bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure-Activity Relationship of Neuroactive Steroids, Midazolam, and Perampanel Toward Mitigating Tetramine-Triggered Activity in Murine Hippocampal Neuronal Networks
Authors: Antrobus Shane , Pressly Brandon , Nik Atefeh Mousavi , Wulff Heike , Pessah Isaac N 
Published: January 2021

Abstract
Tetramethylenedisulfotetramine (tetramine or TETS), a potent convulsant, triggers abnormal electrical spike activity (ESA) and synchronous Ca2+ oscillation (SCO) patterns in cultured neuronal networks by blocking gamma-aminobutyric acid (GABAA) receptors. Murine hippocampal neuronal/glial cocultures develop extensive dendritic connectivity between glutamatergic and GABAergic inputs and display two distinct SCO patterns when imaged with the Ca2+ indicator Fluo-4: Low amplitude SCO events (LASE) and High amplitude SCO events (HASE) that are dependent on TTX-sensitive network electrical spike activity (ESA). Acute TETS (3.0 µM) increased overall network SCO amplitude and decreased SCO frequency by stabilizing HASE and suppressing LASE while increasing ESA. In multielectrode arrays, TETS also increased burst frequency and synchronicity. In the presence of TETS (3.0 µM), the clinically used anticonvulsive perampanel (0.1–3.0 µM), a noncompetitive AMPAR antagonist, suppressed all SCO activity, whereas the GABAA receptor potentiator midazolam (1.0-30 µM), the current standard of care, reciprocally suppressed HASE and stabilized LASE. The neuroactive steroid (NAS) allopregnanolone (0.1–3.0 µM) normalized TETS-triggered patterns by selectively suppressing HASE and increasing LASE, a pharmacological pattern distinct from its epimeric form eltanolone, ganaxolone, alphaxolone, and XJ-42, which significantly potentiated TETS-triggered HASE in a biphasic manner. Cortisol failed to mitigate TETS-triggered patterns and at &gt;1 µM augmented them. Combinations of allopregnanolone and midazolam were significantly more effective at normalizing TETS-triggered SCO patterns, ESA patterns, and more potently enhanced GABA-activated Cl− current, than either drug alone.
Seasonal Variation in Parental Satisfaction With Pediatric Orthopaedics
Authors: Van de Velde Samuel K. , Cola Kristin , Bompadre Viviana , Steinman Suzanne E. 
Published: January 2021

Background:
The degree of parental satisfaction with health care is determined by the family’s characteristics and expectations. Many aspects of human physiology and behavior have seasonal rhythms. The purpose of the present study was to determine whether parental satisfaction scores vary across the year in a pediatric orthopaedic outpatient population.

Methods:
We retrospectively reviewed a total of 22,951 parental satisfaction scores related to outpatient pediatric orthopaedic encounters between October 2015 and April 2019. Parental satisfaction was measured using the provider subdomain of the shortened version of the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS). Families were stratified according to various pediatric orthopaedic subspecialty services.

Results:
The satisfaction scores of all pediatric orthopaedic encounters combined did not vary significantly across the year (P=0.8745). When the families were stratified into groups by pediatric orthopaedic subspecialty clinic, variation in seasons was not associated with statistically significant variation in satisfaction scores for the elective surgery, sports medicine, trauma/fracture care, and hand/upper extremity services. However, satisfaction with the spine service was significantly lower in the winter compared with the summer and fall (73.9±3.8 vs. 83.5±5.3 and 82.6±3.6, respectively; P=0.0147).

Conclusions:
The provision of pediatric spine care in a region with 4 distinct seasons received lower parental satisfaction scores during the winter than during the summer and fall. This seasonal variation is an additional source of bias in the measurement of satisfaction with health care.

Level of Evidence:
Level II—retrospective study.
The Incidence of Vertebral Exostoses in Multiple Hereditary Exostoses and Recommendations for Spinal Screening
Authors: Wininger Austin E. , Chhabra Barkha N. , Haigler Richard E. , Hanson Darrell S. , Scott Allison C. 
Published: January 2021

Background:
Multiple hereditary exostoses (MHE) lead to the development of pedunculated or sessile osteocartilaginous lesions. Vertebral involvement occurs in MHE and encroaching intracanal exostoses can result in devastating consequences. Magnetic resonance imaging (MRI) of the entire spine has been used to screen for vertebral exostoses to detect high-risk patients. The primary purpose of this investigation is to determine the incidence of vertebral and encroaching intracanal exostoses in patients with MHE. A secondary purpose is to determine if pelvis and rib exostoses serve as “harbinger” lesions of vertebral involvement in MHE.

