Miracle-dz/UniFAR-FTUs huggingface dataset:
In Vitro Synergistic Activity of Antimicrobial Agents in Combination against Clinical Isolates of Colistin-Resistant Acinetobacter baumannii

ABSTRACT Emerging resistance to colistin in clinical Acinetobacter baumannii isolates is of growing concern. Since current treatment options for these strains are extremely limited, we investigated the in vitro activities of various antimicrobial combinations against colistin-resistant A. baumannii. Nine clinical isolates (8 from bacteremia cases and 1 from a pneumonia case) of colistin-resistant A. baumannii were collected in Asan Medical Center, Seoul, South Korea, between January 2010 and December 2012. To screen for potential synergistic effects, multiple combinations of two antimicrobials among 12 commercially available agents were tested using the multiple-combination bactericidal test (MCBT). Checkerboard tests were performed to validate these results. Among the 9 colistin-resistant strains, 6 were pandrug resistant and 3 were extensively drug resistant. With MCBT, the most effective combinations were colistin-rifampin and colistin-teicoplanin; both combinations showed synergistic effect against 8 of 9 strains. Colistin-aztreonam, colistin-meropenem, and colistin-vancomycin combinations showed synergy against seven strains. Colistin was the most common constituent of antimicrobial combinations that were active against colistin-resistant A. baumannii. Checkerboard tests were then conducted in colistin-based combinations. Notably, colistin-rifampin showed synergism against all nine strains (100%). Both colistin-vancomycin and colistin-teicoplanin showed either synergy or partial synergy. Colistin combined with another β-lactam agent (aztreonam, ceftazidime, or meropenem) showed a relatively moderate effect. Colistin combined with ampicillin-sulbactam, tigecycline, amikacin, azithromycin, or trimethoprim-sulfamethoxazole demonstrated limited synergism. Using MCBT and checkerboard tests, we found that only colistin-based combinations, particularly those with rifampin, glycopeptides, or β-lactams, may confer therapeutic benefits against colistin-resistant A. baumannii.
Photochemistry of Coronene in Cosmic Water Ice Analogs at Different Concentrations

This work presents the photochemistry of ultraviolet (UV) irradiated coronene in water ices at 15 K studied using mid-infrared Fourier transform (FTIR) spectroscopy for C24H12:H2O at concentrations of (1:50), (1:150), (1:200), (1:300), and (1:400). Previous UV irradiation studies of anthracene:H2O, pyrene:H2O, and benzo[ghi]perylene:H2O ices at 15 K have shown that aromatic alcohols and ketones, as well as CO2 and H2CO, are formed at very low temperatures. Likewise, here, in addition to the coronene cation, hydroxy-, keto-, and protonated coronene (coronene H+) are formed. The rate constants for the decay of neutral coronene and for the formation of photoproducts have been derived. It is shown that Polycyclic Aromatic Hydrocarbons (PAHs) and their UV induced PAH:H2O photoproducts have mid-infrared spectroscopic signatures in the 5–8 μm region that can contribute to the interstellar ice components described by Boogert et al. as C1–C5. Our results suggest that oxygenated and hydrogenated PAHs could be in UV-irradiated regions of the interstellar medium where water-rich ices are important.
Can We Provide Low Intrarenal Pressures with Good Irrigation Flow by Decreasing the Size of Ureteral Access Sheaths?

