bluuebunny/crossref_metadata_2025_split huggingface dataset:
Practice Change From Intermittent Medication Boluses to Bolusing From a Continuous Infusion in Pediatric Critical Care: A Quality Improvement Project
Authors: Hochstetler Jessica L. , Thompson A. Jill , Ball Natalie M. , Evans Melissa C. , Frame Shaun C. , Haney A. Lauren , Little Amelia K. , O’Donnell Jaime L. , Rickett Bryna M. , Mack Elizabeth H. 
Published: April 2018

Objectives:
To determine whether implementing a guideline to bolus medications from continuous infusions in PICUs affects nursing satisfaction, patient safety, central line entries, medication utilization, or cost.

Design:
This is a pre- and postimplementation quality improvement study.

Setting:
An 11-bed ICU and 14-bed cardiac ICU in a university-affiliated children’s hospital.

Patients:
Patients less than 18 years old admitted to the PICU or pediatric cardiac ICU receiving a continuous infusion of dexmedetomidine, midazolam, fentanyl, morphine, vecuronium, or cisatracurium from May 2015 to May 2016, excluding November 2015 (washout period), were eligible for inclusion.

Interventions:
Change in practice from administering bolus doses from an automated dispensing machine to administering bolus medications from continuous infusion in PICUs.

Measurements and Main Results:
Timing studies were conducted pre- and post implementation in 29 and 26 occurrences, respectively. The median time from the decision to give a bolus until it began infusing decreased by 169 seconds (p < 0.01). Nursing satisfaction increased from 19.3% pre- to 100% post implementation. Safety was assessed via barcode scanning compliance, which decreased by 1.4% for patients and 1% for medications, and smart pump limit overrides. The percentage of infusion pump bolus overrides increased as expected, with the majority (99%) of these exceeding soft maximum limits by less than two-fold. Central line entries were unaffected post implementation. To assess medication utilization, a total of 50 patients in each intervention group were selected for retrospective chart review. Daily fentanyl boluses increased from one to three (p = 0.021). However, midazolam infusion dose and fentanyl infusion duration decreased (p = 0.026 and p = 0.005, respectively). Medication utilization was otherwise unchanged post implementation (p > 0.05). Annualized cost avoidance was $124,160.

Conclusions:
Implementation of bolus medications from continuous infusion in PICUs significantly decreased time to begin a bolus dose and increased nursing satisfaction. The practice change also improved medication utilization without negatively impacting patient safety.
Our Surgical Repair for Macrostomia with Two Novel Small Triangular Flaps: Long-Term Follow-Up and Results
Authors: Tsumoto Jumpei , Imai Keisuke , Masuoka Takeshi , Sakahara Daisuke , Kawamoto Koji , Kang Songsu , Komune Hiroyuki 
Published: April 2018

Summary:
The surgical methods for repairing congenital macrostomia should be carefully selected from both functional and aesthetic points of view. The surgical correction of macrostomia results in normal orbicularis oris function and symmetry of the repaired lip. In this article, the authors report their novel technique and the results obtained, assessed retrospectively. Twelve primary cases of macrostomia underwent surgical repair between 1996 and 2013. The age at surgery ranged from 3 to 78 months. The authors’ operative procedure uses two small triangular flaps with a superficial layer of orbicularis muscle to preserve the dynamic action of muscle fibers attached to the skin of the triangular flaps, with suturing across the orbicularis muscle bundles. The optimal length of a medial small triangular flap is 1.5 to 2.0 mm, and the length of a lateral flap is 5 to 8 mm. Evaluation was based on the degree of symmetry of the lips as a ratio of the affected side to the unaffected side, and the scar characteristics. The follow-up period in this retrospective study ranged from 3 to 21 years. The same method was applied to all 12 cases in the reconstruction of a natural appearance and dynamic function of the oral commissure, and the results over several years showed satisfactory outcomes. The authors’ technique is very useful in the primary surgery for macrostomia, as the dynamic action of muscle fibers is preserved, if the muscle is not dissected from the skin in the cleft margin that includes the two medial small triangular flaps.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, V.
Surgeon Volume and the Outcomes of Dupuytren’s Surgery: Results from a Dutch Multicenter Study
Authors: Zhou Chao , Ceyisakar Iris E. , Hovius Steven E. R. , Feitz Reinier , Slijper Harm P. , Lingsma Hester F. , Selles Ruud W. 
Published: April 2018

Background:
For many major surgical procedures, the outcomes are better when performed by surgeons with higher procedure volumes. The purpose of this study was to examine the relations between surgeon procedure volume and the outcomes of Dupuytren’s surgery.