Methods:
A retrospective chart review was performed on 39 patients (21 male and 18 female individuals) with MHE who underwent routine spinal screening with noncontrast entire spine MRI. The average age at screening was 12.3 years (range, 3 to 17 y). Screening was ordered consecutively on patients seen during the study period who were between ages 8 and 18 years or had complaints that could be related to encroaching intracanal exostoses.

Results:
The incidence of vertebral exostoses in this cohort of 39 patients with MHE was 28% (11 total). An encroaching intracanal exostosis was seen in 3 patients (2 cervical, 1 thoracic). Nonencroaching vertebral exostoses were discovered in 8 patients. Sufficient pelvis and rib imaging to determine the presence of pelvis and rib exostoses was available in 8 of those with vertebral exostoses and 19 of those with no vertebral exostoses on screening MRI. In this cohort, the sensitivity and specificity of the presence of both pelvis and rib exostoses for determining the presence of spinal involvement in MHE are 88% and 5%, respectively.

Conclusions:
Based on the results of this cohort, vertebral exostoses are common in MHE, and screening MRI of the entire spine can be used to determine which patients need close observation. If a more selective screening protocol is utilized, an entire spine MRI could be obtained for patients who desire increased physical activity levels or for patients with both pelvis and rib exostoses. At a minimum, treating physicians should monitor patients with MHE closely for neurological symptoms and have a low threshold to obtain advanced spinal imaging.

Level of Evidence:
Level III—diagnostic.
A Novel Nomogram for Survival Prediction of Patients with Spinal Metastasis From Prostate Cancer
Authors: Liu Yujie , Li Lin , Jiang Dongjie , Yang Minglei , Gao Xin , Lv Kai , Xu Wei , Wei Haifeng , Wan Wei , Xiao Jianru 
Published: January 2021

Study Design.
A retrospective study of 84 patients with spinal metastasis from prostate cancer (SMPCa) was performed.

Objective.
The aim of this study was to predict the survival of patients with SMPCa by establishing an effective prognostic nomogram model, associating with the affecting factors and compare its efficacy with the existing scoring models.

Summary of Background Data.
Prostate cancer (PCa) is the second most frequently malignant cancer causing death in men, and the spine is the most common site of bone metastatic burden. The aim of this study was to establish a prognostic nomogram for survival prediction of patients with SMPCa, explore associated factors, and compare the effectiveness of the new nomogram prediction model with the existing scoring systems.

Methods.
Included in this study were 84 SMPCa patients who were admitted in our spinal tumor center between 2006 and 2018. Their clinical data were retrospectively analyzed by univariate and multivariate analyses to identify independent variables that enabled to predict prognosis. A nomogram, named Changzheng Nomogram for Survival Prediction (CNSP), was established on the basis of preoperative independent variables, and then subjected to bootstrap re-samples for internal validation. The predictive accuracy and discriminative ability were measured by concordance index (C-index). Receiver-operating characteristic (ROC) analysis with the corresponding area under the ROC was used to estimate the prediction efficacy of CNSP and compare it with the four existing prognostic models Tomita, Tokuhashi, Bauer, and Crnalic.

Results.
A total of seven independent variables including Gleason score (P = 0.001), hormone refractory (P < 0.001), visceral metastasis (P < 0.001), lymphocyte to monocyte ratio (P = 0.009), prostate-specific antigen (P = 0.018), fPSA/tPSA (P = 0.029), Karnofsky Performance Status (P = 0.039) were identified after accurate analysis, and then entered the nomogram with the C-index of 0.87 (95% confidence interval, 0.84–0.90). The calibration curves for probability of 12-, 24-, and 36-month overall survival (OS) showed good consistency between the predictive risk and the actual risk. Compared with the previous prognostic models, the CNSP model was significantly more effective than the four existing prognostic models in predicting OS of the SMPCa patients (p < 0.05).

