bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Multiple Antenatal Courses of Corticosteroids on Neonatal Growth and Development Until Six Months
Authors: Maryam Kaveh B , Baghbahadorani Fahimeh Kaveh , Bostan Atefeh , Dehkordi Ali Hassanpour , Sedehi Morteza 
Published: April 2020

PURPOSEPreterm birth is associated with multiple complications, such as respiratory distress syndrome, intracranial hemorrhage, and arterial duct openness, resulting in high mortality in preterm infants. This study aimed to evaluate the effect of multiple antenatal courses of corticosteroids on neonatal growth and development until six months.MethodsIn our retrospective study, the history of corticosteroid exposure was extracted from the maternal medical record and history of the drug prescription. Based on the antenatal corticosteroids exposure, newborns were assigned into the first group (i. e., no exposure or exposure to a single dose of corticosteroid), the second group (exposure to one course of corticosteroid therapy), and the third group (i. e., exposure to more than one course of corticosteroid therapy). The newborn characteristics at birth and duration of hospitalization were recorded in each group. After discharge, weight, height, and head circumference were determined at two months intervals for six months. Neonatal evolution and ability were also studied based on the Milestones checklist. Data were analyzed by t‐test and expressed as Mean ± SD.ResultsThere were no significant differences in the mean birth weight and Apgar scores at minutes 1 and 5 among groups (p > 0.05). Besides, mean weight, head circumference, and height at months 2, 4, and 6 were not significantly different among the studied groups (p > 0.05). The mean score of the Milestones checklist, including motion, language, activity, and social‐emotional scores, did not differ significantly between the study groups at months 2, 4, and 6 (p > 0.05). The duration of hospitalization was not significantly different among the studied groups (p > 0.05). However, the mean duration of hospitalization in the first group (9.67 days) was more than those in the second and third groups (7.05 and 6.35 days).ConclusionTreatment with repeated doses of corticosteroids reduced the duration of hospitalization; however, it did not significantly affect the growth and abilities of newborns.
Constructing Physical 3D Models Enhances Comprehension of Anatomical Concepts in Allopathic Medical Students: A Pilot Study
Authors: Cannell Ruslana M. , Saied Arman , Kirshman Nathalie , Panchal Dhruvi D. , Vu Baoanh , Hassan Sherif S. 
Published: April 2020

BackgroundStudies have shown that the use of physical 3D anatomy models enhance understanding of complex anatomical structures.
1 However, these studies have been limited to specific medical and veterinary schools. This study examines whether creating physical 3D anatomy models will also provide learning enhancements to allopathic medical students at California University of Science and Medicine (CUSM) taking anatomy courses to diversify pre‐existing data.MethodsFirst and second year allopathic medical students constructed physical 3D anatomy models during art workshops at the CUSM in San Bernardino, CA. Art workshops were held one to two times per course block. During the workshops, participants built physical 3D models that were relevant to the material that was being studied during the respective medical school block. At the end of workshops, participants completed a survey that asked about their learning style and how the workshops affected their understanding of the given anatomy topic. The learning styles are defined as: visual ‐‐ learn best by producing graphs, flow charts, and diagrams, aural ‐‐ learn best by listening, read/write ‐‐ learn best by reading printed words, and kinesthetic ‐‐ learn best through “multisensory learning experiences” by applying information using most of their senses.
2ResultsThe majority of participants (87.5%) reported that building the physical 3D anatomy models enhanced their understanding of the associated anatomy concept. One participant reported their understanding of the anatomy concept remained unchanged. 87.5% of participants stated having a visual learning style as opposed to a read/write (25%), aural (12.5%), or kinesthetic (12.5%) learning styles
2. The discrepancy in percentages is due to students selecting multiple learning styles.ConclusionOur initial study shows promising results that constructing physical 3D anatomy models can enrich allopathic medical student’s learning of related anatomy concepts. Furthermore, our study revealed that the majority of participants preferred visual learning techniques which could play a role in the increased comprehension of anatomy concepts from building 3D models. In future studies, we will survey participants to gauge for depth of understanding of anatomical concepts, other than the participants’ perceived understanding. In addition, we will evaluate if specific learning styles affect the ability for allopathic medical students to grasp anatomical concepts following assembly of physical 3D models.
Roles of Mediator subunit MED26 in Regulation of Post‐initiation Events in RNA Pol II Transcription
Authors: Ranjan Amol , Chen Shiyuan , Goode Zach , Sato Shigeo , Sato Chieri , Takahashi Hidehisa , Conaway Ronald , Conaway Joan W. 
Published: April 2020

