bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can a Situational Judgment Test Identify Trainees at Risk of Professionalism Issues? A Multi-Institutional, Prospective Cohort Study
Authors: Cullen Michael J. , Zhang Charlene , Sackett Paul R. , Thakker Krima , Young John Q. 
Published: May 2022

Purpose
To determine whether overall situational judgment test (SJT) scores are associated with programs’ clinical competency committee (CCC) ratings of trainee professionalism, any concerning behavior, and concerning behavior requiring active remediation at 2 time periods.

Method
In fall 2019, trainees from 17 U.S. programs (16 residency, 1 fellowship) took an online 15-scenario SJT developed to measure 7 dimensions of professionalism. CCC midyear and year-end (6 months and 1 year following SJT completion, respectively) professionalism scores and concern ratings were gathered for academic year 2019–2020. Analyses were conducted to determine whether overall SJT scores related to overall professionalism ratings, trainees displaying any concerns, and trainees requiring active remediation at both time periods.

Results
Overall SJT scores correlated positively with midyear and year-end overall professionalism ratings (r = .21 and .14, P < .001 and = .03, respectively). Holding gender and race/ethnicity constant, a 1 standard deviation (SD) increase in overall SJT score was associated with a .20 SD increase in overall professionalism ratings at midyear (P = .005) and a .22 SD increase at year-end (P = .001). Holding gender and race/ethnicity constant, a 1 SD increase in overall SJT score decreased the odds of a trainee displaying any concerns by 37% (odds ratio [OR] 95% confidence interval [CI]: [.44, .87], P = .006) at midyear and 34% (OR 95% CI: [.46, .95], P = .025) at year-end and decreased the odds of a trainee requiring active remediation by 51% (OR 95% CI: [.25, .90], P = .02) at midyear.

Conclusions
Overall SJT scores correlated positively with midyear and year-end overall professionalism ratings and were associated with whether trainees exhibited any concerning behavior at midyear and year-end and whether trainees needed active remediation at midyear. Future research should investigate whether other potential professionalism measures are associated with concerning trainee behavior.
Early Neurodevelopmental Outcomes Following Exposure to General Anesthesia in Infancy: EGAIN, a Prospective Cohort Study
Authors: Bong Choon Looi , Ho Duncun , Allen John Carson , Lim Gillian Si-Min , Tan Hong-Kuang , Broekman Birit F.P. , Fabila Teddy , Reddy Satish , Koh Woon-Puay , Swee-Kim Tan Josephine , Meaney Michael , Rifkin-Graboi Anne 
Published: May 2022

Background:
General anesthesia (GA) is known to worsen neural outcomes in animals, but human research assessing early-life GA exposure and neurodevelopment show inconsistent findings. We investigated the effects of a single GA exposure for minor surgery on the neurodevelopment of healthy children at multiple time-points, using clinical assessments along with behavioral and neurophysiological measures rarely used in human research.

Methods:
GA-exposed children were a prospective cohort of 250 full-term, healthy infants who underwent GA for minor surgery before 15 months. Nonexposed children were from a separate cohort of similar age, sex, ethnicity, and maternal education. In both cohorts, clinical measures (Bayley Scales of Infant and Toddler Development-III [BSID-III] and Child Behavior Checklist [CBCL1½-5]) were assessed at 24 months, and experimental tests (memory and attentional) and neurophysiology (event-related potentials) at 6 and 18 months.

Results:
At 24 months, there were no differences between GA-exposed and nonexposed children in the cognitive, language, motor, and socioemotional domains of the BSDI-III; however, GA-exposed children had poorer parental-reported scores in BSID-III general adaptability (94.2 vs. 99.0 [mean difference, 4.77; 97.3% confidence interval, −9.29, −0.24]; P=0.020) and poorer internalizing behavior scores on CBCL1½-5 (52.8 vs. 49.4 [mean difference, 3.35; 97.3% confidence interval, 0.15-6.55]; P=0.021). For experimental measures, GA-exposed children showed differences in 4 tests at 6 and 18 months.

