bluuebunny/crossref_metadata_2025_split huggingface dataset:
Venoarterial Extracorporeal Membrane Oxygenation Versus Conventional Therapy in Severe Pediatric Septic Shock*
Authors: Oberender Felix , Ganeshalingham Anusha , Fortenberry James D. , Hobson Michael J. , Houmes Robert J. , Morris Kevin P. , Numa Andrew , Hoq Mohammad M. , Donath Susan , Beca John , Butt Warwick 
Published: July 2018

Objectives:
The role of venoarterial extracorporeal membrane oxygenation in the treatment of severe pediatric septic shock continues to be intensely debated. Our objective was to determine whether the use of venoarterial extracorporeal membrane oxygenation in severe septic shock was associated with altered patient mortality, morbidity, and/or length of ICU and hospital stay when compared with conventional therapy.

Design:
International multicenter, retrospective cohort study using prospectively collected data of children admitted to intensive care with a diagnosis of severe septic shock between the years 2006 and 2014.

Setting:
Tertiary PICUs in Australia, New Zealand, Netherlands, United Kingdom, and United States.

Patients:
Children greater than 30 days old and less than 18 years old.

Interventions:
None.

Measurements and Main Results:
Of 2,452 children with a diagnosis of sepsis or septic shock, 164 patients met the inclusion criteria for severe septic shock. With conventional therapy (n = 120), survival to hospital discharge was 40%. With venoarterial extracorporeal membrane oxygenation (n = 44), survival was 50% (p = 0.25; CI, –0.3 to 0.1). In children who suffered an in-hospital cardiac arrest, survival to hospital discharge was 18% with conventional therapy and 42% with venoarterial extracorporeal membrane oxygenation (Δ = 24%; p = 0.02; CI, 2.5–42%). Survival was significantly higher in patients who received high extracorporeal membrane oxygenation flows of greater than 150 mL/kg/min compared with children who received standard extracorporeal membrane oxygenation flows or no extracorporeal membrane oxygenation (82%, 43%, and 48%; p = 0.03; CI, 0.1–0.7 and p < 0.01; CI, 0.2–0.7, respectively). Lengths of ICU and hospital stay were significantly longer for children who had venoarterial extracorporeal membrane oxygenation.

Conclusions:
The use of venoarterial extracorporeal membrane oxygenation in severe pediatric sepsis is not by itself associated with improved survival. However, venoarterial extracorporeal membrane oxygenation significantly reduces mortality after cardiac arrest due to septic shock. Venoarterial extracorporeal membrane oxygenation flows greater than 150 mL/kg/min are associated with almost twice the survival rate of conventional therapy or standard-flow extracorporeal membrane oxygenation.
Care Coordination in Emergency Departments for Children and Adolescents With Behavioral Health Conditions
Authors: Lynch Sean , Witt Whitney , Ali Mir M. , Teich Judith L. , Mutter Ryan , Gibbons Brent , Walsh Christine 
Published: July 2018

Background
Increasing numbers of children are receiving care for behavioral health conditions in emergency departments (EDs). However, studies of mental health–related care coordination between EDs and primary and/or specialty care settings are limited. Such coordination is important because ED care alone may be insufficient for patients' behavioral health needs.

Methods
We analyzed claims during the year 2014 from Truven Health Analytics MarketScan Medicaid and Commercial databases for outpatient services and prescription drugs for youth 2 to 18 years old with continuous enrollment. We applied a standard care coordination measure to insurance claims data in order to examine whether youth received a primary care or specialty follow-up visit within 7 days following an ED visit with a psychiatric diagnosis. We calculated descriptive statistics to evaluate differences in care coordination by enrollees' demographic, insurance, and health-related characteristics. In addition, we constructed a multivariate logistic regression model to detect the factors associated with the receipt of care coordination.

Results
The total percentages of children who received care coordination were 45.8% (Medicaid) and 46.6% (private insurance). Regardless of insurance coverage type, children aged 10 to 14 years had increased odds of care coordination compared with youth aged 15 to 18 years. Children aged 2 to 5 years and males had decreased odds of care coordination.