Mediator is a conserved multi‐protein complex that transduces regulatory signals from gene‐specific transcription factors to RNA polymerase II and its regulatory factors to control transcription. Mediator subunit MED26 has been implicated in control of post‐initiation steps in transcription. Its N‐terminal domain binds two types of complexes containing elongation factor ELL, the Little Elongation Complexes (LECs) and Super Elongation Complexes (SECs) (
Takahashi et al., 2011). MED26 regulates expression of non‐polyadenylated snRNA genes, at least in part by recruiting LECs (
Takahashi et al., 2015). In assays using PRO‐seq to measure the location of transcribing Pol II in MED26 mutant cells, we observed an increase in mapped reads extending past the normal transcription termination sites of LEC regulated snRNA genes as well as genes encoding replication‐dependent histone transcripts, which, like snRNAs, are not polyadenylated (
Takahashi, Ranjan, et al., 2020). These observations suggest a new role for MED26‐containing Mediator in control of 3′‐end processing and transcription termination at these genes.MED26‐containing Mediator also helps recruit SECs to c‐myc and several other protein coding genes to regulate phosphorylation of the Rpb1 CTD and, most likely, transcription elongation (
Takahashi et al., 2011); however, whether MED26 contributes to these processes globally is unknown. In this study, we used genome‐wide approaches to examine the consequences of MED26 mutation in regulation of post‐initiation events including CTD phosphorylation and elongation, assessed by measuring the distribution of transcriptionally active Pol II across gene bodies. We observed that MED26 mutation alters Pol II distribution and reduces CTD Ser2 phosphorylation (Ser2P) at many protein‐coding genes, mostly towards their 3′‐ends. Moreover, MED26 mutation is associated with a remarkable shift of Ser2P towards 5′‐ends at many protein‐coding genes. Notably, 5′‐enrichment of Ser2P in MED26 mutant cells appeared independent of changes in gene expression. We hypothesize that because of a defect in Mediator’s ability to recruit elongation complexes, MED26 mutation could generally slow Pol II elongation and trigger premature termination.Support or Funding InformationThis research was supported by the Stowers Institute for Medical Research and the Helen Nelson Medical Research Fund of the Greater Kansas City Community Foundation
Therapeutic Overview of Neuromuscular Signaling Responses in Myasthenia Gravis Patients following Surgical vs Non‐Surgical Treatment
Authors: Sainvil Frantz , Tulp Orien Lee , Einstein George P. 
Published: April 2020

Myasthenia gravis (MG) is one of the most common disorder of neuromuscular signaling, where it has a reported prevalence of between13 to 21 patients per 100,000 population, representing 37,000 to 61,000 confirmed cases in the USA. There is no single approach to treat the condition, and currently no cures are known. The purpose of this study was to review two of the primary therapeutic protocols for treating MG by Meta Analysis, in an attempt to determine which of the leading two protocols (thymectomy vs. neostigmine bromide (NBR)) was associated with the most optimistic outcome. The symptoms commonly experienced by people with MG include muscle weakness and generalized fatigue. In healthy patients, the presynaptic terminals release acetylcholine (ACh) from the motor nerve terminal in quanta. The ACh quanta diffuse across the synaptic cleft and impinge on ACh receptors on the post synaptic membrane of the muscle that causes depolarization from the neuromuscular cleft, and which results in a contractile event in the affected muscle. In MG patients, the post synaptic membrane (ACh receptors) are typically damaged at least in part due to immunological or sometimes genetic abnormalities.. Tumors of the thymus gland are also commonly observed in patients with MG. In MG, B‐cells interact with helper T‐cells to produce anti‐ACh receptor antibodies. The destruction of the thymus’ tolerance can thus result in an immunologic attack on the post‐synaptic ACh receptors. MG can be treated with cholinesterase inhibitors such as NBR or extended transsternal thymectomy. This study utilized a Meta‐analysis approach for data interpretation of surgical vs NBR in order to compare neuromuscular signaling on MG’s patients who are treated with cholinesterase inhibitors versus those who are treated surgically. The results of this study concluded that neuromuscular signaling in MG patients who have had surgical interventions have better and more successful outcomes that those patients that received the NBR treatment only.Support or Funding InformationSupported by Institutional Resources of USAT Montserrat and the Einstein Medical InstituteSupport or Funding InformationSupported by Institutional Resources of USAT Montserrat, the University of Health and Humanities Virgin Islands and the Einstein Medical Institute
Discriminative Stimulus Effects of Mu Opioid Receptor Agonists in Rats Discriminating Fentanyl: Differential Antagonism by Naltrexone
Authors: Flynn Shawn , France Charles 
Published: April 2020

