bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementing a Warm Handoff Between Hospital and Skilled Nursing Facility Clinicians
Authors: Campbell Britton Meredith , Hodshon Beth , Chaudhry Sarwat I. 
Published: August 2018

Objectives
Care transitions between hospitals and skilled nursing facilities (SNFs) are associated with disruptions in patient care and high risk for adverse events. Communication between hospital-based and SNF-based clinicians is often suboptimal; there have been calls to foster direct, real-time communication between sending and receiving clinicians to enhance patient safety. This article described the implementation of a warm handoff between hospital and SNF physicians and advanced practice providers at the time of hospital discharge.

Methods
Before patient transfer, hospital clinicians called SNF clinicians to provide information relevant to the continuation of safe patient care and offer SNF clinicians the opportunity to ask clarifying questions. The calls were documented in the hospital discharge summary.

Results
A total of 2417 patient discharges were eligible for inclusion. Warm handoffs were documented at an increasing rate throughout implementation of the intervention, beginning with 15.78% (n = 3) in stage 1, then 20.27% (n = 75) in stage 2, and finally 46.89% (n = 951) in stage 3. The overall average rate of documentation was 42.57%. Participant feedback indicated that clinicians were most concerned about understanding the purpose of the warm handoff, managing their workload, and improving the efficiency of the process.

Conclusions
Use of a warm handoff showed promise in improving communication during hospital-SNF patient transfers. However, the implementation also highlighted specific barriers to the handoff related to organizational structures and clinician workload. Addressing these underlying issues will be critical in ensuring continued participation and support for efforts that foster direct communication among clinicians from different healthcare institutions.
Efficacy and Safety of a Tofacitinib-based Immunosuppressive Regimen After Kidney Transplantation: Results From a Long-term Extension Trial
Authors: Busque Stephan , Vincenti Flavio G. , Tedesco Silva Helio , O’Connell Philip J. , Yoshida Atsushi , Friedewald John J. , Steinberg Steven M. , Budde Klemens , Broeders Emine N. , Kim Yon Su , Hahn Carolyn M. , Li Huihua , Chan Gary 
Published: August 2018

Background
Tofacitinib is an oral Janus kinase inhibitor. This open-label, long-term extension (LTE) study (NCT00658359) evaluated long-term tofacitinib treatment in stable kidney transplant recipients (n = 178) posttransplant.

Methods
Patients who completed 12 months of cyclosporine (CsA) or tofacitinib treatment in the phase IIb parent study (NCT00483756) were enrolled into this LTE study, evaluating long-term tofacitinib treatment over months 12 to 72 posttransplant. Patients were analyzed by tofacitinib less-intensive (LI) or more-intensive (MI) regimens received in the parent study. For both groups, tofacitinib dose was reduced from 10 to 5 mg twice daily by 6 months into the LTE. Patients were followed up through month 72 posttransplant, with a focus on month 36 results.

Results
Tofacitinib demonstrated similar 36-month patient and graft survival rates to CsA. Biopsy-proven acute rejection rates at month 36 were 11.2% for CsA, versus 10.0% and 7.4% (both P > 0.05) for tofacitinib LI and MI, respectively. Least squares mean estimated glomerular filtration rates were 9 to 15 mL/min per 1.73 m2 higher for tofacitinib versus CsA at month 36. The proportions of patients with grade 2/3 interstitial fibrosis and tubular atrophy in month 36 protocol biopsies were 20.0% for LI and 18.2% for MI (both P > 0.05) versus 33.3% for CsA. Kaplan-Meier cumulative serious infection rates at month 36 were numerically higher for tofacitinib LI (43.9%; P = 0.45) and significantly higher for MI (55.9%; P < 0.05) versus CsA (37.1%).