Conclusions:
GA-exposed children did not differ from unexposed children in cognitive, language or motor outcomes at 24 months, but exhibited poorer parent-reported behavior scores. Differences in infant behavior and neurophysiology were detected at 6 and 18 months. Neurophysiological assessments may complement clinically relevant assessments to provide greater insights into neurodevelopment following early GA exposure.
Proteomics of Coagulopathy Following Injury Reveals Limitations of Using Laboratory Assessment to Define Trauma-Induced Coagulopathy to Predict Massive Transfusion
Authors: Moore Hunter B. , Neal Matthew D. , Bertolet Marnie , Joughin Brian A. , Yaffe Michael B. , Barrett Christopher D. , Bird Molly A. , Tracy Russell P. , Moore Ernest E , Sperry Jason L. , Zuckerbraun Brian S. , Park Myung S. , Cohen Mitchell J. , Wisniewski Stephen R. , Morrissey James H. ,   TACTIC Investigators
Published: May 2022

Objective:
Trauma-induced coagulopathy (TIC) is provoked by multiple mechanisms and is perceived to be one driver of massive transfusions (MT). Single laboratory values using prothrombin time (INR) or thrombelastography (TEG) are used to clinically define this complex process. We used a proteomics approach to test whether current definitions of TIC (INR, TEG, or clinical judgment) are sufficient to capture the majority of protein changes associated with MT.

Methods:
Eight level I trauma centers contributed blood samples from patients available early after injury. TIC was defined as INR >1.5 (INR-TIC), TEG maximum amplitude <50 mm (TEG-TIC), or clinical judgment (Clin-TIC) by the trauma surgeon. MT was defined as >10 units of red blood cells in 24 hours or >4 units RBC/hour during the first 4 hours. SomaLogic proteomic analysis of 1305 proteins was performed. Pathways associated with proteins dysregulated in patients with each TIC definition and MT were identified.

Results:
Patients (n = 211) had a mean injury severity score of 24, with a MT and mortality rate of 22% and 12%, respectively. We identified 578 SOMAscan analytes dysregulated among MT patients, of which INR-TIC, TEG-TIC, and Clin-TIC patients showed dysregulation only in 25%, 3%, and 4% of these, respectively. TIC definitions jointly failed to show changes in 73% of the protein levels associated with MT, and failed to identify 26% of patients that received a massive transfusion. INR-TIC and TEG-TIC patients showed dysregulation of proteins significantly associated with complement activity. Proteins dysregulated in Clin-TIC or massive transfusion patients were not significantly associated with any pathway.

Conclusion:
These data indicate there are unexplored opportunities to identify patients at risk for massive bleeding. Only a small subset of proteins that are dysregulated in patients receiving MT are statistically significantly dysregulated among patients whose TIC is defined based solely on laboratory measurements or clinical assessment.
The utility of routine dual-energy x-ray absorptiometry scans in matched-pair cadaveric biomechanical trauma research
Authors: Black Natalie R. , Morris Randal P. , Chen Jie 
Published: May 2022

Background:
Performing cadaveric dual-energy x-ray absorptiometry (DEXA) scanning is a routine part of orthopaedic biomechanical research, but it is not without cost. Matched pairs are often used in biomechanical studies to further equalize comparison groups. Despite the widespread use of matched-pair analysis, the practical utility of obtaining routine DEXA scans remains unknown. The authors’ objective was to determine the value of DEXA scans in biomechanical cadaveric trauma studies.

Methods:
The authors identified 10 sequential journal articles from the Journal of Orthopaedic Trauma from February 2013 to February 2019 that were biomechanical studies with two comparison groups using matched pairs, which were DEXA-scanned prior to experimentation. For each study, the authors determined the number of pairs used, number of pairs discarded, any significant differences in bone density between groups compared, and how density results were reported for individual specimens or pairs.

Results:
None of the 113 matched pairs reported in these studies were discarded because of DEXA scan results. There were inconsistencies between studies on reported units of measurement and how the specimens were compared. No significant differences in density between the compared groups were reported in the 10 studies. No studies disclosed the bone density for any individual specimen or score difference for any individual pair.

Conclusions:
As currently used in the literature, routine DEXA scans of cadaveric matched-pair specimens do not typically lead to any modification of experimental design or reporting of results.

Level of Evidence:
Level IV.
Update in Management of Craniosynostosis
Authors: Xue Amy S. , Buchanan Edward P. , Hollier Larry H. 
Published: May 2022

Learning Objectives:
After studying this article, the participant should be able to: 1. Understand the craniofacial dysmorphology of craniosynostosis, and the variation of each type. 2. Identify the functional concerns and learn the rationale behind timing of operative intervention. 3. Approach each dysmorphology critically and identify the operative intervention needed to improve form and function 4. Understand and address the specific issues related to syndromic craniosynostosis and be able to delineate management plan.

