bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Signs to Categorize Shock and Target Vasoactive Medications in Warm Versus Cold Pediatric Septic Shock*
Authors: Walker Sarah B. , Conlon Thomas W. , Zhang Bingqing , Mensinger Janell L. , Fitzgerald Julie C. , Himebauch Adam S. , Glau Christie , Nishisaki Akira , Ranjit Suchitra , Nadkarni Vinay , Weiss Scott L. 
Published: July 2020

Objectives:
Determine level of agreement among clinical signs of shock type, identify which signs clinicians prioritize to determine shock type and select vasoactive medications, and test the association of shock type-vasoactive mismatch with prolonged organ dysfunction or death (complicated course).

Design:
Retrospective observational study.

Setting:
Single large academic PICU.

Patients:
Patients less than 18 years treated on a critical care sepsis pathway between 2012 and 2016.

Interventions:
None.

Measurements and Main Results:
Agreement among clinical signs (extremity temperature, capillary refill, pulse strength, pulse pressure, and diastolic blood pressure) was measured using Fleiss and Cohen’s κ. Association of clinical signs with shock type and shock type-vasoactive mismatch (e.g., cold shock treated with vasopressor rather than inotrope) with complicated course was determined using multivariable logistic regression. Of 469 patients, clinicians determined 307 (65%) had warm and 162 (35%) had cold shock. Agreement across all clinical signs was low (κ, 0.25; 95% CI, 0.20–0.30), although agreement between extremity temperature, capillary refill, and pulse strength was better than with pulse pressure and diastolic blood pressure. Only extremity temperature (adjusted odds ratio, 26.6; 95% CI, 15.5–45.8), capillary refill (adjusted odds ratio, 15.7; 95% CI, 7.9–31.3), and pulse strength (adjusted odds ratio, 21.3; 95% CI, 8.6–52.7) were associated with clinician-documented shock type. Of the 86 patients initiated on vasoactive medications during the pathway, shock type was discordant from vasoactive medication (κ, 0.14; 95% CI, –0.03 to 0.31) and shock type-vasoactive mismatch was not associated with complicated course (adjusted odds ratio, 0.3; 95% CI, 0.1–1.02).

Conclusions:
Agreement was low among common clinical signs used to characterize shock type, with clinicians prioritizing extremity temperature, capillary refill, and pulse strength. Although clinician-assigned shock type was often discordant with vasoactive choice, shock type-vasoactive mismatch was not associated with complicated course. Categorizing shock based on clinical signs should be done cautiously.
Dexmedetomidine Sedation in Mechanically Ventilated Critically Ill Children: A Pilot Randomized Controlled Trial
Authors: Erickson Simon J. , Millar Johnny , Anderson Brian J. , Festa Marino S. , Straney Lahn , Shehabi Yahya , Long Debbie A. ,   for the Baby SPICE Investigators and the Australian and New Zealand Intensive Care Society Paediatric Study Group (ANZICS-PSG)
Published: July 2020

Objectives:
To assess the feasibility, safety, and efficacy of a sedation protocol using dexmedetomidine as the primary sedative in mechanically ventilated critically ill children.

Design:
Open-label, pilot, prospective, multicenter, randomized, controlled trial. The primary outcome was the proportion of sedation scores in the target sedation range in the first 48 hours. Safety outcomes included device removal, adverse events, and vasopressor use. Feasibility outcomes included time to randomization and protocol fidelity.

Setting:
Six tertiary PICUs in Australia and New Zealand.

Patients:
Critically ill children, younger than 16 years old, requiring intubation and mechanical ventilation and expected to be mechanically ventilated for at least 24 hours.

Interventions:
Children randomized to dexmedetomidine received a dexmedetomidine-based algorithm targeted to light sedation (State Behavioral Scale –1 to +1). Children randomized to usual care received sedation as determined by the treating clinician (but not dexmedetomidine), also targeted to light sedation.

