bluuebunny/crossref_metadata_2025_split huggingface dataset:
Redesigning Hospital Diabetes Education
Authors: Smith Kelly M. , Baker Kelley M. , Bardsley Joan K. , McCartney Patricia , Magee Michelle 
Published: July 2018

Background:
Methods to deliver diabetes education are needed to support patient safety and glycemic control in the transition from hospital to home.

Purpose:
This study examined barriers and facilitators of integrating web-based, iPad-delivered diabetes survival skills education (DSSE) into the nursing inpatient unit workflow.

Methods:
Nurses, nurse managers, and patient care technicians (PCTs) from 3 medical-surgical and 2 behavioral health units participated in semistructured interviews and focus groups.

Results:
Four themes emerged: educational program and content; platform usability; tablet feasibility (eg, theft prevention, infection control, and charging); and workflow considerations. Behavioral health unit-specific concerns were also identified. Findings indicated that nurses and PCTs were eager to find approaches to deliver DSSE.

Conclusions:
Implementation of a web-based DSSE program for inpatients needs adaptation to overcome challenges at the patient, care team, and process levels.
Fatal Transorbital Intracranial Penetrating Injury Due to a Bicycle Brake Handle
Authors: Sathish K , Chaudhari Vinod Ashok , Murthy Abilash Srinivasa 
Published: July 2018

Abstract
Transorbital intracranial injuries are uncommon and mostly accidental in nature. These injuries are usually associated with high mortality. The key to preventing this mortality involves an early diagnosis of intracranial injuries and immediate and appropriate management. Any delay can pose a serious risk to the patient’s life. A case of a 55-year-old man who had experienced an accidental self-fall while riding a bicycle is presented. Initially, he was treated at a primary health center. He was referred to the tertiary care institute due to unavailability of ancillary investigation at the primary health center. He was declared dead on arrival at the casualty in the tertiary institute. On autopsy, it was observed that the injury above the right side of the upper eyelid was penetrating the right side roof of the orbit and the right cerebral cortex and brainstem. The highlighting feature of the case is that, despite the fatal penetrating brain injury, the eyeball did not sustain any major injury.
Rethinking Regenerative Medicine From a Transplant Perspective (and Vice Versa)
Authors: Orlando Giuseppe , Murphy Sean V. , Bussolati Benedetta , Clancy Marc , Cravedi Paolo , Migliaccio Giovanni , Murray Patricia 
Published: July 2018

Abstract
No field in health sciences has more interest than organ transplantation in fostering progress in regenerative medicine (RM) because the future of no other field more than the future of organ transplantation will be forged by progress occurring in RM. In fact, the most urgent needs of modern transplant medicine, namely, more organs to satisfy the skyrocketing demand and immunosuppression-free transplantation, cannot be met in full with current technologies and are at risk of remaining elusive goals. Instead, in the past few decades, groundbreaking progress in RM is suggesting a different approach to the problem. New, RM-inspired technologies among which decellularization, 3-dimensional printing and interspecies blastocyst complementation, promise organoids manufactured from the patients' own cells and bear potential to render the use of currently used allografts obsolete. Transplantation, a field that has traditionally been immunology-based, is therefore destined to become a RM-based discipline. However, the contours of RM remain unclear, mainly due to the lack of a universally accepted definition, the lack of clarity of its potential modalities of application and the unjustified and misleading hype that often follows the reports of clinical application of RM technologies. All this generates excessive and unmet expectations and an erroneous perception of what RM really is and can offer. In this article, we will (1) discuss these aspects of RM and transplant medicine, (2) propose a definition of RM, and (3) illustrate the state of the art of the most promising RM-based technologies of transplant interest.
Deep Profiling of the CD8+ T-cell Compartment Identifies Activated Cell Subsets and Multifunctional Responses Associated With Control of Cytomegalovirus Viremia
Authors: Ferreira Victor H. , Kumar Deepali , Humar Atul 
Published: July 2018

Background.
Human cytomegalovirus (HCMV) is a common opportunistic pathogen in transplant recipients. Patterns of viremia and reactivation are influenced by the host immune response, including CD8+ T cells. However, the cellular deficits or phenotypic differences that account for differential outcomes during HCMV viremia are incompletely understood.

