bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unplanned PICU Readmission in a Middle-Income Country: Who Is at Risk and What Is the Outcome?*
Authors: Mat Bah Mohd Nizam , Syed Mohamed Sharifah Adlena , Abdullah Nisah , Alias Emieliyuza Yusnita 
Published: June 2020

Objectives:
To study the rate of unplanned PICU readmission, determine the risk factors and its impact on mortality.

Design:
A single-center retrospective cross-sectional study.

Setting:
Tertiary referral PICU in Johor, Malaysia.

Patients:
All children admitted to the PICU over 8 years were included. Patients readmitted into PICU after the first PICU discharge during the hospitalization period were categorized into “early” (within 48 hr) and “late” (after 48 hr), and factors linked to the readmissions were identified. The mortality rate was determined and compared between no, early, and late readmission.

Interventions:
None.

Measurements and Main Results:
There were 2,834 patients in the study with 70 early and 113 late readmissions. Therefore, the rate of early and late PICU readmission was 2.5% (95% CI, 1.9–3.0%) and 3.9% (95% CI, 3.2–4.7%), respectively. The median length of stay of the second PICU admission for early and late readmissions was 2.7 days (interquartile range, 1.1–7.0 d) and 3.2 days (interquartile range, 1.2–7.5 d), respectively. The majority of early and late readmissions had a similar diagnosis with their first PICU admission. Multivariable multinomial logistic regression revealed a Pediatric Index Mortality 2 score of greater than or equal to 15, chronic cardiovascular condition, and oxygen supplement upon discharge as independent risk factors for early PICU readmission. Meanwhile, an infant of less than 1 year old, having cardiovascular, other congenital and genetic chronic conditions and being discharged between 8 am and 5 pm was an independent risk factor for late readmission. There was no significant difference in the mortality rate of early (12.9%), late (13.3%), and no readmission (10.7%).

Conclusions:
Despite the lack of resources and expertise in lower- and middle-income countries, the rate and factors for PICU readmission are similar to those in high-income countries. However, PICU readmission has no statistically significant association with mortality.
Mobile Extracorporeal Membrane Oxygenation: 5-Year Experience of a French Pediatric and Neonatal Center
Authors: Soreze Yohan , Smagghue Gabriel , Hervieux Erik , Julliand Sabestien , Genuini Mathieu , Piloquet Jean-Eudes , Rapp Mélanie , Starck Julie , Léger Pierre-Louis , Rambaud Jérôme 
Published: June 2020

Objectives:
Extracorporeal membrane oxygenation is an established therapy for refractory cardiac and/or pulmonary failure that is not available in all centers. When infants and children require extracorporeal membrane oxygenation, they are sometimes placed on extracorporeal membrane oxygenation support in peripheral centers where extracorporeal membrane oxygenation is not available and then transferred on extracorporeal membrane oxygenation to specialized centers. The objective of this study is to first describe one of the largest cohorts of infants and children transported by a mobile unit while on extracorporeal membrane oxygenation.

Design:
We undertook a single-center retrospective study that included patients transported while on extracorporeal membrane oxygenation between November 1, 2014, and May 31, 2019.

Patients:
All patients transported by our mobile extracorporeal membrane oxygenation unit during the study period were included. Computerized data collection was approved by the French Data Protection Authority (Commission nationale de l'informatique et des libertés n° 2121127V0).

Main Results:
Over the study period, our extracorporeal membrane oxygenation mobile team transported 80 patients on extracorporeal membrane oxygenation among which 20 were newborns (25%) and 60 were children of 1 month to 17 years old (75%); 57 patients were on venoarterial-extracorporeal membrane oxygenation (71%) and 23 on venovenous-extracorporeal membrane oxygenation (29%). The average duration of transport was 8.4 hours with a median of 8 hours; the average distance travelled was 189 ± 140 km. Transport was by air and then ground for 50% of the patients and by ground for 42%. We observed a significant decrease in the Vasoactive-Inotropic Score (125 vs 99; p = 0.005) and Paco
2 levels (67 vs 49 mm Hg; p = 0.0005) after arrival in our unit. Survival rate 6 months after PICU discharge was 46% (37). There was a statistically significant relationship between initial lactate level and mortality (p = 0.02). We observed minor adverse events in 39% of the transports and had no mortality during transport.

