Miracle-dz/UniFAR-FTUs huggingface dataset:
Risk Factors for Acquisition of Fluoroquinolone or Aminoglycoside Resistance in Addition to Carbapenem Resistance in Pseudomonas Aeruginosa

Background: Carbapenems, fluoroquinolones (FQs), and aminoglycosides (AGs) are key drugs for treating Pseudomonas aeruginosa infections, and accumulation of drug resistances make antibiotic therapy difficult. Methods: We evaluated 169 patients with imipenem (IPM)-resistant P. aeruginosa and compared patient background and microbiological characteristics between groups with or without FQ resistance. Similar analyses were performed for AG. Results: Of the 169 IPM-resistant strains, 39.1% showed resistance to FQs and 7.1% to AGs. The frequency of exposure to FQs within 90 days previously was higher in the group with FQ resistance (45.5%) than in the group without FQ resistance (13.6%). Similarly, 33.3% of patients in the group with AG resistance had been previously administered AGs, higher than the 7.6% of patients without AG resistance. Frequencies of metallo-β-lactamase (MBL) production were higher in the group with FQ or AG resistance (16.7% or 33.3%) than in the group without FQ or AG resistance (2.9% or 6.4%). Multivariate analyses showed exposures to FQs or AGs were related to the respective resistances. MBL production was a common factor for resistance to FQs or AGs, in addition to IPM-resistant P. aeruginosa. Conclusion: As well as promoting appropriate use of antibiotics, MBL production should be detected as a target of intervention for infection control.
University of Birmingham Discovery of peptide ligands targeting a specific ubiquitin-like domain-binding site in the deubiquitinase USP11

Ubiquitin specific proteases (USPs) reverse ubiquitination and regulate virtually all cellular processes. Defined non-catalytic domains in USP4 and USP15 are known to interact with E3 ligases and substrate recruitment factors. No such interactions have been reported for these domains in the paralog USP11,
Characterization of a model to induce hyperlipidemia in feed-restricted dairy cows

Graphical Abstract Summary: The objectives of this study were to induce hyperlipidemia and characterize the responses and safety of the intervention in dry Holstein cows at 8 months of gestation. Cows were fed for ad libitum intake from day 1 to 5 and restricted to 41% of the net energy for lactation required from day 6 to 13. On day 14, cows were off feed and received an i.v. of solution of 10% tyloxapol at 120 mg/kg body weight to block hydrolysis of triacylglycerols in lipoprotein particles. Blood was sampled for 720 minutes, and vital signs were monitored for 30 minutes. Tyloxapol infusion progressively increased the concentrations of lipids in serum. Some cows showed a transient reaction to the treatment that lasted 20 minutes, but treatment was not associated with negative consequences to health of cows and the offspring. This model can be used to study intermediary lipid metabolism in dry late-gestation dairy cows.
Supporting Methods

The targeted sequencing cohort (TR) samples were obtained from the archives of the Dermatology Section of the Departments of Pathology and Dermatology at the University of California San Francisco. The exome sequencing cohort (EX) was acquired from Memorial Sloan Kettering Cancer Center. The study was approved by the Institutional Review Boards of both institutions. Following the manufacturers’ protocols, DNA was extracted using Qiagen DNeasy Blood & Tissue Kit and libraries were prepared for sequencing using the NuGen Ovation Ultralow DR Multiplex System 9-16 (p/n 0331-32). Hybrid capture of the whole exome (EX) and of a targeted panel of 293 cancer-associated genes (TR) was performed using the Agilent SureSelectXT Human All Exon V4+UTRs library (p/n 5190-4638) and the Roche Nimblegen SeqCap EZ Choice Library (p/n 06266339001), respectively. DNA library preparation on the C0902 cell line followed a protocol similar to the samples in cohort TR, and a custom target panel different from that used in the TR set, but similarly focused to about 380 genes (Table 1, main text). Multiplexed samples were sequenced on an Illumina HiSeq 2500 instrument. Sequencing reads were aligned to the UCSC reference human genome (hg19; NCBI build 37) with the Burrows-Wheeler Aligner (BWA) version 0.7. 5 [1]. PCR duplicates were flagged with Picard MarkDuplicates, and indel realignment and base quality recalibration were performed with the Genome Analysis Toolkit (GATK) to produce the BAM files used as input to CNVkit. CNVkit analysis was performed with default settings and bin sizes shown in Table 1, main text. For the TR and EX cohorts, a pooled reference was constructed from the paired normal samples, and for C0902, a reference constructed from four unrelated normal tissue samples.
Untangling the R2* contrast in multiple sclerosis: A combined MRI-histology study at 7.0 Tesla.