Measurements and Main Results:
Sedation with dexmedetomidine as the primary sedative resulted in a greater proportion of sedation measurements in the light sedation range (State Behavioral Scale –1 to +1) over the first 48 hours (229/325 [71%] vs 181/331 [58%]; p = 0.04) and the first 24 hours (66/103 [64%] vs 48/116 [41%]; p < 0.001) compared with usual care. Cumulative midazolam dosage was significantly reduced in the dexmedetomidine arm compared with usual care (p = 0.002).There were more episodes of hypotension and bradycardia with dexmedetomidine (including one serious adverse event) but no difference in vasopressor requirements. Median time to randomization after intubation was 6.0 hours (interquartile range, 2.0–9.0 hr) in the dexmedetomidine arm compared with 3.0 hours (interquartile range, 1.0–7.0 hr) in the usual care arm (p = 0.24).

Conclusions:
A sedation protocol using dexmedetomidine as the primary sedative was feasible, appeared safe, achieved early, light sedation, and reduced midazolam requirements. The findings of this pilot study justify further studies of sedative agents in critically ill children.
Current State of Nutrition Education in Pediatric Critical Care Medicine Fellowship Programs in the United States and Canada
Authors: De Souza Bradley J. , Callif Charles , Staffa Steven J. , Mehta Nilesh M. , Wolbrink Traci A. 
Published: July 2020

Objectives:
To assess the current state of nutrition education provided during pediatric critical care medicine fellowship.

Design:
Cross-sectional survey.

Setting:
Program directors and fellows from pediatric critical care medicine fellowship programs in America and Canada.

Subjects:
Seventy current pediatric critical care medicine fellows and twenty-five pediatric critical care medicine fellowship program directors were invited to participate.

Interventions:
Participants were asked demographic questions related to their fellowship programs, currently utilized teaching methods, perceptions regarding adequacy and effectiveness of current nutrition education, and levels of fellow independence, comfort, confidence, and expectations in caring for the nutritional needs of patients.

Measurements and Main Results:
Surveys were sent to randomly selected program directors and fellows enrolled in pediatric critical care medicine fellowship programs in America and Canada. Twenty program directors (80%) and 60 fellows (86%) responded. Ninety-five percent of programs (19/20) delivered a formal nutrition curriculum; no curriculum was longer than 5 hours per academic year. Self-reported fellow comfort with nutrition topics did not improve over the course of fellowship (p = 0.03), with the exception of nutritional aspects of special diets. Sixty-five percent of programs did not hold fellows responsible for writing daily parenteral nutrition prescriptions. There was an inverse relationship between total number of fellows in a pediatric critical care medicine program and levels of comfort in ability to provide parenteral nutrition support (p = 0.01). Program directors perceived their nutritional curriculum to be more effective than did their fellows (p ≤ 0.001).

Conclusions:
Nutrition education was reported as highly underrepresented in pediatric critical care medicine fellowship curricula. The majority of programs rely on allied health care professionals to prescribe parenteral nutrition, which may influence trainee independence in the provision of nutritional therapies. Improving the format of current nutrition curriculums, by relying on more active teaching methods, may improve the delivery and efficacy of nutrition education. The impact of novel training interventions on improving the competency and safety of enteral and parenteral nutrition delivery in the PICU must be further examined.
Nurse-Implemented Goal-Directed Strategy to Improve Pain and Sedation Management in a Pediatric Cardiac ICU
Authors: Lincoln Patricia A. , Whelan Katherine , Hartwell Lauren P. , Gauvreau Kimberlee , Dodsen Brenda L. , LaRovere Joan M. , Thiagarajan Ravi R. , Hickey Patricia A. , Curley Martha A. Q. 
Published: July 2020

Objectives:
To assess the impact of a nurse-implemented goal-directed sedation strategy on patient care and nursing practice in a pediatric cardiac ICU.

Design:
Quality improvement project with a pre-post interval measurement plan.

Setting:
Thirty-one bed pediatric cardiac ICU in a freestanding tertiary care children’s hospital.