Conclusions
It is of concern that fewer than half of patients received care coordination following an ED visit. Factors such as behavioral health workforce shortages, wait times for an appointment with a provider, and lack of reimbursement for care coordination may help explain these results.
A Pragmatic Study to Evaluate the Use of a Rapid Diagnostic Test to Detect Group A Streptococcal Pharyngitis in Children With the Aim of Reducing Antibiotic Use in a UK Emergency Department
Authors: Bird Chris , Winzor Gemma , Lemon Katherine , Moffat Alasdair , Newton Tina , Gray Jim 
Published: July 2018

Objective
Sore throat is a common presentation to the children's emergency department (ED), and many patients are likely prescribed antibiotics unnecessarily. We aimed to reduce antibiotic prescribing for sore throat in our UK ED through use of an established scoring system combined with a rapid diagnostic test (RDT) to detect group A streptococcal (GAS) pharyngitis.

Methods
AB single-subject and diagnostic accuracy studies were used to measure both antibiotic prescribing rates over time and the performance of the McIsaac clinical score combined with RDT to screen for and treat GAS pharyngitis. All children between the age of 6 months and 16 years with symptoms of sore throat were eligible for inclusion. The study adhered to SQUIRE guidelines.

Results
During 2014 and 2016, antibiotic prescribing rates for 210 children at baseline (median age, 3 years) and 395 children during the intervention (median age, 2 years) were assessed. The baseline prescribing rate was 79%, whereas rates after intervention were 24% and 27%, respectively. The RDT had an acceptable false-negative rate of 7.9%, poor sensitivity of 64.3%, and a negative predictive value of 92.1% when compared with conventional throat culture. A McIsaac score of 3 or more had good sensitivity (92.11%) but very low specificity (12.62%) for predicting GAS infection.

Conclusions
Despite poor RDT sensitivity and the McIsaac score's poor specificity in children, their use in combination decreased antibiotic prescribing rates in a children's ED setting.
The Pediatric Disease Spectrum in an Emergency Department at a Tertiary Care Center in Beirut, Lebanon
Authors: El Zahran Tharwat , El Warea Mohammad , Bachir Rana , Hitti Eveline 
Published: July 2018

Objective
The aim of this study was to identify the most common diagnoses for pediatric emergency department (ED) visits at a tertiary care center in Lebanon.

Methods
A retrospective chart review of pediatric patients (aged ≤18 years) presenting to the American University of Beirut Medical Center ED during 2010–2011 was completed. The common diagnoses among 5 age groups (<1, 1–4, 5–9, 10–14, and 15–18 years) in 3 categories (all pediatric ED visits, treat and release, admitted visits) were assessed. Diagnoses were classified according to the Clinical Classifications Software. Descriptive statistics and Pearson χ2 test were used.

Results
A total of 12,637 pediatric ED visits were included. The majority (90.2%) were among the treat-and-release group. The mean age for all patients was 7.2 years, 57.1% of whom were males. The top 5 most common diagnoses for all ED visits included fever of unknown origin, external injuries, upper respiratory tract infections, open wounds, and abdominal pain. Cardiac conditions were the most common reason for admission in children younger than 1 year, intestinal infection among 1 to 4 years old, pneumonia among 5 to 9 years old, and appendicitis among 10 to 14 and 15 to 18 years. Seasonal analysis showed fever of unknown origin to be the most common diagnosis across all seasons.

Conclusions
This study is the first to assess pediatric ED visits in a Lebanese setting. The top most common reason was communicable diseases, with fever of unknown origin being the most common reason for all visits, contrary to North America where injury and poisoning are the most common. Noncommunicable diseases (cardiac, pneumonia, gastroenteritis, and appendicitis) were common reasons for admission in different age groups.
Decreased Risk of Delirium With Use of Regional Analgesia in Geriatric Trauma Patients With Multiple Rib Fractures
Authors: O’Connell Kathleen M. , Quistberg D. Alex , Tessler Robert , Robinson Bryce R. H. , Cuschieri Joseph , Maier Ronald V. , Rivara Frederick P. , Vavilala Monica S. , Bhalla Paul I. , Arbabi Saman 
Published: July 2018

Objective:
The aim of this study was to examine the risk of delirium in geriatric trauma patients with rib fractures treated with systemic opioids compared with those treated with regional analgesia (RA).

Summary of Background Data:
Delirium is a modifiable complication associated with increased morbidity and mortality. RA may reduce the need for opioid medications, which are associated with delirium in older adults.