Conclusion.
The overall performance of the CNSP model was satisfactory and could be used to estimate the survival outcome of individual patients more precisely and thus help clinicians design more specific and individualized therapeutic regimens.

Level of Evidence: 4
Accuracy and Reliability of Standing Lateral Lumbar Radiographs for Measurements of Spinopelvic Parameters
Authors: Wu Jingye , Wei Feng , Ma Lin , Li Jianing , Zhang Ning , Tian Wei , Sun Yuqing 
Published: January 2021

Study Design.
Retrospective observational study.

Objective.
To assess the accuracy and reliability of standing lateral lumbar radiographs for measurements of spinopelvic parameters, compared with whole-spine EOS® images.

Summary of Background Data.
Lateral lumbar radiographs are commonly used for measurements of spinopelvic parameters. However, variable magnifications by fan-beam x-ray projection at margins may cause measurement errors.

Methods.
Fifty consecutive patients with standing lateral lumbar radiographs and whole-spine EOS® images were retrospectively reviewed from March to July in 2019. Two orthopedic surgeons (observers) independently measured the spinopelvic parameters including pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), and lumbar lordosis (LL) on the computers. These spinopelvic parameters of each patient were measured twice on both lateral lumbar radiograph and EOS® image by two observers with the usage of Surgimap software. The measurement difference and agreement of each parameter value between lateral lumbar radiographs and EOS® images were analyzed by paired t test and the interclass correlation coefficient (ICC) respectively. Intra- and inter-observer's reliabilities of both imaging methods were assessed by ICC.

Results.
The measurement difference of each spinopelvic parameter on EOS® images and lateral lumbar radiographs was less than 1° on average. Only the measurement difference of PI value revealed statistically significant (P = 0.020) with 0.9° discrepancy (95% confidential interval: 0.2–1.6), which indicated no clinical significance. The ICC values of lateral lumbar radiographs and EOS® images were more than 0.870 (range, 0.872–0.976), thus showed good to excellent measurement agreement between both imaging methods. All the ICC values for evaluating intra- and inter-observer reliability were greater than 0.960 (range, 0.963–0.993), indicating excellent reliability for observer's measurements.

Conclusion.
Measurements of spinopelvic parameters (PI, PT, SS, and LL) on standing lateral lumbar radiographs are accurate and reliable, which are comparable to whole-spine EOS® images.

Level of Evidence: 3
Anticoagulation in Elective Spine Cases
Authors: Thota Dharani Rohit , Bagley Carlos A. , Tamimi Mazin Al , Nakonezny Paul A. , Van Hal Michael 
Published: January 2021

Study Design
Retrospective cohort study with propensity matched cohorts.

Objective
The purpose of this study was to evaluate the association of anticoagulation with VTE and hematoma complications after spine surgery.

Summary of Background Data
One of the major complications of surgery is VTE which can range in presentation. Spine surgery is an especially complex balance between minimizing the risk of a VTE event and also the increased risk of a hematoma which can lead to devastating neurological outcomes.

Methods
The elective spine surgery cases at a single academic center between 2015 and 2017 were identified. A total of 3790 patients were initially identified. Two hundred sixty patients were excluded. The cohort was then matched using a propensity score. This matched a single patient who did not receive anticoagulation to a single patient who did within the institution. This left a total of 1776 patients with 888 patients in each arm.

Results
The incidence of VTE, PE, and unplanned reoperation for hematoma in this cohort was 0.96%, 0.34%, and 1.13%, respectively. Predicted odds of VTE and PE were not significantly different; however, the odds of an unplanned reoperation for hematoma (odds ratio [OR] = 7.535, 95% confidence interval [CI]: 2.004–28.340, P = 0.002) were greater for those who received pharmacological anticoagulation in our institutional cohort.

Conclusion
In this study, anticoagulation does not lead to lower rates of VTE events, but it increases the risk of symptomatic hematomas which require a return trip to the OR. While this was not a randomized controlled trial, we attempted to correct for this with propensity matching. Future randomized control trials would be needed.

Level of Evidence: 3
Predictive Factors Affecting Surgical Outcomes in Patients with Degenerative Lumbar Spondylolisthesis
Authors: Inose Hiroyuki , Kato Tsuyoshi , Onuma Hiroaki , Morishita Shingo , Matsukura Yu , Yuasa Masato , Hirai Takashi , Yoshii Toshitaka , Okawa Atsushi 
Published: January 2021

Study Design.