Cyanide is a potent toxic agent, and the few available antidotes are not amenable to rapid deployment in mass exposures. As a result, there are ongoing efforts to exploit different animal models to identify novel countermeasures. We have created a pipeline that combines high-throughput screening in zebrafish with subsequent validation in two mammalian small animal models as well as a porcine large animal model. We found that zebrafish embryos in the first 3 days post fertilization (dpf) are highly resistant to cyanide, becoming progressively more sensitive thereafter. Unbiased analysis of gene expression in response to several hours of ultimately lethal doses of cyanide in both 1 and 7 dpf zebrafish revealed modest changes in iron-related proteins associated with the age-dependent cyanide resistance. Metabolomics measurements demonstrated significant age-dependent differences in energy metabolism during cyanide exposure which prompted us to test modulators of the tricarboxylic acid cycle and related metabolic processes as potential antidotes. In cyanide-sensitive 7 dpf larvae, we identified several such compounds that offer significant protection against cyanide toxicity. Modulators of the pyruvate dehydrogenase complex, as well as the small molecule sodium glyoxylate, consistently protected against cyanide toxicity in 7 dpf zebrafish larvae. Together, our results indicate that the resistance of zebrafish embryos to cyanide toxicity during early development is related to an altered regulation of cellular metabolism, which we propose may be exploited as a potential target for the development of novel antidotes against cyanide poisoning.
Acute graft-versus-host disease: grade and outcome in patients with chronic myelogenous leukemia. Working Party Chronic Leukemia of the European Group for Blood and Marrow Transplantation.

Acute graft-versus-host disease (aGVHD) has been classified according to the Seattle criteria as grades 0, I, II, III, and IV for 20 years. The predictive value of such detailed grading is a matter of debate; publications usually report GVHD as present or absent or as absent, moderate, or severe. The Working Party Chronic Leukemia of the European Group for Bone Marrow Transplantation analyzed data of 1,294 patients transplanted from an allogeneic donor for chronic myelogenous leukemia (CML) in first chronic phase and tested the predictive value of aGVHD grading for the following end-points: day 100 mortality (D100M), transplant-related mortality (TRM), relapse incidence (RI), leukemia-free survival (LFS), and survival (SURV). aGVHD was absent in 462 patients (35.7%), grade I occurred in 335 (25.8%), grade II in 264 (20.5%), grade III in 110 (8.5%), and grade IV in 123 patients (9.5%). A total of 297 patients (23%) died within 100 days, 495 patients (38%) died of any TRM, and 100 patients (8%) died of relapse. D100M according to grades 0, I, II, III, and IV was 17%, 13%, 19%, 38%, and 70%, respectively, with significant difference between 0-II versus III-IV. TRM was 28%, 27%, 43%, 68%, and 92%, respectively, with a distinct separation between 0-I versus II-IV. RI showed a continuous decrease of 37%, 30%, 23%, 18%, and 8%, respectively, with increasing aGVHD. LFS was 45%, 51%, 44%, 26%, and 7%, respectively, and was best for patients with grade I aGVHD. This finding was also reflected in a better overall survival (60%, 64%, 53%, 30%, and 8%, respectively). The better LFS for grade I aGVHD patients compared with patients with grade 0 or II aGVHD was confirmed (P = .05) in a multivariate analysis. These data document the value of the present 5-point grading of aGVHD, ie, different outcome is observed depending on endpoint analyzed. Restricting information about aGVHD to presence or absence is not warranted.
Direct Cardiac Reprogramming From Developmental Biology to Cardiac Regeneration