Methods:
Cohort study of patients ≥65 years admitted to a regional trauma center from 2011 to 2016. Inclusion factors were ≥ 3 rib fractures, blunt trauma mechanism, and admission to intensive care unit (ICU). Exclusion criteria included head AIS ≥3, spine AIS ≥3, dementia, and death within 24 hours. The primary outcome was delirium positive ICU days, defined using the CAM-ICU assessment. Delirium incident rate ratios (IRRs) and 95% confidence intervals (95% CIs) were estimated using generalized linear mixed models with Poisson distribution and robust standard errors.

Results:
Of the 144 patients included in the study, 27 (19%) received Acute Pain Service consultation and RA and 117 (81%) received opioid-based systemic analgesia. Patients with RA had more severe chest injury than those without. The risk of delirium decreased by 24% per day per patient with use of RA (IRR 0.76, 95% CI 0.61 to 0.96). Individual opioid use, as measured in daily morphine equivalents (MEDs), was significantly reduced after initiation of RA (mean difference −7.62, 95% CI −14.4 to −0.81).

Conclusion:
Although use of RA techniques in geriatric trauma patients with multiple rib fractures was associated with higher MED, opioid use decreased after RA initiation and Acute Pain Service consultation, and the risk of delirium was lower.
Patterns of Initial Opioid Prescribing to Opioid-Naive Patients
Authors: Larach Daniel B. , Waljee Jennifer F. , Hu Hsou-Mei , Lee Jay S. , Nalliah Romesh , Englesbe Michael J. , Brummett Chad M. 
Published: July 2018

Objective:
To determine the proportion of initial opioid prescriptions for opioid-naive patients prescribed by surgeons, dentists, and emergency physicians. We hypothesized that the percentage of such prescriptions grew as scrutiny of primary care and pain medicine opioid prescribing increased and guidelines were developed.

Summary of Background Data:
Data regarding the types of care for which opioid-naive patients are provided initial opioid prescriptions are limited.

Methods:
A retrospective cross-sectional study using a nationwide insurance claims dataset to study US adults aged 18 to 64 years. Our primary outcome was a change in opioid prescription share for opioid-naive patients undergoing surgical, emergency, and dental care from 2010 to 2016; we also examined the type and amounts of opioid filled.

Results:
From 87,941,718 analyzed lives, we identified 16,292,018 opioid prescriptions filled by opioid-naive patients. The proportion of prescriptions for patients receiving surgery, emergency, and dental care increased by 15.8% from 2010 to 2016 (P < 0.001), with the greatest increases related to surgical (18.1%) and dental (67.8%) prescribing. In 2016, surgery patients filled 22.0% of initial prescriptions, emergency medicine patients 13.0%, and dental patients 4.2%. Surgical patients’ mean total oral morphine equivalents per prescription increased from 240 mg (SD 509) in 2010 to 403 mg (SD 1369) in 2016 (P < 0.001). Over the study period, surgical patients received the highest proportion of potent opioids (90.2% received hydrocodone or oxycodone).

Conclusions:
Initial opioid prescribing attributable to surgical and dental care is increasing relative to primary and chronic pain care. Evidence-based guideline development for surgical and dental prescribing is warranted in order to curb iatrogenic opioid morbidity and mortality.
The Accuracy of Low-dose Computed Tomography Protocol in Patients With Suspected Acute Appendicitis
Authors: Sippola Suvi , Virtanen Johanna , Tammilehto Ville , Grönroos Juha , Hurme Saija , Niiniviita Hannele , Lietzen Elina , Salminen Paulina 
Published: July 2018

Objective:
To compare diagnostic accuracy of contrast enhanced low-dose computed tomography (CT) accomplished in the OPTICAP trial phantom phase to standard CT in patients with suspected acute appendicitis.

Background:
Increasing use of CT as the gold standard in diagnosing acute appendicitis has raised concerns regarding radiation exposure. Unenhanced low-dose CT protocols have shown similar diagnostic accuracy with standard CT for diagnosing appendicitis. To our knowledge, there are no other trials in which the same patient with suspected acute appendicitis underwent both standard and low-dose CT allowing interpatient comparison.

Methods:
OPTICAP is an interpatient protocol sequence randomized noninferiority single-center trial performed at Turku University Hospital between November, 2015 and August, 2016. Sixty patients with suspected acute appendicitis and body mass index <30 kg/m2 were enrolled to undergo both standard and low-dose contrast enhanced CT scans, which were categorized as normal, uncomplicated or complicated appendicitis by 2 radiologists in blinded manner. All patients with CT confirmed appendicitis underwent appendectomy to obtain histopathology.

