bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coming Together to Save Babies: Our Institution’s Quality Improvement Collaborative to Improve Infant Safe Sleep Practices
Authors: Macklin Jamie R. , Bagwell Gail , Denny Sarah A. , Goleman Jane , Lloyd Julia , Reber Kris , Stoverock Linda , McClead Richard E. 
Published: October 2020

Introduction:
Many hospitalized infants are not observed in an American Academy of Pediatrics-recommended safe sleep environment, which can translate to unsafe sleep practices at home. We implemented this collaborative to reduce our county’s sleep-related death rate by improving infant safe sleep practices in the freestanding children’s hospital setting and increasing safe sleep screening and education in our clinics and emergency departments (EDs).

Methods:
Physicians from our institution’s primary care clinics, EDs, neonatal intensive care units, and general inpatient units created and led multidisciplinary safe sleep teams. Teams have used standardized data tools to collect information on infant patient ages and sleep position and environment, both in the hospital and at home. Based on audit data, teams have implemented multiple Plan-Do-Study-Act cycles during this collaborative. We have calculated changes in safe sleep practices in the hospital and changes in screening and education on safe sleep behaviors over time.

Results:
Our teams have significantly increased compliance with safe sleep practices in the inpatient and neonatal intensive care unit settings (P < 0.01). We have also increased screening and education on appropriate safe sleep behaviors by ED and primary care providers (P < 0.01). Our county’s sleep-related death rate has not significantly decreased during the collaborative.

Conclusions:
Our collaborative has increased American Academy of Pediatrics-recommended safe sleep practices in our institution, and we decreased sleep-related deaths in our primary care network. We have created stronger ties to our community partners working to decrease infant mortality rates. More efforts will be needed, both within and outside of our institution, to lower our community’s sleep-related death rate.
Long-Term Orthognathic Considerations in the Pierre Robin Sequence Patient
Authors: Pfaff Miles J. , De Leon Fransia , Le Laura , Haveles Christos , Liu Claire , Berthiaume Emily , Ayeroff Julia R. , Wilson Libby F. , Lee Justine C. 
Published: October 2020

Background:
One of the arguments against early intervention for micrognathia in Pierre Robin sequence is the concept that the growth of the mandible will eventually “catch up.” Long-term growth of the mandible and occlusal relationships of conservatively managed Pierre Robin sequence patients remain unknown. In this study, the authors evaluated the orthognathic surgery requirements for Pierre Robin sequence patients at skeletal maturity.

Methods:
Orthognathic surgical requirements of conservatively managed Pierre Robin sequence and isolated cleft patients (aged ≥13 years) at two institutions were reviewed and analyzed using t test, chi-square test, and Fisher’s exact test. Values of p < 0.05 were considered statistically significant.

Results:
Of the Pierre Robin sequence patients (n = 64; mean age ± SD, 17.9 ± 2.9 years), 65.6 percent were syndromic (primarily Stickler and velocardiofacial syndrome), 96.9 percent had a cleft palate, and 39.1 percent required orthognathic surgery at skeletal maturity. Nonsyndromic and syndromic Pierre Robin sequence patients demonstrated no differences in occlusal relationships or mandibular surgery frequency. The majority of Pierre Robin sequence patients requiring mandibular advancement had a class II occlusion. Comparison of Pierre Robin sequence patients to isolated cleft palate patients (n = 17) revealed a comparable frequency of orthognathic surgery between the two; however, Pierre Robin sequence patients did require mandibular advancement surgery at a greater frequency than cleft palate patients (p = 0.006).

