bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Patients' Perspective of Important Glucocorticoid Effects
Authors: Mirza Serene Z. , Cheah Jonathan T. L. , Ghosh Nilasha , Robson Joanna C. , Hill Catherine L. , Singh Jasvinder , Mackie Sarah L. , Navarro-Millán Iris , Simon Lee S. , Goodman Susan M. 
Published: January 2020

Background/Objective
The objective of this cohort study was to understand the positive and negative effects of glucocorticoids (GCs) in patients with systemic lupus erythematosus and myositis from the patients' perspective with the aim of developing a patient-reported outcome measure.

Methods
Included patients were asked to participate in 1 of 5 nominal groups where demographic information and a quality-of-life questionnaire were collected. Patients were asked 2 open-ended questions on (1) benefits and (2) harms related to GC use. We used the Nominal Group Technique, a highly structured consensus method in which responses are generated, shared, and ranked. Descriptive statistics were used to summarize the results. Nominal group sessions took place from April to May 2019.

Results
Of 206 patients who were approached, 21 patients participated, 17 with systemic lupus erythematosus and 4 with myositis, predominantly women with more than 10 years of steroid use. The domains ranked highest for GC benefits were disease control (55 votes), fast onset of action (30 votes), increased energy (10 votes), and pain relief (10 votes). The highest-ranked negative effects were bone loss (38 votes) and weight gain (16 votes); psychological effects and damaged internal organs each received 12 votes.

Conclusions
The top-ranked GC effects—both benefits and harms—among patients with systemic rheumatic disease are consistent with the top domains associated with GC use reported with other inflammatory diseases. This study informs the development of a comprehensive patient-reported outcome measure that can be used across inflammatory diseases.
Ultrasound Time-Harmonic Elastography of the Pancreas
Authors: Burkhardt Christian , Tzschätzsch Heiko , Schmuck Rosa , Bahra Marcus , Jürgensen Christian , Pelzer Uwe , Hamm Bernd , Braun Jürgen , Sack Ingolf , Marticorena Garcia Stephan Rodrigo 
Published: January 2020

Objectives
Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive tumor with a very low 5-year survival rate of 8%. The aims of this study are to determine reference values and physiologic confounders in healthy pancreas and to assess the diagnostic accuracy of ultrasound time-harmonic elastography (THE) in the detection of PDAC.

Materials and Methods
From March 2017 through May 2019, a total of 54 study participants with healthy pancreas (n = 33, CTR) or PDAC (n = 21) were prospectively enrolled. Repeatability of THE was tested in a CTR subgroup (n = 5) undergoing repeat measurement on 4 different days. Interobserver variability was analyzed in 10 healthy volunteers. Age-matched and sex-matched subgroups of CTR (n = 13) and PDAC (n = 13) were compared. In participants with histopathologically proven PDAC, measurements were performed separately in tumorous (PDAC-T) and nontumorous pancreatic tissue (PDAC-NT). Diagnostic performance of pancreatic THE was assessed by receiver operating characteristic curve analysis.

Results
Time-harmonic elastography was highly repeatable (intraclass correlation coefficient, 0.99), and interobserver agreement was excellent (intraclass correlation coefficient, 0.97). Shear wave speed (SWS) of PDAC-T (mean [95% confidence interval] in meters per second, 1.88 ± 0.07 [1.84–1.92]) was higher than SWS of CTR (1.63 ± 0.04 [1.60–1.66], P < 0.001) and PDAC-NT (1.59 ± 0.03 [1.57–1.61], P < 0.001). The exploratory diagnostic performance of THE in separating PDAC-T was excellent (area under the receiver operating characteristic curve, 1.0). Tumorous pancreatic ductal adenocarcinoma was distinguished from CTR and PDAC-NT with cutoff values of 1.73 m/s and 1.70 m/s, respectively.

