bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of Response to Inhaled Nitric Oxide and Duration of Mechanical Ventilation in Pediatric Acute Respiratory Distress Syndrome*
Authors: Dowell Jasmine C. , Thomas Neal J. , Yehya Nadir 
Published: November 2017

Objectives:
Literature regarding appropriate use of inhaled nitric oxide for pediatric acute respiratory distress syndrome is sparse. This study aims to determine if positive response to inhaled nitric oxide is associated with decreased mortality and duration of mechanical ventilation in pediatric acute respiratory distress syndrome.

Design:
Retrospective cohort study.

Setting:
Large pediatric academic medical center.

Patients or Subjects:
One hundred sixty-one children with pediatric acute respiratory distress syndrome and inhaled nitric oxide exposure for greater than or equal to 1 hour within 3 days of pediatric acute respiratory distress syndrome onset.

Interventions:
Patients with greater than or equal to 20% improvement in oxygenation index or oxygen saturation index by 6 hours after inhaled nitric oxide initiation were classified as “responders.”

Measurements and Main Results:
Oxygenation index, oxygen saturation index, and ventilator settings were evaluated prior to inhaled nitric oxide initiation and 1, 6, 12, and 24 hours following inhaled nitric oxide initiation. Primary outcomes were mortality and duration of mechanical ventilation. Baseline characteristics, including severity of illness, were similar between responders and nonresponders. Univariate analysis showed no difference in mortality between responders and nonresponders (21% vs 21%; p = 0.999). Ventilator days were significantly lower in responders (10 vs 16; p < 0.001). Competing risk regression (competing risk of death) confirmed association between inhaled nitric oxide response and successful extubation (subdistribution hazard ratio = 2.11; 95% CI, 1.41–3.17; p < 0.001). Response to inhaled nitric oxide was associated with decreased utilization of high-frequency oscillatory ventilation and extracorporeal membrane oxygenation and lower hospital charges (difference in medians of $424,000).

Conclusions:
Positive response to inhaled nitric oxide was associated with fewer ventilator days, without change in mortality, potentially via reduced use of high-frequency oscillatory ventilation and extracorporeal membrane oxygenation. Future studies of inhaled nitric oxide for pediatric acute respiratory distress syndrome should stratify based on oxygenation response, given the association with favorable outcomes.
Previous Looks May Be Deceiving
Authors: Woll Christopher , Chen Lei 
Published: November 2017

Abstract
We describe a case of a 17-year-old boy presenting to the emergency department following a presyncopal episode with exertion. His medical history is significant for a murmur, which was determined to be benign in nature after a normal echocardiogram at 12 years of age. His workup in the emergency department included an electrocardiogram, which was significant for left ventricular hypertrophy, and a point-of-care ultrasound, which was significant for severe concentric left ventricular hypertrophy with diastolic dysfunction consistent with hypertrophic cardiomyopathy.
A Rare Case of Infantile Myofibromatosis Presenting to the Emergency Department as Undiagnosed Long Bone Fractures
Authors: McGuire Melissa A. , Hendry Phyllis L. , Hong Nancy 
Published: November 2017

Abstract
Infantile myofibromatosis is a disorder of mesenchymal tumors that usually presents within the first 2 years of life. Most patients initially present because of the presence of visible or palpable subcutaneous tumors. We report a case of a fussy 5-week-old infant who presented to an emergency department with bilateral femur fractures initially thought to be due to nonaccidental trauma or a metabolic bone disorder. She was ultimately diagnosed after admission with infantile myofibromatosis after taking an extensive family history and after further laboratory and radiologic evaluation. There are no previously published cases of undiagnosed infantile myofibromatosis presenting to the emergency department, especially with multiple long bone fractures.
Succession Planning in State Health Agencies in the United States: A Brief Report
Authors: Harper Elizabeth , Leider Jonathon P. , Coronado Fatima , Beck Angela J. 
Published: November 2017

Objective:
Approximately 25% of the public health workforce plans to retire by 2020. Succession planning is a core capability of the governmental public health enterprise; however, limited data are available regarding these efforts in state health agencies (SHAs).

