bluuebunny/crossref_metadata_2025 huggingface dataset:
0941 Defining Disrupted Nighttime Sleep in Pediatric Narcolepsy
Authors: Maski K P , Pizza F , Colclasure A , Steinhart E , Little E , Diniz Behn C , Vandi S , Antelmi E , Plazzi G , Scammell T
Published: May 2020

Introduction

Disrupted nighttime sleep (DNS) is a core narcolepsy symptom subjectively described as spontaneous awakenings during the night, but researchers use varied polysomnogram (PSG) definitions based on sleep state transitions, NREM 1% and poor sleep efficiency. These sleep measures have yet to be validated to determine the best objective measure of DNS. Furthermore, it unknown to what extent DNS occurs in pediatric narcolepsy as children have greater sleep drive than adults. Here, we assess the construct validity of various DNS objective measures and evaluate its diagnostic utility for pediatric Narcolepsy Type 1 (NT1) when combined with a nocturnal Sleep Onset REM period (nSOREMP) in a large cohort of pediatric patients with CNS hypersomnias.

Methods

Retrospective, cross-sectional study of consecutive PSGs and multiple sleep latency tests (MSLTs) obtained at Boston Children’s Hospital and University of Bologna. Participants were drug-free or drug naïve, ages 6-18 years and slept at least 6 hours during the PSG. We analyzed associations between objective DNS measures and outcomes of self-reported sleep disturbance, Epworth Sleepiness Score, mean sleep latency, NT1 diagnosis, and CSF hypocretin values when available. We then combined the best performing DNS measure with the presence of a nSOREMP to determine the diagnostic value for NT1 using bootstrap analysis. We included n=151 NT1, n=21 narcolepsy type 2 (NT2), n=27 idiopathic hypersomnia (IH) and n= 117 subjectively sleepy controls in this analysis.

Results

Across groups, the Wake and NREM 1 bouts index had the most robust associations with objective sleepiness, subjective sleep disturbance and CSF hypocretin levels (p’s <0.0001). From 1000 bootstrap samples, the Wake/N1 index and presence of a nSOREMP have greater diagnostic accuracy for NT1 than the nSOREMP alone (p<0.0001).

Conclusion

Among a variety of sleep quality measures, we find that a Wake and NREM 1 bout index is the best objective measure of DNS. In combination with a nSOREMP, this DNS measure can aid in pediatric NT1 diagnosis using PSG alone and potentially reduce diagnostic delays.

Support

This study was supported by K23 National Institutes of Health (NINDS, K23 NS104267-01A1) grant and Investigator Initiated Research grant from Jazz Pharmaceuticals, Inc. to Dr. Maski
0953 The Maintenance of Wakefulness Test (MWT) in Pediatric Hypersomnia
Authors: Jaroenying R , Hantragool S , Xu Y , Hossain M M , Simakajornboon N
Published: May 2020

Introduction

The Maintenance of Wakefulness Test (MWT) is a recommended procedure to evaluate the efficacy of treatment for hypersomnia. Limited data have been published on the use of the MWT in children and adolescents. This study aims to describe the clinical characteristics, MWT findings and their implication in the management of children with hypersomnia.

Methods

This study reviewed the charts of children with hypersomnia who had MWT performed at Cincinnati Children’s Hospital Medical Center (CCHMC) between January 1, 2007 and January 31, 2018. Demographics, clinical characteristics, MWT findings, diagnoses and managements of children with hypersomnia were obtained.

Results

Fifty-three patients with hypersomnia who had MWT were included (mean age 17.29 years, range 12.5-22.75 years), 32 (60%) were male, and 40 (75%) were Caucasian. The diagnosis included narcolepsy (41, 77%), idiopathic hypersomnia (7, 13.2%), narcolepsy with OSA (11, 20%) and OSA (4, 7.5%). A mean sleep latency for all studies was 23.24 minutes (range 1.25-40 minutes). Twenty seven (50.9%) patients had mean sleep latency >20 minutes (passed MWT) which indicate adequate control of treatment, while 26 (49.1%) had mean sleep latency <20 minutes (failed MWT) including 5 (9.4%) with mean sleep latency <8 minutes. There was no difference between patients who had passed MWT and failed MWT in the mean of Epworth sleepiness scale (12 vs 11), age (16.8 vs 17.6 years), or BMI (29.2 vs 26.3). Higher percentage of narcolepsy with cataplexy was found in patients who failed MWT (46.2% vs 22.2%, P 0.06). Findings from the MWT caused the changes of management in 25/26 (96.1%) who failed MWT, and 8/27 (29.6%) who passed MWT (P<0.001).

Conclusion

Our result suggests that the MWT has clinical usefulness in evaluating responses to treatment for conditions associated with hypersomnia in children. Changes in management occurred in almost all patient who failed MWT. Interesting, there was no difference in subjective sleepiness between adolescents who passed and failed MWT, indicating the need to obtain objective data in this population. Future study is required to explore normative MWT data in pediatric population and to compare MWT with other tools such as driving simulation test.

Support

None
0956 Vitamin D and Sleep in Children
Authors: Al-Shawwa B , Ehsan Z , Ingram D G
Published: May 2020

Introduction

The impact of vitamin D on human health including sleep has been well described in adults. Its deficiency has been associated with multiple sleep disorders such as decrease in sleep duration, worsening of sleep quality and even obstructive sleep apnea. Such correlation is less evident in pediatric population. In the current study, we examined the relationship between sleep architecture and vitamin D status in children referred to a sleep clinic.