BACKGROUND AND PURPOSE Flexible ureterorenoscopy (F-URS) plays a major role in the management of kidney stones. Ureteral access sheaths (UAS) are important tools for F-URS. In this study, we aimed to evaluate the difference in intrarenal pressures between different flexible ureteroscopes while using the same UAS and to calculate the irrigation flow variance. MATERIALS AND METHODS Eight different flexible ureteroscopes were tested with five different UAS on an artificial kidney model to measure intrarenal pressures and irrigation flow. Irrigation at 60 cmH2O pressure was performed; the pressure and the irrigation flow amount were recorded with different states of the operator channel: Free, with the laser fiber (272 μm), and with the nitinol basket (1.9F) inside. RESULTS The highest pressure recorded was 46.68 cmH2O with Wolf Boa and 9.5/11.5F Cook Medical UAS. All the ureteroscopes that fit inside the 10/12F Coloplast ReTrace provided pressures below 40 cmH2O. The inner diameter of the 10/12F Rocamed Bi-Flex is actually 11F, so intrarenal pressures were lower and irrigation flow was higher. With the 11/13F Boston Scientific Navigator HD and 12/14F Coloplast ReTrace, the pressures were very low. The irrigation flow measurements were in concordance with pressure measurements. CONCLUSION The ureteroscope sizes diminished with advancements in technology. Small-sized ureteroscopes can provide low intrarenal pressures with good irrigation flow when used with convenient small-sized access sheaths. The compatibility between the ureteroscopes and UASs should be anticipated by all endourologists and considered during F-URS. The advantages of 10/12 UASs in terms of intrarenal pressure and irrigational flow should make these access sheaths an interesting first-line choice.
Electrophysiological Evidence for the Development of a Self-Sustained Large-Scale Epileptic Network in the Kainate Mouse Model of Temporal Lobe Epilepsy

Most research on focal epilepsy focuses on mechanisms of seizure generation in the primary epileptic focus (EF). However, neurological deficits that are not directly linked to seizure activity and that may persist after focus removal are frequent. The recruitment of remote brain regions of an epileptic network (EN) is recognized as a possible cause, but a profound lack of experimental evidence exists concerning their recruitment and the type of pathological activities they exhibit. We studied the development of epileptic activities at the large-scale in male mice of the kainate model of unilateral temporal lobe epilepsy using high-density surface EEG and multiple-site intracortical recordings. We show that, along with focal spikes and fast ripples that remain localized to the injected hippocampus (i.e., the EF), a subpopulation of spikes that propagate across the brain progressively emerges even before the expression of seizures. The spatiotemporal propagation of these generalized spikes (GSs) is highly stable within and across animals, defining a large-scale EN comprising both hippocampal regions and frontal cortices. Interestingly, GSs are often concomitant with muscular twitches. In addition, while fast ripples are, as expected, highly frequent in the EF, they also emerge in remote cortical regions and in particular in frontal regions where GSs propagate. Finally, we demonstrate that these remote interictal activities are dependent on the focus in the early phase of the disease but continue to be expressed after focus silencing at later stages. Our results provide evidence that neuronal networks outside the initial focus are progressively altered during epileptogenesis. SIGNIFICANCE STATEMENT It has long been held that the epileptic focus is responsible for triggering seizures and driving interictal activities. However, focal epilepsies are associated with heterogeneous symptoms, calling into question the concept of a strictly focal disease. Using the mouse model of hippocampal sclerosis, this work demonstrates that focal epilepsy leads to the development of pathological activities specific to the epileptic condition, notably fast ripples, that appear outside of the primary epileptic focus. Whereas these activities are dependent on the focus early in the disease, focus silencing fails to control them in the chronic stage. Thus, dynamical changes specific to the epileptic condition are built up outside of the epileptic focus along with disease progression, which provides supporting evidence for network alterations in focal epilepsy.
Comparison of the CAS-POL and IOM samplers for determining the knockdown efficiencies of water sprays on float coal dust

ABSTRACT Float coal dust, generated by mining operations, is distributed throughout mine airways by ventilating air designed to purge gases and respirable dust. Float coal dust poses an explosion hazard in the event of a methane ignition. Current regulation requires the application of inert rock dust in areas subjected to float coal dust in order to mitigate the hazard. An alternate method using water sprays, which have been effective in controlling respirable dust hazards, has been proposed as a way to control float coal dust generated on longwall faces. However, the knockdown efficiency of the proposed water sprays on float coal dust needs to be verified. This study used gravimetric isokinetic Institute of Occupational Medicine (IOM) samplers alongside a real-time aerosol monitor (Cloud Aerosol Spectrometer with polarization; CAS-POL) to study the effects of spray type, operating pressure, and spray orientation on knockdown efficiencies for seven different water sprays. Because the CAS-POL has not been used to study mining dust, the CAS-POL measurements were validated with respect to the IOM samplers. This study found that the CAS-POL was able to resolve the same trends measured by the IOM samplers, while providing additional knockdown information for specific particle size ranges and locations in the test area. In addition, the CAS-POL data was not prone to the same process errors, which may occur due to the handling of the IOM filter media, and was able to provide a faster analysis of the data after testing. This study also determined that pressure was the leading design criteria influencing spray knockdown efficiency, with spray type also having some effect and orientation having little to no effect. The results of this study will be used to design future full-scale float coal dust capture tests involving multiple sprays, which will be evaluated using the CAS-POL.
End-to-End Learning of Communications Systems Without a Channel Model