Summary:
Craniosynostosis is a condition in which premature fusion of one or more cranial sutures lead to abnormal head shape and growth restriction of the brain. Nonsyndromic craniosynostosis occurs in isolation, and usually involves a single suture, whereas syndromic craniosynostosis may involve multiple sutures and is associated with extracraniofacial findings. Although surgical management can be similar, the treatment plan must take into consideration issues specific to the syndromes. This article aims to provide a concise overview of the authors’ current understanding regarding the presentation, treatment principle, surgical option, and debates in craniosynostosis.
Nonreplantable Total Scalp Avulsion Reconstruction with Acellular Biologic Matrix and Long-Term Outcome
Authors: Anderson Spencer R. , Gupta Nishtha , Johnson R. Michael 
Published: May 2022

Abstract
Total scalp avulsion is a significant injury typically occurring as a result of industrial accidents involving high-speed rotary machines. Although ideal, scalp replantation is uncommon secondary to the nature of the injury and lack of viable microvas-cular anastomosis targets. Therefore, these defects are often reconstructed with microvascular free tissue transfer, with or without skin grafting. We present a unique case of a patient with total scalp avulsion achieving complete, stable skin coverage over partially intact periosteum using only spare parts of the amputated scalp as a temporary full-thickness graft and porcine urinary bladder matrix, thus, avoiding significant donor site morbidity or extensive surgery. At 4 years postoperative, the scalp coverage remains stable.
Burn Injury-Induced Extracellular Vesicle Production and Characteristics
Authors: Yang Xiaoyuan , Chatterjee Victor , Zheng Ethan , Reynolds Amanda , Ma Yonggang , Villalba Nuria , Tran Thanh , Jung Michelle , Smith David J. , Wu Mack H. , Yuan Sarah Y. 
Published: May 2022

ABSTRACT
Extracellular vesicles (EVs) are nano-sized membrane-bound particles containing biologically active cargo molecules. The production and molecular composition of EVs reflect the physiological state of parent cells, and once released into the circulation, they exert pleiotropic functions via transferring cargo contents. Thus, circulating EVs not only serve as biomarkers, but also mediators in disease processes or injury responses. In the present study, we performed a comprehensive analysis of plasma EVs from burn patients and healthy subjects, characterizing their size distribution, concentration, temporal changes, cell origins, and cargo protein contents. Our results indicated that burn injury induced a significant increase in circulating EVs, the response peaked at the time of admission and declined over the course of recovery. Importantly, EV production correlated with injury severity, as indicated by the total body surface area and depth of burn, requirement for critical care/ICU stay, hospitalization length, wound infection, and concurrence of sepsis. Burn patients with inhalation injury showed a higher level of EVs than those without inhalation injury. We also evaluated patient demographics (age and sex) and pre-existing conditions (hypertension, obesity, and smoking) and found no significant correlation between these conditions and overall EV production. At the molecular level, flow cytometric analysis showed that the burn-induced EVs were largely derived from leukocytes and endothelial cells (ECs), which are known to be activated postburn. Additionally, a high level of zona-occludens-1 (ZO-1), a major constituent of tight junctions, was identified in burn EV cargos, indicative of injury in tissues that form barriers via tight junctions. Moreover, when applied to endothelial cell monolayers, burn EVs caused significant barrier dysfunction, characterized by decreased transcellular barrier resistance and disrupted cell–cell junction continuity. Taken together, these data suggest that burn injury promotes the production of EVs containing unique cargo proteins in a time-dependent manner; the response correlates with injury severity and worsened clinical outcomes. Functionally, burn EVs serve as a potent mediator capable of reducing endothelial barrier resistance and impairing junction integrity, a pathophysiological process underlying burn-associated tissue dysfunction. Thus, further in-depth characterization of circulating EVs will contribute to the development of new prognostic tools or therapeutic targets for advanced burn care.
Regional mortality variations among older adults in India: Evidence from Demographic Health Survey
Authors: Akhtar Saddaf Naaz , Saikia Nandita 
Published: May 2022