Post-hoc analysis of 5-year follow-up data from a prospective randomized multicenter trial.

Objective.
The purpose of this study was to identify preoperative factors that predict poor postoperative outcomes and define clinically important abnormal instabilities in degenerative lumbar spondylolisthesis.

Summary of Background Data.
Current evidence regarding prognostic factors affecting clinical outcomes after surgery for degenerative lumbar spondylolisthesis is still limited. Moreover, there is no consensus regarding parameters that define clinically important abnormal instability in patients with degenerative lumbar spondylolisthesis.

Methods.
This post-hoc analysis from a prospective randomized trial that compared the effectiveness of decompression, decompression with fusion, and decompression with stabilization for degenerative lumbar spondylolisthesis at the L4/5 level included 70 patients with a 5-year follow-up period. We investigated the correlation between the postoperative recovery rate and preoperative radiographic parameters. We then investigated differences between the good recovery and poor recovery groups.

Results.
Japanese Orthopaedic Association and visual analogue scale scores improved postoperatively. Of the 70 patients analyzed, 13 were judged to be in the poor recovery group based on their recovery rate. The recovery rate significantly correlated with the intervertebral angle at L4/5. Univariate analysis showed that while the degree of vertebral slippage and the presence of angulation were not associated with poor recovery, the intervertebral angle at L4/5 and the presence of translation were associated with poor recovery. Lastly, multiple stepwise logistic regression analysis revealed the intervertebral angle at L4/5 and the presence of translation as independent predictors of poor recovery after surgery for lumbar degenerative spondylolisthesis.

Conclusion.
While the degree of vertebral slippage and the presence of angulation were not associated with poor recovery after surgery for lumbar degenerative spondylolisthesis, postoperative outcomes were associated with the intervertebral angle and the presence of translation. Careful preoperative measurement of these factors may help to predict poor postoperative outcomes.

Level of Evidence: 3
Improving Outcomes for Children Requiring Extracorporeal Membrane Oxygenation Therapy Following Hematopoietic Stem Cell Transplantation
Authors: Olson Taylor L. , O’Neil Erika R. , Kurtz Kristen J. , MacLaren Graeme , Anders Marc M. 
Published: January 2021

OBJECTIVES:
The objective of this study was to provide an updated review of survival for pediatric hematopoietic stem cell transplantation patients requiring extracorporeal membrane oxygenation therapy as well as characterize the demographics, clinical variables, and complications associated with mortality.

DESIGN:
Retrospective database review of the Extracorporeal Life Support Organization Registry from 1990 to 2019.

SETTING:
Extracorporeal membrane oxygenation centers reporting to Extracorporeal Life Support Organization.

PATIENTS:
Patients treated with extracorporeal membrane oxygenation greater than 28 days to 18 years old with International Classification of Diseases Ninth Revision, International Classification of Diseases Tenth Revision, and current procedural terminology codes consistent with hematopoietic stem cell transplantation were included.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Demographics, year of extracorporeal membrane oxygenation run, clinical variables, comorbid diagnoses, and extracorporeal membrane oxygenation complications were assessed in relation to the primary study outcome of survival to hospital discharge. Ninety patients were included in the final analysis. The overall survival rate for the study period was 19%. However, the survival rate in the last decade (2010–2019) improved to 26% (p = 0.01; odds ratio 9.4 [1.2–74.8]). Factors associated with decreased survival included comorbid malignancy, elevated peak inspiratory pressure in conventionally ventilated patients, and pulmonary and metabolic complications on extracorporeal membrane oxygenation.

CONCLUSIONS:
Pediatric patients posthematopoietic stem cell transplantation supported with extracorporeal membrane oxygenation have improving survival rates over time. With 26% of patients (16/62) surviving to hospital discharge in the last decade (2010–2019), history of hematopoietic stem cell transplantation may no longer be considered an absolute contraindication to extracorporeal membrane oxygenation. As advancements are made in hematopoietic stem cell transplantation therapies and extracorporeal membrane oxygenation management, the indications for life-saving extracorporeal membrane oxygenation support among patients posthematopoietic stem cell transplantation may expand accordingly.
Viral strategies for circumventing p53: the case of severe acute respiratory syndrome coronavirus
Authors: Cardozo Camila Martin , Hainaut Pierre 
Published: January 2021

Purpose of review
Virtually all viruses have evolved molecular instruments to circumvent cell mechanisms that may hamper their replication, dissemination, or persistence. Among these is p53, a key gatekeeper for cell division and survival that also regulates innate immune responses. This review summarizes the strategies used by different viruses and discusses the mechanisms deployed by SARS-CoV to target p53 activities.