Conclusions:
We describe one of the largest cohorts of infants and children transported by a mobile unit while on extracorporeal membrane oxygenation. Our findings confirm that it is safe to start extracorporeal membrane oxygenation in a referring center and to transport patients using an extracorporeal membrane oxygenation mobile team. The only risk factor associated with higher mortality was an initially elevated lactate level.
A Quality Improvement Project to Improve First Case On-time Starts in the Pediatric Operating Room
Authors: Pashankar Dinesh S. , Zhao Anna M. , Bathrick Rebecca , Taylor Cindy , Boules Heidi , Cowles Robert A. , Grossman Matthew 
Published: June 2020

Background:
Delays in the operating room (OR) can lead to increased hospital costs as well as patient and provider dissatisfaction. Starting the first case on time in the OR can potentially prevent subsequent delays. We designed a quality improvement project to improve the first case on-time starts in the pediatric OR at a tertiary care children’s hospital.

Methods:
Following the collection of baseline data, we formed an interdisciplinary team. We analyzed the causes of delay and used the Six Sigma methodology of Define, Measure, Analyze, Improve, and Control. We identified key drivers and implemented several low-cost interventions using Plan-Do-Study-Act cycles. Major interventions included preoperative care coordination, strategic staggering of OR cases, and introduction of “Wow Bucks” incentives. We monitored start times and the delay in minutes for all first cases weekly. The OR minutes saved per week were calculated and used to estimate cost savings.

Results:
We studied a total of 1981 first-start cases from May 2018 to October 2019. The first case on-time starts improved from 62% to 77% over the study period. There was a significant improvement in total minutes delayed for all the first cases from 197.9 minutes per week down to 133 minutes per week (P < 0.05). Estimated cost savings were $4,023 per week due to improved OR utilization.

Conclusions:
A multidisciplinary collaborative team approach using quality improvement tools can improve on-time starts in the pediatric OR.
Neural progenitor cells-secreted exosomal miR-210 induced by hypoxia influences cell viability
Authors: Zhao Ming , Gao Yan , Wang Fei , Cheng Xiang , Zhao Tong , Zhao Yongqi , Fan Ming , Zhu Lingling 
Published: June 2020

Hypoxia as a microenvironment is essential for the development of neural stem/progenitor cells (NSCs/NPCs). Our previous studies showed that mild hypoxia can promote proliferation of NPCs. However, the underlying mechanisms are remaining unknown. In the present study, we explored the impact of hypoxia on miR-210 secretion and its effect on cell viability. We found that short time or long time of hypoxia treatment could increase the expression of miR-210, but also promoted its secretion into the medium. The results of exosomes isolation and quantitative real-time PCR showed that hypoxia increased the levels of miR-210 in the exosome enriched from the medium. In addition, the secreted miR-210 can be absorbed by recipient NPCs. The resutls of cell viability assay showed that low levels of secreted miR-210 slightly increased cell viability of NPCs. In contrast, high levels of secreted miR-210 exhibited an inhibitory effect on cell viability. These effects were blocked by an miR-210-specific inhibitor. Taken together, hypoxia increased secretion of miR-210 in exosomes and exhibited a differential effect on cell viability of recipient NPCs.
Video abstract: https://links.lww.com/WNR/A588.
Lagging strand encoding promotes adaptive evolution
Authors: Merrikh Christopher N. , Harris Leonard A. , Mangiameli Sarah , Merrikh Houra 
Published: June 2020