Patients:
Postoperative pediatric cardiac surgery patients.

Interventions:
The implementation of cardiac-Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE), a nurse-implemented goal directed strategy to improve pain and sedation management in a pediatric cardiac ICU which included daily team discussion of the patient’s trajectory of illness (acute, titration, or weaning phase), prescription of a sedation target score based on the patient’s trajectory of illness, arousal assessments, and opioid and/or sedative titration. Withdrawal Assessment Scores were used to assess and manage iatrogenic withdrawal symptoms.

Measurements and Main Results:
Data related to opioid and sedation use, pain and sedation scores, and the occurrence and management of iatrogenic withdrawal symptoms were reviewed on 1,243 patients during four separate time periods: one pre-implementation and three discontinuous post-implementation time intervals. Patient age and complexity were consistent across the data collection periods. Post-implementation opioids and benzodiazepines use was reduced about 50% without a concomitant increase in the use of other sedative classes. Few post-intervention patients were discharged from the pediatric cardiac ICU or to home on methadone (pediatric cardiac ICU: pre 19% to post 3%; hospital: pre 12% to post 1.3%). Documentation of pain, sedation, and withdrawal scores became more consistent and nurses reported satisfaction with their patient’s comfort management.

Conclusions:
The implementation of a nurse-driven goal-directed plan such as cardiac-RESTORE to manage pediatric cardiac ICU patient pain and sedation is possible, sustainable, and associated with reduced sedative and methadone use.
Nitrincola iocasae sp. nov., a bacterium isolated from sediment collected at a cold seep field in the South China Sea
Authors: Zhang Huan , Wang Hao , Chen Hao , Sun Qinglei , Zhong Zhaoshan , Wang Minxiao , Cao Lei , Lian Chao , Zhou Li , Li Chaolun 
Published: July 2020

A novel bacterium, designated strain KXZD1103T, was isolated from sediment collected at a cold seep field of the Formosa Ridge in the South China Sea. Cells were Gram-stain-negative, facultatively anaerobic, motile, oxidase- and catalase-positive, and grew optimally at 28 °C, pH 6.0–pH 7.0 and in the presence of 1–3 % (w/v) NaCl. The major cellular fatty acids were summed feature 8 (C18 : 1
ω7c/C18 : 1
ω6c), summed feature 3 (C16 : 1
ω7c/C16 : 1
ω6c) and C16 : 0. The major respiratory ubiquinone was Q-8. The predominant polar lipids were diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol. Analysis of 16S rRNA gene sequences revealed that strain KXZD1103T grouped with members of the genus

Nitrincola

, with

Nitrincola lacisaponensis

4CAT (98.1 % sequence similarity) and

Nitrincola schmidtii

R4-8T (97.7 %) as its closest neighbours. Genome sequencing revealed a genome size of 4.17 Mb and a DNA G+C content of 50.1 %. Genomic average nucleotide identity values for strain KXZD1103T with the type strains within the genus

Nitrincola

ranged from 71.0 to 75.7 %, while the in silico DNA–DNA hybridization values for strain KXZD1103T with these strains ranged from 16.1 to 21.6 %. On the basis of the results of phylogenetic, phenotypic and chemotaxonomic analyses, strain KXZD1103T is considered to represent a novel species of the genus

Nitrincola

, for which the name Nitrincola iocasae sp. nov. is proposed. The type strain is KXZD1103T (=KCTC 72678T=MCCC 1K04283T).
Association between Alzheimer’s disease and COVID-19: A bidirectional Mendelian randomization
Authors: Liu Di , Zhang Xiaoyu , Cao Weijie , Zhang Jie , Song Manshu , Xing Weijia , Wang Wei , Meng Qun , Wang Youxin 
Published: July 2020

