Miracle-dz/UniFAR-FTUs huggingface dataset:
Monitoring microevolution of OXA-48-producing Klebsiella pneumoniae ST147 in a hospital setting by SMRT sequencing

Objectives Carbapenemase-producing Klebsiella pneumoniae pose an increasing risk for healthcare facilities worldwide. A continuous monitoring of ST distribution and its association with resistance and virulence genes is required for early detection of successful K. pneumoniae lineages. In this study, we used WGS to characterize MDR blaOXA-48-positive K. pneumoniae isolated from inpatients at the University Medical Center Göttingen, Germany, between March 2013 and August 2014. Methods Closed genomes for 16 isolates of carbapenemase-producing K. pneumoniae were generated by single molecule real-time technology using the PacBio RSII platform. Results Eight of the 16 isolates showed identical XbaI macrorestriction patterns and shared the same MLST, ST147. The eight ST147 isolates differed by only 1-25 SNPs of their core genome, indicating a clonal origin. Most of the eight ST147 isolates carried four plasmids with sizes of 246.8, 96.1, 63.6 and 61.0 kb and a novel linear plasmid prophage, named pKO2, of 54.6 kb. The blaOXA-48 gene was located on a 63.6 kb IncL plasmid and is part of composite transposon Tn1999.2. The ST147 isolates expressed the yersinabactin system as a major virulence factor. The comparative whole-genome analysis revealed several rearrangements of mobile genetic elements and losses of chromosomal and plasmidic regions in the ST147 isolates. Conclusions Single molecule real-time sequencing allowed monitoring of the genetic and epigenetic microevolution of MDR OXA-48-producing K. pneumoniae and revealed in addition to SNPs, complex rearrangements of genetic elements.
Systematic regional lymph node dissection for upper tract urothelial carcinoma improves patient survival

Objective Unlike for bladder cancer, the impact of regional lymph node dissection for upper tract urothelial carcinoma is unclear. We explored whether patient survival was influenced by systematic regional lymph node dissection, using resection templates according to the main tumor location, during radical nephroureterectomy for upper tract urothelial carcinoma. Methods The systematic regional lymph node dissection group was defined as cases in which the dissection of nodes and surrounding tissues followed the established template, and the non-systematic regional lymph node dissection group as cases undergoing limited or no lymph node dissection. We performed radical nephroureterectomy on 98 consecutive patients with various stages of upper tract urothelial carcinoma from May 1994 to September 2014 at our institution. Of these, 77 patients with cTanyN0M0 of upper tract urothelial carcinoma undergoing radical nephroureterectomy were grouped into systematic regional lymph node dissection or non-systematic regional lymph node dissection cohorts according to the extent of dissection, and their outcomes compared. Results Forty-four patients were categorized as systematic regional lymph node dissection and 33 as non-systematic regional lymph node dissection, including 17 with more limited nodal dissection and 16 with no nodal dissection. Five-year recurrence-free survival and cancer-specific survival were significantly higher in the systematic regional lymph node dissection (93% and 94%, respectively) than in the non-systematic regional lymph node dissection group (75% and 77% recurrence-free survival and cancer-specific survival, respectively). Further, 5-year recurrence-free survival and cancer-specific survival of muscle-invasive upper tract urothelial carcinoma (pT2-4) were significantly higher in the systematic regional lymph node dissection (87% and 91%, respectively) than in the non-systematic regional lymph node dissection group (59% and 62%, respectively) (P = 0.0237 and P = 0.0224). Neither recurrence-free survival nor cancer-specific survival was significantly prolonged by systematic dissection in patients with pTis-1 histology. Conclusions Systematic regional lymph node dissection during radical nephroureterectomy for cTanyN0M0 upper tract urothelial carcinoma patients has a significantly beneficial impact on survival compared with patients undergoing more limited dissection, especially in the cases involving muscle invasion.
Exploring fungus–plant N transfer in a tripartite ant–plant–fungus mutualism