Recent findings
We propose a typology for the strategies used by different viruses to address p53 functions: hit and run (e.g. IAV, ZIKV), hide and seek (e.g. HIV1), kidnap and exploit (e.g. EBV, HSV1), dominate and suppress (e.g. HR HPV). We discuss the mechanisms by which SARS nsp3 protein targets p53 for degradation and we speculate on the significance for Covid-19 pathogenesis and risk of cancer.

Summary
p53 may operate as an intracellular antiviral defense mechanism. To circumvent it, SARS viruses adopt a kidnap and exploit strategy also shared by several viruses with transforming potential. This raises the question of whether SARS infections may make cells permissive to oncogenic DNA damage.
Content Evaluation of Integrated Plastic Surgery Residency Program Websites Regarding Sub-internships
Authors: Dayani Fara , Rahgozar Paymon 
Published: January 2021

Background:
Sub-internships are an integral part of the residency application process for competitive specialties, including plastic and reconstructive surgery (PRS). This study evaluates the quality of online information regarding sub-internships offered by PRS programs.

Methods:
All the US integrated PRS residency programs were identified on Fellowship and Residency Electronic Interactive Database. Each program’s website was assessed for the presence of 4 criteria: mention of a sub-internship offered, contact information of rotation coordinator, learning objectives, and a web page dedicated solely to the sub-internship. Each residency program was assigned a website sub-internship (WSI) score from 0 to 4 accordingly.

Results:
We identified 81 residency programs. Fifty-two residency program received a score of 0, and 6 programs received a score of 4. The mean WSI score was 1.0 for community-based programs, compared with 0.98 for university-based programs (P = 0.93). There was a correlation between WSI score and number of faculty (r = 0.52; P < 0.0000) and number of residents per year (r = 0.34; P = 0.002). In logistic regression model, number of faculty [odds ratio (OR), 1.18; P = 0.003], large program size (OR, 12.1; P = 0.009), and southeast location (OR, 30.3; P = 0.034) were found to be important predictors for PRS programs to mention at least one criterion.

Conclusions:
A majority of the programs did not have any online information available on their websites regarding plastic surgery sub-internships. There is no difference between academic and community-based programs with regard to the quality of information. Programs with more trainees and faculty have higher odds of providing information about sub-internships offered at their institution.
Globalization of Plastic and Reconstructive Surgery: A Continent, Country, and State-Level Analysis of Publications
Authors: Liechty Andrew E. , Sherpa James R. , Trejo Jonathan S. , French Mackenzie M. , Kneib Cameron J. , Cho Daniel Y. , Friedrich Jeffrey B. 
Published: January 2021

Background:
Over the past decade, there has been a worldwide increase in plastic and reconstructive surgery research as well as increased interest in global collaboration. However, little is known about who is contributing to this global expansion or the trends of individual countries. The aim of our study was to analyze the output of Plastic and Reconstructive Surgery (PRS) over a decade to elucidate trends in the plastic surgery field.

Methods:
The country of origin for all first authors of articles published by PRS from 2010 to 2019 were determined and date extracted using PubMed2XL. The change in frequency of publications over the decade by country, continental contributions, as well as state-level analysis within the United States were analyzed.

Results:
From 2010 to 2019, there were a total number of 8680 publications with an increase in total articles from 747 to 1049 per year. 54 countries contributed over the decade, with the United States producing the most followed by Italy, China, Canada, and the UK. The top producing states were Texas, New York, California, Massachusetts, and Pennsylvania.

Conclusions:
The last decade (2010–2019) saw a large international increase in research, not only with the total number of publications, but also in the diversity of originating country. Our work shows a shift away from a US-focused journal to incorporate more work from our international colleagues, as research is conducted in centers across the globe.