Results:
The low-dose protocol was not inferior to standard protocol in terms of diagnostic accuracy; 79% [95% confidence interval (CI) 66%–89%) accurate diagnosis in low-dose and 80% (95% CI 67%–90%) in standard CT by primary radiologist. Accuracy to categorize appendicitis severity was 79% for both protocols. The mean radiation dose of low-dose CT was significantly lower compared with standard CT (3.33 and 4.44 mSv, respectively).

Conclusion:
Diagnostic accuracy of contrast enhanced low-dose CT was not inferior to standard CT in diagnosing acute appendicitis or distinguishing between uncomplicated and complicated acute appendicitis in patients with a high likelihood of acute appendicitis. Low-dose CT enabled significant radiation dose reduction.
Quantitative single-molecule three-color Förster resonance energy transfer by photon distribution analysis
Authors: Barth Anders , von Voithenberg Lena Voith , Lamb Don C. 
Published: July 2018

AbstractSingle-molecule Förster resonance energy transfer (FRET) is a powerful tool to study conformational dynamics of biomolecules. Using solution-based single-pair FRET by burst analysis, conformational heterogeneities and fluctuations of fluorescently labeled proteins or nucleic acids can be studied by monitoring a single distance at a time. Three-color FRET is sensitive to three distances simultaneously and can thus elucidate complex coordinated motions within single molecules. While three-color FRET has been applied on the single-molecule level before, a detailed quantitative description of the obtained FRET efficiency distributions is still missing. Direct interpretation of three-color FRET data is additionally complicated by an increased shot noise contribution when converting photon counts to FRET efficiencies. However, to address the question of coordinated motion, it is of special interest to extract information about the underlying distance heterogeneity, which is not easily extracted from the FRET efficiency histograms directly. Here, we present three-color photon distribution analysis (3C-PDA), a method to extract distributions of inter-dye distances from three-color FRET measurements. We present a model for diffusion-based three-color FRET experiments and apply Bayesian inference to extract information about the physically relevant distance heterogeneity in the sample. The approach is verified using simulated data sets and experimentally applied to triple-labeled DNA duplexes. Finally, 3C-FRET experiments on the Hsp70 chaperone BiP reveal conformational coordinated changes between individual domains. The possibility to address the co-occurrence of intramolecular distances makes 3C-PDA a powerful method to study the coordination of domain motions within biomolecules during conformational changes.SignificanceIn solution-based single-molecule Förster resonance energy transfer (FRET) experiments, biomolecules are studied as they freely diffuse through the observation volume of a confocal microscope, resulting in bursts of fluorescence from single molecules. Using three fluorescent labels, one can concurrently measure three distances in a single molecule but the experimentally limited number of photons is not sufficient for a straight-forward analysis. Here, we present a probabilistic framework, called three-color photon distribution analysis (3C-PDA), to extract quantitative information from single-molecule three-color FRET experiments. By extracting distributions of interdye distances from the data, the method provides a three-dimensional description of the conformational space of biomolecules, enabling the detection of coordinated movements during conformational changes.
Convergent evolution of psilocybin biosynthesis by psychedelic mushrooms
Authors: Awan Ali R. , Winter Jaclyn M. , Turner Daniel , Shaw William M. , Suz Laura M. , Bradshaw Alexander J. , Ellis Tom , Dentinger Bryn T.M. 
Published: July 2018

AbstractPsilocybin is a psychoactive compound with clinical applications produced by dozens of mushroom species1. There has been a longstanding interest in psilocybin research with regard to treatment for addiction2, depression3, and end-of-life suffering4. However, until recently very little was known about psilocybin biosynthesis and its ecological role. Here we confirm and refine recent findings5 about the genes underpinning psilocybin biosynthesis, discover that there is more than one psilocybin biosynthesis cluster in mushrooms, and we provide the first data directly addressing psilocybin’s ecological role. By analysing independent genome assemblies for the hallucinogenic mushrooms Psilocybe cyanescens and Pluteus salicinus we recapture the recently discovered psilocybin biosynthesis cluster5,6 and show that a transcription factor previously implicated in its regulation is actually not part of the cluster. Further, we show that the mushroom Inocybe corydalina produces psilocybin but does not contain the established biosynthetic cluster, and we present an alternative cluster. Finally, a meta-transcriptome analysis of wild-collected mushrooms provides evidence for intra-mushroom insect gene expression of flies whose larvae grow inside Psilocybe cyanescens. These larvae were successfully reared into adults. Our results show that psilocybin does not confer complete protection against insect mycophagy, and the hypothesis that it is produced as an adaptive defense compound may need to be reconsidered.
NAD consumption by PARP1 in response to DNA damage triggers metabolic shift critical for damaged cell survival
Authors: Murata Michael M. , Kong Xiangduo , Moncada Emmanuel , Chen Yumay , Wang Ping , Berns Michael W. , Yokomori Kyoko , Digman Michelle A. 
Published: July 2018

