bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Association Between Patient-reported Clinical Factors and 30-day Acute Care Utilization in Chronic Heart Failure
Authors: Chen Jinying , Sadasivam Rajani , Blok Amanda C. , Ritchie Christine S. , Nagawa Catherine , Orvek Elizabeth , Patel Kanan , Houston Thomas K. 
Published: December 2019

Background:
Heart failure patients have high rates of repeat acute care use. Current efforts for risk prediction often ignore postdischarge data.

Objective:
To identify postdischarge patient-reported clinical factors associated with repeat acute care use.

Research Design:
In a prospective cohort study that followed patients with chronic heart failure for 30 days postdischarge, for 7 days after discharge (or fewer days if patients used acute care within 7 days postdischarge), patients reported health status, heart failure symptoms, medication management, knowledge of follow-up plans, and other issues using a daily interactive automatic phone call.

Subjects:
A total of 156 patients who had responded to phone surveys.

Measures:
The outcome variable was dichotomous 30-day acute care use (rehospitalization or emergency department visit). We examined the association between each patient-reported issue and the outcome, using multivariable logistic regression to adjust for confounders.

Results:
Patients were 63 years old (SD=12.4), with 51% African-American and 53% women. Within 30 days postdischarge, 30 (19%) patients used acute care. After adjustment, poor health status [odds ratio (OR)=3.53; 95% confidence interval (CI), 1.06–11.76], pain (OR=2.44; 95% CI, 1.02–5.84), and poor appetite (OR=3.05; 95% CI, 1.13–8.23) were positively associated with 30-day acute care utilization. Among 58 reports of pain in follow-up nursing notes, 39 (67%) were noncardiac, 2 (3%) were cardiac, and 17 (29%) were indeterminate.

Conclusions:
Patient-reported poor health status, pain, and poor appetite were positively associated with 30-day acute care utilization. These novel postdischarge markers require further study before incorporation into risk prediction to drive quality improvement efforts.
The Impact of Morphine Equivalent Daily Dose Threshold Guidelines on Prescribed Dose in a Workers’ Compensation Population
Authors: Heins Sara E. , Castillo Renan C. 
Published: December 2019

Background:
Prescription opioid overdose has increased markedly and is of great concern among injured workers receiving workers’ compensation insurance. Given the association between high daily dose of prescription opioids and negative health outcomes, state workers’ compensation boards have disseminated Morphine Equivalent Daily Dose (MEDD) guidelines to discourage high-dose opioid prescribing.

Objective:
To evaluate the impact of MEDD guidelines among workers’ compensation claimants on prescribed opioid dose.

Methods:
Workers’ compensation claims data, 2010–2013 from 2 guideline states and 3 control states were utilized. The study design was an interrupted time series with comparison states and average monthly MEDD was the primary outcome. Policy variables were specified to allow for both instantaneous and gradual effects and additional stratified analyses examined evaluated the policies separately for individuals with and without acute pain, cancer, and high-dose baseline use to determine whether policies were being targeted as intended.

Results:
After adjusting for covariates, state fixed-effects, and time trends, policy implementation was associated with a 9.26 mg decrease in MEDD (95% confidence interval, −13.96 to −4.56). Decreases in MEDD also became more pronounced over time and were larger in groups targeted by the policies.

Conclusions:
Passage of workers’ compensation MEDD guidelines was associated with decreases in prescribed opioid dose among injured workers. Disseminating MEDD guidelines to doctors who treat workers’ compensation cases may address an important risk factor for opioid-related mortality, while still allowing for autonomy in practice. Further research is needed to determine whether MEDD policies influence prescribing behavior and patient outcomes in other populations.
Effect of Target Fortification on Osmolality and Microbiological Safety of Human Milk Over Time
Authors: Piemontese Pasqua , Liotto Nadia , Menis Camilla , Mallardi Domenica , Tabasso Chiara , Perrone Michela , Bezze Elena , Plevani Laura , Roggero Paola , Mosca Fabio 
Published: December 2019