Conclusions
Long-term tofacitinib continued to be effective in preventing renal allograft acute rejection and preserving renal function. However, long-term tofacitinib and mycophenolic acid product combination was associated with persistent serious infection risk.
The Landscape of Enteric Pathogen Exposure of Young Children in Public Domains of Low-Income, Urban Kenya: The Influence of Exposure Pathway and Spatial Range of Play on Multi-Pathogen Exposure Risks
Authors: Medgyesi Danielle , Sewell Daniel , Senesac Reid , Cumming Oliver , Mumma Jane , Baker Kelly K. 
Published: August 2018

AbstractBackgroundYoung children are infected by a diverse variety of enteric pathogens in low-income, high-burden countries. Little is known about which conditions pose the greatest risk for enteric pathogen exposure and infection. Young children frequently play in residential public areas around their household, including areas contaminated by human and animal feces, suggesting these exposures are particularly hazardous.ObjectivesThe objective of this study was to examine how the dose of six types of common enteric pathogens, and the probability of exposure to one or multiple enteric pathogens for young children playing at public play areas in Kisumu, Kenya is influenced by the type and frequency of child play behaviors that result in ingestion of soil or surface water, as well as by spatial variability in the number of public areas children are exposed to in their neighborhood.MethodsA Bayesian framework was employed to obtain the posterior distribution of pathogen doses for a certain number of contacts. First, a multivariate random effects tobit model was used to obtain the posterior distribution of pathogen concentrations, and their interdependencies, in soil and surface water, based upon empirical data of enteric pathogen contamination in three neighborhoods of Kisumu. Then, exposure doses were estimated using behavioral contact parameters from previous studies, and contrasted under different exposure conditions.ResultsMulti-pathogen exposure of children at public play areas was common. Pathogen doses and the probability of multi-pathogen ingestion increased with: higher frequency of environmental contact, especially for surface water; larger volume of soil or water ingested; and with play at multiple sites in the neighborhood versus single site play.DiscussionChild contact with surface water and soil at public play areas in their neighborhood is an important cause of exposure to enteric pathogens in Kisumu, and behavioral, environmental, and spatial conditions are determinants of exposure.
Allele frequency dynamics in a pedigreed natural population
Authors: Chen Nancy , Juric Ivan , Cosgrove Elissa J. , Bowman Reed , Fitzpatrick John W. , Schoech Stephan J. , Clark Andrew G. , Coop Graham 
Published: August 2018

ABSTRACTA central goal of population genetics is to understand how genetic drift, natural selection, and gene flow shape allele frequencies through time. However, the actual processes underlying these changes - variation in individual survival, reproductive success, and movement - are often difficult to quantify. Fully understanding these processes requires the population pedigree, the set of relationships among all individuals in the population through time. Here, we use extensive pedigree and genomic information from a long-studied natural population of Florida Scrub-Jays (Aphelocoma coerulescens) to directly characterize the relative roles of different evolutionary processes in shaping patterns of genetic variation through time. We performed gene dropping simulations to estimate individual genetic contributions to the population and model drift on the known pedigree. We found that observed allele frequency changes are generally well predicted by accounting for the different genetic contributions of founders. Our results show that the genetic contribution of recent immigrants is substantial, with some large allele frequency shifts that otherwise may have been attributed to selection actually due to gene flow. We identified a few SNPs under directional short-term selection after appropriately accounting for gene flow. Using models that account for changes in population size, we partitioned the proportion of variance in allele frequency change through time. Observed allele frequency changes are primarily due to variation in survival and reproductive success, with gene flow making a smaller contribution. This study provides one of the most complete descriptions of short-term evolutionary change in allele frequencies in a natural population to date.
Spatiotemporal Dynamics of Molecular Pathology in Amyotrophic Lateral Sclerosis
Authors: Maniatis Silas , Äijö Tarmo , Vickovic Sanja , Braine Catherine , Kang Kristy , Mollbrink Annelie , Fagegaltier Delphine , Andrusivová Žaneta , Saarenpää Sami , Saiz-Castro Gonzalo , Cuevas Miguel , Watters Aaron , Lundeberg Joakim , Bonneau Richard , Phatnani Hemali 
Published: August 2018