Methods

Retrospective-cohort study in a tertiary care children’s hospital over a one-year period. Children who underwent an in-laboratory-overnight-polysomnogram and had a 25-hydroxy vitamin D level (25-OH-vitD) obtained within 120 days of the sleep study were included. Patients with obstructive or central sleep apnea were excluded. Data from polysomnograms (PSG) and Pediatric Sleep Questionnaires (PSQ) were collected and analyzed.

Results

A total of 39 patients were included in the study with mean age of 6.6 years and 46% females. Twenty (51%) patients had vitamin D deficiency (25-OH-vitD less than 30 ng/ml). Children with vitamin D deficiency had less total sleep time (470.3 minutes +/-35.6 vs 420.3 minutes +/-61.7, p=0.004) and poorer sleep efficiency (91.9 % +/-5.6 vs 84.5 % +/-9.5, p=0.015) compared to vitamin D sufficient children. In addition, vitamin D deficient children had later weekday bedtimes (21:02 +/- 1:01 vs 20:19 +/- 0:55, p=0.037) and later weekend bedtimes (21:42 +/- 0:59 vs 20:47 +/- 1:08, p=0.016) with tendency for later wake up time that did not reach statistical significance. The remainder of polysomnographic findings and PSQ data were not different between the two groups.

Conclusion

Vitamin D deficiency in children is associated with objectively measured decreased sleep duration and poorer sleep efficiency. Furthermore, vitamin D deficiency was associated with delayed bedtimes, suggesting that vitamin D may influence circadian rhythm. Future prospective studies in children would be helpful in validating the effect of vitamin D on sleep.

Support

None
0975 Iron Infusion Protocol For Restless Leg Syndrome In Pediatric Patients
Authors: Taravath S , Peedin M
Published: May 2020

Introduction

Iron dextran protocols have been studied for adults with restless leg syndrome; this study aims to determine the benefit of iron infusions (iron dextran or sucrose) in the improvement or resolution of restless sleep in pediatric patients.

Methods

IRB approval was granted by New Hanover Regional Medical Center. A retrospective chart review was performed using the hospital’s electronic medical record (EMR). A data report was requested for all pediatric patients who received the iron dextran protocol. Patients who received at least one dose of iron dextran or iron sucrose per the protocol were included. Manual data collection included patient demographics, CBCs, iron panels, the dose of iron they received, polysomnogram results, symptom resolution (as described by the physician), and adverse events.

Results

Between January 1, 2017 and January 3, 2018, 55 patients received iron dextran per the weight-based protocol. Patients’ ages ranged from 23 months to 17 years and 5 months old. Of the 55 patients, 27 patients (49%) had documented restless leg syndrome and/or symptoms of leg pain or movement during sleep. All patients experienced restlessness or difficulty sleeping prior to the infusion. Of the 27 patients who experienced leg pain, 10 patients (37%) experienced an improvement in their leg pain or restlessness. Fifty-five percent (55%) of patients in this group reported an improvement in sleep symptoms.

Conclusion

Iron dextran protocols have been studied for adults with restless leg syndrome, but this is the first published data for a weight-based protocol in pediatric patients. While only 27 patients included in this study had a diagnosis of restless leg syndrome or leg pain symptoms, all patients experienced restlessness or other negative sleep symptoms.

Overall, most patients with restless leg syndrome experienced an improvement in their leg and sleep symptoms. No patients reported worsening of symptoms. Intravenous iron dextran infusion may greatly improve the quality of life for children with restless leg syndrome or poor sleep quality. With the overall safety of the iron infusions, this protocol’s benefits outweigh their risks and should be considered in this patient population.

Support
0992 Prevalence Of Insufficient Sleep Duration And Consequences On Daytime Sleepiness, Mood And Academic Performance In Thai Adolescents
Authors: Rojrattanadumrong R , Sudnawa K K , Areekul W , Jaroenying R
Published: May 2020

Introduction

Insufficient sleep duration in adolescents is key public health concerns in many societies. This study aims to assess the prevalence of insufficient sleep duration and the association between short sleep with daytime sleepiness, depressive symptoms, and anxiety among Thai adolescents.

Methods

Thai adolescents aged 11 -18 years completed a self-administered questionnaire including Phramongkutklao Hospital Sleep disorders center Questionnaire, Pittsburg Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), The Children depress Inventory (CDI) scale and Child Anxiety Related Emotional Disorder (SCARED).

Results

232 adolescents with the mean age of 14.58 (range 11-18) years participated in this survey. The average total sleep time was 7.44 hours. The overall prevalence of insufficient sleep duration (sleep duration <8 hours) was 37.5% and the small difference was found between males (42.0%) and females (32.7%). Compared with those who had a sleep length of 8 hours and more, insufficient sleep duration group exhibited higher in BMI and less in Grade Point Average (GPA). Subjective sleep insufficiency among Thai adolescent also had higher percentage of subjects with ESS ≥10 (43.2% vs 21.3%, P <0.001), depressive symptoms (56.3% vs 39.3%, P 0.012) and anxiety (54.0% vs 38.6%, P 0.022) compare to those with adequate sleep duration.