ABSTRACTObjectives:The fortification of human milk can result in increased osmolality, which may be associated with adverse effects for preterm infants. To evaluate the effect of target fortification on the osmolality and microbiological safety of donor human milk and raw mature milk during the first 72 hours of storage.Methods: We performed target fortification of 63 pasteurized donor human milk (PDHM) and 54 raw mature milk (RMM) samples in a laminar flow hood. Osmolality (mOsm/kg) was evaluated before fortification (T0), immediately after fortification (T1), at 6 (T2), 24 (T3), 48 (T4), and 72 hours (T5) after fortification. Microbiological analysis was performed at T0, T4, and T5. During the study, all samples were stored at 4°C.Results:Mean osmolality at each study point for PDHM and RMM were, respectively: T0: 291.4 ± 11.0 versus 288.4 ± 5.6 (P = 0.06); T1: 384.8 ± 16.7 versus 398.3 ± 23.7; T2: 393.9 ± 17.7 versus 410.1 ± 27.0; T3: 397.8 ± 17.6 versus 417.9 ± 26.1; T4: 400.0 ± 16.5 versus 420.2 ± 24.9; T5: 399.6 ± 16.5 versus 425.2 ± 25.8 (P < 0.001 from T1 to T5). Microbiological analyses were negative at each study points for PDHM. At T0 16.1% of RMM samples had positive cultures, whereas the bacterial count remained stable thought the study.Conclusions:PDHM's osmolality increases during the first 6 hours after fortification and remains stable and safe until 72 hours. RMM's osmolality increases during the first 24 hours and remains stable and safe until 72 hours. The storage at 4°C and the manipulation of PDHM and RMM samples in a laminar flow hood seem to be safe and preserve the microbiological safety of fortified pasteurized human milk until 72 hours.
Late Rescue Collaborative: Reducing Non-ICU Arrests*
Authors: Dean Nathan P. , Ghebremariam Emanuel , Szeles Rosemary , Levin Amanda , Colyer Jessica , Steinhorn Robin H. 
Published: December 2019

Objective:
To reduce the frequency of non-ICU arrests through the implementation of an intramural collaborative focused on patient deterioration.

Design:
Prospective quality improvement project.

Setting:
Single-center, free-standing, tertiary children’s hospital.

Patients:
All patients admitted to acute care units.

Interventions:
The Late Rescue Collaborative was formed in 2014 to monitor compliance with hospital escalation protocols and evaluate episodes of patient deterioration. The collaborative is a multidisciplinary team of physicians, nurses, and respiratory care providers. Three monthly meetings occur: 1) individual acute care unit–based meetings to evaluate trends and performance; 2) hospital-wide multidisciplinary whole group meetings to review hospital trends in deterioration and share lessons learned; and 3) steering committee to determine areas of focus. Based on these three meetings, unit- and hospital-based interventions have been put in place to improve recognition of deterioration and promote early rescue.

Measurements and Main Results:
Rates of rapid response team activations, unplanned transfers, and non-ICU arrest are reported. Non-ICU arrest rates fell from a baseline of 0.31 per 1,000 non-ICU patient days to a new centerline of 0.11 and sustained for 36 months. Days between non-ICU arrests increased from a baseline of 15.5 days in year 2014 to a new centerline of 61.5 days and sustained for 37 months. Mortality following non-ICU arrests fell from four in 2014 and 2015 to zero in years 2016–2018.

Conclusion:
The Late Rescue Collaborative is an effective tool to improve patient safety by reducing non-ICU arrests.
Accuracy of Remote Interpretation of Pediatric Emergency Ultrasound Over Third Generation Networks Across Continents
Authors: Whitney Rachel E. , Riera Antonio , Chen Lei 
Published: December 2019

Objective
This study aimed to evaluate live-stream videos for evaluation of pediatric emergency medicine ultrasound using a third generation (3G) network.

Methods
The interrater reliability of a remote 3G network live-streaming assessment of ultrasound scans for abdominal free fluid, intussusception, and hip effusions was evaluated. Fifty-eight deidentified 6-second video clips in .mp4 format of focused assessment with sonography in trauma scans were downloaded to a laptop. A “bedside” ultrasound expert evaluated each scan and marked it positive or negative for the presence of free fluid. Using an iPhone 3G, Skype was used to connect to the second ultrasound expert located in Addis Ababa, Ethiopia, who reviewed the same scans. When the remote expert returned to the United States, evaluation of the scans was repeated as a second bedside reviewer. Interrater reliability was assessed using the κ statistic and percent agreement. This process was repeated for 44 intussusception scans and 28 hip effusion scans.

Results
The κ values (95% confidence interval) between the bedside and remote evaluators for focused assessment with sonography in trauma, intussusception, and hip effusion were 0.748 (0.576–0.92), 0.816 (0.648–0.984), and 0.764 (0.519–1.0), respectively. The percent agreements after adjusting for chance were 86%, 80%, and 88%, respectively. The κ values between the bedside assessments by each evaluator were 0.851 (0.71–0.992), 0.8 (0.616–0.984), and 0.747 (0.479–0.884), respectively. The percent agreements after adjusting for chance were 92%, 81%, and 88%, respectively.