The idea of end-to-end learning of communications systems through neural network (NN)-based autoencoders has the shortcoming that it requires a differentiable channel model. We present in this paper a novel learning algorithm which alleviates this problem. The algorithm iterates between supervised training of the receiver and reinforcement learning (RL)-based training of the transmitter. We demonstrate that this approach works as well as fully supervised methods on additive white Gaussian noise (AWGN) and Rayleigh block-fading (RBF) channels. Surprisingly, while our method converges slower on AWGN channels than supervised training, it converges faster on RBF channels. Our results are a first step towards learning of communications systems over any type of channel without prior assumptions.
Incidence of cardiovascular disease in a historical cohort of Danish firefighters

Objectives Firefighters are exposed to multiple cardiovascular hazards, but few epidemiological studies have addressed their cardiovascular morbidity. The objective of this study was therefore to examine the incidence of cardiovascular diseases (CVD) in Danish firefighters. Methods We used individual historical employment records on 11.691 male Danish firefighters supplied by trade unions and fire agencies. The Supplementary Pension Fund Register was used to establish two occupational reference groups (a random sample from the male employed population and military employees). Information on CVD incidence was retrieved from the nationwide Danish National Patient Registry. SIRs and Poisson regression analyses (incidence rate ratio) were used for estimation of risks, including 95% CIs. Results In comparison with the population sample, the age-adjusted and calendar time-adjusted SIR for all CVDs combined was increased in firefighters (SIR=1.10, 95% CI 1.05 to 1.15). The risk was also elevated for the most frequent outcomes, including angina pectoris (SIR=1.16, 95% CI 1.08 to 1.24), acute myocardial infarction (SIR=1.16, 95% CI 1.06 to 1.26), chronic ischaemic heart disease (SIR=1.15, 95% CI 1.06 to 1.24) and atrial fibrillation/flutter (SIR=1.25, 95% CI 1.14 to 1.36). This analysis showed the most elevated SIRs for CVD in full-time firefighters compared with part-time/volunteer firefighters. Both types of firefighters employed <15 years had an increased risk of CVD. Similar risk patterns appeared in comparisons with the military. Internal analysis supported external findings. Conclusion The risk of overall CVD, including the most frequent subtypes was modestly increased in Danish firefighters and was most elevated in full-time firefighters compared with other male employees.
Intraarterial treatment for acute ischemic stroke.

Canada to legalise physician-assisted dying In a decision noting that physicians currently legally assist patients who wish to die in Belgium, Colombia, Luxembourg, the Netherlands, Switzerland, and three US states, on February 6, Canada’s Supreme Court set the stage for Canadian doctors to soon join their ranks. Apparently, all nine judges in Canada’s Supreme Court agreed in this ruling—a rare unanimity in such a controversial subject. The current law against physician-assisted dying will remain in place for another 12 months. In the meantime, it falls to the colleges of Canadian medical professionals, the Canadian Parliament, and possibly provincial legislatures to respond with laws or regulations that respect the Constitutional rights of patients and providers. Lancet 2015;385:678.
Direct screening for chromatin status on DNA barcodes in yeast delineates the regulome of H3K79 methylation by Dot1

Given the frequent misregulation of chromatin in cancer, it is important to understand the cellular mechanisms that regulate chromatin structure. However, systematic screening for epigenetic regulators is challenging and often relies on laborious assays or indirect reporter read-outs. Here we describe a strategy, Epi-ID, to directly assess chromatin status in thousands of mutants. In Epi-ID, chromatin status on DNA barcodes is interrogated by chromatin immunoprecipitation followed by deep sequencing, allowing for quantitative comparison of many mutants in parallel. Screening of a barcoded yeast knock-out collection for regulators of histone H3K79 methylation by Dot1 identified all known regulators as well as novel players and processes. These include histone deposition, homologous recombination, and adenosine kinase, which influences the methionine cycle. Gcn5, the acetyltransferase within the SAGA complex, was found to regulate histone methylation and H2B ubiquitination. The concept of Epi-ID is widely applicable and can be readily applied to other chromatin features. DOI: http://dx.doi. org/10.7554/eLife.18919. 001
Pelvic Congestion Syndrome: Systematic Review of Treatment Success

