allogeneic hematopoietic stem cell transplant (HCT) can overcome the detrimental survival effect of VHR or unfavorable karyotype. The study included 67 patients with PMF or secondary MF who received HCT at the Mayo Clinic and in whom pretransplant cytogenetic information was available. Dynamic international prognostic scoring system (DIPSS) risk distribution was 13% high, 66% intermediate‐2 and 21% intermediate‐1. Cytogenetic risk distribution was 11% VHR, 34% unfavorable and 55% favorable. At median post‐HCT follow‐up of 60 months for living patients (range 34‐170), 28 (42%) deaths were recorded. Five‐year survival was 62% and was not affected by VHR or unfavorable karyotype (P = .68). The salutary effect of HCT in patients with VHR or unfavorable karyotype was also apparent during analysis of a combined dataset that included a nontransplant cohort of 383 patients with PMF; multivariable analysis of the combined dataset (n = 450) resulted in HRs (95% CI) of 2.4 (1.6‐3.6) for absence of transplant, 3.3 (2.2‐4.8) for VHR karyotype, 1.6 (1.2‐2.1) for unfavorable karyotype, 2.9 (2.0‐4.2) for DIPSS high and 1.7 (1.4‐2.2) for DIPSS intermediate‐2. These observations were further confirmed by analysis of more stringently matched case‐control subset cohorts and provide the evidence for the therapeutic preference of HCT in cytogenetically high risk patients with MF.
β-Lactam Antibiotics with a High Affinity for PBP2 Act Synergistically with the FtsZ-Targeting Agent TXA707 against Methicillin-Resistant Staphylococcus aureus

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) is a multidrug-resistant pathogen that poses a significant risk to global health today. We have developed a promising new FtsZ-targeting agent (TXA707) with potent activity against MRSA isolates resistant to current standard-of-care antibiotics. We present here results that demonstrate differing extents of synergy between TXA707 and a broad range of β-lactam antibiotics (including six cephalosporins, two penicillins, and two carbapenems) against MRSA. To explore whether there is a correlation between the extent of synergy and the preferential antibacterial target of each β-lactam, we determined the binding affinities of the β-lactam antibiotics for each of the four native penicillin-binding proteins (PBPs) of S. aureus using a fluorescence anisotropy competition assay. A comparison of the resulting PBP binding affinities with our corresponding synergy results reveals that β-lactams with a high affinity for PBP2 afford the greatest degree of synergy with TXA707 against MRSA. In addition, we present fluorescence and electron microscopy studies that suggest a potential mechanism underlying the synergy between TXA707 and the β-lactam antibiotics. In this connection, our microscopy results show a disruption of septum formation in TXA707-treated MRSA cells, with a concomitant mislocalization of the PBPs from midcell to nonproductive peripheral sites. Viewed as a whole, our results indicate that PBP2-targeting β-lactam antibiotics are optimal synergistic partners with FtsZ-targeting agents for use in combination therapy of MRSA infections.
Contrast Agent–Induced High Signal Intensity in Dentate Nucleus on Unenhanced T1-Weighted Images: Comparison of Gadodiamide and Gadoxetic Acid

Objective The aim of this study was to evaluate whether an association exists between T1-signal increase in the dentate nucleus (DN) on unenhanced magnetic resonance imaging and previous administration of gadoxetic acid and gadodiamide. Materials and Methods This retrospective study was approved by the institutional review board; the requirement for informed patient consent was waived. A total of 132 patients (male-female ratio, 86:46; mean age, 68.8 ± 11.6 years) who underwent imaging between December 2000 and April 2016 were divided into 4 groups: patients with 5 or more administrations of gadoxetic acid (“gadoxetic acid ≥5 administrations” group), only 1 administration of gadoxetic acid (“gadoxetic acid 1 administration” group), no gadolinium-based contrast agent (GBCA) administration or chronic liver disease (CLD; “no GBCA administration and no CLD” group), and 5 or more administrations of gadodiamide (“gadodiamide ≥5 administrations” group). Unenhanced T1-weighted images were quantitatively analyzed by 2 radiologists. Intergroup comparison of DN-to-pons signal intensity ratios was performed by the Dunn test, with the no GBCA administration and no CLD group as control. Interobserver agreement was assessed by intraclass correlation coefficients. Results The DN-to-pons ratio of the “gadodiamide ≥5 administrations” group was significantly higher (P < 0.0001) and those of the “gadoxetic acid ≥5 administrations” and “gadoxetic acid 1 administration” groups did not differ significantly (P = 0.3912 and 1.0000, respectively) compared with the DN-to-pons ratio of the “no GBCA administration and no CLD” group. The interobserver intraclass correlation coefficient for measurement of DN-to-pons ratio was excellent (0.835; 95% confidence interval, 0.767–0.883). Conclusions Hyperintensity in the DN on unenhanced T1-weighted images is associated with previous administration of gadodiamide but not gadoxetic acid. Although the number of administrations for the 2 GBCA groups was identical, the administered dose of gadoxetic acid was only a quarter the amount of gadolinium as those with gadodiamide. This difference might influence the results of this study.