Methods:
We analyzed 2016 Workforce Gaps Survey data regarding succession planning in SHAs using the US Office of Personnel Management's (OPM's) succession planning model, including 6 domains and 27 activities. Descriptive statistics were calculated for all 41 responding SHAs.

Results:
On average, SHAs self-reported adequately addressing 11 of 27 succession planning activities, with 93% of SHAs adequately addressing 1 or more activities and 61% adequately addressing 1 or more activities in each domain.

Conclusions:
The majority of OPM-recommended succession planning activities are not being addressed, and limited succession planning occurs across SHAs. Greater activity in the OPM-identified succession planning domains may help SHAs contend with significant turnover and better preserve institutional knowledge.
How Can Safer Care Be Achieved? Patient Safety Officers’ Perceptions of Factors Influencing Patient Safety in Sweden
Authors: Ridelberg Mikaela , Roback Kerstin , Nilsen Per 
Published: November 2017

Objective
This study aimed to survey health care professionals in Sweden on the factors that they believe have been most important in reaching the current level of patient safety and achieving safer care in the future as well as the characteristics of the county councils that have been the most successful in achieving safe care.

Methods
The study population consisted of 222 patient safety officers, that is, health care professionals with strategic positions in patient safety work in the county councils. A postal questionnaire was used for data collection.

Results
The survey response rate was 70%. The factors that were considered most important for the current level of patient safety were efforts to reduce the use of antibiotics; Swedish patient safety law; and internal discussions with the county council management, heads of health care units, health care providers, and so on. The factors that were considered most important to achieve safer care in the future were improved communication between health care practitioners and patients, improved organizational culture, improved communication, and patient safety knowledge as a compulsory component of basic education for health care practitioners.

Conclusions
Several factors rated highly for achieving the current level of patient safety are part of the government-supported financial incentive plan. Patient safety is attributed to a broad range of factors, and many solutions might contribute to improved patient safety in the future. The most successful county councils are characterized by leadership support for patient safety, well-organized patient safety work, long-term commitment to patient safety, and an organizational culture that is conducive to patient safety.
Dentists Survey on Adverse Events During Their Clinical Training
Authors: Osegueda-Espinosa Alfredo Alan , Sánchez-Pérez Leonor , Perea-Pérez Bernardo , Labajo-González Elena , Acosta-Gio A. Enrique 
Published: November 2017

Background
Adverse events (AEs) begin challenging the safe practice of dentistry early when students start treating patients at dental school. We assessed the frequency with which dentists caused common AEs during their undergraduate clinical training.

Methods
A convenience sample of dentists, graduated from more than 34 dental schools in Mexico and other Spanish speaking countries, answered a confidential, self-administered questionnaire with closed-format questions on common AEs they caused and their active errors that could have led to AEs in the teaching clinics.

Results
Of 207 participants, 80% had graduated recently. As undergraduates, 79% caused AEs; 38% admitted to causing one adverse event, 41% to causing two or more, and 36% committed active errors that could have hurt patients. No significant associations between AEs and sex or type of school were observed.

Conclusions
The results indicate that dental students caused AEs or committed errors that placed patients at risk, during their clinical training.

Practical Implications
Dental schools must identify challenges to patient safety at their teaching clinics and introduce risk reduction strategies to protect their patients and foster a safety culture in dental education.
Anastomotic Leak Does Not Impact Oncologic Outcomes After Preoperative Chemoradiotherapy and Resection for Rectal Cancer
Authors: Jang Jae Hyuck , Kim Hee Cheol , Huh Jung Wook , Park Yoon Ah , Cho Yong Beom , Yun Seong Hyeon , Lee Woo Yong , Yu Jeong Il , Park Hee Chul , Park Young Suk , Park Joon Oh 
Published: November 2017

Objective:
The aim of this study was to evaluate the relationship of anastomotic leakage, local recurrence, and overall survival in rectal cancer patients treated with preoperative chemoradiotherapy (CRT) and curative resection.

Background:
Little is known about the association between anastomotic leakage and oncologic outcomes after preoperative CRT.

Methods:
A total of 698 consecutive primary rectal cancer patients after preoperative CRT between April 19, 2000, and December 27, 2013, were retrospectively reviewed. Forty-seven patients who had anastomotic leakage were compared with 651 patients who had no anastomotic leakage.