Methods:
The authors conducted an observational study from 2011 to 2014 at six dedicated hand surgery practice sites in The Netherlands. Five hundred eighty-eight patients underwent surgery for Dupuytren’s contracture performed by one of the 16 surgeons. The main exposure variable was annual surgeon volume. Outcome measures were the degree of residual contracture, full release rate, and any postoperative adverse event examined within 3 months of surgery.

Results:
Mean annual surgeon volume was 51 among the 16 surgeons(range; 4-86) procedures. The majority of patients had primary disease (79 percent) and underwent open fasciectomy (74 percent). Multivariable regression analyses showed that surgeon volume was linearly related to all three outcomes, and identified no optimal volume threshold. Performing 10 additional procedures annually was independently associated with nearly 0.8 degree less residual contracture (p = 0.002), 9 percent higher odds of attaining a full release (p = 0.037), and 11 percent lower odds of an adverse event (p < 0.001). Nonetheless, patient-related factors had larger impacts on all three clinical outcomes than surgeon volume.

Conclusions:
In this study of practicing hand surgeons, surgeon volume varied widely, and a higher volume was associated with less postoperative residual contracture, higher full release rates, and fewer adverse events. This implies that increasing surgeon’s procedure volume provides an opportunity for improving the outcomes of Dupuytren’s surgery.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, III.
Opportunistic Bone Density Measurement on Abdomen and Pelvis Computed Tomography to Predict Fracture Risk in Women Aged 50 to 64 Years Without Osteoporosis Risk Factors
Authors: Fang Jieming , Franconeri Andrea , Boos Johannes , Nimhuircheartaigh Jennifer , Zhang Zheng , Brook Alexander , Brook Olga R. 
Published: April 2018

ObjectiveThe aim of this study is to evaluate opportunistic vertebral bone density measurement in abdominal and pelvic computed tomography (CT) to predict future osteoporotic fracture in women aged 50 to 64 years without known osteoporosis risk factors.MethodsConsecutive female patients 50 to 64 years old without osteoporosis risk factors with 2 CT examinations more than 10 years apart were included. Vertebral height and bone density in each vertebra from T10 to L5 were measured. Vertebral fractures were diagnosed on CT preformed 10 years after the original CT and through online medical records.ResultsThirty (15%) of 199 patients developed osteoporotic fracture. Bone density was lower in patients who developed fractures compared with those who did not (P< 0.05). Development of osteoporotic fracture of any grade was predicted for patients having bone density less than 180 HU at L4 with sensitivity of 90% (95% confidence interval, 74%–97%) and specificity of 43% (95% confidence interval, 34%–50%).ConclusionsOpportunistic bone density screening can identify women at elevated risk of developing fractures within 10 years.
Overall Disability Sum Score for Clinical Assessment of Neurological Involvement in Eosinophilic Granulomatosis With Polyangiitis
Authors: Padoan Roberto , Marconato Maddalena , Felicetti Mara , Cinetto Francesco , Cerchiaro Mariachiara , Rizzo Francesca , Marcolongo Renzo , Punzi Leonardo , Agostini Carlo , Schiavon Franco 
Published: April 2018