AbstractParalysis occurring in amyotrophic lateral sclerosis (ALS) results from denervation of skeletal muscle as a consequence of motor neuron degeneration. Interactions between motor neurons and glia contribute to motor neuron loss, but the spatiotemporal ordering of molecular events that drive these processes in intact spinal tissue remains poorly understood. Here, we use spatial transcriptomics to obtain gene expression measurements of mouse spinal cords over the course of disease, as well as of postmortem tissue from ALS patients, to characterize the underlying molecular mechanisms in ALS. We identify novel pathway dynamics, regional differences between microglia and astrocyte populations at early time-points, and discern perturbations in several transcriptional pathways shared between murine models of ALS and human postmortem spinal cords.One Sentence SummaryAnalysis of the ALS spinal cord using Spatial Transcriptomics reveals spatiotemporal dynamics of disease driven gene regulation.
Rapid and efficient C-terminal labeling of nanobodies for DNA-PAINT
Authors: Fabricius Valentin , Lefèbre Jonathan , Geertsema Hylkje , Marino Stephen F. , Ewers Helge 
Published: August 2018

AbstractSingle molecule localization-based approaches to superresolution microscopy (SMLM) create images that resolve features smaller than the diffraction limit of light by rendering them from the sequentially measured positions of thousands of individual molecules. New SMLM approaches based on the transient binding of very bright dyes via DNA-DNA interaction (DNA-PAINT) allow the resolution of dyes only a few nanometers apartin vitro. This imaging of cellular structures requires the specific association of dyes to their targets, which results in an additional “linkage error”. This error can be minimized by using extremely small, single-domain antibody-based binders such as nanobodies, but the DNA-oligomers used in DNA-PAINT are of significant size in comparison to nanobodies and may interfere with binding. We have here developed an optimized procedure based on enzymatic labeling and click-chemistry for the coupling of DNA oligomers to the nanobody C-terminus, which is located on the opposite side of the epitope-binding domain. Our approach allows for straightforward labeling, purification and DNA-PAINT imaging. We performed high efficiency labeling of two different nanobodies and show dual color multiplexed SMLM to demonstrate the general applicability of our labeling scheme.
Software tools for automated transmission electron dmicroscopy
Authors: Schorb Martin , Haberbosch Isabella , Hagen Wim JH , Schwab Yannick , Mastronarde David N 
Published: August 2018

AbstractIn the recent years, electron microscopy in the life sciences has witnessed increasing demand for high-throughput data collection in both structural and cellular biology. We present a combination of software tools that enable automated acquisition guided by image analysis for a wide variety of Transmission Electron Microscopy applications. Using these tools, we demonstrate dose-reduction in single particle cryo-EM experiments, fully automated acquisition of every single cell in a plastic section and automated targeting of features on serial sections for 3D volume imaging even across multiple grids.
The Nonsense-Mediated mRNA Decay pathway degrades dendritically-targeted mRNAs to regulate long-term potentiation and cognitive function
Authors: Notaras Michael , Allen Megan , Longo Francesco , Volk Nicole , Toth Miklos , Li Jeon Noo , Klann Eric , Colak Dilek 
Published: August 2018

AbstractSynaptic plasticity relies on new protein synthesis in dendrites that involves the selective translation of specific mRNAs. This requires a tight control of mRNA levels in dendrites. Consistently, RNA translation and degradation pathways have been recently linked to neurodevelopmental and neuropsychiatric diseases, suggesting a role for RNA regulation in synaptic plasticity and cognition. Despite being the only RNA regulatory pathway that is associated with multiple mental illnesses, the Nonsense-Mediated mRNA Decay (NMD) pathway presents an unexplored regulatory mechanism for synaptic function and plasticity. NMD is a highly conserved and selective RNA degradation pathway that exerts its function in a cell- and spatiotemporally-specific manner. Here, we show that neuron-specific disruption of NMD in adulthood attenuates learning, memory, hippocampal LTP, and potentiates perseverative/repetitive behavior. While it is known that local translation of specific mRNAs in dendrites enables synaptic plasticity, the tightly-controlled mechanisms that regulate local quantity of specific mRNAs remains poorly understood. We report that the NMD pathway operates within dendrites to regulate GluR1 surface levels. Specifically, NMD modulates the internalization of GluR1 and promotes its local synthesis in dendrites. We identified AMPK as a mechanistic substrate for NMD that contributes to the NMD-mediated regulation of GluR1 by limiting total GluR1 levels. These data establish that NMD regulates synaptic plasticity, cognition, and local protein synthesis in dendrites, providing fundamental insight into the neuron-specific function of NMD within the brain.
Atomic-level characterization of conformational transition and substrate binding of xCT transporter
Authors: Sharma M. , Rohithaswa A. C. 
Published: August 2018