Results:
Of 698 patients, 47 (6.7%) patients had anastomotic leakage. Among these 47 patients, 39 (83.0%) had grade C leak that required urgent operation, while 8 (17.0%) had grade B leak that was managed expectantly or by percutaneous drainage. The median follow-up period was 47.6 months (range, 27.1 to 68.9 months). One hundred twenty (17.2%) recurrences were identified among all patients. The median overall disease-free survival was 43 months (range, 22.4 to 66.7 months). Five-year disease-free survival did not differ significantly between the 2 groups (80.5% vs 80.4%, P = 0.839). Five-year local recurrence-free survival did not differ significantly either between the 2 groups (93.7% vs 94.9%, P = 0.653). Five-year overall survival rates of patients with or without leakage were 90.9% and 86.3%, respectively (P = 0.242). Five-year cancer-specific survival rates of patients with or without leakage were 92.2% and 86.3%, respectively (P = 0.248).

Conclusion:
After preoperative CRT, an anastomotic leak is not associated with a significant increase in local recurrence or long-term survival in rectal cancer.
One-Year Outcomes of a Cohort of Renal Transplant Patients Related to BMI in a Steroid-Sparing Regimen
Authors: Bellini Maria Irene , Koutroutsos Kostas , Galliford Jack , Herbert Paul E. 
Published: November 2017

Background
The prevalence of overweight and obese kidney transplant recipients (KTR) has risen in parallel to the obesity epidemic that has affected the general population over the last two decades. At present, there is an ongoing debate regarding the suitability for transplantation of obese patients.

Methods
Data were prospectively collected on consecutive single organ KTR transplanted between January 2014 and March 2016. The patients were stratified according to their body mass index (BMI) using the World Health Organization classification. As a measure of allograft function Modification of Diet in Renal Disease, estimated glomerular filtration rate was used at 3, 6, and 12 months posttransplant.

Results
We included 370 KTR: 126 of 370 women; median age, 52.7 years (range, 19-77 years), followed up for a median of 19.5 ± 8.6 months. In total, 155 (41.9%) KTR were underweight or of normal BMI at transplant, whereas 148 (40%) were overweight, and 67 (18.1%) were classified as obese (47 [12.7%] class 1, 11 [3%] class 2, 9 [2.4%] class 3). Overweight and obese KTR had a higher incidence of pretransplant diabetes (P = 0.021), but no difference was found in new-onset hyperglycemia posttransplant (P = 0.35). There was also no difference in posttransplant hospital length of stay (P = 0.386). Obese and overweight KTR had a significantly lower estimated glomerular filtration rate than underweight and normal BMI KTR at 3 and 6 months posttransplant, a finding that did not persist at 1 year follow-up. Overall, 23 patients lost their grafts, and 20 patients died during follow-up. Kaplan Meier analysis showed no difference in allograft loss between the different BMI groups (log rank P = 0.7).

Conclusions
In this single-center study, which used short-term data, overweight and obese patients were shown not to have inferior outcomes regarding renal function 1 year posttransplant.
Two C++ Libraries for Counting Trees on a Phylogenetic Terrace
Authors: Biczok R. , Bozsoky P. , Eisenmann P. , Ernst J. , Ribizel T. , Scholz F. , Trefzer A. , Weber F. , Hamann M. , Stamatakis A. 
Published: November 2017

AbstractMotivationThe presence of terraces in phylogenetic tree space, that is, a potentially large number of distinct tree topologies that have exactly the same analytical likelihood score, was first described by Sanderson et al, (2011). However, popular software tools for maximum likelihood and Bayesian phylogenetic inference do not yet routinely report, if inferred phylogenies reside on a terrace, or not. We believe, this is due to the unavailability of an efficient library implementation to (i) determine if a tree resides on a terrace, (ii) calculate how many trees reside on a terrace, and (iii) enumerate all trees on a terrace.ResultsIn our bioinformatics programming practical we developed two efficient and independent C++ implementations of the SUPERB algorithm by Constantinescu and Sankoff (1995) for counting and enumerating the trees on a terrace. Both implementations yield exactly the same results and are more than one order of magnitude faster and require one order of magnitude less memory than a previous 3rd party python implementation.AvailabilityThe source codes are available under GNU GPL at https://github.com/terraphastContactAlexandros.Stamatakis@h-its.org
No kissing in the nucleus: Unbiased analysis reveals no evidence of trans chromosomal regulation of mammalian immune development
Authors: Johanson Timothy M. , Coughlan Hannah D. , Lun Aaron T.L. , Bediaga Naiara G. , Naselli Gaetano , Garnham Alexandra L. , Harrison Leonard C. , Smyth Gordon K. , Allan Rhys S. 
Published: November 2017