Conclusions
Pancreatic ultrasound THE has high repeatability and provides excellent imaging contrast based on SWS, allowing detection of PDAC without overlap to nontumorous pancreatic tissue.
Treatment Strategy for Radical Resection of Giant Neurofibroma
Authors: Liu Fei , Din Feixue , Gu Chuan , Lv Lin , Wang Xiuxia , Luo Xusong , Sun Di , Yang Jun 
Published: January 2020

Abstract
The management of giant neurofibroma is a challenge for clinical surgeons. Abundant malformed vessels exist in the tumor, and life-threatening hemorrhage can occur during operation. Moreover, repairing huge defects after radical resection is challenging. Hence, subtotal resection and debulking are more frequently performed than total resection. Although subtotal resection or debulking may reduce morbidity, it inevitably leads to a high rate of recurrence. In addition, subtotal resection or debulking does not decrease surgical risk; on the contrary, when operating on the tumor body, the rate of hemorrhage is much higher in case of subtotal resection and debulking than in radical resection. In this study, 9 patients with giant neurofibroma were retrospectively reviewed. The tumor size ranged from 12 × 9 cm to 60 × 70 cm. Preoperative angiography and magnetic resonance imaging scanning are performed to clarify the tumor features. All patients underwent radical resection, and in-operation blood loss ranged from 300 to 2600 mL. The resection defects were repaired by anterolateral thigh free flap in 2 patients and skin grafts in 7 patients. Partial skin necrosis occurred in 4 patients, and the necrosis area can be repaired with adjacent survived skin by changing the dressing several times. No tumor recurrence was recorded during routine follow-up (range, 12–39 months). The treatment strategy for radical resection of giant neurofibroma proves effective, and the technique of reusing the skin provides sufficient material for covering a large defect without the morbidity associated with a new donor. Thus, tumor removal and wound repair can be accomplished in one stage.
Vocal Cord Paralysis as a Complication of Endotracheal Intubation
Authors: Evman Melis Demirag , Selcuk Ayse Adin 
Published: January 2020

Abstract
Endotracheal intubation is a commonly used method for securing airway. It is considered to be safe but it can still lead to some complications of the airway. Recurrent nerve paralysis due to endotracheal intubation is a rare complication. Pathophysiology is explained as neuropraxia of RLN's compression between the tube and the lamina of the thyroid cartilage or between arytenoid and cricoid cartilages due to tube cuff pressure or tube itself. In literature, unilateral vocal cord paralysis (VCP) due to intubation is more common than bilateral paralysis. In the presented case report, a young patient stayed intubated for only 3 days in intensive care unit who experienced bilateral VCP 2 days after extubation. He had total recovery 5 days after emergency tracheotomy suggesting neuropraxia of the nerve. Neuropraxia of RLN resulting in bilateral VCP due to inappropriate size or excess cuff pressure of the intubation tube may be the underlying reasons. The clinicians must be aware of complications of intubation and should apply appropriate treatment method as soon as possible. Appropriate size and cuff pressure should be chosen for endotracheal intubation.
Identification and Recent Approaches for Evaluation and Management of Dentofacial and Otolaryngologic Concerns for Patients With Freeman-Burian Syndrome: Principles for Global Treatment
Authors: Poling Mikaela I. , Dufresne Craig R. 
Published: January 2020

Abstract
Freeman-Burian syndrome (FBS), formerly Freeman-Sheldon syndrome, is a complex myopathic craniofacial syndrome. Functional craniofacial deformities resulting in respiratory, eating, auditory, or speech impairments often are present to varying degrees in this unique population. There are few references in the literature addressing diagnosis, evaluation, operative counseling, and craniofacial management of FBS, and guidance was absent. As part of a clinical practice guideline development process for FBS, the authors have reviewed dental and oral health concerns, hearing loss, paranasal sinusitis, dysphagia, and dysphasia management for patients with FBS. Searching PubMed and Google Scholar has yielded 14 results describing dentofacial and otorhinolaryngologic concerns in FBS. There is a significant paucity of scholarship on FBS, presenting considerable knowledge gaps. Craniofacial muscles may be preferentially impacted by fibrous tissue replacement. The lack of available objective data should not reduce clinical vigilance to the possibility that fibrous tissue replacement may influence almost any aspect of the patient's presentation, thus necessitating nonstandard treatment deviations. Based on the decades of experience with this challenging patient population, the authors feel much can be done to afford patients with FBS a good and productive quality of life through exquisite medical surveillance, rapid intervention in acute upper respiratory disturbances, conservative operative intervention, and longitudinal lifestyle structuring by the patients.
Educational Resources in Craniofacial Surgery: The Case for User-Friendly Digital Simulators
Authors: Kantar Rami S. , Alfonso Allyson R. , Ramly Elie P. , Diaz-Siso J. Rodrigo , Flores Roberto L. 
Published: January 2020

Introduction:
Digital simulators are potential solutions to challenges facing surgical education. The authors sought to evaluate the reach and utilization of a freely-accessible craniofacial surgery digital educational simulator. More importantly, we compare usage patterns between web-based and mobile-based platforms.