AbstractxCT is a component of heterodimeric amino acids transporter system Xc- that has been known to work at the cross-roads of maintaining neurological processes and regulating antioxidant defense. xCT is a sodium-independent amino acid antiporter, that imports L- cystine and exports L-glutamate in a 1:1 ratio. The transporter has 12 transmembrane domains with intracellular N- and C-termini, which can undergo various conformational changes while switching the ligand accessibilities from intracellular to extracellular site. In the present study, we generated two homology models of human xCT in two distinct conformations: inward facing occluded state and outward facing open state. We investigated the conformational transitions within these two states by employing series of targeted molecular dynamics simulations. Our results indicated the substrate translocation channel composed of transmembrane helices TMs 1, 3, 6, 8, and 10. Further, we analyzed the ligand binding within the intermediate conformations obtained from the transition simulations. We docked anionic L-cystine and L-glutamate within the cavities alone or in combination to assess the two distinct binding scenarios for xCT as antiporter. We also assessed the interactions between the ligand and xCT and observed that ligands bind to similar residues within the channel, and these residues are essential for substrate binding/permeation. In addition, we analyzed the correlations between ligand binding and conformational transition and observed conformations that are representatives for intermediate ligand bound states. The results presented in the study provide insights into the interplay of conformational transition and ligand binding as xCT goes from one probable conformation to another while transporting the ligand. And the data thus adds to the existing evidence of alternating access mechanism pertaining to the functioning of transporters.
Mapping Transgene Insertion Sites Reveals Complex Interactions Between Mouse Transgenes and Neighboring Endogenous Genes
Authors: Laboulaye Mallory A. , Duan Xin , Qiao Mu , Whitney Irene E. , Sanes Joshua R. 
Published: August 2018

ABSTRACTTransgenic mouse lines are routinely employed to label and manipulate distinct cell types. The transgene generally comprises cell-type specific regulatory elements linked to a cDNA encoding a reporter or other proteins. However, off-target expression seemingly unrelated to the regulatory elements in the transgene is often observed, and sometimes suspected to reflect influences related to the site of transgene integration in the genome. To test this hypothesis, we used a proximity ligation-based method, Targeted Locus Amplification (TLA), to map the insertion sites of three well-characterized transgenes that appeared to exhibit insertion site-dependent expression in retina. The nearest endogenous genes to transgenes HB9-GFP, Mito-P, and TYW3 are Cdh6, Fat4 and Khdrbs2, respectively. For two lines, we demonstrate that expression reflects that of the closest endogenous gene (Fat4 and Cdh6), even though the distance between transgene and endogenous gene is 550 and 680 kb, respectively. In all three lines, the transgenes decrease expression of the neighboring endogenous genes. In each case, the affected endogenous gene was expressed in at least some of the cell types that the transgenic line has been used to mark and study. These results provide insights into the effects of transgenes and endogenous genes on each other’s expression, demonstrate that mapping insertion site is valuable for interpreting results obtained with transgenic lines, and indicate that TLA is a reliable method for integration site discovery.
Common ancestry of heterodimerizing TALE homeobox transcription factors across Metazoa and Archaeplastida
Authors: Joo Sunjoo , Wang Ming Hsiu , Lui Gary , Lee Jenny , Barnas Andrew , Kim Eunsoo , Sudek Sebastian , Worden Alexandra Z. , Lee Jae-Hyeok 
Published: August 2018