Conclusions:
The present study found that 39.1 percent of conservatively managed Pierre Robin sequence patients required orthognathic surgery at skeletal maturity, of which the vast majority required mandibular advancement for class II malocclusion. These data suggest that mandibular micrognathia in conservatively managed Pierre Robin sequence patients may not resolve over time and may require surgical intervention.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Risk, II.
Patterns of oncogene co-expression at single cell resolution in cancer influence survival
Authors: Hoppe Michal Marek , Jaynes Patrick , Shuangyi Fan , Peng Yanfen , Hoang Phuong Mai , Xin Liu , De Mel Sanjay , Poon Limei , Chan Esther , Lee Joanne , Ong Choon Kiat , Tang Tiffany , Lim Soon Thye , Nagarajan Chandramouli , Grigoropoulos Nicholas Francis , Tan Soo-Yong , Hue Susan Swee-Shan , Chang Sheng-Tsung , Chuang Shih-Sung , Li Shaoying , Khoury Joseph D. , Choi Hyungwon , Harris Carl , Bottos Alessia , Gay Laura J. , Runge Hendrik F. P. , Moutsopoulos Ilias , Mohorianu Irina , Hodson Daniel J. , Farinha Pedro , Mottok Anja , Scott David W. , Kumar Gayatri , Kannan Kasthuri , Chng Wee-Joo , Chee Yen Lin , Ng Siok-Bian , Tripodo Claudio , Jeyasekharan Anand D. 
Published: October 2020

AbstractBackgroundCancers often overexpress multiple clinically relevant oncogenes. However, it is not known if multiple oncogenes within a cancer combine uniquely in specific cellular sub-populations to influence clinical outcome. We studied this phenomenon using the prognostically relevant oncogenes MYC, BCL2 and BCL6 in Diffuse Large B-Cell Lymphoma (DLBCL).MethodsQuantitative multispectral imaging simultaneously measured oncogene co-expression at single-cell resolution in reactive lymphoid tissue (n=12) and four independent cohorts (n=409) of DLBCL. Mathematically derived co-expression phenotypes were evaluated in DLBCLs with immunohistochemistry (n=316) and eight DLBCL cohorts with gene expression data (n=4186). Bulk and single-cell RNA sequencing was performed on patient-derived B-cells with induced co-expression of MYC, BCL2 and BCL6.ResultsUnlike in non-malignant lymphoid tissue where the co-expression of MYC, BCL2 and BCL6 in a B-cell is limited, DLBCLs show multiple permutations of oncogenic co-expression in malignant B-cells. The percentage of cells with a unique combination MYC+BCL2+BCL6-(M+2+6-) consistently predicts survival in contrast to that of other combinations (including M+2+6+). An estimated percentage of M+2+6-cells can be derived from any quantitative measurement of the component individual oncogenes, and correlates with survival in immunohistochemistry and gene expression datasets. Comparative transcriptomic analysis of DLBCLs and transformed patient-derived B-cells identifies cyclin D2 (CCND2) as a potential BCL6-repressed regulator of proliferation in the M+2+6-population.ConclusionsUnique patterns of oncogene co-expression at single-cell resolution affect clinical outcomes in DLBCL. Similar analyses evaluating oncogenic combinations at the cellular level may impact diagnostics and target discovery in other cancers.
Associations between Affect, Physical Activity, and Anxiety Among US Children During COVID-19
Authors: Alves Jasmin M. , Yunker Alexandra G. , DeFendis Alexis , Xiang Anny H. , Page Kathleen A. 
Published: October 2020