Methods:
A 3-way collaboration between academic, non-profit (myFace, New York, NY), and biotechnology (Biodigital, New York, NY) stakeholders in 2015 produced the Craniofacial Interactive Virtual Assistant Pro (CIVA-Pro). CIVA-Pro is a freely-accessible craniofacial surgery digital educational simulator. In addition to the web-based platform, a mobile-based platform was launched in 2017. Usage analytics were collected and analyzed.

Results:
Since its launch, 751 registered users from 117 countries had accessed CIVA-Pro. The total number of sessions was 9531, including 7500 web and 2031 mobile sessions. The total screen time was 403.9 hours, 290.3 for the web and 113.6 for the mobile platform. Comparison of the mean monthly screen time and number of monthly sessions between platforms since 2017 demonstrated a significantly higher mean monthly screen time (60.1 ± 33.2 versus 29.4 ± 16.5 hours; P = 0.002) and number of sessions (110.2 ± 36.1 versus 58.1 ± 31.9; P < 0.0001) for the mobile-based platform. The mean screen time per session was comparable (P = 0.86).

Conclusion:
A freely available digital craniofacial surgery educational simulator designed for surgical trainees can achieve significant global reach. Significantly higher utilization of the mobile-based platform of the simulator as compared to the web-based platform reinforces the need to invest in user-friendly, easily accessible, and widely available digital educational resources by key stakeholders to ensure optimal plastic surgery trainee education.
BK Polyomavirus-specific T Cells as a Diagnostic and Prognostic Marker for BK Polyomavirus Infections After Pediatric Kidney Transplantation
Authors: Ahlenstiel-Grunow Thurid , Sester Martina , Sester Urban , Hirsch Hans H. , Pape Lars 
Published: January 2020

Background.
After kidney transplantation, uncontrolled BK polyomavirus (BKPyV) replication causes kidney graft failure through BKPyV-associated nephropathy (BKPyVAN), but markers predicting outcome are missing. BKPyV-specific T cells may serve as a predictive marker to identify patients at risk of persistent DNAemia and BKPyVAN.

Methods.
Out of a total of 114 pediatric kidney recipients transplanted between 2008 and 2018, 36 children with posttransplant BKPyV-DNAemia were identified. In a prospective noninterventional study, BKPyV-specific CD4 and CD8 T cells were measured in 32 of 36 viremic pediatric kidney recipients using intracellular cytokine staining and flow cytometry. The course of the BKPyV replication was monitored with regard to duration of BKPyV-DNAemia and need of therapeutic intervention and diagnosis of proven BKPyVAN.

Results.
Levels of BKPyV-specific T cells negatively correlated with subsequent duration of BKPyV-DNAemia. Patients with BKPyV-specific CD4 T cells ≥0.5 cells/µL and/or BKPyV-specific CD8 T cells ≥0.1 cells/µL had transient, self-limiting DNAemia (PPV 1.0, NPV 0.86). BKPyV-specific CD4 and CD8 T cells below these thresholds were found in children with persistent BKPyV-DNAemia and biopsy-proven BKPyVAN with need for therapeutic intervention. After reducing immunosuppressive therapy, levels of BKPyV-specific CD4 T cells increased while plasma BKPyV-DNAemia declined.