: Heart disease affects millions worldwide and is a progressive condition involving loss of cardiomyocytes. The human heart has limited endogenous regenerative capacity and is thus an important target for novel regenerative medicine approaches. Although cell-based regenerative therapies hold promise, cellular reprogramming of endogenous cardiac fibroblasts, which represent more than half of the cells in the mammalian heart, may be an attractive alternative strategy for regenerating cardiac muscle. Recent advances leveraging years of developmental biology point to the feasibility of generating de novo cardiomyocyte-like cells from terminally differentiated nonmyocytes in the heart in situ after ischemic damage. Here, we review the progress in cardiac reprogramming methods and consider the opportunities and challenges that lie ahead in refining this technology for regenerative medicine. ( Circ Res . 2013;113:915-921.) Steps Toward Safe Cell Therapy Using Induced Pluripotent Stem Cells [ Circ Res . 2013;112:523–533] iPSCs in Cardiovascular Drug Discovery [ Circ Res . 2013;112:534–548] Immunogenicity of Pluripotent Stem Cells and Their Derivatives [ Circ Res . 2013;112:549–561] Progress in the Reprogramming of Somatic Cells [ Circ Res . 2013;112:562–574] Direct Cardiac Reprogramming: From Developmental Biology to Cardiac Regeneration Use of iPSCs to Generate Cardiac Myocytes and Repair Infarcted Myocardium Genomic Stability Issues Associated With the Reprogramming Process Differentiation of iPSCs Into Mature Myocytes
UCSD Performance-Based Skills Assessment: Development of a New Measure of Everyday Functioning for Severely Mentally 111 Adults

Instruments to assess everyday functioning have utilized self-report, proxy report, clinician ratings, or direct observation of performance. Each of these methods has strengths and weaknesses. In this article we argue for the inclusion of performance-based measures of functional capacity in studies of severely mentally ill persons and describe a new measure, the UCSD Performance-Based Skills Assessment (UPSA). We administered the UPSA to 50 middle-aged and older outpatients with schizophrenia or schizoaffective disorder, and 20 normal comparison subjects. Participants' performance in five domains of functioning (Household Chores; Communication; Finance; Transportation; and Planning Recreational Activities) was assessed in standardized role-play situations. Administration of the UPSA required an average of 30 minutes to complete. Interrater reliability of ratings was excellent Patients' performance was significantly more impaired than that of normal subjects. Among patients, the UPSA performance correlated significantly with severity of negative symptoms and of cognitive impairment but not with that of positive or depressive symptoms. The UPSA scores correlated highly with those on another performance-based measure. We believe that UPSA would be useful for assessing everyday functioning in severely mentally ill adults.
Estrogen receptor α gene polymorphisms and risk of Alzheimer’s disease: evidence from a meta-analysis

Objective: Human estrogen receptor α (ESR1) , a member of the nuclear receptor superfamily of ligand-activated transcription factors, is one of the key mediators of hormonal response in estrogen-sensitive tissues. Accumulating evidence has demonstrated that two of the most widely studied single-nucleotide polymorphisms in ESR1 – PvuII (T/C, rs223493) and Xbal (A/G, rs9340799) – are possibly associated with Alzheimer’s disease (AD). However, individual study results are still controversial. Materials and methods: We searched PubMed, Embase, Web of Science, Science Direct, SpringerLink, and the Chinese National Knowledge Infrastructure databases for eligible studies assessing the association of ESR1 polymorphisms and AD risk (last search performed in November 2013). Thereafter, a meta-analysis of 13,192 subjects from 18 individual studies was conducted to evaluate the association between ESR1 polymorphisms and susceptibility to AD. Results: The results indicated that a significant association was found between the ESR1 PvuII polymorphism and AD risk in Caucasian populations (CC + CT versus TT, odds ratio [OR] 1.14, 95% confidence interval [CI] 1.02–1.28, P = 0.03; CT versus TT, OR 1.16, 95% CI 1.02–1.31, P = 0.02), whereas no evidence of association was found in Asian populations. Nevertheless, we did not find any significant association between the ESR1 XbaI polymorphism and AD risk for any model in Caucasian and Asian populations (all P  0.05). Conclusion: Based on this meta-analysis, we conclude that the ESR1 PvuII polymorphism might be a risk factor in AD development in Caucasian populations, not in Asian populations. Further confirmation is needed from better-designed and larger
End-Stage Renal Disease : In Vivo Diffusion-Tensor Imaging of Silent White Matter Damage 1

Materials and Methods: This study was approved by an institutional review board; written informed consent was obtained. From March 2007 to December 2007, 34 patients (16 men, 18 women; mean age, 40.0 years; range, 26–50 years) with ESRD who were undergoing dialysis and 35 control subjects (16 men, 19 women; mean age, 38.3 years; range, 25–49 years) were enrolled. There was no significant sex or age difference between the ESRD and control groups. By using a 1.5-T imager, fractional anisotropy (FA) data obtained at diffusion-tensor magnetic resonance (MR) imaging (echo-planar imaging, 33 directions; b value, 1000 sec/mm) and at T2-weighted fluid-attenuated inversion recovery (FLAIR) MR imaging of the bilateral parietal, frontal, occipital, and temporal lobe white matter, as well as the genu and splenium of the corpus callosum, were compared. The Cognitive Abilities Screening Instrument (CASI) was administered to all participants at imaging.
North Atlantic Mesoscale Eddy Detection and Marine Species Distribution