AbstractBackgroundStudies on regional mortality variations among older adults in India are poorly documented. Therefore, we intend to estimate the impact of individual and district level determinants on regional mortality variations among the older adults in India. Additionally, we have performed decomposition analysis to evaluate the contribution of socioeconomic and demographic factors in the inter-regional mortality variations among older adults in India.MethodsWe performed a two-level logistic regression model using data from Demographic Health Survey (2015-16) for India to quantify the impact of socio-demographic and ecomonic characteristics. We have also analyzed multivariate decomposition approach to determine the role of determinants in regional mortality variations among older adults.ResultsThe multilevel analyses results revealed that regional mortality variations exist at both individual and district levels among older adults in India. Our finding identified that older adults living in the Central region have a higher mortality risk than in Northern regions. The decomposition results showed that the Central, Eastern and North-eastern regions have significantly higher average number of excess mortality compared to other regions among older adults. The district-level literacy, insurance coverage, electricity supply and public health facilities also showed a significant impact on district level mortality among older adults in India.ConclusionOur study insights extremely important determinants for India’s public health. In order to eliminate these mortality gaps, there is a need for solid support from the state and central government to bridge the socio-demographic and economic development in India at the regional level. As a result, policy should include efforts to improve health outcomes among older adults at early stages.
Genome-wide analyses of early-onset acute myocardial infarction identify 29 novel loci by whole genome sequencing
Authors: Jeon Yeonsu , Jeon Sungwon , Choi Whan-Hyuk , An Kyungwhan , Choi HanSol , Kim Byoung-Chul , Kim Weon , Lee Sang Yeob , Bae Jang-Whan , Hwang Jin-Yong , Kang Min Gyu , Kim Yeonkyung , Kang Younghui , Kim Yeo Jin , Kim Byung Chul , Bhak Jong , Shin Eun-Seok 
Published: May 2022

AbstractEarly-onset acute myocardial infarction (AMI) may have a higher genetic predisposition than late-onset AMI does. The present study aimed to identify and characterize germline variants that affect early-onset AMI using whole-genome sequencing (WGS). We performed a genome-wide association study based on WGS of 1,239 Koreans, including 596 early-onset AMI patients and 643 healthy individuals. Patients with AMI who underwent percutaneous coronary intervention (PCI) caused by atherothrombotic occlusive lesions were included in the study. A total of 29 novel loci were found to be associated with early-onset AMI. These loci are involved in thrombosis, fibrinolysis, inflammation, and lipid metabolism. One of the associated single nucleotide variants (SNVs), rs1614576, located upstream of PRKCB, is known to be associated with thrombus formation. Additionally, the results revealed a novel locus, rs78631167, located upstream of PLAUR which plays a critical role in regulating plasminogen activation and is related to fibrinolysis. The association between early-onset AMI and rs9357455, which is located upstream of PHACTR1 that regulates inflammation in AMI, was found. Moreover, we could identify a lipid metabolism related genetic risk locus, rs5072, in the APOA1-AS gene. This study provides new evidence supporting the genetic association between early-onset AMI and thrombosis and fibrinolysis, as well as inflammation and lipid metabolism, by analyzing the whole-genome of 596 patients with early-onset AMI who have been treated with PCI. Our findings highlight potential genetic markers for the prediction and management of AMI, as well as for understanding the etiology of AMI.
Predicting recognition between T cell receptors and epitopes using contextualized motifs
Authors: Jokinen Emmi , Dumitrescu Alexandru , Huuhtanen Jani , Gligorijević Vladimir , Mustjoki Satu , Bonneau Richard , Heinonen Markus , Lähdesmäki Harri 
Published: May 2022

AbstractWe introduce TCRconv, a deep learning model for predicting recognition between T-cell receptors and epitopes. TCRconv uses a deep protein language model and convolutions to extract contextualized motifs and provides state-of-the-art TCR-epitope prediction accuracy. Using TCR repertoires from COVID-19 patients, we demonstrate that TCRconv can provide insight into T-cell dynamics and phenotypes during the disease.
Porcine placenta extract upregulates ceramide synthase 3 expression via the PPARδ/ILK/Akt/mTOR/STAT3 pathway
Authors: Aioi Akihiro , Muromoto Ryuta , Kashiwakura Jun-ichi , Mogami Sho , Nishikawa Megumi , Ogawa Shigeyuki , Matsuda Tadashi 
Published: May 2022