Conclusion

High amount of Thai adolescents with poor sleep duration were observed in the study, consistency with prior surveys. Insufficiency sleep duration group had significantly increased daytime sleepiness, mood and anxiety problems among Thai adolescents. These findings emphasized the development of interventions to improve sleep duration in Thai adolescents and more sample size should be achieved in the future.

Support

None
0993 Impact Of Changing School Start Times On Parent Sleep
Authors: Meltzer L J , Plog A E , McNally J , Wahlstrom K L
Published: May 2020

Introduction

No studies have previously considered how healthy school start times impact parents. Since parent and child sleep schedules, in particular wake time, are associated, we examined whether changing school start times would impact parent sleep (elementary school [ES] 9:00am to 8:00am, middle school [MS] 8:00am to 8:50am, high school [HS] 7:10am to 8:20am).

Methods

Parents of students (grades K-12) completed online surveys pre-change, one-year, and two-years post-change (2017 n=11,579; 2018 n=8,884; 2019 n=8,796), reporting weekday bedtime and wake time (sleep duration calculated bedtime to wake time). Four PROMIS sleep questions asked about sleep “quality”, feeling “alert” upon waking, feeling “tired” during the day, and “daytime problems” because of sleep. Finally, parents were asked one-year post-change how happy they were about the new school start times.

Results

Parents with only ES students reported earlier bedtimes and wake times (10 and 13 minutes). Parents with >1 HS student woke later (HS only: 22 minutes; MS and HS: 25 minutes; ES and HS: 10 minutes; all 3 levels: 14 minutes) and slept longer (HS only: 19 minutes; MS and HS: 21 minutes; ES and HS: 12 minutes; all 3 levels: 18 minutes), with changes maintained two years. Similarly, parents of only ES students reported no change in sleep quality/impairment. Post-change, more parents with >1 MS or HS student reported good sleep quality (average increase=6.9%), feeling alert (average increase=5.8%), not feeling tired (average increase=5.0%), and having few daytime problems (average increase=4.2%), with benefits maintained two-years post-change. Across levels, parents who were “very happy” about start time changes slept longer than “very unhappy” parents (12-30 minutes); however, across levels, child sleep did not differ between happy and unhappy parents.

Conclusion

This is the first study to examine the impact of changing start times on parents of students in grades K-12. Study results show no significant impact on parents of elementary students. However, similar to students, parents of middle/high school students reported later wake times and increased sleep duration. Notably, parents’ happiness with start time changes was related to parent, but not student, sleep duration.

Support

Robert Wood Johnson Foundation’s Evidence for Action Grant
0998 Health Care Utilization of Pediatric Sleep Disorders in Cerner Health Facts Database
Authors: Al-Shawwa B , Glynn E , Hoffman M , Ehsan Z , Ingram D
Published: May 2020

Introduction

This study was aimed to identify health care utilization of sleep disorders in pediatrics and adults by using Cerner health facts database.

Methods

Health facts database has unidentified health records from all the participating facilities that have Cerner as their electronic medical records software. There are 68.7 million patients in the data warehouse with about 506.9 million encounters in about 100 healthcare systems. Sleep disorders are mostly seen in outpatient settings and therefore this study included outpatient records between the years 2010 to 2017.

Results

There were 20.5 million patients with total of 127.4 million outpatient encounters. In pediatric patients (ages 0-18 years), healthcare utilization of major sleep diagnoses per 100,000 encounters showed sleep related breathing disorders are the most commonly seen followed by parasomnia, insomnia, sleep movement disorders, hypersomnolence then circadian rhythm disorders (820.1, 258.1, 181.6, 68.3, 48.1 and 16.2 per 100,000 encounters). However, for adult patients the ranking was: sleep related breathing disorders, insomnia, sleep related movement disorders, hypersomnolence, parasomnia then circadian rhythm disorders (1352.6, 511.6, 166.3, 79.1, 25.7 and 4.2 per 100,000 encounters). Further analysis for the age groups showed bimodal pattern for sleep related breathing disorders and sleep movement disorders with the highest utilization were between the ages of 2-11 year and 40-60 years. Adolescents (age 12-18 years) showed increase utilization in the areas of circadian rhythm disorders.

Conclusion

Patients with sleep disorders have relatively low health care utilization despite high prevalence of these sleep disorders in the general population. This may highlight underrecognized sleep problem or decreased access to health care. In addition, this study highlights the effect of age on different sleep disorders which may have an impact on allocating resources.

Support

None
Pregabalin reduces oxaliplatin-induced oxidative neurotoxicity through modulation of TRPV1 channels in DBTRG neuronal cell line
Authors: Ataizi Zeki Serdar , Ertilav Kemal
Published: May 2020