AbstractWe investigated how emotional responses (positive and negative affect), physical activity (PA), and sedentary behaviors related to anxiety among US children during the COVID-19 pandemic. Sixty-four typically-developing children (63% girls) age 9-15 years old completed two virtual visits during height of “stay-at-home” measures between April 22 – July 29, 2020. Children completed 24-hour PA recalls, state portion of State-Trait Anxiety Inventory for Children (STAIC), and the shortened 10-item Positive and Negative Affect Schedule for Children (PANAS-C). Children reported state anxiety scores that were more than 5 standard deviations greater than values from healthy pediatric populations prior to the pandemic. Children with higher positive affect and who reported more time in PA reported less state anxiety. Sedentary and leisure screen time were positively correlated with negative affect. Our findings suggest that maintaining positive affect, engaging in PA, and limiting leisure screen time may be important for child mental health during stressful periods.Statement of RelevanceThere is increasing concern regarding how the COVID-19 pandemic may impact the psychological and physical health of children. To date, studies on mental health during the pandemic in children are limited. We investigated links between activity levels and psychological outcomes in children during the height of the “stay-at-home” measures. We found that children had anxiety scores that were more than 5 standard deviations greater than normative values from healthy pediatric populations prior to the pandemic, and 94% of children exceeded the American Academy of Pediatrics recommendations on leisure screen time. Positive affect and physical activity were associated with reduced anxiety levels in children during the pandemic. These findings highlight the important mental health benefits of maintaining positive affect, engaging in physical activity, and limiting leisure screen time for children, especially during stressful periods.
Early intervention is the key to success in COVID-19 control
Authors: Binny Rachelle N. , Baker Michael G. , Hendy Shaun C. , James Alex , Lustig Audrey , Plank Michael J. , Ridings Kannan M. , Steyn Nicholas 
Published: October 2020

AbstractNew Zealand responded to the COVID-19 pandemic with a combination of border restrictions and an Alert Level system that included strict stay-at-home orders. These interventions were successful in containing the outbreak and ultimately eliminating community transmission of COVID-19. The timing of interventions is crucial to their success. Delaying interventions may both reduce their effectiveness and mean that they need to be maintained for a longer period. Here, we use a stochastic branching process model of COVID-19 transmission and control to simulate the epidemic trajectory in New Zealand and the effect of its interventions during its COVID-19 outbreak in March-April 2020. We use the model to calculate key measures, including the peak load on the contact tracing system, the total number of reported COVID-19 cases and deaths, and the probability of elimination within a specified time frame. We investigate the sensitivity of these measures to variations in the timing of interventions and show that changing the timing of Alert Level 4 (the strictest level of restrictions) has a far greater impact than the timing of border measures. Delaying Alert Level 4 restrictions results in considerably worse outcomes and implementing border measures alone, without Alert Level 4 restrictions, is insufficient to control the outbreak. We conclude that the rapid response in introducing stay-at-home orders was crucial in reducing the number of cases and deaths and increasing the probability of elimination.
Phenome-wide screening of GWAS data reveals the complex causal architecture of obesity
Authors: García-Marín Luis M. , Campos Adrián I. , Kho Pik-Fang , Martin Nicholas G. , Cuéllar-Partida Gabriel , Rentería Miguel E. 
Published: October 2020

ABSTRACTObjectiveIn the present study, we sought to identify causal relationships between obesity and other complex traits and conditions using a data-driven hypothesis-free approach that uses genetic data to infer causal associations.MethodsWe leveraged available summary-based genetic data from genome-wide association studies on 1,498 phenotypes and applied the latent causal variable method (LCV) between obesity and all traits.ResultsWe identified 110 traits with significant causal associations with obesity. Notably, obesity influenced 26 phenotypes associated with cardiovascular diseases, 22 anthropometric measurements, nine with the musculoskeletal system, nine with behavioural or lifestyle factors includingloneliness or isolation, six with respiratory diseases, five with body bioelectric impedances, four with psychiatric phenotypes, four related to the nervous system, four with disabilities or long-standing illness, three with the gastrointestinal system, three with use of analgesics, two with metabolic diseases, one with inflammatory response and one with the neurodevelopmental disorderADHD, among others.ConclusionsOur results indicate that obesity causally affects a wide range of traits and comorbid diseases, thus providing an overview of the metabolic, physiological, and neuropsychiatric impact of obesity on human health.
Characterizing the Modern Light Environment and its Influence on Circadian Rhythms
Authors: Khodasevich Dennis , Tsui Susan , Keung Darwin , Skene Debra J. , Revell Victoria , Martinez Micaela E. 
Published: October 2020