The opioid crisis continues despite the availability of medications that are effective in some patients. A significant number of deaths caused by opioids involve fentanyl and/or one of its very potent analogues (e.g., carfentanil). Many fentanyl analogs have not been studied extensively in vivo. The current study compared the discriminative stimulus effects of fentanyl and carfentanil and their antagonism by naltrexone. Seven male Sprague‐Dawley rats were trained to discriminate a 0.01 mg/kg fentanyl from saline while responding under a fixed‐ratio 10 schedule of food presentation. Dose effect curves were determined for the opioid receptor agonists alone: fentanyl (0.001–0.1 mg/kg) and carfentanil (0.0001–0.0032 mg/kg). Dose effect curves for fentanyl and carfentanil were then redetermined following a 15‐minute pretreatment with 0.1 mg/kg naltrexone. All drugs were delivered intraperitoneally. Fentanyl and carfentanil dosedependently increased responding on the fentanyl‐associated lever and at larger doses decreased the rate of lever pressing. Carfentanil was approximately 10‐fold more potent than fentanyl at eliciting >90% responding on the fentanyl‐associated lever. Pretreatment with 0.1 mg/kg naltrexone shifted the fentanyl dose‐effect curve 10‐fold rightward whereas the same dose of naltrexone shifted the carfentanil curve only 3‐fold rightward. Differences in the effectiveness of naltrexone to attenuate the discriminative stimulus effects of fentanyl and carfentanil suggests that there may be differences in how fentanyl and carfentanil exert their discriminative stimulus effects. Further evaluation of potential pharmacological and behavioral differences between fentanyl and carfentanil is needed and might provide important insights regarding the apparently increased toxicity of carfentanil, compared with other opioids, in humans.Support or Funding InformationAQ‐0039 from the Welch Foundation
Flexible Intramedullary Nailing of Femoral Shaft Fractures in Children Weighing ≥40 kg: A Systematic Review and Meta-analysis
Authors: Makarewich Christopher A. , Talwar Divya , Baldwin Keith D. , Swarup Ishaan 
Published: April 2020

Background:
Pediatric femur fractures are commonly treated with flexible intramedullary nails (FIN). However, there is controversy regarding the effect of patient weight on outcomes and complications. The purpose of this meta-analysis was to review the literature and describe implant choice, analyze complication, and reoperation rates; as well as the report clinical and radiographic outcomes of FIN in pediatric patients weighing ≥40 kg with femoral shaft fractures.

Methods:
A systematic review was performed of all retrospective and prospective studies focusing on the use of FIN in heavy children in Medline, Cochrane, and Web of Science databases. Data extraction was performed and summarized using descriptive statistics. Quality assessment was performed using the Newcastle-Ottawa Scale. Meta-analysis was performed for complications using pooled data from included studies.

Results:
The initial search strategy yielded 177 references, and after exclusions, 5 studies were included. The majority of studies were retrospective, and the most commonly used implants in heavier patients were titanium FIN and stainless steel Enders FIN. There were higher rates of radiographic nonunion and malunion, complications, and reoperations for refracture; and nonunion in heavier children treated with FIN. Meta-analysis performed on 4 applicable studies showed the overall complication rate was higher in the heavier patients compared with lighter patients (30.6% vs. 11.1%) with a relative risk of 1.20 [95% confidence interval (CI), 1.02-1.41]. Heavier patients also had higher rates of major complications (relative risk, 1.32; 95% CI, 1.03-1.69) but similar minor complications (relative risk, 1.13; 95% CI, 0.90-1.41).