As a member of the platinum drug group, oxaliplatin (OXAL) is used to treat brain tumors, although its use is limited through excessive calcium ion (Ca2+) influx and reactive oxygen species (ROS) production in neurons. The Ca2+ permeable transient receptor potential vanilloid 1 (TRPV1) channel is activated by ROS, and its activity might be reduced by the antioxidant property of pregabalin (PREGAB). This study aimed to investigate the protective action of PREGAB against OXAL-induced oxidative neurotoxicity in human glioblastoma (DBTRG) cells. The DBTRG cells were divided into four treatment groups: control, PREGAB (500 µM for 1 h), OXAL (25 µM for 24 h), and PREGAB + OXAL. In the laser confocal microscope and plate reader analyses, apoptosis, mitochondrial membrane depolarization (JC-1), cell death (propidium iodide/Hoechst rate), and ROS-level production increased by activating TRPV1 in the cells using the OXAL treatment, although the cell viability values decreased. However, these values were recovered in the PREGAB + OXAL group using PREGAB and TRPV1 inhibitor (capsazepine) treatments. In the patch-clamp analyses, OXAL-induced TRPV1 channel activation in the OXAL group also decreased in the PREGAB + OXAL group using the PREGAB and capsazepine treatments. In conclusion, the apoptosis and oxidant actions of OXAL were increased by activation of the TRPV1 channel, but this effect was diminished by the PREGAB treatment. PREGAB treatment has the potential to be an effective strategy in the treatment of OXAL-induced oxidative neurotoxicity.
Socioeconomic Disparities in Colon Cancer Survival
Authors: Wiese Daniel , Stroup Antoinette M. , Maiti Aniruddha , Harris Gerald , Lynch Shannon M. , Vucetic Slobodan , Henry Kevin A.
Published: May 2020

Background:

Residential histories linked to cancer registry data provide new opportunities to examine cancer outcomes by neighborhood socioeconomic status (SES). We examined differences in regional stage colon cancer survival estimates comparing models using a single neighborhood SES at diagnosis to models using neighborhood SES from residential histories.

Methods:

We linked regional stage colon cancers from the New Jersey State Cancer Registry diagnosed from 2006 to 2011 to LexisNexis administrative data to obtain residential histories. We defined neighborhood SES as census tract poverty based on location at diagnosis and across the follow-up period through 31 December 2016 based on residential histories (average, time-weighted average, time-varying). Using Cox proportional hazards regression, we estimated associations between colon cancer and census tract poverty measurements (continuous and categorical), adjusted for age, sex, race/ethnicity, regional substage, and mover status.

Results:

Sixty-five percent of the sample was nonmovers (one census tract); 35% (movers) changed tract at least once. Cases from tracts with >20% poverty changed residential tracts more often (42%) than cases from tracts with <5% poverty (32%). Hazard ratios (HRs) were generally similar in strength and direction across census tract poverty measurements. In time-varying models, cases in the highest poverty category (>20%) had a 30% higher risk of regional stage colon cancer death than cases in the lowest category (<5%) (95% confidence interval [CI] = 1.04, 1.63).

Conclusion:

Residential changes after regional stage colon cancer diagnosis may be associated with a higher risk of colon cancer death among cases in high-poverty areas. This has important implications for postdiagnostic access to care for treatment and follow-up surveillance. See video abstract: http://links.lww.com/EDE/B705.
The impact of measurement error in modeled ambient particles exposures on health effect estimates in multilevel analysis
Authors: Samoli Evangelia , Butland Barbara K. , Rodopoulou Sophia , Atkinson Richard W. , Barratt Benjamin , Beevers Sean D. , Beddows Andrew , Dimakopoulou Konstantina , Schwartz Joel D. , Yazdi Mahdieh Danesh , Katsouyanni Klea
Published: May 2020

Background:

Various spatiotemporal models have been proposed for predicting ambient particulate exposure for inclusion in epidemiological analyses. We investigated the effect of measurement error in the prediction of particulate matter with diameter <10 µm (PM10) and <2.5 µm (PM2.5) concentrations on the estimation of health effects.

Methods:

We sampled 1,000 small administrative areas in London, United Kingdom, and simulated the “true” underlying daily exposure surfaces for PM10 and PM2.5 for 2009–2013 incorporating temporal variation and spatial covariance informed by the extensive London monitoring network. We added measurement error assessed by comparing measurements at fixed sites and predictions from spatiotemporal land-use regression (LUR) models; dispersion models; models using satellite data and applying machine learning algorithms; and combinations of these methods through generalized additive models. Two health outcomes were simulated to assess whether the bias varies with the effect size. We applied multilevel Poisson regression to simultaneously model the effect of long- and short-term pollutant exposure. For each scenario, we ran 1,000 simulations to assess measurement error impact on health effect estimation.

Results:

For long-term exposure to particles, we observed bias toward the null, except for traffic PM2.5 for which only LUR underestimated the effect. For short-term exposure, results were variable between exposure models and bias ranged from −11% (underestimate) to 20% (overestimate) for PM10 and of −20% to 17% for PM2.5. Integration of models performed best in almost all cases.

Conclusions:

No single exposure model performed optimally across scenarios. In most cases, measurement error resulted in attenuation of the effect estimate.
Micropulse Trans-scleral Cyclophotocoagulation in Patients With Glaucoma: 1- and 2-Year Treatment Outcomes
Authors: de Crom Ronald M.P.C. , Slangen Caroline G.M.M. , Kujovic-Aleksov Stefani , Webers Carroll A.B. , Berendschot Tos T.J.M. , Beckers Henny J.M.
Published: May 2020

Précis:

Micropulse trans-scleral cyclophotocoagulation (TSCPC) is an effective and safe IOP-lowering treatment for patients with primary or secondary glaucoma.

Purpose:

To investigate the 1-year and 2-year effect on intraocular pressure (IOP) and safety profile of micropulse TSCPC in patients with glaucoma.

Methods:

Patients with glaucoma underwent a standardized micropulse TSCPC (MicroPulse P3 probe, Iridex cyclo G6 laser system, Mountain View, CA) at the University Eye Clinic Maastricht from November 2016 to May 2018. Patients with at least 12 months of follow-up were included.