2 Acknowledgement.3 Introduction.5 Methods.9 Sea Level Anomaly Maps.9 Eddy Detection.11 Pelagic Longline Fishery Catch Data.14 Sampling.16 Analysis.17 Results and Discussion.18 Eddy Detection. ,. 18 Sampling.19 Marine Species Distribution.20 Future Research.26 Literature Cited.27
Comparison of robotic and laparoscopic hysterectomy for benign gynecologic disease.

To the Editor: The Rosero et al article has examined important inpatient data comparing outcomes in patients with benign disease undergoing robotic or laparoscopic hysterectomy. It is important to note, however, that these data are from the national inpatient sample, and experience from high-volume centers has proven that many minimally invasive procedures performed robotically are performed through an outpatient approach. Patients undergoing minimally invasive surgery often are discharged either the same day or the next day. A recent 5-year comparison of quality metrics in patients with benign disease undergoing robotically assisted hysterectomy showed a decreased length of stay (LOS) and rate of readmissions before 30 days after surgery compared with nonrobotic cases. These findings differ from those of Rosero and those of Wright, whose recent article in JAMA reported no difference in quality outcomes. Differences between these studies most likely are related to volume, skills, and standardization of surgical pathways. As surgeons, we should adhere to the Institute for Healthcare Improvement Triple Aim: better care, better health, lower cost. To reach this goal, we recommendmore minimally invasive and fewer open surgeries. It is well-established that minimally invasive surgery offers the best outcomes for patients with benign and malignant gynecologic conditions. However, despite the fact that until 2005 it had been approximately 40 years since the early publications on this approach, most hysterectomies in the United States were performed through laparotomy. Only after the robotic-assisted platform was introduced did the rate of open surgery begin to decrease significantly. Laparotomy results in the highest cost, owing to the associated LOS and shortterm and long-term complications and sequelae, including infections, wound complications, readmissions, adhesive disease, and incision-related hernia. One solution as we enter the era of health care reform is to make individual surgeon outcomes transparent and accessible to patients. We recommend the development of a prospective registry for benign and malignant (excluding ovarian cancer) surgery among institutions. Registry data for patient view should be simple to understand and can include LOS, readmissions before 30 days, and total volume and route of hysterectomy procedures. Only then can our patients be informed adequately about quality outcomes and be able to decide where, by whom, and how to have their surgery performed.
The solitary traveller: why do people travel on their own?

This thesis focuses on an under-researched area of tourism individualised travel by examining non-institutionalised solitary travellers. The purpose of the study is to discover precisely why non-institutionalised solitary travellers travel alone. In order to understand the travel behaviour and motivation of solitary travellers, they are contrasted with group tourists. To be able to tackle this research problem, Grounded Theory is chosen as the most appropriate approach, for the following reasons. First, Grounded Theory is a methodology which makes its greatest contribution in areas about which little is known. Second, its aim is to generate rather than to test theory. Based on the computer-assisted content analysis and interpretation of relatively neglected qualitative data obtained from interviews and diaries, sixteen socio-psychological justifications for solo travel are empirically identified. From these responses, a taxonomy of non-institutionalised solitary travellers is inductively constructed. It consists of two basic types. First, there are those who travel alone because they simply have no available travel companion, referred to as "solitary travellers by default". Second, there are those individuals who deliberately travel on their own, and who are regarded as "solitary travellers by choice". The elaboration of such a distinction is the primary contribution made by this research to tourism knowledge. A secondary contribution is realised by confronting the data on solitary travellers and group tourists with the extant literature on tourist typologies an exercise that raises a number of issues about the mythical status of the fonner. As a result, an alternative taxonomy is generated that consists of two distinct types of tourists individualistic and collectivistic. The individualistic tourist is someone for whom internal personal values. (e.g., sense of accomplishment) are the most important principles in life, who has motives stemming from ego-enhancement (e.g., personal development), and for whom travel means the investment of personal cultural capital. The collectivistic Q. ~-';:i j cCik tourist, on the other hand, is someone who assigns greater priority to external \Ca.9~ c.l personal values (e.g., sense of belonging), whose motives originatehn tqe anomie. ~ '~~J . conditions of society, and for whom travel is little more than a shdrt break [toni ~ . routine. I::. ". ='~~~. ~. '';' ~,. "",_''''_~_-;'''I"qJ. '''''i1l:'l'''':''''''''~~·-'''. , . :. ,. ;e . ,-:'; . ;. , . -"',-~. In.31;QL~\j::. :t.L~. ",. -. =. I ~)1~ 'ii :I,1Q L___ ! l'1i\ M£~t__~ ~u\. o~ I
Low-power three-degree-of-freedom Lorentz force microelectromechanical system mirror for optical applications