AimThe aim of this study was to verify the application of Overall Disability Sum Score (ODSS) for standardized clinical assessment of neurological involvement in patients with eosinophilic granulomatosis with polyangiitis (EGPA) and its correlation with treatment response and long-term outcomes.MethodsConsecutive EGPA patients referred to our tertiary vasculitis center were retrospectively evaluated. Patients' neurological damage and disability were systematically assessed with Vasculitis Damage Index and ODSS.ResultsFifty EGPA patients were included in the study with a median follow-up of 75 months (9–180 months). Twenty-five (50%) developed peripheral neuropathy, 17 (68%) presented mononeuritis multiplex, whereas 8 (32%) had symmetric polyneuropathy. Patients with neurological involvement were older (56.3 ± 13.4 vs. 44.4 ± 12.1 years,P< 0.0009), more frequently antineutrophil cytoplasmic antibody positive (48% vs. 16%,P= 0.015), and were more likely to have renal involvement (24% vs. 0%,P= 0.022). An early clinical response to therapy was observed within 6 months of treatment, resulting in a significant decrease in ODSS, which fell from the baseline value of 4.2 ± 2.4 to 2.9 ± 1.5 (P= 0.0001), whereas only a slow decreasing pattern was noted over the long-term period. However, all subjects developed neurological impairment and disability despite remission from active vasculitis. Patients with ODSS of greater than 3 at baseline (n = 13 [52%]) retained a higher score at the last examination (P< 0.001), predicting a low therapeutic response. Furthermore, ODSS of greater than 3 was found associated with more neurological relapses (53.8% vs. 0%,P= 0.027).ConclusionOverall Disability Sum Score could be a rapid, simple, reliable instrument to evaluate the severity of disability and nerve damage due to neurological involvement caused by vasculitis and to predict, at presentation, improvement and risk of neurological worsening.
Convergent evidence for predispositional effects of brain gray matter volume on alcohol consumption
Authors: Baranger David AA , Demers Catherine H. , Elsayed Nourhan M. , Knodt Annchen R. , Radtke Spenser R. , Desmarais Aline , Agrawal Arpana , Heath Andrew C. , Barch Deanna M. , Squeglia Lindsay M. , Williamson Douglas E. , Hariri Ahmad R. , Bogdan Ryan 
Published: April 2018

ABSTRACTBackgroundAlcohol use has been reliably associated with smaller subcortical and cortical regional gray matter volumes (GMVs). Whether these associations reflect shared predisposing risk factors and/or causal consequences of alcohol use remains poorly understood.MethodsData came from 3 neuroimaging samples (total n=2,423), spanning childhood/adolescence to middle age, with prospective or family-based data. First, we identified replicable GMV correlates of alcohol use. Next, we used family-based and longitudinal data to test whether these associations may plausibly reflect a predispositional liability for alcohol use, and/or a causal consequence of alcohol use. Finally, we evaluated whether GWAS-defined genomic risk for alcohol consumption is enriched for genes preferentially expressed in regions identified in our neuroimaging analyses, using heritability and gene-set enrichment, and transcriptome-wide association study (TWAS) approaches.ResultsSmaller right dorsolateral prefrontal cortex (DLPFC; i.e., middle and superior frontal gyri) and insula GMVs were associated with increased alcohol use across samples. Family-based and prospective longitudinal data suggest these associations are genetically conferred and that DLPFC GMV prospectively predicts future use and initiation. Genomic risk for alcohol use was enriched in gene-sets preferentially expressed in the DLPFC and associated with differential expression of C16orf93, CWF19L1, and C18orf8 in the DLPFC.ConclusionsThese data suggest that smaller DLPFC and insula GMV plausibly represent predispositional risk factors for, as opposed to consequences of, alcohol use. Alcohol use, particularly when heavy, may potentiate these predispositional risk factors. DLPFC and insula GMV represent promising biomarkers for alcohol consumption liability and related psychiatric and behavioral phenotypes.
Performance of an IAVI-African Network of Clinical Research Laboratories in Standardized ELISpot and Peripheral Blood Mononuclear Cell Processing in Support of HIV Vaccine Clinical Trials
Authors: Langat Robert , Farah Bashir , Indangasi Jackton , Ogola Simon , Omosa-Manyonyi Gloria , Anzala Omu , Bizimana Jean , Tekirya Emmanuel , Ngetsa Caroline , Silwamba Moses , Muyanja Enoch , Chetty Paramesh , Jangano Maureen , Hills Nancy , Gilmour Jill , Dally Len , Cox Josephine H. , Hayes Peter 
Published: April 2018