AbstractBackgroundIn observational studies, Alzheimer’s disease (AD) has been associated with an increased risk of Coronavirus disease 2019 (COVID-19), and the prognosis of COVID-19 can affect nervous systems. However, the causality between these conditions remains to be determined.MethodsThis study sought to investigate the bidirectional causal relations of AD with COVID-19 using two-sample Mendelian randomization (MR) analysis.ResultsWe found that genetically predicted AD was significantly associated with higher risk of severe COVID-19 (odds ratio [OR], 3.329; 95% confidence interval [CI], 1.139-9.725; P=0.028). It’s interesting that genetically predicted severe COVID-19 was also significantly associated with higher risk of AD (OR, 1.004; 95% CI, 1.001-1.007; P=0.018). In addition, the two strong genetic variants associated with severe COVID-19 was associated with higher AD risk (OR, 1.018; 95% CI, 1.003-1.034; P=0.018). There is no evidence to support that genetically predicted AD was significantly associated with COVID-19 susceptibility, and vice versa. No obvious pleiotropy bias and heterogeneity were observed.ConclusionOverall, AD may causally affect severe COVID-19, and vice versa, performing bidirectional regulation through independent biological pathways.
METFORMIN USE IS ASSOCIATED WITH REDUCED MORTALITY IN A DIVERSE POPULATION WITH COVID-19 AND DIABETES
Authors: Crouse Andrew B. , Grimes Tiffany , Li Peng , Might Matthew , Ovalle Fernando , Shalev Anath 
Published: July 2020

ABSTRACTBACKGROUNDCoronavirus disease-2019 (COVID-19) is a growing pandemic with an increasing death toll that has been linked to various comorbidities as well as racial disparity. However, the specific characteristics of these at-risk populations are still not known and approaches to lower mortality are lacking.METHODSWe conducted a retrospective electronic health record data analysis of 25,326 subjects tested for COVID-19 between 2/25/20 and 6/22/20 at the University of Alabama at Birmingham Hospital, a tertiary health care center in the racially diverse Southern U.S. The primary outcome was mortality in COVID-19-positive subjects and the association with subject characteristics and comorbidities was analyzed using simple and multiple linear logistic regression.RESULTSThe odds ratio of contracting COVID-19 was disproportionately high in Blacks/African- Americans (OR 2.6; 95%CI 2.19-3.10; p<0.0001) and in subjects with obesity (OR 1.93; 95%CI 1.64-2.28; p<0.0001), hypertension (OR 2.46; 95%CI 2.07-2.93; p<0.0001), and diabetes (OR 2.11; 95%CI 1.78-2.48; p<0.0001). Diabetes was also associated with a dramatic increase in mortality (OR 3.62; 95%CI 2.11-6.2; p<0.0001) and emerged as an independent risk factor in this diverse population even after correcting for age, race, sex, obesity and hypertension. Interestingly, we found that metformin treatment was independently associated with a significant reduction in mortality in subjects with diabetes and COVID-19 (OR 0.33; 95%CI 0.13-0.84; p=0.0210).CONCLUSIONThus, these results suggest that while diabetes is an independent risk factor for COVID-19- related mortality, this risk is dramatically reduced in subjects taking metformin, raising the possibility that metformin may provide a protective approach in this high risk population.
Mitochondrial state determines functionally divergent stem cell population in planaria
Authors: Haroon Mohamed Mohamed , Lakshmanan Vairavan , Sarkar Souradeep R. , Lei Kai , Vemula Praveen Kumar , Palakodeti Dasaradhi 
Published: July 2020