AbstractPorcine placenta extract (PPE) is widely accepted as an ingredient in complementary and alternative medicine and previous studies have reported its availability, however, its underlying action mechanism remains unclear. In this study, we investigated the underlying mechanism of porcine placenta extract-induced ceramide synthase 3 upregulation. PPE enhanced the expression of ceramide synthase 3 at both the mRNA and protein levels in HaCaT cells. Moreover, porcine placenta extract-induced ceramide synthase3 upregulation was suppressed by the Akt inhibitor, suggesting the involvement of Akt in the underlying mechanism. As the PI3K inhibitor did not affect porcine placenta extract-induced ceramide synthase 3 upregulation, the factors upstream of Akt were estimated. Inhibition and small interfering RNA experiments demonstrated that the peroxisome proliferator-activated receptors δ (PPAR δ) and integrin-linked kinase (ILK) are involved in the phosphorylation of Akt. Next, we explored the factors downstream of Akt and found that porcine placenta extract induced phosphorylation of the STAT3 while porcine placenta extract-induced upregulation of ceramide synthase 3 was significantly suppressed by the inhibitor of the mTOR, suggesting that the mTOR/STAT3 pathway is involved in the downstream of Akt. These results demonstrate that porcine placenta extract upregulates CerS3 expression via the PPARδ/ILK/Akt/mTOR/STAT3 pathway.
Selective detection of m6A derived from mRNA using the Phospho-tag m6A assay
Authors: Mirza Aashiq H. , Attarwala Nabeel , Gross Steven S. , Chen Qiuying , Jaffrey Samie R. 
Published: May 2022

ABSTRACTN6-methyladenosine (m6A) is a modified nucleotide found in mRNA, ribosome RNA (rRNA) and small nuclear RNA (snRNA). m6A in mRNA has important roles in regulating mRNA stability, splicing, and other processes. Numerous studies have described m6A as a dynamic modification using mass spectrometry-based quantification of m6A in mRNA samples prepared from different cellular conditions. However, these results have been questioned based on the finding that the mRNA purification protocols often result in varying levels of rRNA contamination. Additionally, mRNA purification protocols disproportionately enrich for the 3’ ends of mRNA, a region that is enriched in m6A. To address these problems, we developed the Phospho-tag m6A assay, a highly efficient method for quantifying m6A specifically from mRNA. In this assay, a series of selective RNase digestion steps is performed, which results in m6A from rRNA and snRNA being liberated as m6A monophosphate, while m6A from mRNA is mostly liberated as m6A nucleoside. m6A levels are normalized to transcript levels, using m7G monophosphate liberated by yDcpS decapping enzyme as a surrogate for mRNA levels. Notably, this approach uses total cellular RNA, rather than purified mRNA, which simplifies the steps for m6A detection and overcomes the 3’-end biases associated with mRNA purification. Overall, the Phospho-tag m6A provides a simple and efficient method for quantification of mRNA-derived m6A from total RNA samples.
Modulation of I-wave generating pathways with repetitive paired-pulse transcranial magnetic stimulation: A TMS-EEG study
Authors: Sasaki Ryoki , Hand Brodie J. , Semmler John G. , Opie George M. 
Published: May 2022

AbstractObjectivesRepetitive paired-pulse transcranial magnetic stimulation (iTMS) at indirect (I) wave intervals increases motor-evoked potentials (MEPs) produced by TMS to primary motor cortex (M1). However, the effects of iTMS at early and late intervals on the plasticity of specific I-wave circuits remains unclear. The current study therefore aimed to assess how the timing of iTMS influences intracortical excitability within early and late I-wave circuits. To investigate the cortical effects of iTMS more directly, changes due to the intervention were also assessed using combined TMS-electroencephalography (EEG).Material and MethodsEighteen young adults (24.6 ± 4.2 years) participated in four sessions in which iTMS targeting early (1.5 ms interval; iTMS1.5) or late (4.0 ms interval; iTMS4.0) I-waves was applied over M1. Neuroplasticity was assessed using both posterior-to-anterior (PA) and anterior-to-posterior (AP) stimulus directions to record MEPs and TEPs before and after iTMS. SICF at inter-stimulus intervals of 1.5 and 4.0 ms was also used to index I-wave activity.ResultsMEP amplitude was increased after iTMS (P < 0.01) and this was greater for PA responses (P < 0.01), but not different between iTMS intervals (P = 0.9). Irrespective of iTMS interval and coil current, SICF was facilitated after the intervention (P < 0.01). While the N45 produced by AP stimulation was reduced by iTMS1.5 (P = 0.04), no other changes in TEP amplitude were observed.ConclusionThe timing of iTMS failed to influence which I-wave circuits were potentiated by the intervention. In contrast, reductions in the N45 suggest that the neuroplastic effects of iTMS may include disinhibition of intracortical inhibitory processes.