Conclusions:
Heavier children have worse radiographic outcomes and higher complication rates with the use of FIN for femoral shaft fractures. Additional research is needed to determine the effect of FIN material on clinical outcomes in heavier children, and the relationship between weight and other known risk factors for poor outcome in FIN, such as length stability.

Level of Evidence:
Level III—systematic review of level-III studies.
Impact of Bilateral Infiltrates on Inflammatory Biomarker Levels and Clinical Outcomes of Children With Oxygenation Defect
Authors: Kohne Joseph G. , Dahmer Mary K. , Weeks Heidi M. , Kaciroti Niko , Quasney Michael W. , Sapru Anil , Curley Martha A. Q. , Matthay Michael , Flori Heidi 
Published: April 2020

Objectives:
The 2015 definition for pediatric acute respiratory distress syndrome did not require the presence of bilateral infiltrates. We tested the hypothesis that pediatric patients meeting oxygenation criteria for pediatric acute respiratory distress syndrome but without bilateral infiltrates would have different inflammatory biomarker levels and clinical outcomes than those with bilateral infiltrates.

Design:
Secondary analysis of a prospective cohort study.

Setting:
Twenty-two PICUs.

Patients:
Four-hundred forty-six patients age 2 weeks to 17 years intubated for respiratory failure with oxygenation index greater than or equal to 4 or oxygenation saturation index greater than or equal to 5 on the day of intubation or the day after.

Interventions:
None.

Measurements and Main Results:
Patients with bilateral infiltrates, either on the day of intubation or within the following 2 days, were compared with children who never developed bilateral infiltrates. Two analyses were performed to test 1) whether bilateral infiltrates are associated with elevated interleukin-1 receptor antagonist or interleukin-8 and 2) whether bilateral infiltrates are associated with worse clinical outcomes. Patients with bilateral infiltrates more often had a primary diagnosis of pneumonia (41% vs 28%; p = 0.02) and less often asthma (8% vs 23%; p < 0.01). After controlling for age, gender, and primary diagnosis, interleukin-1 receptor antagonist was higher on study days 1 and 2 in patients with bilateral infiltrates. There was no difference in interleukin-8 levels. After adjusting for age, gender, Pediatric Risk of Mortality score, and severity of oxygenation defect, presence of bilateral infiltrates was associated with longer duration of mechanical ventilation in survivors (hazard ratio, 0.64; 95% CI, 0.49–0.82; p < 0.01); this association was independent of primary diagnosis. Overall mortality was 9%; mortality was higher in those without bilateral infiltrates (14% vs 8%; p = 0.04).

Conclusions:
Children meeting pediatric acute respiratory distress syndrome oxygenation criteria with bilateral infiltrates on chest radiograph experience a more intense early inflammatory response. Bilateral infiltrates are associated with longer time on the ventilator independent of oxygenation defect severity.
Association Between Arterial Carbon Dioxide Tension and Clinical Outcomes in Venoarterial Extracorporeal Membrane Oxygenation*
Authors: Diehl Arne , Burrell Aidan J. C. , Udy Andrew A. , Alexander Peta M. A. , Rycus Peter T. , Barbaro Ryan P. , Pellegrino Vincent A. , Pilcher David V. 
Published: April 2020

Objectives:
The manipulation of arterial carbon dioxide tension is associated with differential mortality and neurologic injury in intensive care and cardiac arrest patients; however, few studies have investigated this relationship in patients on venoarterial extracorporeal membrane oxygenation. We investigated the association between the initial arterial carbon dioxide tension and change over 24 hours on mortality and neurologic injury in patients undergoing venoarterial extracorporeal membrane oxygenation for cardiac arrest and refractory cardiogenic shock.

Design:
Retrospective cohort analysis of adult patients recorded in the international Extracorporeal Life Support Organization Registry.

Setting:
Data reported to the Extracorporeal Life Support Organization from all international extracorporeal membrane oxygenation centers during 2003-2016.