SummaryMitochondrial state changes were shown to be critical for stem cell function. However, variation in the mitochondrial content in stem cells and the implication, if any, on differentiation is poorly understood. Here, using cellular and molecular studies, we show that the planarian pluripotent stem cells (PSCs) have low mitochondrial mass compared to its progenitors. Further, the mitochondrial mass correlated with OxPhos and inhibiting the transition to OxPhos dependent metabolism in cultured cells resulted in higher PIWI-1Highneoblasts. Transplantation experiments provided functional validation that neoblasts with low mitochondrial mass are the true PSCs. In summary, we show that low mitochondrial mass is a hallmark of PSCs in planaria and provide a mechanism to isolate live, functionally active, PSCs from different cell cycle stages (G0/G1 and S, G2/M). Our study demonstrates that the change in mitochondrial metabolism, a feature of PSCs is conserved in planaria and highlights its role in organismal regeneration.
Gene expression evolution in pattern-triggered immunity withinArabidopsis thalianaand across Brassicaceae species
Authors: Winkelmüller Thomas M. , Entila Frederickson , Anver Shajahan , Piasecka Anna , Song Baoxing , Dahms Eik , Sakakibara Hitoshi , Gan Xiangchao , Kułak Karolina , Sawikowska Aneta , Krajewski Paweł , Tsiantis Miltos , Garrido-Oter Ruben , Fukushima Kenji , Schulze-Lefert Paul , Laurent Stefan , Bednarek Paweł , Tsuda Kenichi 
Published: July 2020

AbstractPlants recognize surrounding microbes by sensing microbe-associated molecular patterns (MAMPs) to activate pattern-triggered immunity (PTI). Despite their significance for microbial control, the evolution of PTI responses remains largely uncharacterized. Employing comparative transcriptomics of sixArabidopsis thalianaaccessions and three additional Brassicaceae species for PTI responses to the MAMP flg22, we identified a set of genes with expression changes under purifying selection in the Brassicaceae species and genes exhibiting species-specific expression signatures. Variation in flg22-triggered transcriptome and metabolome responses across Brassicaceae species was incongruent with their phylogeny while expression changes were strongly conserved withinA. thaliana, suggesting directional selection for some species-specific gene expression. We found the enrichment of WRKY transcription factor binding sites in 5’-regulatory regions in conserved and species-specific responsive genes, linking the emergence of WRKY-binding sites with the evolution of gene responses in PTI. Our findings advance our understanding of transcriptome evolution during biotic stress.
Ultrasound to identify lupus patients with inflammatory joint symptoms with a better response to therapy: The USEFUL longitudinal multicentre study
Authors: Mahmoud Khaled , Zayat Ahmed S , Md Yusof Md Yuzaiful , Dutton Katherine , Teh Lee Suan , Yee Chee-Seng , D’Cruz David , Ng Nora , Isenberg David , Ciurtin Coziana , Conaghan Philip G , Emery Paul , Edwards Christopher J , Hensor Elizabeth MA , Vital Edward M 
Published: July 2020

AbstractObjectiveTo determine whether SLE patients with inflammatory joint symptoms and ultrasound-synovitis achieve better clinical responses to glucocorticoid compared to patients with normal scans. Secondary objectives included identification of clinical features predicting ultrasound-synovitis.MethodsA longitudinal muticentre study of SLE patients with physician-diagnosed inflammatory joint pain was undertaken. Clinical assessments, patient-reported outcomes, and bilateral hands and wrist ultrasound were collected at 0-, 2- and 6-weeks after intramuscular methylprednisolone 120mg. The primary outcome (determined via internal pilot analysis) was EMS-VAS at 2-weeks, adjusted for the baseline value, comparing patients with positive (GS≥2 and/or PD≥1) and negative ultrasound. Post-hoc analyses adjusting for fibromyalgia were performed.ResultsOf 133 patients recruited, 78/133 had positive ultrasound, but only 68% of these had ≥1 swollen joint. Of 66/133 patients with ≥1 swollen joint, 20% had negative ultrasound. Positive ultrasound was associated with joint swelling, symmetrical small joint distribution and serology. In full analysis set (n=133) there was no difference in baseline-adjusted EMS-VAS at week 2 (−7.7mm 95% CI − 19.0mm, 3.5mm, p=0.178). After excluding 32 fibromyalgia patients, response was significantly better in patients with positive ultrasound at baseline (baseline-adjusted EMS-VAS at 2-weeks - 12.1 mm, 95% CI −22.2mm, −0.1mm, p=0.049). This difference was greater when adjusted for treatment (−12.8mm (95% CI −22mm, −3mm), p=0.007). BILAG and SLEDAI responses were higher in ultrasound-positive patients.ConclusionsIn SLE patients without fibromyalgia, those with positive ultrasound had a better clinical response to therapy. Imaging-detected synovitis should be used to select SLE patients for therapy and enrich clinical trials.
New tyrosinases with a broad spectrum of action against contaminants of emerging concern: Insights fromin silicoanalyses
Authors: Senra Marcus V. X. , Fonseca Ana Lúcia 
Published: July 2020