Abstract Pelvic venous insufficiency is now a well-characterized etiology of pelvic congestion syndrome (PCS). The prevalence of CPP is 15% in females aged 18 to 50 years in the United States and up to 43.4% worldwide. In addition to individual physical, emotional, and quality-of-life implications of CPP, there are profound healthcare and socioeconomic expenses with estimated annual direct and indirect costs in the United States in excess of 39 billion dollars. PCS consists of clinical symptoms with concomitant anatomic and physiologic abnormalities originating in venous insufficiency. The etiology of PCS is diverse involving both mechanical and hormonal factors contributing to venous dilatation (>5 mm) and insufficiency. Factors affecting the diagnosis of PCS include variance of causes and clinical presentations of pelvic pain and relatively low sensitivity of noninvasive diagnostic imaging and laparoscopy to identify insufficiency compared with catheter venogram. A systematic review of the literature evaluating patient outcomes following percutaneous treatment of PCS is presented.
The WOX11–LBD16 Pathway Promotes Pluripotency Acquisition in Callus Cells During De Novo Shoot Regeneration in Tissue Culture

De novo shoot regeneration in tissue culture undergoes at least two phases. Explants are first cultured on auxin-rich callus-inducing medium (CIM) to produce a group of pluripotent cells termed callus; the callus is then transferred to cytokinin rich shoot-inducing medium (SIM) to promote the formation of shoot progenitor cells, from which adventitious shoots may differentiate. Here, we show that the Arabidopsis thaliana transcription factor gene LATERAL ORGAN BOUNDARIES DOMAIN16 (LBD16) is involved in pluripotency acquisition in callus cells. LBD16, which is activated by WUSCHEL RELATED HOMEOBOX11 (WOX11), is specifically expressed in the newly formed callus on CIM and its expression decreases quickly when callus is moved to SIM. Blocking the WOX11-LBD16 pathway results in the loss of pluripotency in callus cultured on CIM, leading to shooting defects on SIM. Further analysis showed that LBD16 may function in the establishment of the root primordium-like identity in the newly formed callus, indicating that the root primordium-like identity is the cellular nature of pluripotency in callus cells. Additionally, LBD16 promotes cell division during callus initiation. Our study clarified that the WOX11-LBD16 pathway promotes pluripotency acquisition in callus cells.
The bactericidal effect of silver nanoparticles

Nanotechnology is expected to open new avenues to fight and prevent diseases using atomic scale tailoring of materials. Rapid development of bio-nanotechnology and material research leads to a new way in combating bacteria and searching specific properties of nanomaterials. Presently, the increased resistance of bacteria against strong antibiotics offers to nanomaterial research a chance to help alleviating this problem. The present work studies the bactericidal effect of silver nanoparticles in the range of 7-50 nm on Gram-negative bacteria and Gram-positive bacteria. The colloid silver nanoparticles was
Soy Formula and Epigenetic Modifications: Analysis of Vaginal Epithelial Cells from Infant Girls in the IFED Study