AbstractDNA damage signaling is critical for the maintenance of genome integrity and cell fate decision. Poly(ADP-ribose) polymerase 1 (PARP1) is a DNA damage sensor rapidly activated in a damage dose and complexity-dependent manner playing a critical role in the initial chromatin organization and DNA repair pathway choice at damage sites. However, the cell-wide consequence of its activation in damaged cells is not well delineated. Using the phasor approach to fluorescence lifetime imaging microscopy (FLIM) and fluorescence-based biosensors in combination with laser microirradiation, we found a rapid cell-wide increase of the bound/free NADH ratio in response to nuclear DNA damage, which is triggered by NAD+ depletion by PARP activation. This change is linked to the metabolic balance shift to oxidative phosphorylation (oxphos) over glycolysis. Inhibition of the respiratory chain resulted in rapid PARP-dependent ATP reduction and intracellular acidification, and eventually, PARP-dependent, AIF-independent, apoptosis indicating that oxphos becomes critical for damaged cell survival. The results reveal the novel pro-survival effect of PARP activation through a change in cellular metabolism, and demonstrate how unique applications of advanced fluorescence imaging technologies in combination with laser microirradiation can be a powerful tool to interrogate damage-induced metabolic changes at high spatiotemporal resolution in a live cell.
Absence of GdX/UBL4A protects against inflammatory bowel diseases by regulating NF-κB signaling in DCs and macrophages
Authors: Liu Chunxiao , Zhou Yifan , Li Mengdi , Wang Ying , Yang Shigao , Feng Yarui , Wang Yinyin , Wang Yangmeng , Ren Fangli , Li Jun , Dong Zhongjun , Chin Y Eugene , Fu Xinyuan , Wu Li , Chang Zhijie 
Published: July 2018

AbstractNuclear factor-kappa B (NF-κB) activation is critical for innate immune responses. Here we report that the UBL4A (Ubiquitin-like protein 4A, also named GdX) enhances dendritic cells (DCs) and macrophages (Mφ)-mediated innate immune defenses by positively regulating NF-κB signaling. GdX-deficient mice were resistant to LPS-induced endotoxin shock and DSS-induced colitis. DC- or Mφ-specific GdX-deficient mice displayed alleviated mucosal inflammation, and the production of pro-inflammatory cytokines by GdX-deficient DCs and Mφ was reduced. Mechanistically, we found that PTPN2 (TC45) and PP2A form a complex with RelA (p65) to mediate its dephosphorylation whereas GdX interrupts the TC45/PP2A/p65 complex formation and restrict p65 dephosphorylation by trapping TC45. Our study provides a mechanism by which NF-κB signaling is positively regulated by an adaptor protein GdX in DC or Mφ to maintain the innate immune response. Targeting GdX could be a strategy to reduce over-activated immune response in inflammatory diseases.
Fast-backward replay of sequentially memorized items in humans
Authors: Huang Qiaoli , Jia Jianrong , Han Qiming , Luo Huan 
Published: July 2018

AbstractStoring temporal sequences of events (i.e., sequence memory) is fundamental to many cognitive functions. However, how the sequence order information is maintained and represented in working memory and its behavioral significance, particularly in human subjects, remains unknown. Here, we recorded electroencephalography (EEG) in combination with a temporal response function (TRF) method to dissociate item-specific neuronal reactivations. We demonstrate that serially remembered items are successively reactivated during memory retention. The sequential replay displays two interesting properties compared to the actual sequence. First, the item-by-item reactivation is compressed within a 200-400 ms window, suggesting that external events are associated within a plasticity-relevant window to facilitate memory consolidation. Second, the replay is in a temporally reversed order and is strongly related to the recency effect in behavior. This fast-backward replay, previously revealed in rat hippocampus and demonstrated here in human cortical activities, might constitute a general neural mechanism for sequence memory and learning.