AbstractTyrosinases (EC 1.14.18.1) are type-3 copper metalloenzymes with strong oxidative capacities and low allosteric selectivity to phenolic and non-phenolic aromatic compounds that have been used as biosensors and biocatalysts to mitigate the impacts of environmental contaminants over aquatic ecosystems. However, the widespread use of these polyphenol oxidases is limited by elevated production costs and restricted knowledge on their spectrum of action. Here, six tyrosinase homologs were identified and characterized from the genomes of 4 widespread freshwater ciliates using bioinformatics. Binding energies between 3D models of these homologs and ~1000 contaminants of emerging concern (CECs), including fine chemicals, pharmaceuticals, personal care products, illicit drugs, natural toxins, and pesticides were estimated through virtual screening, suggesting their spectrum of action and potential uses in environmental biotechnology might be considerably broader than previously thought. Moreover, considering that many ciliates, including those caring tyrosinase genes within their genomes are fast-growing unicellular microeukaryotes that can be efficiently culturable at large-scales underin vitroconditions, should be regarded as potential low-cost sources for the production of relevant biotechnological molecules.
Ad26-vector based COVID-19 vaccine encoding a prefusion stabilized SARS-CoV-2 Spike immunogen induces potent humoral and cellular immune responses
Authors: Bos Rinke , Rutten Lucy , van der Lubbe Joan E.M. , Bakkers Mark J.G. , Hardenberg Gijs , Wegmann Frank , Zuijdgeest David , de Wilde Adriaan H. , Koornneef Annemart , Verwilligen Annemiek , van Manen Danielle , Kwaks Ted , Vogels Ronald , Dalebout Tim J. , Myeni Sebenzile K. , Kikkert Marjolein , Snijder Eric J. , Li Zhenfeng , Barouch Dan H. , Vellinga Jort , Langedijk Johannes P.M. , Zahn Roland C. , Custers Jerome , Schuitemaker Hanneke 
Published: July 2020

AbstractDevelopment of effective preventative interventions against SARS-CoV-2, the etiologic agent of COVID-19 is urgently needed. The viral surface spike (S) protein of SARS-CoV-2 is a key target for prophylactic measures as it is critical for the viral replication cycle and the primary target of neutralizing antibodies. We evaluated design elements previously shown for other coronavirus S protein-based vaccines to be successful, e.g. prefusion-stabilizing substitutions and heterologous signal peptides, for selection of a S-based SARS-CoV-2 vaccine candidate. In vitro characterization demonstrated that the introduction of stabilizing substitutions (i.e., furin cleavage site mutations and two consecutive prolines in the hinge region of S1) increased the ratio of neutralizing versus non-neutralizing antibody binding, suggestive for a prefusion conformation of the S protein. Furthermore, the wild type signal peptide was best suited for the correct cleavage needed for a natively-folded protein. These observations translated into superior immunogenicity in mice where the Ad26 vector encoding for a membrane-bound stabilized S protein with a wild type signal peptide elicited potent neutralizing humoral immunity and cellular immunity that was polarized towards Th1 IFN-γ. This optimized Ad26 vector-based vaccine for SARS-CoV-2, termed Ad26.COV2.S, is currently being evaluated in a phase I clinical trial (ClinicalTrials.gov Identifier: NCT04436276).