Results:

A total of 141 eyes of 136 patients were included. The mean age was 67.2±14.5 years, and 56.6% of patients were male individuals. The glaucoma subtypes treated were primary glaucoma (n=99) and secondary glaucoma (n=42). Prior glaucoma surgery was performed in 59 of 141 eyes (41.8%). The mean preoperative IOP was 23.5±9.4 mm Hg. The mean postoperative IOP dropped to 16.8±8.4, 17.0±7.8, and 16.8±9.2 mm Hg, after 12, 18, and 24 months, respectively. The mean number of IOP-lowering medications used preoperatively was 3.3±1.4. The mean number of medications used at 12, 18, and 24 months was respectively 2.6±1.5, 2.5±1.4, and 2.2±1.5. Postoperative complications included cystic macular edema (n=2), hypotony maculopathy (n=1), fibrinous/uveitic reaction (n=1), and rejection of corneal graft (n=1), all reversible after treatment. One patient developed persisting hypotony in the late postoperative period.

Conclusions:

Micropulse TSCPC is a safe and effective treatment for lowering both IOP and the number of IOP-lowering medications. Micropulse TSCPC can also be considered as a good alternative treatment option for patients after failed incisional glaucoma surgery or patients who are at high risk for incisional surgery.
Just-in-Time Simulation to Guide Workflow Design for Coronavirus Disease 2019 Difficult Airway Management*
Authors: Daly Guris Rodrigo J. , Doshi Anushree , Boyer Donald L. , Good Grace , Gurnaney Harshad G. , Rosenblatt Samuel , McGowan Nancy , Widmeier Keith , Kishida Mizue , Nadkarni Vinay , Nishisaki Akira , Wolfe Heather A.
Published: May 2020

Objectives:

The coronavirus disease 2019 pandemic has required that hospitals rapidly adapt workflows and processes to limit disease spread and optimize the care of critically ill children.

Design and Setting:

As part of our institution’s coronavirus disease 2019 critical care workflow design process, we developed and conducted a number of simulation exercises, increasing in complexity, progressing to intubation wearing personal protective equipment, and culminating in activation of our difficult airway team for an airway emergency.

Patients and Interventions:

In situ simulations were used to identify and rework potential failure points to generate guidance for optimal airway management in coronavirus disease 2019 suspected or positive children. Subsequent to this high-realism difficult airway simulation was a real-life difficult airway event in a patient suspected of coronavirus disease 2019 less than 12 hours later, validating potential failure points and effectiveness of rapidly generated guidance.

Measurements and Main Results:

A number of potential workflow challenges were identified during tabletop and physical in situ manikin-based simulations. Experienced clinicians served as participants, debriefed, and provided feedback that was incorporated into local site clinical pathways, job aids, and suggested practices. Clinical management of an actual suspected coronavirus disease 2019 patient with difficult airway demonstrated very similar success and anticipated failure points. Following debriefing and assembly of a success/failure grid, a coronavirus disease 2019 airway bundle template was created using these simulations and clinical experiences for others to adapt to their sites.

Conclusions:

Integration of tabletop planning, in situ simulations, and debriefing of real coronavirus disease 2019 cases can enhance planning, training, job aids, and feasible policies/procedures that address human factors, team communication, equipment choice, and patient/provider safety in the coronavirus disease 2019 pandemic era.
Children in Critical Care Due to Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Experience in a Spanish Hospital
Authors: García-Salido Alberto , Leoz-Gordillo Inés , Martínez de Azagra-Garde Amelia , Nieto-Moro Montserrat , Iglesias-Bouzas María Isabel , García-Teresa María Ángeles , Cabrero-Hernández Marta , De Lama Caro-Patón Gema , Gochi Valdovinos Ainhoa , González-Brabin Anthony , Serrano-González Ana
Published: May 2020

Objectives:

Spain has been one of the countries most severely affected by the coronavirus disease 2019. This study aims to describe a series of children admitted to a PICU due to coronavirus disease 2019 infection.

Design:

Prospective observational study.

Setting:

Tertiary hospital in Madrid, Spain.

Patients:

Children admitted to the PICU with severe acute respiratory syndrome coronavirus 2 (severe acute respiratory syndrome coronavirus 2) infection, from March 1, 2020, to April 15, 2020.

Interventions:

Observational study.

Measurements and Main Results:

Epidemiologic data, previous clinical characteristics, support therapy needed, imaging tests, laboratory observations on admission, and pharmacologic therapy. Eleven children were admitted to the PICU, with suspected coronavirus disease 2019; the polymerase chain reaction test was positive in seven. The median age was 100.7 months (range, 0.5–162). Five were admitted from the emergency department and two from the ward. The Pediatric Sequential Organ Failure Assessment score was 3 (range, 0–9), and Pediatric Risk of Mortality II score was 4 (range, 0–16). All children were previously healthy except one (allogeneic hematopoietic stem cell transplantation). Respiratory symptoms and fever were prevalent. A chest radiograph led to a pneumonia diagnosis. Not all patients presented with lymphopenia on admission. d-Dimer and ferritin were elevated. All patients needed oxygen therapy through a nasal cannula; five patients received high-flow nasal cannula therapy, which was later substituted with noninvasive ventilation in four. Mechanical ventilation was necessary in two patients on the first day of PICU admission. Two children required mechanical ventilation and inotropic support. Tocilizumab was applied in two intubated children. Also, four children received heparin. No patients died.