SummaryIt has been proposed that interactions between mammalian chromosomes, or transchromosomal interactions (also known as kissing chromosomes), regulate gene expression and cell fate determination. Here we aimed to identify novel transchromosomal interactions in immune cells by high-resolution genome-wide chromosome conformation capture. Although we readily identified stable interactions incis,and also between centromeres and telomeres on different chromosomes, surprisingly we identified no gene regulatory transchromosomal interactions in either mouse or human cells, including previously described interactions. We suggest that advances in the chromosome conformation capture technique and the unbiased nature of this approach allow more reliable capture of interactions between chromosomes than previous methods. Overall our findings suggest that stable transchromosomal interactions that regulate gene expression are not present in mammalian immune cells and that lineage identity is governed bycis,nottranschromosomal interactions.
Neurogenic decisions require a cell cycle independent function of the CD25B phosphatase
Authors: Bonnet Frédéric , Roussat Mélanie , Molina Angie , Azais Manon , Belvialar Sophie , Gautrais Jacques , Pituello Fabienne , Agius Eric 
Published: November 2017

ABSTRACTA fundamental issue in developmental biology and in organ homeostasis is understanding the molecular mechanisms governing the balance between stem cell maintenance and differentiation into a specific lineage. Accumulating data suggest that cell cycle dynamics plays a major role in the regulation of this balance. Here we show that the G2/M cell cycle regulator CDC25B phosphatase is required in mammals to finely tune neuronal production in the neural tube. We show that in chick neural progenitors, CDC25B activity is both required and sufficient to stimulate neurogenic divisions and to promote neuronal differentiation. We design a mathematical model showing that within a limited period of time, cell cycle length modifications cannot account for changes in the ratio of the mode of division. Using a CDC25B point mutation that cannot interact with CDK, we show that part of CDC25B activity on neurogenic divisions is independent of its action on the cell cycle.
Bottom-up and top-down control of dispersal across major organismal groups: a coordinated distributed experiment
Authors: Fronhofer Emanuel A. , Legrand Delphine , Altermatt Florian , Ansart Armelle , Blanchet Simon , Bonte Dries , Chaine Alexis , Dahirel Maxime , De Laender Frederik , De Raedt Jonathan , di Gesu Lucie , Jacob Staffan , Kaltz Oliver , Laurent Estelle , Little Chelsea J. , Madec Luc , Manzi Florent , Masier Stefano , Pellerin Felix , Pennekamp Frank , Schtickzelle Nicolas , Therry Lieven , Vong Alexandre , Winandy Laurane , Cote Julien 
Published: November 2017

AbstractOrganisms rarely experience a homogeneous environment. Rather, ecological and evolutionary dynamics unfold in spatially structured and fragmented landscapes, with dispersal as the central process linking these dynamics across spatial scales. Because dispersal is a multi-causal and highly plastic life-history trait, finding general drivers that are of importance across species is challenging but highly relevant for ecological forecasting.We here tested whether two fundamental ecological forces and main determinants of local population dynamics, top-down and bottom-up control, generally explain dispersal in spatially structured communities. In a coordinated distributed experiment spanning a wide range of actively dispersing organisms, from protozoa to vertebrates, we show that bottom-up control, that is resource limitation, consistently increased dispersal. While top-down control, that is predation risk, was an equally important dispersal driver as bottom-up control, its effect depended on prey and predator space use and whether dispersal occurred on land, in water or in the air: species that routinely use more space than their predators showed increased dispersal in response to predation, specifically in aquatic environments. After establishing these general causes of dispersal, we used a metacommunity model to show that bottom-up and top-down control of dispersal has important consequences for local population fluctuations as well as cascading effects on regional metacommunity dynamics. Context-dependent dispersal reduced local population fluctuations and desynchronized dynamics between communities, two effects that increase population and community stability.Our study provides unprecedented insights into the generality of the positive resource dependency of dispersal as well as a robust experimental test of current theory predicting that predator-induced dispersal is modulated by prey and predator space use. Our experimental and theoretical work highlights the critical importance of the multi-causal nature of dispersal as well as its cascading effects on regional community dynamics, which are specifically relevant to ecological forecasting.
The C-terminal extension landscape of naturally presented HLA-I ligands
Authors: Guillaume Philippe , Picaud Sarah , Baumgaertner Petra , Montandon Nicole , Schmidt Julien , Speiser Daniel E , Coukos George , Bassani-Sternberg Michal , Fillipakopoulos Panagis , Gfeller David 
Published: November 2017