AbstractCells may be able to promote adaptive evolution in a gene-specific and temporally-controlled manner. Genes encoded on the lagging strand have a higher mutation rate and evolve faster than genes on the leading strand. This effect is likely driven by head-on replication-transcription conflicts, which occur when lagging strand genes are transcribed during DNA replication. We previously suggested that the ability to selectively increase mutagenesis in a subset of genes may provide an adaptive advantage for cells. However, it is also possible that this effect could be neutral or even highly deleterious. Distinguishing between these models is important because, if the adaptive model is correct, it would indicate that 1) head-on conflicts, which are generally deleterious, can also provide a benefit to cells, and 2) cells possess the remarkable ability to fine-tune adaptive evolution. Furthermore, investigating these models may address the long-standing debate regarding whether accelerated evolution through conflicts can be adaptive. To distinguish between the adaptive and neutral models, we conducted single nucleotide polymorphism (SNP) analyses on wild strains of bacteria, from divergent phyla. To test the adaptive hypothesis, we analyzed convergent mutation patterns. As a simple test of the neutral hypothesis, we performedin silicomodeling. Our results show that convergent mutations are enriched in lagging strand genes and that these mutations are unlikely to have arisen by chance. Additionally, we observe that convergent mutation frequency has a stronger positive correlation with gene-length in lagging strand genes. This effect strongly suggests that head-on conflicts between the DNA replication and transcription machineries are a key mechanism driving the formation of convergent mutations. Together, our data indicate that head-on replication-transcription conflicts can promote adaptive evolution in a variety of bacterial species, and potentially other organisms.
In silicoidentification of conservedcis-acting RNA elements in the SARS-CoV-2 genome
Authors: Alhatlani Bader Y. 
Published: June 2020

AbstractAimThe aim of this study was to computationally predict conserved RNA sequences and structures known ascis-acting RNA elements (CREs) located within the SARS-CoV-2 genome.Materials & methodsBioinformatics tools were used to analyse and predictcis-acting regulatory elements by obtaining viral sequences from available databases.ResultsComputational analysis prediction revealed the presence of RNA stem-loop structures within the 3’ end of the ORF1ab region that are analogous to the previously identified SARS-CoV genomic packaging signals. Alignment-based RNA secondary structures prediction of the 5’ end of the SARS-CoV-2 genome identified also conserved CREs.ConclusionThese CREs could be used as potential targets for a vaccine and/or antiviral therapeutics developments; however, further studies would be required to confirm their roles in the SARS-CoV-2 life cycle.
Daptomycin resistance inEnterococcus faeciumcan be delayed by disruption of the LiaFSR stress response pathway
Authors: Prater Amy G. , Mehta Heer H. , Beabout Kathryn , Supandy Adeline , Miller William R. , Tran Truc T. , Arias Cesar A. , Shamoo Yousif 
Published: June 2020

AbstractThe LiaFSR signaling pathway plays a major role in mediating daptomycin (DAP) resistance for bothEnterococcus faecalisandEnterococcus faecium. LiaFSR inhibition induces DAP hypersusceptibility but could also potentially delay the acquisition of DAP resistance in a combinatorial therapy of DAP with a LiaFSR inhibitor. To evaluate the potential efficacy of this approach, the adaptation to DAP by bothE. faecalisandE. faeciumlacking a functional LiaFSR were examined. Here, clinical isolates ofE. faeciumwithliaRdeletions were evolved to DAP resistance usingin vitroexperimental evolution. Genomic analysis of resistant populations was used to identify both the alleles and their relative frequencies in driving DAP resistance. Microscopic and biochemical analyses were then employed to investigate how those adaptive alleles contributed to DAP resistance. We found that deletion ofliaRfrom theE. faeciumgenome significantly delayed the onset of DAP resistance. Unsurprisingly, resistance strategies emerged eventually. These alternative strategies were influenced by both environment and ancestral genome. The delay in the acquisition of DAP resistance whenliaRwas deleted supports the concept of developing a LiaFSR pathway inhibitor to prolong DAP efficacy against enterococci. The loss of a functional LiaFSR pathway reset the adaptive landscape and forced adaptation to progress in new ways that were slower in providing DAP tolerance. The observed adaptive trajectories were strongly influenced by both the environment and ancestral genome.
Stroke increases the expression of ACE2, the SARS-CoV-2 binding receptor, in murine lungs
Authors: Singh Vikramjeet , Beer Alexander , Kraus Andreas , Zhang Xiaoni , Xue Jinhua , Hermann Dirk M , Gunzer Matthias 
Published: June 2020