AbstractHumans have largely supplanted natural light cycles with a variety of artificial light sources and schedules misaligned with day-night cycles. Circadian disruption has been linked to a number of disease processes, but the extent of circadian disruption among the population is unknown. We measured light exposure and wrist temperature among residents of an urban area for a full week during each of the four seasons, as well as light illuminance in nearby outdoor locations. Daily light exposure was significantly lower for individuals, compared to outdoor light sensors, for all four seasons. There was also little seasonal variation in the realized photoperiod experienced by individuals, with the only significant difference between winter and summer. We tested the hypothesis that differential light exposure impacts circadian phase timing, detected via the wrist temperature rhythm. To determine the influence of light exposure on circadian rhythms, we modeled the impact of morning, afternoon, and nighttime light exposure on the timing of the midline-estimating statistic of rhythm (MESOR). We found that morning light exposure and nighttime light exposure had a significant but opposing impact on MESOR timing. Our results demonstrate that nighttime light can shift/alter circadian rhythms to delay the morning transition from nighttime to daytime physiology, while morning light can lead to earlier onset. Our results demonstrate that circadian shifts and disruptions may be a more regular occurrence in the general population than is currently recognized.Significance StatementDisruption of circadian rhythms has been linked to various diseases, but the prevalence of circadian disruption among the general population is unknown. Light plays a pivotal role in entraining circadian rhythms to the 24-hour day. Humans have largely supplanted natural light cycles with electrical lighting and through time spent indoors. We have shown that individuals experience a disconnect from natural light cycles, with low daytime light exposure, high levels of light-at-night, and minimal seasonal variation in light exposure. We identified measurable changes in the timing of wrist temperature rhythms as a function of differential light exposure during the morning and nighttime hours. Our findings suggest that circadian shifts, and potentially disruption, may be common in the general population.
Differences in outcomes following an intensive upper-limb rehabilitation programme for patients with common CNS-acting drug prescriptions
Authors: Johnstone Ainslie , Brander Fran , Kelly Kate , Bestmann Sven , Ward Nick 
Published: October 2020

AbstractDifficulty using the upper-limb is a major barrier to independence for many patients post-stroke or brain injury. High dose rehabilitation can result in clinically significant improvements in function even years after the incident, however there is still high variability in patient responsiveness to such interventions that cannot be explained by age, sex or time since stroke.This retrospective study investigated whether patients prescribed certain classes of CNS-acting drugs - GABA agonists, antiepileptics and antidepressants-differed in their outcomes on the 3 week intensive Queen Square Upper-Limb (QSUL) programme.For 277 stroke or brain injury patients (167 male, median age 52 years (IQR 21), median time since incident 20 months (IQR 26)) upper-limb impairment and activity was assessed at admission to the programme and at 6 months post-discharge, using the upper limb component of the Fugl-Meyer (FM), Action Research Arm Test (ARAT), and Chedoke Arm and Hand Activity Inventory (CAHAI). Drug prescriptions were obtained from primary care physicians at referral. Specification curve analysis (SCA) was used to protect against selective reporting results and add robustness to the conclusions of this retrospective study.Patients with GABA agonist prescriptions had significantly worse upper-limb scores at admission but no evidence for a significant difference in programme-induced improvements was found. Additionally, no evidence of significant differences in patients with or without antiepileptic drug prescriptions on either admission to, or improvement on, the programme was found in this study. Whereas, though no evidence was found for differences in admission scores, patients with antidepressant prescriptions experienced reduced improvement in upper-limb function, even when accounting for anxiety and depression scores.These results demonstrate that, when prescribed typically, there was no evidence that patients prescribed GABA agonists performed worse on this high-intensity rehabilitation programme. Patients prescribed antidepressants, however, performed poorer than expected on the QSUL rehabilitation programme. While the reasons for these differences are unclear, identifying these patients prior to admission may allow for better accommodation of differences in their rehabilitation needs.
Noninvasive Ultrasonic Glymphatic Induction Enhances Intrathecal Drug Delivery
Authors: Aryal Muna , Zhou Quan , Rosenthal Eben L. , Airan Raag D. 
Published: October 2020