Methods.
Peripheral blood mononuclear cells were collected from 20 transplant recipients (10 viremia controllers and 10 noncontrollers) at onset of HCMV viremia and 4 weeks postonset. We used mass cytometry to perform in-depth characterization of cell surface and intracellular CD8+ T cell markers and to compare frequencies of these cells between groups.

Results.
Deep profiling identified 2 central memory T cell subsets at onset and 5 terminally differentiated memory T (TEMRA) cell subsets at 4 weeks that were associated with control of HCMV viremia, in addition to 6 TEMRA subsets at onset and 4 weeks associated with relapsing or remitting HCMV viremia. In general, CD8+ T-cell clusters associated with poorly controlled HCMV viremia lacked markers of activation or terminal differentiation including CD38, CD69, CD25, CD57, and HLA-DR. We also measured the production of 8 HCMV-specific effector molecules (TNFα, IFNγ, interleukin 2, granzyme B, perforin, macrophage inflammatory protein 1β, interleukin 10, and CD107a) in CD8+ T cells. Viremia controllers had greater diversity of HCMV-specific multifunctional responses at both time points, including significantly higher frequencies of HCMV-specific TNFα+IFNγ+ CD8+ T cells at onset. These multifunctional cells had a phenotype consistent with activated TEM/TEMRA cells.

Conclusions.
Uncontrolled CMV viremia is associated with specific clusters of memory T-cell subsets and lower frequencies of HCMV-specific multifunctional CD8+ T cells.
DNA Methylation Explains a Subset of Placental Gene Expression Differences Based on Ancestry and Altitude
Authors: Gundling William E. , Pantham Priyadarshini , Illsley Nicholas P , Echalar Lourdes , Zamudio Stacy , Wildman Derek E. 
Published: July 2018

Abstract:Objectives: The most pronounced effect of high altitude (>2700m) on reproductive outcomes is reduced birth weight. Indigenous Bolivians (Andean Native Americans) residing for generations at high altitudes have higher birth weights relative to more recent migrants of primarily European ancestry. Previous research demonstrated that the placenta is a key contributor to the preservation of Andean birth weight at high altitude. Our current research investigated how gene expression and epigenetics contributes to the conservation of birth weight at high altitude by examining mRNA expression and DNA methylation differences between placentas of Andeans and those of European ancestry residing at high and low altitude.Methods: Genome-wide mRNA expression and DNA methylation of villous placenta tissue was quantified utilizing microarray technology. Subjects were of Andean and European ancestry and resident at high (3600m) or low (400m) altitudes. Differentially expressed genes (DEGs) associated with altitude or ancestry were identified (FDR<0.1, |fold change|>1.25). To predict which DEGs could be regulated by methylation we tested for correlation between gene expression and methylation values.Results: 69 DEGs associated with altitude (n=36) or ancestry (n=34) were identified. Altitude-associated DEGs included members of the AP-1 transcription factor family. Ancestry-associated DEGs were implicated in inflammatory pathways and associated with pro-angiogenic macrophages. More ancestry-associated DEGs correlated significantly (n=17) (FDR<0.1) with promoter or gene body methylation (p=0.0242) when compared to altitude associated DEGs (n=8).Conclusions:Compared to altitude-associated DEGs, methylation regulates more ancestry-associated DEGs, potentially allowing for rapid modification in the expression of inflammatory genes to attract pro-angiogenic macrophages as a means of promoting placental capillary growth in Andeans, regardless of altitude.
Dynamics of Cas10 Govern Discrimination between Self and Nonself in Type III CRISPR-Cas Immunity
Authors: Wang Ling , Mo Charlie Y. , Wasserman Michael R. , Rostøl Jakob T. , Marraffini Luciano A. , Liu Shixin 
Published: July 2018