Background: Early-life exposure to estrogenic compounds affects the development of the reproductive system in rodent models and humans. Soy products, which contain phytoestrogens such as genistein, are one source of exposure in infants fed soy formula, and they result in high serum concentrations. Objectives: Our goal was to determine whether soy exposure is associated with differential DNA methylation in vaginal cells from soy-fed infant girls. Methods: Using the Illumina HumanMethylation450 BeadChip, we evaluated epigenome-wide DNA methylation in vaginal cells from four soy formula–fed and six cow formula–fed girls from the Infant Feeding and Early Development (IFED) study. Using pyrosequencing we followed up the two most differentially methylated sites in 214 vaginal cell samples serially collected between birth and 9 months of age from 50 girls (28 soy formula–fed and 22 cow formula–fed). With a mouse model, we examined the effect of neonatal exposure to genistein on gene specific mRNA levels in vaginal tissue. Results: The epigenome-wide scan suggested differences in methylation between soy formula–fed and cow formula–fed infants at three CpGs in the gene proline rich 5 like (PRR5L) (p < 104). Pyrosequencing of the two feeding groups found that methylation levels progressively diverged with age, with pointwise differences becoming statistically significant after 126 days. Genistein-exposed mice showed a 50% decrease in vaginal Prr5l mRNA levels compared to controls. Conclusions: Girls fed soy formula have altered DNA methylation in vaginal cell DNA which may be associated with decreased expression of an estrogen-responsive gene. Citation: Harlid S, Adgent M, Jefferson WN, Panduri V, Umbach DM, Xu Z, Stallings VA, Williams CJ, Rogan WJ, Taylor JA. 2017. Soy formula and epigenetic modifications: analysis of vaginal epithelial cells from infant girls in the IFED study. Environ Health Perspect 125:447–452; http://dx.doi. org/10.1289/EHP428
Do clinical trials reflect reality? A systematic review of inclusion/exclusion criteria in trials of renal transplant immunosuppression

Renal transplant recipients and donors are becoming increasingly more marginal, with more expanded criteria (ECD) and donation after circulatory death (DCD) donors and older recipients. Despite this, high‐risk donors and recipients are often excluded from clinical trials, leading to uncertainty about the generalizability of findings. We extracted data regarding inclusion/exclusion criteria from 174 trials of immunosuppression in renal transplant recipients published over a 5‐year period and compared criteria with those specified in published trial registries. Frequently reported donor exclusion criteria were age (16.1%), donor type and cold ischaemic time (22.4%). Common recipient exclusion criteria included upper age limit (38.5%), high panel reactive antibody (PRA) (42.5%) and previous transplantation (39.7%). Inclusion/exclusion criteria recorded in trial registries matched those reported in the manuscript in only 6 (7.8%) trials. Of registered trials, 51 (66.2%) trials included additional criteria in the manuscript, 51 (66.2%) were missing criteria in the manuscript specified in the protocol, and in 19 (24.7%) key criteria changed from the protocol to the manuscript. Our findings suggest many recent immunosuppression trials have restrictive inclusion criteria which may not be reflective of current renal transplant populations. Discrepancies between trial protocols and published reports raise the possibility of selection bias.
A Novel RNase 3/ECP Peptide for Pseudomonas aeruginosa Biofilm Eradication That Combines Antimicrobial, Lipopolysaccharide Binding, and Cell-Agglutinating Activities

ABSTRACT Eradication of established biofilm communities of pathogenic Gram-negative species is one of the pending challenges for the development of new antimicrobial agents. In particular, Pseudomonas aeruginosa is one of the main dreaded nosocomial species, with a tendency to form organized microbial communities that offer an enhanced resistance to conventional antibiotics. We describe here an engineered antimicrobial peptide (AMP) which combines bactericidal activity with a high bacterial cell agglutination and lipopolysaccharide (LPS) affinity. The RN3(5-17P22-36) peptide is a 30-mer derived from the eosinophil cationic protein (ECP), a host defense RNase secreted by eosinophils upon infection, with a wide spectrum of antipathogen activity. The protein displays high biofilm eradication activity that is not dependent on its RNase catalytic activity, as evaluated by using an active site-defective mutant. On the other hand, the peptide encompasses both the LPS-binding and aggregation-prone regions from the parental protein, which provide the appropriate structural features for the peptide's attachment to the bacterial exopolysaccharide layer and further improved removal of established biofilms. Moreover, the peptide's high cationicity and amphipathicity promote the cell membrane destabilization action. The results are also compared side by side with other reported AMPs effective against either planktonic and/or biofilm forms of Pseudomonas aeruginosa strain PAO1. The ECP and its derived peptide are unique in combining high bactericidal potency and cell agglutination activity, achieving effective biofilm eradication at a low micromolar range. We conclude that the designed RN3(5-17P22-36) peptide is a promising lead candidate against Gram-negative biofilms.