Conclusions
Live-stream video conference using cellphones over 3G network is a feasible and accurate method for consultation of ultrasound scans from a remote location.
Determination of the Pretibial Soft Tissue Thickness in Children
Authors: Al-Shibli Amal , Lim Rodrick , Poonai Naveen , Istasy Victor , Lin Kangrui , Kilgar Jennifer 
Published: December 2019

Objective
The EZ-IO intraosseous (IO) needle is available in 2 needle sizes for children based on the patient weight. To date, there is no published evidence validating the use of weight-based scaling in children. We hypothesized that pretibial subcutaneous tissue thickness (PSTT) does not correspond with patient weight but rather with age and body mass index (BMI). Our objective was to describe the relationship of a patient's PSTT to their weight, age, and BMI in children less than 40 kg.

Method
One hundred patients who weighed less than 40 kg were recruited prospectively from October 2013 to April 2015 at a tertiary care pediatric emergency department. All sonographic assessments were performed by 1 of 2 emergency physicians certified in point-of-care ultrasound. A single sonographic image was taken over the proximal tibia corresponding to the site of IO insertion. In patients where both sonographers performed independent measurements, a Pearson correlation coefficient was determined. Univariate linear regression was performed to determine the relationship between age, weight, and BMI with PSTT.

Results
One hundred participants were recruited and ranged in age from 10 days to 14 years (mean [SD], 5.01 [3.14] years). Fifty-seven percent of participants were male. Patients' weights ranged from 3.5 to 39.3 kg (mean [SD], 21.42 [9.12] kg), and BMI ranged from 12.1 to 45.0 kg/m2 (mean [SD], 17.31 [4.00]). The mean (SD) PSTT across participants was 0.68 (0.2) cm. The intraclass correlation coefficient for agreement between the 2 sonographers was moderate (intraclass correlation coefficient, 0.602 [confidence interval, 0.385–0.757]). There were significant positive correlations between BMI and PSTT (r = 0.562, P = <0.001) as well as weight and PSTT (r = 0.293, P < 0.003). There was a weak correlation between age and PSTT (0.065, P = 0.521).

Conclusions
Pretibial subcutaneous tissue thickness correlates most strongly with BMI, followed by weight, and weakly with age. Our findings suggest that current IO needle length recommendations should be based on BMI rather than weight. This would suggest that clinicians need to be aware that young patients in particular with large BMIs may pose problems with current weight-based needle length recommendations.
Are Postoperative Intravenous Antibiotics Indicated After Laparoscopic Appendicectomy for Simple Appendicitis? A Prospective Double-blinded Randomized Controlled Trial
Authors: Mennie Nicole , Panabokke Gayathri , Chang Annette , Tanny Sharman Tan , Cheng Wei , Pacilli Maurizio , Ferguson Peter , Nataraja Ramesh M. 
Published: December 2019

Background:
There is limited evidence for the use of postoperative antibiotics for simple appendicitis (SA) in children. Our aim was to conduct a prospective double-blinded randomized controlled trial to investigate this after a laparoscopic appendicectomy.

Methods:
Following ethical approval, children (≤16 years) undergoing appendicectomy were recruited at a single institution. Patients were randomized intraoperatively to receive either 2 postoperative intravenous doses of placebo or antibiotics (Abx). All patients received a dose of Abx at induction of anesthesia. Primary outcome was the incidence of postoperative wound infection (WI), and secondary outcome was the incidence of intra-abdominal abscess formation. Data are reported as number of cases (%), median (range), relative risk, and analyzed using Mann Whitney U test, Chi-square test, as appropriate, a P-value ≤0.05 was considered significant.

Results:
A total of 304 patients were randomized. Sixty-one were subsequently excluded due to protocol violations or recruitment errors; therefore, 243 were included in the final analysis. One hundred twenty-two patients received placebo and 121 Intravenous Abx. There was no difference between the sex (50F/72 M vs 47F/74 M, P = 0.8), median age (12.4 vs 12.2 years, P = 0.5), and postoperative length of stay in a hospital (27.2 vs 25.6 hours, P = 0.7). There was also no difference in the preoperative blood results. A total of 9 WIs occurred: 8/122 (6.6%) placebo versus 1/121 (0.8%) Abx, P = 0.01 [relative risk for WI 7.9 (95% confidence interval: 1.0–62.4)]. There were no intra-abdominal abscess in either groups.