AbstractImmunological assays performed in different laboratories participating in multi-centre clinical trials must be standardized in order to generate comparable and reliable data. This entails standardized procedures for sample collection, processing, freezing and storage. The International AIDS Vaccine Initiative (IAVI) partnered with local institutions to establish Good Clinical Laboratory Practice (GCLP)-accredited laboratories to support clinical trials in Africa, Europe and Asia. Here we report on the performance of seven laboratories based in Africa and Europe in the interferon-gamma enzyme-linked immunospot (IFN-γ ELISpot) assay and peripheral blood mononuclear cell (PBMC) processing over four years. Characterized frozen PBMC samples from 48 volunteer blood packs processed at a central laboratory were sent to participating laboratories. For each stimulus, there were 1751 assays performed over four years. 98% of these ELISpot data were within acceptable ranges with low responses to mock stimuli. There were no significant differences in ELISpot responses at five laboratories actively conducting immunological analyses in support of IAVI sponsored clinical trials or HIV research. In a separate study, 1,297 PBMC samples isolated from healthy HIV-1 negative participants in clinical trials of two prophylactic HIV vaccine candidates were analysed for PBMC yield from fresh blood and cell recovery and viability following freezing and thawing. 94 % and 96 % of samples had fresh PBMC viabilities and cell yields within the pre-defined acceptance criteria while for frozen PBMC, 99 % and 96 % of samples had acceptable viabilities and cell recoveries respectively, along with acceptable ELISpot responses in 95%. These findings demonstrate the competency of laboratories across different continents to generate comparable and reliable data in support of clinical trials.ImportanceThere is a need for the establishment of an African network of laboratories to support large clinical trials across the continent to support and further the development of vaccine candidates against emerging infectious diseases such as Ebola, Zika and dengue viruses and the continued HIV-1 pandemic. This is particularly true in sub-Saharan Africa where the HIV-1 pandemic is most severe. In this report we have demonstrated by using standardized SOPs, training, equipment and reagents that GCLP-accredited clinical trial laboratories based in Africa and Europe can process clinical trial samples and maintain cell integrity and functionality demonstrated by IFN-γ ELISpot testing, producing comparable and reliable data.
Improvements to the rice genome annotation through large-scale analysis of RNA-Seq and proteomics datasets
Authors: Ren Zhe , Qi Da , Pugh Nina , Li Kai , Wen Bo , Zhou Ruo , Xu Shaohang , Liu Siqi , Jones Andrew R 
Published: April 2018

AbstractRice (Oryza sativa) is one of the most important worldwide crops. The genome has been available for over 10 years and has undergone several rounds of annotation. We created a comprehensive database of transcripts from 29 public RNA sequencing datasets, officially predicted genes from Ensembl plants, and common contaminants in which to search for protein-level evidence. We re-analysed nine publicly accessible rice proteomics datasets. In total, we identified 420K peptide spectrum matches from 47K peptides and 8,187 protein groups. 4168 peptides were initially classed as putative novel peptides (not matching official genes). Following a strict filtration scheme to rule out other possible explanations, we discovered 1,584 high confidence novel peptides. The novel peptides were clustered into 692 genomic loci where our results suggest annotation improvements. 80% of the novel peptides had an ortholog match in the curated protein sequence set from at least one other plant species. For the peptides clustering in intergenic regions (and thus potentially new genes), 101 loci were identified, for which 43 had a high-confidence hit for a protein domain. Our results can be displayed as tracks on the Ensembl genome or other browsers supporting Track Hubs, to support re-annotation of the rice genome.
The molecular structure of Schistosoma mansoni PNP isoform 2 provides insights into the nucleotide selectivity of PNPs
Authors: Torini Juliana Roberta , Romanello Larissa , Batista Fernanda Aparecida Heleno , Serrão Vitor Hugo Balasco , Faheem Muhammad , Zeraik Ana Eliza , Bird Louise , Nettleship Joanne , Reddivari Yamini , Owens Ray , DeMarco Ricardo , Borges Júlio César , Brandão-Neto José , Pereira Humberto D’Muniz 
Published: April 2018