Conclusions:

On the whole, the children were previously healthy and are more than 1 year old. Respiratory symptoms were the leading cause of PICU admission, making respiratory support the principal therapy. Patients requiring mechanical ventilation showed deterioration on the first day of admission. These children seemed to require close monitoring, and multicenter studies are necessary.
Impact of a Standardized Clinical Pathway for Suspected and Confirmed Ileocolic Intussusception
Authors: Shubin Corinne E. , Rutman Lori E. , Stanescu A. Luana , Vora Surabhi B. , Drugas George T. , Leu Michael G. , Burns Rebekah A.
Published: May 2020

Introduction:

Clinical pathways for specific diagnoses may improve patient outcomes, decrease resource utilization, and diminish costs. This study examines the impact of a clinical pathway for emergency department (ED) care of suspected and confirmed pediatric ileocolic intussusception.

Methods:

Our multidisciplinary team designed an intussusception clinical pathway and implemented it in a tertiary children’s hospital ED in October 2016. Process measures included the proportion of patients who underwent abdominal radiography, had laboratory studies, received antibiotics, or required admission following reduction of intussusception. The primary outcome measure was the cost per encounter. Balancing measures included unplanned ED visits within 72 hours of discharge. Data analyzed compared 24 months before and 21 months following pathway implementation.

Results:

After pathway implementation, the use of abdominal radiography in patients with suspected intussusception decreased from 50% to 12%. In patients with confirmed intussusception, laboratory studies decreased from 58% to 25%, antibiotic use decreased from 100% to 2%, and hospital admissions decreased from 100% to 12%. The average cost per encounter for confirmed intussusception decreased from $6,724 to $2,975. There was a small increase in unplanned returns to the ED within 72 hours but no increase in readmissions after pathway implementation.

Conclusion:

Implementation of a standardized ED pathway for the management of suspected and confirmed pediatric ileocolic intussusception is associated with a reduction in abdominal radiographs, improved antibiotic stewardship, reduction in laboratory studies, fewer inpatient admissions, and decreased cost, with no compromise in patient safety.
Understanding the impact of preprocessing pipelines on neuroimaging cortical surface analyses
Authors: Bhagwat Nikhil , Barry Amadou , Dickie Erin W. , Brown Shawn T. , Devenyi Gabriel A. , Hatano Koji , DuPre Elizabeth , Dagher Alain , Chakravarty M. Mallar , Greenwood Celia M. T. , Misic Bratislav , Kennedy David N. , Poline Jean-Baptiste
Published: May 2020

The choice of preprocessing pipeline introduces variability in neuroimaging analyses that affects the reproducibility of scientific findings. Features derived from structural and functional MR imaging data are sensitive to the algorithmic or parametric differences of preprocessing tasks, such as image normalization, registration, and segmentation to name a few. Therefore it is critical to understand and potentially mitigate the cumulative biases of pipelines in order to distinguish biological effects from methodological variance. Here we use an open structural MR imaging dataset (ABIDE), supplemented with the Human Connectome Project (HCP), to highlight the impact of pipeline selection on cortical thickness measures. Specifically, we investigate the effect of 1) software tool (e.g. ANTs, CIVET, FreeSurfer), 2) cortical parcellation (DKT, Destrieux, Glasser), and 3) quality control procedure (manual, automatic). We divide our statistical analyses by 1) method type, i.e. task-free (unsupervised) versus task-driven (supervised), and 2) inference objective, i.e. neurobiological group differences versus individual prediction. Results show that software, parcellation, and quality control significantly impact task-driven neurobiological inference. Additionally, software selection strongly impacts neurobiological and individual task-free analyses, and quality control alters the performance for the individual-centric prediction tasks. This comparative performance evaluation partially explains the source of inconsistencies in neuroimaging findings. Furthermore, it underscores the need for more rigorous scientific workflows and accessible informatics resources to replicate and compare preprocessing pipelines to address the compounding problem of reproducibility in the age of large-scale, data-driven computational neuroscience.
Physiological Artefacts and the Implications for Brain-Machine-Interface Design
Authors: Sorkhabi Majid Memarian , Benjaber Moaad , Brown Peter , Denison Timothy
Published: May 2020

The accurate measurement of brain activity by Brain-Machine-Interfaces (BMI) and closed-loop Deep Brain Stimulators (DBS) is one of the most important steps in communicating between the brain and subsequent processing blocks. In conventional chest-mounted systems, frequently used in DBS, a significant amount of artifact can be induced in the sensing interface, often as a common-mode signal applied between the case and the sensing electrodes. Attenuating this common-mode signal can be a serious challenge in these systems due to finite commonmode-rejection-ratio (CMRR) capability in the interface. Emerging BMI and DBS devices are being developed which can mount on the skull. Mounting the system on the cranial region can potentially suppress these induced physiological signals by limiting the artifact amplitude. In this study, we model the effect of artifacts by focusing on cardiac activity, using a current-source dipole model in a torso-shaped volume conductor. Performing finite element simulation with the different DBS architectures, we estimate the ECG common mode artifacts for several device architectures. Using this model helps define the overall requirements for the total system CMRR to maintain resolution of brain activity. The results of the simulations estimate that the cardiac artifacts for skull-mounted systems will have a significantly lower effect than non-cranial systems that include the pectoral region. It is expected that with a pectoral mounted device, a minimum of 60-80 dB CMRR is required to suppress the ECG artifact, while in cranially-mounted devices, a 20 dB CMRR is sufficient, in the worst-case scenario. The methods used for estimating cardiac artifacts can be extended to other sources such as motion/muscle sources. The susceptibility of the device to artifacts has significant implications for the practical translation of closed-loop DBS and BMI, including the choice of biomarkers and the design requirements for insulators and lead systems.
SciSight: Combining faceted navigation and research group detection for COVID-19 exploratory scientific search
Authors: Hope Tom , Portenoy Jason , Vasan Kishore , Borchardt Jonathan , Horvitz Eric , Weld Daniel S. , Hearst Marti A. , West Jevin
Published: May 2020