Patients:
Adult patients (≥ 18 yr old) supported with venoarterial extracorporeal membrane oxygenation.

Interventions:
None.

Measurements and Main Results:
A total of 7,168 patients had sufficient data for analysis at the initiation of venoarterial extracorporeal membrane oxygenation, 4,918 of these patients had arterial carbon dioxide tension data available at 24 hours on support. The overall in-hospital mortality rate was 59.9%. A U-shaped relationship between arterial carbon dioxide tension tension at extracorporeal membrane oxygenation initiation and in-hospital mortality was observed. Increased mortality was observed with a arterial carbon dioxide tension less than 30 mm Hg (odds ratio, 1.26; 95% CI, 1.08–1.47; p = 0.003) and greater than 60 mm Hg (odds ratio, 1.28; 95% CI, 1.10–1.50; p = 0.002). Large reductions (> 20 mm Hg) in arterial carbon dioxide tension over 24 hours were associated with important neurologic complications: intracranial hemorrhage, ischemic stroke, and/or brain death, as a composite outcome (odds ratio, 1.63; 95% CI, 1.03–2.59; p = 0.04), independent of the initial arterial carbon dioxide tension.

Conclusions:
Initial arterial carbon dioxide tension tension was independently associated with mortality in this cohort of venoarterial extracorporeal membrane oxygenation patients. Reductions in arterial carbon dioxide tension (> 20 mm Hg) from the initiation of extracorporeal membrane oxygenation were associated with neurologic complications. Further prospective studies testing these associations are warranted.
Utility of Driving Pressure and Mechanical Power to Guide Protective Ventilator Settings in Two Cohorts of Adult and Pediatric Patients With Acute Respiratory Distress Syndrome: A Computational Investigation
Authors: Saffaran Sina , Das Anup , Laffey John G. , Hardman Jonathan G. , Yehya Nadir , Bates Declan G. 
Published: April 2020

Objectives:
Mechanical power and driving pressure have been proposed as indicators, and possibly drivers, of ventilator-induced lung injury. We tested the utility of these different measures as targets to derive maximally protective ventilator settings.

Design:
A high-fidelity computational simulator was matched to individual patient data and used to identify strategies that minimize driving pressure, mechanical power, and a modified mechanical power that removes the direct linear, positive dependence between mechanical power and positive end-expiratory pressure.

Setting:
Interdisciplinary Collaboration in Systems Medicine Research Network.

Subjects:
Data were collected from a prospective observational cohort of pediatric acute respiratory distress syndrome from the Children’s Hospital of Philadelphia (n = 77) and from the low tidal volume arm of the Acute Respiratory Distress Syndrome Network tidal volume trial (n = 100).

Interventions:
Global optimization algorithms evaluated more than 26.7 million changes to ventilator settings (approximately 150,000 per patient) to identify strategies that minimize driving pressure, mechanical power, or modified mechanical power.

Measurements and Main Results:
Large average reductions in driving pressure (pediatric: 23%, adult: 23%), mechanical power (pediatric: 44%, adult: 66%), and modified mechanical power (pediatric: 61%, adult: 67%) were achievable in both cohorts when oxygenation and ventilation were allowed to vary within prespecified ranges. Reductions in driving pressure (pediatric: 12%, adult: 2%), mechanical power (pediatric: 24%, adult: 46%), and modified mechanical power (pediatric: 44%, adult: 46%) were achievable even when no deterioration in gas exchange was allowed. Minimization of mechanical power and modified mechanical power was achieved by increasing tidal volume and decreasing respiratory rate. In the pediatric cohort, minimum driving pressure was achieved by reducing tidal volume and increasing respiratory rate and positive end-expiratory pressure. The Acute Respiratory Distress Syndrome Network dataset had limited scope for further reducing tidal volume, but driving pressure was still significantly reduced by increasing positive end-expiratory pressure.

Conclusions:
Our analysis identified different strategies that minimized driving pressure or mechanical power consistently across pediatric and adult datasets. Minimizing standard and alternative formulations of mechanical power led to significant increases in tidal volume. Targeting driving pressure for minimization resulted in ventilator settings that also reduced mechanical power and modified mechanical power, but not vice versa.