AbstractPurine nucleoside phosphorylases (PNPs) play an important role in the blood fluke parasite Schistosoma mansoni as a key enzyme of the purine salvage pathway. Here we present the structural and kinetic characterization of a new PNP isoform from S. mansoni, named as SmPNP2. Screening of different ligands using a thermofluorescence approach indicated cytidine and cytosine as potential ligands. The binding of cytosine was confirmed by isothermal titration calorimetry, with a KD of 27 μM, and kinetic parameters for cytidine catalysis were obtained by ITC resulting in a KM of 76.3 μM. SmPNP2 also displays catalytic activity against inosine and adenosine, making it the first described PNP with robust catalytic activity towards both pyrimidines and purines. Crystallographic structures of SmPNP2 with different ligands were obtained and comparison of these structures with the previously described S. mansoni PNP (SmPNP1) provided clues for the unique capability of SmPNP2 to bind pyrimidines. When compared with the structure of SmPNP1, substitutions in the vicinity of SmPNP2 active site alter the architecture of the nucleoside base binding site allowing an alternative binding mode for nucleosides, with a 180° rotation from the canonical binding mode. The remarkable plasticity of this binding site deepens the understanding of the correlation between structure and nucleotide selectivity, offering new ways to analyses PNP activity.Author SummarySchistosoma mansoni is a human parasite dependent on purine salvage for purine bases supply. Purine nucleoside phosphorylase (PNP) is a key enzyme in this pathway. It carries two PNP isoforms, one previously characterized (SmPNP1) and one unknown (SmPNP2). Here we present the crystallographic structure of SmPNP2 and its complex with cytosine, cytidine, ribose-l-phosphate, adenine, hypoxanthine, and tubercidin. Cytidine and cytosine were identified as ligands of SmPNP2 using a thermofluorescence approach. Binding of cytosine was proven by Isothermal Titration Calorimetry (ITC) and cytidine, inosine, and adenosine kinetic parameters were also obtained. Purine bases showed different binding in the active site, rotated 180° from the canonical binding mode. It’s the first report showing a Low Molecular Mass PNP capable of catalyzing both types of nucleotide bases. The SmPNP2 odd behavior sheds a new light on the Schistosoma mansoni’s life cycle metabolic adaptation.
Design of Transcranial Magnetic Stimulation Coils with Optimal Trade-off between Depth, Focality, and Energy
Authors: Gomez Luis J. , Goetz Stefan M. , Peterchev Angel V. 
Published: April 2018

ABSTRACTBackgroundTranscranial magnetic stimulation (TMS) is a noninvasive brain stimulation technique used for research and clinical applications. Existent TMS coils are limited in their precision of spatial targeting (focality), especially for deeper targets.ObjectiveThis paper presents a methodology for designing TMS coils to achieve optimal trade-off between the depth and focality of the induced electric field (E-field), as well as the energy required by the coil.MethodsA multi-objective optimization technique is used for computationally designing TMS coils that achieve optimal trade-offs between stimulation focality, depth, and energy (fdTMS coils). The fdTMS coil winding(s) maximize focality (minimize stimulated volume) while reaching a target at a specified depth and not exceeding predefined peak E-field strength and required coil energy. Spherical and MRI-derived head models are used to compute the fundamental depth–focality trade-off as well as focality–energy trade-offs for specific target depths.ResultsAcross stimulation target depths of 1.0–3.4 cm from the brain surface, the stimulated volume can be theoretically decreased by 42%–55% compared to existing TMS coil designs. The stimulated volume of a figure-8 coil can be decreased by 36%, 44%, or 46%, for matched, doubled, or quadrupled energy. For matched focality and energy, the depth of a figure-8 coil can be increased by 22%.ConclusionComputational design of TMS coils could enable more selective targeting of the induced E-field. The presented results appear to be the first significant advancement in the depth–focality trade-off of TMS coils since the introduction of the figure-8 coil three decades ago, and likely represent the fundamental physical limit.DECLARATION OF INTERESTThe fdTMS technology described in this paper is subject to a provisional patent application by Duke University with the authors as inventors. Additionally: L.J.G. is inventor on a patent pertaining to the design of focal multicoil TMS systems. S.M.G. is inventor on patents and patent applications; he has received royalties from Rogue Research, TU Muenchen, and Porsche; furthermore, he has been provided with research support and patent fee reimbursement from Magstim Co. A.V.P. is inventor on patents and patent applications, and has received research and travel support as well as patent royalties from Rogue Research; research and travel support, consulting fees, as well as equipment loan from Tal Medical / Neurex; patent application and research support from Magstim; and equipment loans from MagVenture, all related to technology for transcranial magnetic stimulation.