Background and Aims The plant Hirtella physophora, the ant Allomerus decemarticulatus and a fungus, Trimmatostroma sp. , form a tripartite association. The ants manipulate both the plant trichomes and the fungus to build galleries under the stems of their host plant used to capture prey. In addition to its structural role, the fungus also improves nutrient uptake by the host plant. But it still remains unclear whether the fungus plays an indirect or a direct role in transferring nutrients to the plant. This study aimed to trace the transfer of N from the fungus to the plant's stem tissue. Methods Optical microscopy and transmission electron microscopy (TEM) were used to investigate the presence of fungal hyphae in the stem tissues. Then, a 15N-labelling experiment was combined with a nanoscale secondary-ion mass spectrometry (NanoSIMS 50) isotopic imaging approach to trace the movement of added 15N from the fungus to plant tissues. Key Results The TEM images clearly showed hyphae inside the stem tissue in the cellular compartment. Also, fungal hyphae were seen perforating the wall of the parenchyma cell. The 15N provisioning of the fungus in the galleries resulted in significant enrichment of the 15N signature of the plant's leaves 1 d after the 15N-labelling solution was deposited on the fungus-bearing trap. Finally, NanoSIMS imaging proved that nitrogen was transferred biotrophically from the fungus to the stem tissue. Conclusions This study provides evidence that the fungi are connected endophytically to an ant-plant system and actively transfer nitrogen from 15N-labelling solution to the plant's stem tissues. Overall, this study underlines how complex the trophic structure of ant-plant interactions is due to the presence of the fungus and provides insight into the possibly important nutritional aspects and tradeoffs involved in myrmecophyte-ant mutualisms.
Mixed Timescale Cross-Layer Optimization for Multi-Antenna D2D Networks

A mixed timescale cross-layer resource optimization scheme is proposed for a multi- antenna device-to-device (D2D) network. We consider the two timescale joint optimization of beamforming, routing and flow control, where the short-term beamforming control at each transmit device is adaptive to the local real-time CSI, while the long-term routing and flow control is adaptive to the global topology and channel statistics of the D2D network. We propose a stochastic cutting plane algorithm to find the global optimal solution of the joint optimization problem. The proposed solution has low signaling overhead and does not require explicit knowledge of the channel statistics. Simulations show that the proposed solution achieves significant performance gain over several baselines.
TaxoGen: Constructing Topical Concept Taxonomy by Adaptive Term Embedding and Clustering

Taxonomy construction is not only a fundamental task for semantic analysis of text corpora, but also an important step for applications such as information filtering, recommendation, and Web search. Existing pattern-based methods extract hypernym-hyponym term pairs and then organize these pairs into a taxonomy. However, by considering each term as an independent concept node, they overlook the topical proximity and the semantic correlations among terms. In this paper, we propose a method for constructing topic taxonomies, wherein every node represents a conceptual topic and is defined as a cluster of semantically coherent concept terms. Our method, TaxoGen, uses term embeddings and hierarchical clustering to construct a topic taxonomy in a recursive fashion. To ensure the quality of the recursive process, it consists of: (1) an adaptive spherical clustering module for allocating terms to proper levels when splitting a coarse topic into fine-grained ones; (2) a local embedding module for learning term embeddings that maintain strong discriminative power at different levels of the taxonomy. Our experiments on two real datasets demonstrate the effectiveness of TaxoGen compared with baseline methods.
Effects of Dopamine Donor Pretreatment on Graft Survival after Kidney Transplantation: A Randomized Trial.