ABSTRACTAdaptive immune systems are required to accurately distinguish between self and nonself in order to defend against invading pathogens while avoiding autoimmunity. Type III CRISPR-Cas systems employ guide RNAs that recognize complementary RNA molecules to trigger the degradation of both the target transcript and its template DNA. These systems can broadly eliminate foreign targets with multiple mutations, but still effectively curb immunity against the host. The molecular basis for these unique features remains unknown. Here we use single-molecule fluorescence microscopy to study the interaction between a type III-A ribonucleoprotein complex and various RNA substrates. We find that Cas10—the DNase effector of the complex—displays rapid conformational fluctuations on foreign RNA targets, but is locked in a static configuration on self RNA. Single-stranded DNA promotes Cas10’s occupancy at a selected set of conformational states, which is also sensitively modulated by target mutations and predictive of CRISPR interference activity. These findings highlight the central role of the internal dynamics of CRISPR-Cas complexes in self/nonself discrimination and target specificity.
PIP4Ks Suppress Insulin Signaling Through a Catalytic-Independent Mechanism
Authors: Wang Diana G. , Paddock Marcia N. , Lundquist Mark R. , Sun Janet Y. , Mashadova Oksana , Amadiume Solomon , Bumpus Timothy W. , Hodakoski Cindy , Hopkins Benjamin D. , Fine Matthew , Hill Amanda , Jonathan Yang T. , Baskin Jeremy M. , Dow Lukas E. , Cantley Lewis C. 
Published: July 2018

SUMMARYInsulin stimulates conversion of phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) to phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P3), which mediates downstream cellular responses. PI(4,5)P2is produced by phosphatidylinositol-4-phosphate 5-kinases (PIP5Ks) and byphosphatidylinositol-5-phosphate 4-kinases (PIP4Ks). Here we show that deletion of the three genes that encode PIP4Ks (PIP4K2A, PIP4K2BandPIP4K2C)in vitroresults in a paradoxical increase in PI(4,5)P2and a subsequent increase in insulin-stimulated production of PI(3,4,5)P3. Surprisingly, reintroduction of either wild-type or kinase-dead forms of the PIP4Ks restored cellular PI(4,5)P2levels and insulin stimulation of the PI3K pathway. These effects are explained by an increase in PIP5K activity upon deletion of PIP4Ks, which we demonstrate can suppress PIP5K activityin vitrothrough a direct binding interaction. Collectively, our work reveals an important non-catalytic function of PIP4Ks in suppressing PIP5K-mediated PI(4,5)P2synthesis and insulin-dependent conversion to PI(3,4,5)P3by PI3K enzymes and suggests that pharmacological depletion of PIP4K enzymes using emerging degrader technologies could represent a novel strategy for stimulating insulin signaling.
Antibiotic treatment protocols revisited: The challenges of a conclusive assessment by mathematical modeling
Authors: Uecker Hildegard , Bonhoeffer Sebastian 
Published: July 2018

AbstractHospital-acquired bacterial infections lead to prolonged hospital stays and increased mortality. The problem is exacerbated by antibiotic resistant strains that delay or impede effective treatment. To ensure a successful therapy and to manage antibiotic resistance, treatment protocols that draw on several different antibiotics might be used. This includes the administration of drug cocktails to individual patients (“combination therapy”) but also the random assignment of drugs to different patients (“mixing”) and a regular switch in the default drug used in the hospital from drug A to drug B and back (“cycling”). For the past 20 years, mathematical models have been used to assess the prospects of antibiotic combination therapy, mixing, and cycling. But while tendencies in their ranking across studies have emerged, the picture remains surprisingly inconclusive and incomplete. In this article, we review existing modeling studies and demonstrate by means of examples how methodological factors complicate the emergence of a consistent picture. These factors include the choice of the criterion by which the effects of the protocols are compared, the model implementation, and its analysis. We thereafter discuss how progress can be made and suggest future modeling directions.
TWAS pathway method greatly enhances the number of leads for uncovering the molecular underpinnings of psychiatric disorders
Authors: Chatzinakos Chris , Lee Donghyung , Cai Na , Vladimirov Vladimir I. , Docherty Anna , Webb Bradley T. , Riley Brien P. , Flint Jonathan , Kendler Kenneth S. , Daskalakis Nikolaos , Bacanu Silviu-Alin 
Published: July 2018