The COVID-19 pandemic has sparked unprecedented mobilization of scientists, generating a deluge of papers that makes it hard for researchers to keep track and explore new directions. Search engines are designed for targeted queries, not for discovery of connections across a corpus. In this paper, we presentSciSight, a system for exploratory searchof COVID-19 research integrating two key capabilities: first, exploring associations between biomedical facets automatically extracted from papers (e.g., genes, drugs, diseases, patient outcomes); second, combining textual and network information to search and visualizegroupsof researchers and their ties. SciSight1has so far served over 15Kusers with over 42Kpage views and 13% returns.
ISL2 is an epigenetically silenced tumor suppressor and regulator of metabolism in pancreatic cancer
Authors: Tufan Turan , Yang Jiekun , Tummala Krishna Seshu , Cingoz Harun , Kuscu Cem , Adair Sara J. , Comertpay Gamze , Nagdas Sarbajeet , Goudreau Bernadette J. , Luleyap Husnu Umit , Hsu Ku-lung , Kashatus Dave F. , Bardeesy Nabeel , Bauer Todd W. , Adli Mazhar
Published: May 2020

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers. Uncovering mechanisms responsible for the heterogeneous clinical features of this disease is an essential step toward developing improved and more specific therapeutic approaches. Here, we sought to identify transcriptional regulators of aggressive PDAC growth throughin vivoCRISPR screening of epigenetic and transcription factors in an orthotopic model. We identified the ISL LIM homeobox 2 (ISL2) gene as a tumor suppressor whose depletion enhances the proliferation of human PDAC cellsin vitroandin vivoand cooperates with activated KRAS to initiate PDAC in a murine model. Conversely, the upregulation ofISL2expression through CRISPR-mediated locus-specific epigenetic editing results in reduced cell proliferation. Importantly,ISL2is epigenetically silenced through DNA methylation in ~60% of PDAC tumors, which correlates with poor patient outcome. Functional studies showed that ISL2 loss rewires metabolic gene expression, and consequently potentiates oxidative phosphorylation while reducing glycolysis. This metabolic shift creates selective vulnerability to small molecule inhibitors of mitochondrial respiration and fatty acid oxidation. Collectively, these findings reveal ISL2 as a novel tumor suppressor whose inactivation drives metabolic reprogramming in an aggressive PDAC subset and point to potential therapeutic vulnerabilities in these tumors.
Choanoflagellates and the ancestry of neurosecretory vesicles
Authors: Göhde Ronja , Naumann Benjamin , Laundon Davis , Imig Cordelia , McDonald Kent , Cooper Benjamin H. , Varoqueaux Frederique , Fasshauer Dirk , Burkhardt Pawel
Published: May 2020

Neurosecretory vesicles are highly specialized trafficking organelles important for metazoan cell-cell signalling. Despite the high anatomical and functional diversity of neurons in metazoans, the protein composition of neurosecretory vesicles in bilaterians appears to be similar. This similarity points towards a common evolutionary origin. Moreover, many key neurosecretory vesicle proteins predate the origin of the first neurons and some even the origin of the first animals (metazoans). However, little is known about the molecular toolkit of these vesicles in non-bilaterian metazoans and their closest unicellular relatives, making inferences about the evolutionary origin of neurosecretory vesicles extremely difficult. By comparing 28 proteins of the core neurosecretory vesicle proteome in 13 different species, we demonstrate that most of the proteins are already present in unicellular organisms. Surprisingly, we find that the vesicle residing SNARE protein synaptobrevin is localized to the vesicle-rich apical and basal pole in the choanoflagellateSalpingoeca rosetta. Our 3D vesicle reconstructions reveal that the choanoflagellatesSalpingoeca rosettaandMonosiga brevicollisexhibit a polarized and diverse vesicular landscape. This study sheds light on the ancestral molecular machinery of neurosecretory vesicles and provides a framework to understand the origin and evolution of secretory cells, synapses, and neurons.
PYK2 controls intestinal inflammation via activation of IRF5 in macrophages
Authors: Ryzhakov Grigory , Almuttaqi Hannah , Corbin Alastair L. , Khoyratty Tariq , Berthold Dorothee , Bullers Samuel , Eames Hayley L , Ai Zhichao , Bonham Sarah , Fischer Roman , Jostins-Dean Luke , Travis Simon P.L. , Kessler Benedikt M. , Udalova Irina A.
Published: May 2020