AbstractBackgroundThe newly emerged severe acute respiratory syndrome coronavirus (SARS-CoV-2) has caused a worldwide pandemic of human respiratory disease. Angiotensin-converting enzyme (ACE) 2 is the key receptor on lung epithelial cells to facilitate initial binding and infection of SARS-CoV-2. The binding to ACE2 is mediated via the spike glycoprotein present on the virus surface. Recent clinical data have demonstrated that patients suffering from stroke are particularly susceptible to severe courses of SARS-CoV-2 infection, thus forming a defined risk group. However, a mechanistic explanation for this finding is lacking. Sterile tissue injuries including stroke induce lymphocytopenia and systemic inflammation that might modulate the expression levels of surface proteins in distant organs. Whether systemic inflammation following stroke can specifically modulate ACE2 expression in the lung has not been investigated.MethodsMice were subjected to transient middle cerebral artery occlusion (MCAO) for 45 min and sacrificed after 24 h and 72 h for analysis of brain and lung tissues. Gene expression and protein levels of ACE2, ACE, IL-6 and IL1β were measured by quantitative PCR and Western blot, respectively. Immune cell populations in lymphoid organs were analyzed by flow cytometry.ResultsStrikingly, 24 h after stroke, we observed a substantial increase in the expression of ACE2 both on the transcriptional and protein levels in the lungs of MCAO mice compared to sham-operated mice. This increased expression persisted until day 3 after stroke. In addition, MCAO increased the expression of inflammatory cytokines IL-6 and IL-1β in the lungs. Higher gene expression of cytokines IL-6 and IL-1β was found in ischemic brain hemispheres and a reduced number of T-lymphocytes were present in the blood and spleen as an indicator of sterile tissue injury-induced immunosuppression.ConclusionsWe demonstrate significantly augmented ACE2 levels and inflammation in murine lungs after experimental stroke. These pre-clinical findings might explain the clinical observation that patients with pre-existing stroke represent a high-risk group for the development of severe SARS-CoV-2 infections. Our studies call for further investigations into the underlying signaling mechanisms and possible therapeutic interventions.HighlightsBrain tissue injury increases ACE2 levels in the lungsBrain injury induces pro-inflammatory cytokine expression in the lungsBrain injury causes parenchymal inflammation and systemic lymphopenia
SARS-CoV-2 infection and replication in human fetal and pediatric gastric organoids
Authors: Giobbe Giovanni Giuseppe , Bonfante Francesco , Zambaiti Elisa , Gagliano Onelia , Jones Brendan C. , Luni Camilla , Laterza Cecilia , Perin Silvia , Stuart Hannah T. , Pagliari Matteo , Bortolami Alessio , Mazzetto Eva , Manfredi Anna , Colantuono Chiara , Di Filippo Lucio , Pellegata Alessandro , Li Vivian Sze Wing , Eaton Simon , Thapar Nikhil , Cacchiarelli Davide , Elvassore Nicola , De Coppi Paolo 
Published: June 2020

AbstractCoronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a global public health emergency. COVID-19 typically manifests as a respiratory illness but an increasing number of clinical reports describe gastrointestinal (GI) symptoms. This is particularly true in children in whom GI symptoms are frequent and viral shedding outlasts viral clearance from the respiratory system. By contrast, fetuses seem to be rarely affected by COVID-19, although the virus has been detected in placentas of affected women. These observations raise the question of whether the virus can infect and replicate within the stomach once ingested. Moreover, it is not yet clear whether active replication of SARS-CoV-2 is possible in the stomach of children or in fetuses at different developmental stages. Here we show the novel derivation of fetal gastric organoids from 8-21 post-conception week (PCW) fetuses, and from pediatric biopsies, to be used as anin vitromodel for SARS-CoV-2 gastric infection. Gastric organoids recapitulate human stomach with linear increase of gastric mucin 5AC along developmental stages, and expression of gastric markers pepsinogen, somatostatin, gastrin and chromogranin A. In order to investigate SARS-CoV-2 infection with minimal perturbation and under steady-state conditions, we induced a reversed polarity in the gastric organoids (RP-GOs) in suspension. In this condition of exposed apical polarity, the virus can easily access viral receptor angiotensin-converting enzyme 2 (ACE2). The pediatric RP-GOs are fully susceptible to infection with SARS-CoV-2, where viral nucleoprotein is expressed in cells undergoing programmed cell death, while the efficiency of infection is significantly lower in fetal organoids. The RP-GOs derived from pediatric patients show sustained robust viral replication of SARS-CoV-2, compared with organoids derived from fetal stomachs. Transcriptomic analysis shows a moderate innate antiviral response and the lack of differentially expressed genes belonging to the interferon family. Collectively, we established the first expandable human gastric organoid culture across fetal developmental stages, and we support the hypothesis that fetal tissue seems to be less susceptible to SARS-CoV-2 infection, especially in early stages of development. However, the virus can efficiently infect gastric epithelium in pediatric patients, suggesting that the stomach might have an active role in fecal-oral transmission of SARS-CoV-2.
Strengthening The Organization and Reporting of Microbiome Studies (STORMS): A Reporting Checklist for Human Microbiome Research
Authors: Mirzayi Chloe , Renson Audrey , Zohra Fatima , Elsafoury Shaimaa , Geistlinger Ludwig , Kasselman Lora , Eckenrode Kelly , van de Wijgert Janneke , Loughman Amy , Marques Francine Z. ,   STORMS Consortium,   Genomic Standards Consortium,   Massive Analysis and Quality Control Society, Segata Nicola , Huttenhower Curtis , Dowd Jennifer B. , Jones Heidi E. , Waldron Levi 
Published: June 2020

AbstractBackgroundHuman microbiome research is a growing field with the potential for improving our understanding and treatment of diseases and other conditions. The field is interdisciplinary, making concise organization and reporting of results across different styles of epidemiology, biology, bioinformatics, translational medicine, and statistics a challenge. Commonly used reporting guidelines for observational or genetic epidemiology studies lack key features specific to microbiome studies.MethodsA multidisciplinary group of microbiome epidemiology researchers reviewed elements of available reporting guidelines for observational and genetic studies and adapted these for application to culture-independent human microbiome studies. New reporting elements were developed for laboratory, bioinformatic, and statistical analyses tailored to microbiome studies, and other parts of these checklists were streamlined to keep reporting manageable.ResultsSTORMS is a 17-item checklist for reporting on human microbiome studies, organized into six sections covering typical sections of a scientific publication, presented as a table with space for author-provided details and intended for inclusion in supplementary materials.ConclusionsSTORMS provides guidance for authors and standardization for interdisciplinary microbiome studies, facilitating complete and concise reporting and augments information extraction for downstream applications.AvailabilityThe STORMS checklist is available as a versioned spreadsheet fromhttps://www.stormsmicrobiome.org/.
Assessing temperature-dependent competition between two invasive mosquito species
Authors: Evans Michelle V , Drake John M , Jones Lindsey , Murdock Courtney C 
Published: June 2020

SUMMARYInvasive mosquitoes are expanding their ranges into new geographic areas and interacting with resident mosquito species. Understanding how novel interactions can affect mosquito population dynamics is necessary to predict transmission risk at invasion fronts. Mosquito life-history traits are extremely sensitive to temperature and this can lead to temperature-dependent competition between competing invasive mosquito species.We explored temperature-dependent competition betweenAedes aegyptiandAnopheles stephensi, two invasive mosquito species whose distributions overlap in India, the Middle East, and North Africa. We followed mosquito cohorts raised at different intraspecific and interspecific densities across five temperatures (16°C - 32°C) to measure traits relevant for population growth and to estimate species' per capita growth rates. We then used these growth rates to derive each species competitive ability at each temperature.We find strong evidence for asymmetric competition at all temperatures, withAe. aegyptiemerging as the dominant competitor. This was primarily due to differences in larval survival and development times across all temperatures that resulted in a higher estimated intrinsic growth rate and competitive tolerance estimate forAe. aegypticompared toAn. stephensi.Synthesis and applications:The spread ofAn. stephensiinto the African continent could lead to urban transmission of malaria, an otherwise rural disease, increasing the human population at risk and complicating malaria elimination efforts. Competition has resulted in habitat segregation of other invasive mosquito species, and our results suggest that it may play a role in determining the distribution ofAn. stephensiacross its invasive range.