Conclusions:
This prospective randomized double blinded randomized controlled trial has revealed a significant decrease in WI rates by giving 2 postoperative intravenous doses of Abx, suggesting postoperative Abx are of benefit in SA.
PERSIST: A programmable RNA regulation platform using CRISPR endoRNases
Authors: DiAndreth Breanna , Wauford Noreen , Hu Eileen , Palacios Sebastian , Weiss Ron 
Published: December 2019

ABSTRACTRegulation of transgene expression is becoming an integral component of gene therapies, cell therapies and biomanufacturing. However, transcription factor-based regulation upon which the majority of such applications are based suffers from complications such as epigenetic silencing, which limits the longevity and reliability of these efforts. Genetically engineered mammalian cells used for cell therapies and biomanufacturing as well as newer RNA-based gene therapies would benefit from post-transcriptional methods of gene regulation, but few such platforms exist that enable sophisticated programming of cell behavior. Here we engineer the 5’ and 3’ untranslated regions of transcripts to enable robust and composable RNA-level regulation through transcript cleavage and, in particular, create modular RNA-level OFF- and ON-switch motifs. We show that genomically introduced transgenes exhibit resistance to silencing when regulated using this platform compared to those that are transcriptionally-regulated. We adapt nine CRISPR-specific endoRNases as RNA-level “activators” and “repressors” and show that these can be easily layered and composed to reconstruct genetic programming topologies previously achieved with transcription factor-based regulation including cascades, all 16 two-input Boolean logic functions, positive feedback, a feed-forward loop and a putative bistable toggle switch. The orthogonal, modular and composable nature of this platform as well as the ease with which robust and predictable gene circuits are constructed holds promise for their application in gene and cell therapies.
Structural studies of thyroid peroxidase show the monomer interacting with autoantibodies in thyroid autoimmune disease
Authors: Williams Daniel E. , Le Sarah N. , Hoke David E. , Chandler Peter G. , Gora Monika , Godlewska Marlena , Banga J. Paul , Buckle Ashley M. 
Published: December 2019

AbstractThyroid peroxidase (TPO) is a critical membrane-bound enzyme involved in the biosynthesis of multiple thyroid hormones, and is a major autoantigen in autoimmune thyroid diseases such as Graves’ disease and Hashimoto’s thyroiditis. Here we report the biophysical and structural characterisation of two novel TPO constructs containing only the ectodomain of TPO and lacking the propeptide. Both constructs were enzymatically active and able to bind the patient-derived TR1.9 autoantibody. Analytical ultra-centrifugation data suggests that TPO can exist as both a monomer and a dimer. Combined with negative stain electron microscopy and molecular dynamics simulations, these data show that TR1.9 autoantibody preferentially binds the TPO monomer, revealing conformational changes that bring together previously disparate residues into a continuous epitope. In addition to providing plausible structural models of a TPO-autoantibody complex, this study provides validated TPO constructs that will facilitate further characterization, and advances our understanding of the structural, functional and antigenic characteristics of TPO, a molecule behind some of the most common autoimmune diseases.
Estimating the effective sample size in association studies of quantitative traits
Authors: Ziyatdinov Andrey , Kim Jihye , Prokopenko Dmitry , Privé Florian , Laporte Fabien , Loh Po-Ru , Kraft Peter , Aschard Hugues 
Published: December 2019

AbstractThe effective sample size (ESS) is a quantity estimated in genome-wide association studies (GWAS) with related individuals and/or linear mixed models used in analysis. ESS originally measured relative power in family-based GWAS and has recently become important for correcting GWAS summary statistics in post-GWAS analyses. However, existing ESS approaches have been overlooked and based on empirical estimation. This work presents an analytical form of ESS in mixed-model GWAS of quantitative traits, which is derived using the expectation of quadratic form and validated in extensive simulations. We illustrate the performance and relevance of our ESS estimator in common GWAS scenarios and analytically show that (i) family-based studies are consistently underpowered compared to studies of unrelated individuals of the same sample size; (ii) conditioning on polygenic genetic effect by linear mixed models boosts power; and (iii) power of detecting gene-environment interaction can be substantially gained or lost in family-based designs depending on exposure distribution. We further analyze UK Biobank dataset in two samples of 336,347 unrelated and 68,910 related individuals. Analysis in unrelated individuals reveals a high accuracy of our ESS estimator compared to the existing empirical approach; and analysis of related individuals suggests that the loss in effective sample size due to relatedness is at most 0.94x. Overall, we provide an analytical form of ESS for guiding GWAS designs and processing summary statistics in post-GWAS analyses.
Inventive nesting behaviour in the keyhole waspPachodynerus nasidensLatreille (Hymenoptera: Vespidae) in Australia, and the risk to aviation safety
Authors: House Alan P.N. , Ring Jackson G. , Shaw Philip P. 
Published: December 2019