Conclusions.
This study found that BKPyV-specific T cell levels may help to distinguish patients with transient, self-limiting BKPyV-DNAemia from those with persisting BKPyV-DNAemia and biopsy-proven BKPyVAN, who would benefit from individualized therapeutic interventions such as reduced immunosuppression. Thereby the risk for rejection because of unnecessary reduction of immunosuppression in case of self-limiting BKPyV-DNAemia can be minimized.
Azithromycin Partially Mitigates Dysregulated Repair of Lung Allograft Small Airway Epithelium
Authors: Ling Kak-Ming , Garratt Luke W. , Banerjee Balarka , Lavender Melanie A. , Wrobel Jeremy P. , Musk Michael , Martinovich Kelly M. , Shaw Nicole C. , Iosifidis Thomas , Looi Kevin , Kicic-Starcevich Elizabeth , Sutanto Erika N. , Yerkovich Stephanie T. , Chambers Daniel C. , Stick Stephen M. , Kicic Anthony 
Published: January 2020

Background.
Dysregulated airway epithelial repair following injury is a proposed mechanism driving posttransplant bronchiolitis obliterans (BO), and its clinical correlate bronchiolitis obliterans syndrome (BOS). This study compared gene and cellular characteristics of injury and repair in large (LAEC) and small (SAEC) airway epithelial cells of transplant patients.

Methods.
Subjects were recruited at the time of routine bronchoscopy posttransplantation and included patients with and without BOS. Airway epithelial cells were obtained from bronchial and bronchiolar brushing performed under radiological guidance from these patients. In addition, bronchial brushings were also obtained from healthy control subjects comprising of adolescents admitted for elective surgery for nonrespiratory-related conditions. Primary cultures were established, monolayers wounded, and repair assessed (±) azithromycin (1 µg/mL). In addition, proliferative capacity as well as markers of injury and dysregulated repair were also assessed.

Results.
SAEC had a significantly dysregulated repair process postinjury, despite having a higher proliferative capacity than large airway epithelial cells. Addition of azithromycin significantly induced repair in these cells; however, full restitution was not achieved. Expression of several genes associated with epithelial barrier repair (matrix metalloproteinase 7, matrix metalloproteinase 3, the integrins β6 and β8, and β-catenin) were significantly different in epithelial cells obtained from patients with BOS compared to transplant patients without BOS and controls, suggesting an intrinsic defect.

Conclusions.
Chronic airway injury and dysregulated repair programs are evident in airway epithelium obtained from patients with BOS, particularly with SAEC. We also show that azithromycin partially mitigates this pathology.
Trophic rewilding presents regionally specific opportunities for mitigating climate change
Authors: Sandom Christopher J. , Middleton Owen , Lundgren Erick , Rowan John , Schowanek Simon D. , Svenning Jens-Christian , Faurby Søren 
Published: January 2020

Large-bodied mammalian herbivores can influence processes that exacerbate or mitigate climate change. Herbivore impacts are, in turn, influenced by predators that place top-down forcing on prey species within a given body size range. Here, we explore how the functional composition of terrestrial large-herbivore and -carnivore guilds varies between three mammal distribution scenarios: Present-Natural, Current-Day and Extant-Native Trophic (ENT) Rewilding. Considering the effects of herbivore species weakly influenced by top-down forcing, we quantify the relative influence keystone large-herbivore guilds have on methane emissions, woody vegetation expansion, fire dynamics, large-seed dispersal, and nitrogen and phosphorus transport potential. We find strong regional differences in the number of herbivores under weak top-down regulation between our three scenarios, with important implications for how they will influence climate change relevant processes. Under the Present-Natural non-ruminant, megaherbivore, browsers were a particularly important guild across much of the world. Megaherbivore extinction and range contraction and the arrival of livestock mean large, ruminant, grazers have become more dominant. ENT Rewilding can restore the Afrotropics and the Indo-Malay realm to the Present-Natural benchmark, but causes top-down forcing of the largest herbivores to become commonplace elsewhere. ENT Rewilding will reduce methane emissions, but does not maximize natural climate solution potential.
This article is part of the theme issue ‘Climate change and ecosystems: threats, opportunities and solutions'.
Integrated single cell analysis of human lung fibrosis resolves cellular origins of predictive protein signatures in body fluids
Authors: Mayr Christoph H. , Simon Lukas M. , Leuschner Gabriela , Ansari Meshal , Geyer Philipp E. , Angelidis Ilias , Strunz Maximilian , Singh Pawandeep , Kneidinger Nikolaus , Reichenberger Frank , Silbernagel Edith , Böhm Stephan , Adler Heiko , Hilgendorff Anne , Lindner Michael , Prasse Antje , Behr Jürgen , Mann Matthias , Eickelberg Oliver , Theis Fabian J. , Schiller Herbert B. 
Published: January 2020