AbstractHLA-I molecules play a central role in antigen presentation. They typically bind 9- to 12-mer peptides and their canonical binding mode involves anchor residues at the second and last positions of their ligands. To investigate potential non-canonical binding modes we collected in-depth and accurate HLA peptidomics datasets covering 54 HLA-I alleles and developed novel algorithms to analyze these data. Our results reveal frequent (442 unique peptides) and statistically significant C-terminal extensions for at least eight alleles, including the common HLA-A03:01, HLA-A31:01 and HLA-A68:01. High resolution crystal structure of HLA-A68:01 with such a ligand uncovers structural changes taking place to accommodate C-terminal extensions and helps unraveling sequence and structural properties predictive of the presence of these extensions. Scanning viral proteomes with the new C-terminal extension motifs identifies many putative epitopes and we demonstrate direct recognition by human CD8+ T cells of a C-terminally extended epitope from cytomegalovirus.
Ultra-sensitive mutation detection and genome-wide DNA copy number reconstruction by error corrected circulating tumour DNA sequencing
Authors: Mansukhani Sonia , Barber Louise J. , Moorcraft Sing Yu , Davidson Michael , Woolston Andrew , Griffiths Beatrice , Fenwick Kerry , Herman Bram , Matthews Nik , O’Leary Ben , Hulkki Sanna , De Castro David Gonzalez , Hubank Michael , Patel Anisha , Wotherspoon Andrew , Okachi Aleruchi , Rana Isma , Begum Ruwaida , Davies Matthew , Powles Thomas , von Loga Katharina , Turner Nick , Watkins David , Chau Ian , Cunningham David , Starling Naureen , Gerlinger Marco 
Published: November 2017

AbstractMinimally invasive circulating free DNA (cfDNA) analysis can portray cancer genome landscapes but highly sensitive and specific genetic approaches are necessary to accurately detect mutations with often low variant frequencies. We developed a targeted cfDNA sequencing technology using novel off-the-shelf molecular barcodes for error correction, in combination with custom solution hybrid capture enrichment. Modelling based on cfDNA yields from 58 patients shows that our assay, which requires 25ng of cfDNA input, should be applicable to >95% of patients with metastatic colorectal cancer. Sequencing of a 163.3 kb target region including 32 genes detected 100% of single nucleotide variants with 0.15% variant frequency in cfDNA spike-in experiments. Molecular barcode error correction reduced false positive mutation calls by 98.6%. In a series of 28 patients with metastatic colorectal cancers, 80 out of 91 (88%) mutations previously detected by tumour tissue sequencing were called in the cfDNA. Call rates were similar for single nucleotide variants and small insertions/deletions. Mutations only called in cfDNA but not detectable in matched tumour tissue included, among others, a subclonal resistance driver mutation to anti-EGFR antibodies in theKRASgene, multiple activatingPIK3CAmutations in each of two patients (indicative of parallel evolution), andTP53mutations originating from clonal haematopoiesis. Furthermore, we demonstrate that cfDNA off-target read analysis allows the reconstruction of genome wide copy number aberration profiles from 71% of these 28 cases. This error-corrected ultra-deep cfDNA sequencing assay with a target region that can be readily customized enables broad insights into cancer genomes and evolution.