BACKGROUND AND OBJECTIVES Donor dopamine improves initial graft function after kidney transplantation due to antioxidant properties. We investigated if a 4 µg/kg per minute continuous dopamine infusion administered after brain-death confirmation affects long-term graft survival and examined the exposure-response relationship with treatment duration. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Five-year follow-up of 487 renal transplant patients from 60 European centers who had participated in the randomized, multicenter trial of dopamine donor pretreatment between 2004 and 2007 (ClinicalTrials.gov identifier: NCT00115115). RESULTS Follow-up was complete in 99.2%. Graft survival was 72.6% versus 68.7% (P=0.34), and 83.3% versus 80.4% (P=0.42) after death-censoring in treatment and control arms according to trial assignment. Although infusion times varied substantially in the treatment arm (range 0-32.2 hours), duration of the dopamine infusion and all-cause graft failure exhibited an exposure-response relationship (hazard ratio, 0.96; 95% confidence interval [95% CI], 0.92 to 1.00, per hour). Cumulative frequency curves of graft survival and exposure time of the dopamine infusion indicated a maximum response rate at 7.10 hours (95% CI, 6.99 to 7.21), which almost coincided with the optimum infusion time for improvement of early graft function (7.05 hours; 95% CI, 6.92 to 7.18). Taking infusion time of 7.1 hours as threshold in subsequent graft survival analyses indicated a relevant benefit: Overall, 81.5% versus 68.5%; P=0.03; and 90.3% versus 80.2%; P=0.04 after death-censoring. CONCLUSIONS We failed to show a significant graft survival advantage on intention-to-treat. Dopamine infusion time was very short in a considerable number of donors assigned to treatment. Our finding of a significant, nonlinear exposure-response relationship disclosed a threshold value of the dopamine infusion time that may improve long-term kidney graft survival.
Mechanisms Involved in Porcine Early Embryo Survival following Ethanol Exposure

Alcohol consumption during pregnancy is still a cause of preventable birth defects and developmental disabilities. However, little is known about the impact of ethanol on preimplantation embryos and the molecular mechanisms involved. We aimed to determine the toxicogenomic impacts and the mechanisms involved in preimplantation embryonic survival following 0.2% ethanol exposure in porcine embryos. Gene expression changes were measured with a porcine embryo specific microarray and confirmed by RT-qPCR. When compared with control, ethanol exposure led to a 43% decrease in blastocyst rate and activated pathways associated with oxidative stress and nervous system damage, such as TP53 and TGF. Moreover, we observed a mitochondrial dysfunction in the exposed embryos as revealed by the decrease in Mitotracker Red fluorescence intensity (25 and 41% in 4-cell embryos and blastocysts, respectively) and a modification in the expression of GABRB3, APP, CLU, and MIOX genes. We therefore present evidence of neuronal-like adverse effects on undifferentiated cells suggesting that fetal alcohol spectrum disorder could have its origin as early as in the first week postfertilization.
Toxoplasma gondii LCAT Primarily Contributes to Tachyzoite Egress

Toxoplasma gondii is one of the most successful human pathogens, infecting an estimated 2.5 billion people across the globe. Pathogenesis seen during acute or reactivated toxoplasmosis has been closely tied to the parasite’s intracellular lytic life cycle, which culminates in an event called egress that results in the release of freshly replicated parasites from the infected host cell. Despite the highly destructive, cytolytic nature of this event and its downstream consequences, very little is known about how the parasite accomplishes this step. Previous work has suggested a role for a secreted phospholipase, LCAT, in Toxoplasma egress and roles in cell traversal and egress in the Plasmodium species orthologue. We confirm here that LCAT-deficient tachyzoites are unable to efficiently egress from infected monolayers, and we provide evidence that LCAT catalytic activity is required for its role in egress. ABSTRACT Egress is a crucial phase of the Toxoplasma gondii intracellular lytic cycle. This is a process that drives inflammation and is strongly associated with the pathogenesis observed during toxoplasmosis. Despite the link between this process and virulence, little is known about egress on a mechanistic or descriptive level. Previously published work has suggested that a phospholipase, lecithin-cholesterol acyltransferase (LCAT), secreted from the parasite’s dense granules contributes to parasite growth, virulence, and egress. Here we present evidence from several independent mutant parasite lines confirming a role for LCAT in efficient egress, although no defects in growth or virulence were apparent. We also show via genetic complementation that the catalytic activity of LCAT is required for its role in parasite egress. This work solidifies the contribution of LCAT to egress of T. gondii tachyzoites. IMPORTANCE Toxoplasma gondii is one of the most successful human pathogens, infecting an estimated 2.5 billion people across the globe. Pathogenesis seen during acute or reactivated toxoplasmosis has been closely tied to the parasite’s intracellular lytic life cycle, which culminates in an event called egress that results in the release of freshly replicated parasites from the infected host cell. Despite the highly destructive, cytolytic nature of this event and its downstream consequences, very little is known about how the parasite accomplishes this step. Previous work has suggested a role for a secreted phospholipase, LCAT, in Toxoplasma egress and roles in cell traversal and egress in the Plasmodium species orthologue. We confirm here that LCAT-deficient tachyzoites are unable to efficiently egress from infected monolayers, and we provide evidence that LCAT catalytic activity is required for its role in egress.
Activated Oncogenic Pathway Modifies Iron Network in Breast Epithelial Cells: A Dynamic Modeling Perspective