AbstractThe keyhole wasp (Pachodynerus nasidensLatreille 1812), a mud-nesting wasp native to South and Central America and the Caribbean, is a relatively recent (2010) arrival in Australia. In its native range it is known to use man-made cavities to construct nests. A series of serious safety incidents Brisbane Airport related to the obstruction of vital airspeed measuring pitot probes on aircraft possibly caused by mud-nesting wasps at prompted an assessment of risk. An experiment was designed to determine the species responsible, the types of aircraft most affected, the seasonal pattern of potential risk and the spatial distribution of risk on the airport. A series of replica pitot probes were constructed using 3D-printing technology, representing aircraft with high numbers of movements (landings and take-offs), and mounted at four locations at the airport. Probes were monitored for 39 months. Probes blocked by mud nesting wasps were retrieved and incubated in mesh bags. Emerging wasps were identified to species. Results show that all nests in probes were made byP. nasidens, and peak nesting occurs in the summer months. Nesting success (as proportion of nests with live adult emergents) was optimal between 24 and 31°C and that probes with apertures of more than 3 mm diameter are preferred. Not all areas on the airport are affected equally, with the majority of nests constructed in one area. The proportion of grassed areas within 1000 m of probes was a significant predictor of nesting, and probe volume may determine the sex of emerging wasps.
RhoGAP RGA-8 supports morphogenesis inC. elegansby polarizing epithelia through CDC-42
Authors: Raduwan Hamidah , Sasidharan Shashikala , Burgos Luigy Cordova , Wallace Andre G. , Soto Martha C. 
Published: December 2019

AbstractCDC-42 regulation of non-muscle myosin/NMY-2 is required for polarity maintenance in the one-cell embryo ofC. elegans. CDC-42 and NMY-2 regulate polarity throughout embryogenesis, but their contribution to later events of morphogenesis are less understood. We have shown that epidermal enclosure requires the GTPase CED-10/Rac1 and WAVE/Scar complex, its effector, to promote protrusions that drive enclosure through the branch actin regulator Arp2/3. Our analysis here of RGA-8, a homolog of SH3BP1/Rich1/ARHGAP17/Nadrin, with BAR and RhoGAP motifs, suggests it regulates CDC-42, so that NMY-2 promotes two events of epidermal morphogenesis: ventral enclosure and elongation. Genetic and molecular data suggest RGA-8 regulates CDC-42, and the CDC-42 effectors WSP-1 and MRCK-1, in parallel to F-BAR proteins TOCA-1 and TOCA-2. The RGA-8-CDC-42-WSP-1 pathway enriches myosin in migrating epidermal cells during ventral enclosure. We propose TOCA proteins and RGA-8 use BAR domains to localize and regenerate CDC-42 activity, thus regulating F-actin levels, through the branched actin regulator WSP-1, and myosin polarity through the myosin kinase MRCK-1. Regulated CDC-42 thus polarizes epithelia, to control cell migrations and cell shape changes of embryonic morphogenesis.SummaryRGA-8, a protein with membrane binding and actin regulatory motifs, promotes embryonic morphogenesis by localizing active CDC-42 in developing epithelia, thus controlling actin and actin motors during cell movements.
Microglial Calcium Signaling is Attuned to Neuronal Activity
Authors: Umpierre Anthony D. , Bystrom Lauren L. , Ying Yanlu , Liu Yong U. , Wu Long-Jun 
Published: December 2019

ABSTRACTMicroglial calcium signaling underlies a number of key physiological processesin situ, but has not been studiedin vivoin an awake animal where neuronal function is preserved. Using multiple GCaMP6 variants targeted to microglia, we assessed how microglial calcium signaling responds to alterations in neuronal activity across a wide physiological range. We find that only a small subset of microglial somata and processes exhibited spontaneous calcium transients. However, hyperactive and hypoactive shifts in neuronal activity trigger increased microglial process calcium signaling, often concomitant with process extension. On the other hand, changes in somatic calcium activity are only observed days after severe seizures. Our work reveals that microglia have highly distinct microdomain signaling, and that processes specifically respond to bi-directional shifts in neuronal activity through calcium signaling.