ABSTRACTGenetic signal detection in genome-wide association studies (GWAS) is enhanced by pooling small signals from multiple Single Nucleotide Polymorphism (SNP), e.g. across genes and pathways. Because genes are believed to influence traits via gene expression, it is of interest to combine information from expression Quantitative Trait Loci (eQTLs) in a gene or genes in the same pathway. Such methods, widely referred as transcriptomic wide association analysis (TWAS), already exist for gene analysis. Due to the possibility of eliminating most of the confounding effect of linkage disequilibrium (LD) from TWAS gene statistics, pathway TWAS methods would be very useful in uncovering the true molecular bases of psychiatric disorders. However, such methods are not yet available for arbitrarily large pathways/gene sets. This is possibly due to it quadratic (in the number of SNPs) computational burden for computing LD across large regions. To overcome this obstacle, we propose JEPEGMIX2-P, a novel TWAS pathway method that i) has a linear computational burden, ii) uses a large and diverse reference panel (33K subjects), iii) is competitive (adjusts for background enrichment in gene TWAS statistics) and iv) is applicable as-is to ethnically mixed cohorts. To underline its potential for increasing the power to uncover genetic signals over the state-of-the-art and commonly used non-transcriptomics methods, e.g. MAGMA, we applied JEPEGMIX2-P to summary statistics of most large meta-analyses from Psychiatric Genetics Consortium (PGC). While our work is just the very first step toward clinical translation of psychiatric disorders, PGC anorexia results suggest a possible avenue for treatment.
Plasticity in the glucagon interactome reveals novel proteins that regulate glucagon secretion in αTC1-6 cells
Authors: Asadi Farzad , Dhanvantari Savita 
Published: July 2018

AbstractGlucagon is stored within secretory granules of pancreatic alpha cells until a stimulus, such as a change in microenvironmental conditions, triggers its release. We hypothesized that the secretory response of the alpha cell to various stimuli could be determined by plasticity in the network of proteins that interact with glucagon within alpha cell secretory granules. To answer this question, we isolated secretory granules from alpha TC1-6 cells and identified glucagon-interacting proteins by affinity purification coupled with liquid chromatography/tandem mass spectrometry. Proteomic analyses revealed a network of cytoplasmic and histone proteins. Specifically, the interaction between glucagon and histone H4 and the ER stress protein GRP78 was confirmed through co-immunoprecipitation of secretory granule lysates, and co-localization within secretory granules using high-resolution confocal microscopy. The composition of these networks was altered at different glucose levels (25 mM vs 5.5 mM) and in response to the paracrine inhibitors of glucagon secretion, GABA and insulin. Finally, siRNA-mediated silencing of a subset of nonhistone proteins revealed novel proteins that may regulate glucagon secretion. We have therefore described a novel and dynamic glucagon interactome within alpha cell secretory granules, and suggest that plasticity in the interactome governs the alpha cell secretory response to paracrine and nutritional stimuli.
Sensitivity to Affective Touch Depends on Adult Attachment Style
Authors: Krahé Charlotte , Mohr Mariana von , Gentsch Antje , Guy Lisette , Vari Chiara , Nolte Tobias , Fotopoulou Aikaterini 
Published: July 2018

AbstractAffective touch supports affiliative bonds and social cognition. However, it remains unknown whether pre-existing models of social relating influence the perception of affective touch. Here, we present the first study (N=44) to examine how individual differences in attachment styles relate to the perception of affective touch, as well as to a different non-social modality of interoception, namely cardiac perceived accuracy. Using the gold standard assessment of adult attachment (Adult Attachment Interview), we found that insecure attachment was associated with reduced pleasantness discrimination between affective vs. non-affective, neutral touch. Acknowledging the different traditions in measuring attachment, we also used a well-validated self-report questionnaire that pertains to explicit representations of current close relationships. Using this measure, we found that higher scores on an attachment anxiety dimension (but not an attachment avoidance) were associated with reduced pleasantness discrimination between affective vs. non-affective, neutral touch. Attachment patterns (in both measures) were not related to cardiac perception accuracy. These results corroborate and extend previous literature on the affectivity of touch and its relation with affiliative bonds and social cognition. Given that attachment was not related to perceived cardiac accuracy, these findings point to the specificity of the relationship between affective touch and attachment.
Parkinson’s disease-linked Parkin mutations impair glutamatergic synaptic transmission and plasticity
Authors: Zhu Mei , Cortese Giuseppe P. , Waites Clarissa L. 
Published: July 2018