Dysregulation of iron metabolism in cancer is well documented and it has been suggested that there is interdependence between excess iron and increased cancer incidence and progression. In an effort to better understand the linkages between iron metabolism and breast cancer, a predictive mathematical model of an expanded iron homeostasis pathway was constructed that includes species involved in iron utilization, oxidative stress response and oncogenic pathways. The model leads to three predictions. The first is that overexpression of iron regulatory protein 2 (IRP2) recapitulates many aspects of the alterations in free iron and iron-related proteins in cancer cells without affecting the oxidative stress response or the oncogenic pathways included in the model. This prediction was validated by experimentation. The second prediction is that iron-related proteins are dramatically affected by mitochondrial ferritin overexpression. This prediction was validated by results in the pertinent literature not used for model construction. The third prediction is that oncogenic Ras pathways contribute to altered iron homeostasis in cancer cells. This prediction was validated by a combination of simulation experiments of Ras overexpression and catalase knockout in conjunction with the literature. The model successfully captures key aspects of iron metabolism in breast cancer cells and provides a framework upon which more detailed models can be built.
An interprofessional patient assessment involving medical and nursing students: a qualitative study

ABSTRACT Interprofessional collaboration is fundamental to providing optimal patient care. The readiness of the team entering a framework of interprofessional collaborative practice is critical to its success. In this study, we conducted an interprofessional education (IPE) activity for medical and nursing students in an acute care setting. Over nine occasions, 21 student pairs (one nursing and one medical student per pair) jointly assessed a patient and created a list of problems and interventions to achieve the patient’s goals. Immediately after the activity, students were debriefed to gain insight into their experiences. Debriefing sessions were audiotaped and analysed using a phenomenological approach and four major themes were identified. Overall, students felt responsible for representing their profession and were initially apprehensive about the interprofessional task. Nevertheless, they identified their own shortcomings and recognized the value in their partner’s approach. These realizations promoted convergence on a shared vision to provide optimal care for patients as a team. Acknowledging and understanding these perceptions may help design better ways to improve patient care. This educational model may be utilized by others who are seeking IPE activities in acute care.
Nasopharyngeal carcinoma super-enhancer–driven ETV6 correlates with prognosis

Significance Epigenetic alterations in nasopharyngeal carcinoma (NPC) are very frequent at the DNA level. Histone modifications are frequently altered in cancers. Because histone modifications are reversible, histone-modifying enzymes or other epigenetic regulators are ideal therapeutic targets, and drugs targeting these enzymes have been proven effective in cancer treatment. Understanding the NPC histone code provides unique insights into NPC pathogenesis and will likely contribute to the identification of unique therapeutics. Using genome-wide analyses of histone modifications, we generated an NPC epigenetic landscape and identified a key oncogene whose expression correlated with patient overall survival, suggesting that epigenetic profiling can effectively identify key oncogenic pathways. These studies provide proof-of-concept strategies for further characterization of the NPC epigenome on a larger scale. Nasopharyngeal carcinoma (NPC) most frequently occurs in southern China and southeast Asia. Epidemiology studies link NPC to genetic predisposition, Epstein–Barr virus (EBV) infection, and environmental factors. Genetic studies indicate that mutations in chromatin-modifying enzymes are the most frequent genetic alterations in NPC. Here, we used H3K27ac chromatin immune precipitation followed by deep sequencing (ChIP-seq) to define the NPC epigenome in primary NPC biopsies, NPC xenografts, and an NPC cell line, and compared them to immortalized normal nasopharyngeal or oral epithelial cells. We identified NPC-specific enhancers and found these enhancers were enriched with nuclear factor κB (NF-κB), IFN-responsive factor 1 (IRF1) and IRF2, and ETS family members ETS1 motifs. Normal cell-specific enhancers were enriched with basic leucine zipper family members and TP53 motifs. NPC super-enhancers with extraordinarily broad and high H3K27ac signals were also identified, and they were linked to genes important for oncogenesis including ETV6. ETV6 was also highly expressed in NPC biopsies by immunohistochemistry. High ETV6 expression correlated with a poor prognosis. Furthermore, we defined the EBV episome epigenetic landscapes in primary NPC tissue.
Intention to treat (ITT) analysis as reported in orthodontic randomized controlled trials—evaluations of methodology and recommendations for the accurate use of ITT analysis and handling dropouts