AbstractHomeobox transcription factors (TFs) in the TALE superclass are deeply embedded in the gene regulatory networks that orchestrate embryogenesis. Knotted-like homeobox (KNOX) TFs, homologous to animal MEIS, have been found to drive the haploid-to-diploid transition in both unicellular green algae and land plants via heterodimerization with other TALE superclass TFs, representing remarkable functional conservation of a developmental TF across lineages that diverged one billion years ago. To delineate the ancestry of TALE-TALE heterodimerization, we analyzed TALE endowment in the algal radiations of Archaeplastida, ancestral to land plants. Homeodomain phylogeny and bioinformatics analysis partitioned TALEs into two broad groups, KNOX and non-KNOX. Each group shares previously defined heterodimerization domains, plant KNOX-homology in the KNOX group and animal PBC-homology in the non-KNOX group, indicating their deep ancestry. Protein-protein interaction experiments showed that the TALEs in the two groups all participated in heterodimerization. These results indicate that the TF dyads consisting of KNOX/MEIS and PBC-containing TALEs must have evolved early in eukaryotic evolution, a likely function being to accurately execute the haploid-to-diploid transitions during sexual development.Author summaryComplex multicellularity requires elaborate developmental mechanisms, often based on the versatility of heterodimeric transcription factor (TF) interactions. Highly conserved TALE-superclass homeobox TF networks in major eukaryotic lineages suggest deep ancestry of developmental mechanisms. Our results support the hypothesis that in early eukaryotes, the TALE heterodimeric configuration provided transcription-on switches via dimerization-dependent subcellular localization, ensuring execution of the haploid-to-diploid transition only when the gamete fusion is correctly executed between appropriate partner gametes, a system that then diversified in the several lineages that engage in complex multicellular organization.
Killing from the inside: Intracellular role of T3SS in the fate ofPseudomonas aeruginosawithin macrophages revealed bymgtCandoprFmutants
Authors: Garai Preeti , Berry Laurence , Moussouni Malika , Bleves Sophie , Blanc-Potard Anne-Béatrice 
Published: August 2018

AbstractWhile considered solely an extracellular pathogen, increasing evidence indicates thatPseudomonas aeruginosaencounters intracellular environment in diverse mammalian cell types, including macrophages. In the present study, we have deciphered the intramacrophage fate of wild-typeP. aeruginosaPAO1 strain by live and electron microscopy.P. aeruginosafirst resided in phagosomal vacuoles and subsequently could be detected in the cytoplasm, indicating phagosomal escape of the pathogen, a finding also supported by vacuolar rupture assay. The intracellular bacteria could eventually induce cell lysis. Two bacterial factors, MgtC and OprF, recently identified to be important for survival ofP. aeruginosain macrophages, were found to be involved in bacterial escape from the phagosome as well as cell lysis caused by intracellular bacteria. Strikingly, type III secretion system (T3SS) genes ofP. aeruginosawere down-regulated within macrophages in bothmgtCandoprFmutants. Concordantly, cyclic di-GMP (c-di-GMP) level was increased in both mutants, providing a clue for negative regulation of T3SS inside macrophages. Consistent with the phenotypes and gene expression pattern ofmgtCandoprFmutants, a T3SS mutant(ΔpscN)exhibited defect in phagosomal escape and macrophage lysis driven by internalized bacteria. Importantly, these effects appeared to be largely dependent on the ExoS effector, in contrast with the known T3SS-dependent, but ExoS independent, cytotoxicity caused by extracellularP. aeruginosatowards macrophages. Hence, our work highlights T3SS and ExoS, whose expression is modulated by MgtC and OprF, as key players in the intramacrophage life ofP. aeruginosa, allowing internalized bacteria to evade macrophages.Author summaryThe ability of professional phagocytes to ingest and kill microorganisms is central to host defense andPseudomonas aeruginosahas developed mechanisms to avoid being killed by phagocytes. While considered an extracellular pathogen,P. aeruginosahas been reported to be engulfed by macrophages in animal models. Here, we visualized the fate ofP. aeruginosawithin cultured macrophages, revealing macrophage lysis driven by intracellularP. aeruginosa. Two bacterial factors, MgtC and OprF, recently discovered to be involved in the intramacrophage survival ofP. aeruginosa, appeared to play role in this cytotoxicity caused by intracellular bacteria. We provided evidence that type III secretion system (T3SS) gene expression is lowered intracellularly inmgtCandoprFmutants. We further showed that intramacrophageP. aeruginosauses its T3SS, specifically the ExoS effector, to promote phagosomal escape and cell lysis. We thus describe a transient intramacrophage stage ofP. aeruginosathat could contribute to bacterial dissemination.