AbstractParkinson’s disease (PD)-associated E3 ubiquitin ligase Parkin is enriched at glutamatergic synapses, where it ubiquitinates multiple substrates, suggesting that its mutation/loss-of-function could contribute to the etiology of PD by disrupting excitatory neurotransmission. Here, we evaluate the impact of four common PD-associated Parkin point mutations (T240M, R275W, R334C, G430D) on glutamatergic synaptic function in hippocampal neurons. We find that expression of these point mutants in Parkin-deficient and -null backgrounds alters NMDA and AMPA receptor-mediated currents and cell-surface levels, and prevents the induction of long-term depression. Mechanistically, we demonstrate that Parkin regulates NMDA receptor trafficking through its ubiquitination of GluN1, and that all four mutants are impaired in this ubiquitinating activity. Furthermore, Parkin regulates synaptic AMPA receptor trafficking via its binding and retention of the postsynaptic scaffold Homer1, and all mutants are similarly impaired in this capacity. Our findings demonstrate that pathogenic Parkin mutations disrupt glutamatergic synaptic transmission and plasticity by impeding NMDA and AMPA receptor trafficking, and through these effects likely contribute to the pathophysiology of PD inPARK2patients.
Kinase Driver Mutations in Protein-protein Structure may associate to Disease by Effecting Kinase Stability
Authors: Chen Jing , Xu Yali , Gao Yunjing , Lu Xiaoquan 
Published: July 2018

ABSTRACTActivating mutations are significant drug targets of diseases. Statistical analysis on the mutated amino acids, the mutation characteristic and the related disease information of activating mutations is of great significance for the diagnosis and treatment of diseases. Study on the protein stability by predicting Gibbs free energy (ΔΔG) change after mutation is very helpful for understanding the relationship between protein structure and function. By combining mCSM and disease datasets, this paper studies the effect of mutation on the protein stability and disease. The results show that the mutations in protein may be the cause of disease for PPI structures, which statistically afford significant information for disease related research and medical diagnosis and treatment.
Modeling membrane nanotube morphology: the role of heterogeneity in composition and material properties
Authors: Alimohamadi Haleh , Ovryn Ben , Rangamani Padmini 
Published: July 2018

AbstractMembrane nanotubes have been identified as dynamic structures for cells to connect over long distances. Nanotubes typically appear as thin and cylindrical tubes, but they may also have a beaded architecture along the tube. In this paper, we study the role of membrane mechanics in governing the architecture of these tubes and show that the formation of beadlike structures along the nanotubes can result from local heterogeneities in the membrane either due to protein aggregation or due to membrane composition. We present numerical results that predict how membrane properties, protein density, and local tension compete to create a phase space that governs the morphology of a nanotube. We also find that there is an energy barrier that prevents two beads from fusing. These results suggest that the membrane-protein interaction, membrane composition, and membrane tension closely govern the tube radius, number of beads, and the bead morphology.
How closely do blood gas electrolytes and haemoglobin agree with serum values in adult emergency department patients: An observational study
Authors: Gibbons Michael , Klim Sharon , Mantzaris Arthur , Dillon Oliver , Kelly Anne‐Maree 
Published: July 2018

AbstractObjectiveThe aims of this study were to establish the bias (mean difference) and 95% limits of agreement (LoA) between electrolyte values (sodium and potassium) and haemoglobin between whole blood analysed by the ED resuscitation room blood gas analyser and specimens analysed using standard techniques in the central hospital laboratory and to determine the proportion of analyses falling outside defined clinically acceptable LoA and pathology expert defined standards.MethodsProspective cohort study. Paired blood gas analyser and laboratory samples taken no more than 10 min apart were included. The primary outcome of interest was bias and 95% LoA by Bland–Altman analysis. Subgroup analyses for values outside the normal range were also conducted.ResultsThree hundred and fifty‐two sample pairs were included in the analysis. For sodium concentration the bias was 0.6 mmol/L (95% LoA −3.3 to 4.6 mmol/L). For potassium concentration the bias was 0.21 mmol/L (95% LoA −0.36 to 0.79 mmol/L). For haemoglobin concentration the bias was −1.6 g/dL (95% LoA −10.2 to 6.9 g/dL). For sodium and haemoglobin concentrations, >95% of results fell within the defined clinically acceptable limits. For potassium concentration, >90% of results fell within the defined clinically acceptable limits. In general, serum sodium and potassium concentrations were slightly higher than blood gas levels and for haemoglobin serum levels were slightly lower.ConclusionAgreement between blood gas analysis and laboratory analysis for sodium, potassium and haemoglobin concentrations shows acceptable agreement for use in time critical clinical decision‐making in ED.