Objective To systematically evaluate in five orthodontic journals how many randomized controlled trials (RCTs) use intention to treat (ITT) analysis and to assess the methodological quality of the ITT analysis, and finally, to demonstrate in an academic way how outcomes can be affected when not implementing the ITT analysis. Material and methods A search of the database, Medline, was performed via PubMed for publication type 'randomized controlled trial' published for each journal between 1 January 2013 and 30 April 2017. The five orthodontic journals assessed were the American Journal of Orthodontics and Dentofacial Orthopedics, Angle Orthodontics, European Journal of Orthodontics, Journal of Orthodontics, and Orthodontics and Craniofacial Research. Two independent reviewers assessed each RCT to determine whether the trial reported an ITT or not or if a per-protocol analysis was accomplished. Results The initial search generated 137 possible trials. After applying the inclusion and exclusion criteria, 90 RCTs were included and assessed. Seventeen out of 90 RCTs (18.9%) either reported an ITT analysis in the text and/or supported the ITT by flow diagrams or tables. However, six RCTs applied and reported the ITT analysis correctly, while the majority performed a per-protocol analysis instead. Conclusions Nearly all the trials that applied the ITT analysis incorrectly analysed the results using a per-protocol analysis, and thus, overestimating the results and/or having a reduced sample size which then could produce a diminished statistical power.
Long-term results of the Mitroflow aortic pericardial bioprosthesis in over 800 patients: limited durability and mechanisms of dysfunction†

OBJECTIVES The Mitroflow aortic pericardial bioprosthesis was widely employed in the past. However, some authors have recently reported early structural valve deterioration (SVD) of the Mitroflow LA/LXA model. Thus, we reviewed our experience with the Mitroflow bioprosthesis and studied the risk factors for SVD and mortality. METHODS Records of patients who underwent aortic valve replacement with a Mitroflow bioprosthesis between November 2005 and January 2015 were retrospectively evaluated with Kaplan-Meier, Cox-regression and multistate analysis. Only patients with a complete clinical follow-up were included in the study. Average follow-up was 45 months and ended on 1 April 2016. RESULTS Between November 2005 and January 2015, among the 916 patients undergoing aortic valve replacement with the Mitroflow prosthesis at our Institution, the 832 (90.8%) patients with follow-up information were included into the study. Fifty-two (6.2%) patients developed SVD (stenosis, n = 38; regurgitation, n = 7; mixed, n = 7). Freedom from SVD was 95.4% and 67.9%, at 5 and 9 years, respectively, without differences after stratification according to the prosthesis model ( P = 0.87) and prosthesis size ( P = 0.70). At the multivariable analysis, increasing age was identified as a protective factor against SVD (hazard ratio = 0.94, P < 0.001). Twenty (38.4%) patients with SVD underwent redo aortic valve replacement. At 5 and 9 years, survival was 64.5% and 43.1%, repectively. According to the multistate analysis, the fraction of patients living with degenerated valves at 9 years was 10.0%; 7.1% died following degeneration. CONCLUSIONS The LA/LXA Mitroflow model showed limited long-term durability. Degenerated prostheses showed more stenosis than regurgitation. Patient age played an important role in the development of SVD.