SummaryIntrathecal drug delivery is routinely used to bypass the blood-brain barrier in treating varied central nervous system conditions. However, the utility of intrathecal delivery is limited by poor parenchymal uptake of agents from the cerebrospinal fluid. We demonstrate that a simple noninvasive transcranial ultrasound protocol significantly increases the brain parenchymal uptake of intrathecally administered drugs and antibodies. Essentially, we show that our protocol of transcranial ultrasound can accelerate glymphatic fluid transport from the cisternal space into the parenchymal compartment. Specifically, we administered small (∼1kDa) and large (∼150 kDa) molecule agents into the cisterna magna of rats and then applied low, diagnostic-intensity focused ultrasound in a scanning protocol throughout the brain. Using both real-time magnetic resonance imaging and ex vivo histologic analyses, we observed significantly increased uptake of each agent into the brain parenchyma from the cisternal cerebrospinal fluid, notably with no brain parenchymal damage. The low intensity of the ultrasound and its noninvasiveness underscores the ready path to clinical translation of this technique for whole-brain delivery of a variety of agents. Furthermore, this technique can be used as a means to probe the causal role of the glymphatic system in the variety of disease and physiologic processes to which it has been correlated.eTOC SummaryA translation-ready ultrasound technique enhances the brain penetration of intrathecally delivered agents via upregulating the glymphatic pathway.
One tree, many colonies: colony structure, breeding system and colonization events of host trees in tunnelingMelissotarsusants
Authors: Eyer Pierre-André , Vargo Edward L. , Peeters Christian 
Published: October 2020

AbstractAnts exhibit a striking variety of lifestyles, including highly specialist or mutualist species. The minute blind workers of the African genusMelissotarsuschew tunnels in live trees to accommodate their obligate partner scale insects. Their modified legs are adapted for tunneling, but are unsuited for walking outside, confining these ants to their initial host tree. Here, we investigated whether this unique lifestyle results in complex patterns of genetic diversity at different scales, from the same tree to different populations. Using 19 microsatellite markers, we assessed their mating strategy and colony structure among and across populations in South Africa. We showed that only one queen reproduces within a colony, mated with up to three males. Yet, several inseminated dealate queens are present in colonies; one probably replaces the older queen as colonies age. The reproduction of a single queen per colony at a given time results in genetic differentiation between colonies, even those located on the same tree. Overall, we discussed how the slow process of colony digging under the bark and the lack of worker patrolling above the bark might result in reduced competition between colonies and allow severalsecludedcolonies to cohabit in a cramped space on a tree.
High dimensionality of the stability of a marine benthic ecosystem
Authors: Valdivia Nelson , Aguilera Moisés A. , Broitman Bernardo R. 
Published: October 2020

AbstractStability is a central property of complex systems and encompasses multiple dimensions such as resistance, resilience, recovery, and invariability. How these dimensions correlate among them is focus of recent ecological research, but empirical evidence at regional scales, at which conservation decisions are usually made, remains absent. Using a field-based manipulative experiment conducted in two marine intertidal regions, we analyse the correlations among different aspects of stability in functioning (community cover) and composition of local communities facing a press disturbance. The experiment involved the removal of the local space-dominant species for 35 months in eight sites under different environmental regimes in northern- and southern-central Chile (ca. 30°S and 40°S, respectively). After the disturbance, the magnitude of the initial responses and the recovery patterns were similar among communities dominated by different species, but varied between the functional and compositional response variables, and among four dimensions of stability. The recovery trajectories in function and composition remained mostly uncorrelated across the system. Yet, larger initial functional responses were associated with faster recovery trajectories—high functional resilience, in turn, was associated with both, high and low variability in the pattern of recovery. Finally, the compositional stability dimensions were independent from each other. The results suggest that varying community compositions can perform similar levels of functioning, which might be the result of strong compensatory dynamics among species competing for space in these communities. Knowledge of several, and sometimes independent, aspects of stability is mandatory to fully describe the stability of complex ecological systems.