Abstract. A low-power three-degree-of-freedom scanning micromirror is presented. The 2- × 2-mm mirror is a gimbaless structure, directly supported by single-crystal microsprings. It is actuated by Lorentz force and is able to tilt about two axes and has linear motion in a third-axis. The transient and frequency responses of the micromirror are analyzed. The Lagrange’s equations of motions describing the dynamic behavior of the system are presented and show a good agreement with the experimental results. The fabricated microelectromechanical system mirror demonstrates a tilt angle of 22.8 deg at 247.5 Hz about y-axis, and 13.3 deg at 292.7 Hz about x-axis, in a 0.1 T magnetic field and 20-mA current on the mirror. Power consumption is 2.6 mW of power in tilting motions in resonant operation. With a total DC-drive current of 110 mA, 232-μm linear motion is achieved.
Progress in elucidating the pathophysiological basis of nonrapid eye movement parasomnias: not yet informing therapeutic strategies

: Nonrapid eye movement (NREM) or arousal parasomnias are prevalent conditions in children and young adults, apparently provoked by any medical, physical, mental, or pharmacologic/toxic agent disturbing normal biorhythm and causing sleep fragmentation or abundant amount of slow wave sleep. The nadir and the ascending slope of the first sleep cycle of night sleep are the typical periods when NREM parasomnias, especially sleepwalking may occur on sleep-microstructural level; microarousals are the typical moments allowing NREM parasomnias. While sleep-disturbing factors have a clear precipitating effect, a genetic predisposition appears necessary in most cases. A candidate gene for sleepwalking has been identified on chromosome 20q12-q13.12 in one sleepwalking family. NREM parasomnias have a genetic and clinical link with nocturnal-frontal lobe epilepsies; possibly through an abnormality of the acetylcholine-related sleep-control system. The association of NREM parasomnias with the human leukocyte antigen system might be the sign of an autoimmune background to be further clarified. In the treatment of arousal parasomnias, the main tools are adequate sleep hygiene and the management of underlying conditions. Their pharmacotherapy has remained unresolved; the best options are clonazepam and some of the antidepressants, while a psychotherapy approach is also justified.
A novel multiple-stage antimalarial agent that inhibits protein synthesis

Baragaña, B; Hallyburton, I; Lee, MC; Norcross, NR; Grimaldi, R; Otto, TD; Proto, WR; Blagborough, AM; Meister, S; Wirjanata, G; +55 more. Ruecker, A; Upton, LM; Abraham, TS; Almeida, MJ; Pradhan, A; Porzelle, A; Luksch; Martínez, MS; Luksch, T; Bolscher, JM; Woodland, A; Norval, S; Zuccotto, F; Thomas, J; Simeons, F; Stojanovski, L; Osuna-Cabello, M; Brock, PM; Churcher, TS; Sala, KA; Zakutansky, SE; Jiménez-Díaz, MB; Sanz, LM; Riley, J; Basak, R; Campbell, M; Avery, VM; Sauerwein, RW; Dechering, KJ; Noviyanti, R; Campo, B; Frearson, JA; Angulo-Barturen, I; Ferrer-Bazaga, S; Gamo, FJ; Wyatt, PG; Leroy, D; Siegl, P; Delves, MJ; Kyle, DE; Wittlin, S; Marfurt, J; Price, RN; Sinden, RE; Winzeler, EA; Charman, SA; Bebrevska, L; Gray, DW; Campbell, S; Fairlamb, AH; Willis, PA; Rayner, JC; Fidock, DA; Read, KD; Gilbert, IH; (2015) A novel multiple-stage antimalarial agent that inhibits protein synthesis. Nature, 522 (7556). pp. 315-20. ISSN 0028-0836 DOI: https://doi.org/10.1038/nature14451