AbstractSingle cell genomics enables characterization of disease specific cell states, while improvements in mass spectrometry workflows bring the clinical use of body fluid proteomics within reach. The correspondence of cell state changes in diseased organs to peripheral protein signatures is currently unknown. Here, we leverage single cell RNA-seq and proteomic analysis of large pulmonary fibrosis patient cohorts to identify disease specific changes on the cellular level and their corresponding reflection in body fluid proteomes. We discovered and validated transcriptional changes in 45 cell types across three patient cohorts that translated into distinct changes in the bronchoalveolar lavage fluid and plasma proteome. These protein signatures correlated with diagnosis, lung function, smoking and injury status. Specifically, the altered expression of a novel marker of lung health, CRTAC1, in alveolar epithelium is robustly reflected in patient plasma. Our findings have direct implications for future non-invasive prediction and monitoring of pathological cell state changes in patient organs.Abstract Figure
Healthcare Cost of Stargardt Disease
Authors: Aziz Kanza , Swenor Bonnielin K. , Canner Joseph K. , Singh Mandeep S. 
Published: January 2020

AbstractImportanceStargardt disease (SD) is the most common juvenile macular degeneration and a leading cause of uncorrectable childhood blindness. The progressive and incurable nature of this chronic condition entails a long-term financial burden on affected individuals. The economic costs of SD have not been characterized in detail.ObjectiveTo estimate the direct healthcare cost of SD.DesignCross-sectional analysis of healthcare claims.ParticipantsPatients with an ICD-9 diagnosis code of SD, non-exudative age-related macular degeneration (AMD), or bilateral sensorineural hearing loss (SHL).MethodsOutpatient administrative claims data from the IBM® MarketScan® Commercial Claims and Encounters Database from 2010 to 2014 were analyzed.Main Outcome MeasureAnnual per-patient direct healthcare cost.ResultsA total of 472,428 patients were analyzed (5,015 SD, 369,750 SHL and 97,663 AMD patients respectively). The payment per year of insurance coverage for SD (median: $105.58, IQR: $50.53-$218.71) was higher than that of SHL (median: $51.01, IQR: $25.66-$121.66, p <0.001) and AMD (median: $76.20, IQR: $38.00-$164.86, p <0.001). When adjusted for covariates, the annual payment for SD was $47.83 higher than SHL (p<0.001) and $17.34 higher than AMD (p<0.001).Conclusions and RelevanceThere is a significant direct healthcare cost associated with SD. The annual per-patient cost of SD was higher than SHL, another condition that causes sensory impairment in people of all ages, and nonexudative AMD which causes a similar pattern of visual loss that typically begins later in life. The total lifetime per-patient cost of SD may exceed that of nonexudative AMD.
Genome-wide meta-analysis, fine-mapping, and integrative prioritization identify new Alzheimer’s disease risk genes
Authors: Schwartzentruber Jeremy , Cooper Sarah , Liu Jimmy Z , Barrio-Hernandez Inigo , Bello Erica , Kumasaka Natsuhiko , Johnson Toby , Estrada Karol , Gaffney Daniel J. , Beltrao Pedro , Bassett Andrew 
Published: January 2020

AbstractGenome-wide association studies (GWAS) have discovered numerous genomic loci associated with Alzheimer’s disease (AD), yet the causal genes and variants remain incompletely identified. We performed an updated genome-wide AD meta-analysis, which identified 37 risk loci, including novel associations near genes CCDC6, TSPAN14, NCK2, and SPRED2. Using three SNP-level fine-mapping methods, we identified 21 SNPs with greater than 50% probability each of being causally involved in AD risk, and others strongly suggested by functional annotation. We followed this with colocalisation analyses across 109 gene expression quantitative trait loci (eQTL) datasets, and prioritization of genes using protein interaction networks and tissue-specific expression. Combining this information into a quantitative score, we find that evidence converges on likely causal genes, including the above four genes, and those at previously discovered AD loci including BIN1, APH1B, PTK2B, PILRA, and CASS4.