Inflammatory bowel disease (IBD) is a group of inflammatory disorders of the gastro-intestinal tract caused by a complex combination of genetic and environmental factors. Interferon regulating factor 5 (IRF5) is a multifunctional regulator of immune responses, which plays a key pathogenic role in mouse colitis models and is a genetic risk factor for IBD. A screen of a protein kinase inhibitor library in macrophages revealed a list of putative IRF5 kinases. Among the top hits validated in multiplein vitroassays, protein-tyrosine kinase 2-beta (PTK2B or PYK2) was identified as the only IBD genetic risk factor, known to impact gene expression in myeloid cells1,2. Phospho-proteomics and mutagenesis analyses established that PYK2 directly phosphorylates and activates IRF5 at tyrosine (Y) 171. IRF5 nuclear translocation and recruitment to target genes was impaired in PYK2-deficient cells or in cells treated with PYK2 inhibitors. Importantly, macrophage transcriptomic signature under PYK2 inhibition phenocopied IRF5 deficiency. Treatment with a PYK2 inhibitor reduced pathology and inflammatory cytokine production inHelicobacter hepaticus+ anti-IL-10R antibody induced colitis model. It also decreased levels of pro-inflammatory cytokines in human colon biopsies taken from patients with ulcerative colitis. Thus, we have identified a major role for PYK2 in regulating the inflammatory response and mapped its activity to the IRF5 innate sensing pathway, opening opportunities for therapeutic interference with it in IBD and other inflammatory conditions.
Molecular interaction mechanism of a 14-3-3 protein with a phosphorylated peptide elucidated by enhanced conformational sampling
Authors: Higo Junichi , Kawabata Takeshi , Kusaka Ayumi , Kasahara Kota , Kamiya Narutoshi , Fukuda Ikuo , Mori Kentaro , Hata Yutaka , Fukunishi Yoshifumi , Nakamura Haruki
Published: May 2020

Enhanced conformational sampling, a genetic-algorithm-guided multi-dimensional virtual-system coupled molecular dynamics, can provide equilibrated conformational distributions of a receptor protein and a flexible ligand at room temperature. The distributions provide not only the most stable but also semi-stable complex structures, and propose a ligand–receptor binding process. This method was applied to a system consisting of a receptor protein, 14-3-3ε, and a flexible peptide, phosphorylated Myeloid leukemia factor 1 (pMLF1). The results present comprehensive binding pathways of pMLF1 to 14-3-3ε. We identified four thermodynamically stable clusters of MLF1 on the 14-3-3ε surface, and free-energy barriers among some clusters. The most stable cluster includes two high-density spots connected by a narrow corridor. When pMLF1 passes the corridor, a salt-bridge relay (switching) related to the phosphorylated residue of pMLF1 occurs. Conformations in one high-density spots are similar to the experimentally determined complex structure. Three-dimensional distributions of residues in the intermolecular interface rationally explain the binding-constant changes resultant from alanine–mutation experiment for the residues. We performed a simulation of non-phosphorylated peptide and 14-3-3ε, which demonstrated that the complex structure was unstable, suggesting that phosphorylation of the peptide is crucially important for binding to 14-3-3ε.
Size matters – larger images are better remembered during free viewing
Authors: Masarwa Shaimaa , Kreichman Olga , Gilaie-Dotan Sharon
Published: May 2020

We are constantly exposed to multiple visual scenes, and while freely viewing them without an intentional effort to memorize or encode them, only some are remembered. It has been suggested that image memorability is influenced by multiple factors as depth of processing (1–3), familiarity (4), and visual category (5–7). However, this is typically investigated with intentional (8, 9) or unintentional (10, 11) encoding tasks. Furthermore, since visual memory relies on size-invariant visual perception (12–14), image size is not considered a contributing factor. Here we reasoned that during naturalistic free viewing of images without an encoding task, bigger images would be better remembered due to multiple factors (as vaster expanse of activated visual cortex (15, 16), deeper processing). In an extensive set of experiments participants (n=117) freely viewed small to large images (3°-24°) without any encoding task. Subsequently, they were presented with mid-sized images (50% already seen) and were asked to report if they recall seeing them or not. Larger images were better remembered (~23% more than smaller images), image memorability was proportional to image size, faces were better remembered, and outdoors the least. These were independent of image set, presentation order, or screen resolution. While multiple factors affect image memorability (1–7), here we show that during free viewing with no encoding task, a basic physical image dimension influences its memorability.
Training-induced improvement in working memory tasks results from switching to efficient strategies
Authors: Malinovitch Tamar , Jackoby Hilla , Ahissar Merav
Published: May 2020

It is debated whether training with a working memory (WM) task, particularly n-back, can improve general WM and reasoning skills. Most training studies found substantial improvement in the trained task, with little to no transfer to untrained tasks. We hypothesized that training does not increase WM capacity, but instead provides opportunities to develop an efficient task-specific strategy. We derived a strategy for the task that optimizes WM resources and taught it to participants. In two sessions, 14 participants who were taught this strategy performed as well as 14 participants who had trained for forty sessions without strategy instructions. To understand the mechanisms underlying the no-instruction group’s improvement, participants answered questionnaires during their training period. Their replies show that successful learners discovered the same strategy and improvement was associated with this discovery. We conclude that n-back training allows the discovery of strategies that enable better performance with the same WM resources.
Efficient Method for Protein Crystallization
Authors: Meents Alke , Varanasi Vamsi J. , Huang Frank
Published: May 2020

This paper has been withdrawn by bioRxiv because its content, including the author names, was fabricated and fraudulently submitted in what may have been an attempt to game citation statistics or other metrics.