bluuebunny/crossref_metadata_2025_split huggingface dataset:
Performance of Endobronchial Ultrasound Elastography in the Differentiation of Malignant and Benign Mediastinal Lymph Nodes
Authors: Fournier Clément , Dhalluin Xavier , Wallyn Frederic , Machuron François , Bouchindhomme Brigitte , Copin Marie C. , Valentin Victor 
Published: October 2018

Background:
Little data exists regarding the performance of elastography in EBUS-TBNA. The aim of the study was to evaluate the elastography score proposed and previously published by Izumo, in particular its capacity to perfectly identify benign lymph node, and to discriminate malignant ones.

Methods:
This study included patients undergoing EBUS-TBNA for mediastinal lymph nodes (LN). Before LN needle aspiration, an elastography was performed which allowed a color elastogram to be superimposed on the ultrasound image. Three blinded assessors classified these elastograms into 3 types using the score published by Izumo: type 1 (predominantly not blue), type 2 (partially blue, partially not blue), or type 3 (predominantly blue). These types were then compared with pathology results.

Results:
A total of 217 LN (114 patients) were analyzed: histologic findings identified 97 benign LN (44.7% of the lymph nodes) and 120 malignant LN (55.3%). There were 44 elastographies (20.2%) that were classified as type 1, 90 elastographies (41.5%) classified as type 2, and 83 elastographies (38.3%) classified as type 3. Considering type 1 as benign and type 3 as malignant, sensitivity, specificity, positive predictive value, and negative predictive value were respectively 87.0%, 68.0% , 80.0% , and 77.0%. Ten (23%) of the 44 lymph nodes with a type 1 elastogram were malignant.

Conclusion:
Elastography does not preclude performing TBNA of the lymph nodes. It does not preclude EBUS-TBNA when a type 1 elastogram pattern is found. All lymph nodes visualized should be sampled by EBUS-TBNA, regardless of elastography pattern.
Predictive Potential of Eyelids and Tear Film in Determining Symptoms in Contact Lens Wearers
Authors: Siddireddy Jaya Sowjanya , Tan Jacqueline , Vijay Ajay Kumar , Willcox Mark 
Published: October 2018

SIGNIFICANCE
Early diagnosis of clinical markers of contact lens discomfort can help clinicians set realistic expectations and monitor and provide prophylactic management for contact lens wearers.

PURPOSE
The purpose of this study was to evaluate the potential of eyelid- and tear film–related clinical markers to be used as predictive factors for diagnosing discomfort in contact lens wearers.

METHODS
A cross-sectional study was performed on 30 contact lens wearers (6 male, 24 female) with median age of 23 years (range, 18 to 41 years). Eyelid signs and tear film characteristics were evaluated during a single visit, and subjects completed the Contact Lens Dry Eye Questionnaire to evaluate ocular discomfort. Area under the curve (AUC) statistics and sensitivity and specificity values from receiver operating characteristic curves were analyzed to evaluate the predictive potential of clinical signs in discriminating symptoms of contact lens discomfort.

RESULTS
The presence of foam at meibomian gland orifices (AUC, 0.944; P < .05; sensitivity >0.7), meibomian gland secretion volume (AUC, 0.935; P < .05; sensitivity >0.7), quality (AUC, 0.969; P < .05; sensitivity >0.7), and expressibility (AUC, 0.933; P < .05; sensitivity >0.7) were significant and strong predictors of discomfort in lens wear. Tear evaporation rates with (AUC, 0.779; P < .05; sensitivity >0.7) or without contact lenses (AUC, 0.788; P < .05; sensitivity >0.7), palpebral conjunctival roughness (AUC, 0.859; P < .05; sensitivity >0.7), palpebral conjunctival staining (AUC, 0.817; P < .05; sensitivity >0.7), palpebral conjunctival hyperemia (AUC, 0.746; P < .05; sensitivity >0.7), meibomian gland orifice capping (AUC, 0.873; P < .05; sensitivity >0.7), pouting (AUC, 0.891; P < .05; sensitivity >0.7), and lid-parallel conjunctival folds (AUC, 0.770; P < .05; sensitivity >0.7) were other acceptable discriminators of symptoms of discomfort during contact lens wear. An equation was developed to identify symptomatic from asymptomatic lens wearers based on the significant predictors: Symptom discriminant function score = 3.378 (meibomian gland secretion grade) + 0.224 (meibomian gland morphology grade) + 0.61 (tear evaporation rate without contact lenses) + 0.439 (lid-parallel conjunctival folds grade) − 0.346 (palpebral conjunctival health grade) − 4.625.

CONCLUSIONS
This study demonstrated that clinical signs related to meibomian gland secretions and morphology, tear evaporation, lid-parallel conjunctival folds, and palpebral conjunctival health may successfully predict symptoms of discomfort in contact lens wearers.
Cornea Full-field Displacement and Strain Measurement in Vivo Using Three-dimensional Digital Image Correlation
Authors: Zhang Xueyong , Wang Qing , Wang Like , Xiao Hong , Zhang Daming , Liao Rongfeng , Zheng Yongping 
Published: October 2018

SIGNIFICANCE
Corneal biomechanics are becoming increasingly important for clinical evaluation and diagnosis, such as in refractive surgery, glaucoma, and keratoconus. We developed and used a new technique to measure the full-field displacement and strain of the cornea under elevated intraocular pressure in vivo.

PURPOSE
In this study, we propose a three-dimensional digital image correlation method for the determination of corneal biomechanical properties.

METHODS
Corneal deformation change on the rabbit eyeball was investigated under different inflation conditions with intraocular pressure levels of 2.3, 3.3, 5.3, and 6.9 kPa in vivo.

RESULTS
The proposed method was able to measure the displacement of the corneal surface and to construct real-time full-field three-dimensional deformation vector fields and strain mapping. The results show that the strain distribution is not uniform on the corneal surface at each intraocular pressure level. Compression strains, rather than extensile strains, are dominant at the corneal apex region.

CONCLUSIONS
This technique has the potential to be used as an assistive tool for the determination of corneal biomechanical properties in ophthalmologic investigations.
Case Report: Penetrating Corneal Injury Under an Intact Laser-assisted in Situ Keratomileusis Flap
Authors: Maki Sarah , Hou Joshua H. 
Published: October 2018

SIGNIFICANCE
As the prevalence of post–laser-assisted in situ keratomileusis (LASIK) patients rises, recognition of possible traumatic complications and their management in this population becomes increasingly relevant. Penetrating injuries and intraocular foreign bodies are possible in post-LASIK corneas despite an intact anterior corneal surface. However, with prompt recognition and treatment, excellent visual recovery can be achieved.

PURPOSE
The purpose of this study was to report an interesting case of a penetrating foreign body through an intact LASIK flap.

CASE REPORT
A 48-year-old man presented to an outside provider with right eye pain after his eye was struck by a tree branch. His ocular history was notable for uncomplicated LASIK surgery 4 years before presentation. On initial examination, the patient was diagnosed as having a small corneal abrasion and hyphema. Despite appropriate therapy, his eye continued to subjectively and objectively worsen. Follow-up examination after the injury was notable for a new dense hypopyon. Because of concern for secondary infection, the patient was referred urgently for further evaluation. Upon referral, the patient was noted to have a dense, fibrinous mass located inferiorly in the anterior chamber. Although the cornea was edematous temporally with deep folds, the anterior corneal surface appeared intact without evidence of laceration or flap displacement. Concern for endophthalmitis prompted anterior chamber washout, where a large vegetative foreign body was recovered despite an intact anterior corneal surface and LASIK. Post-operative anterior-segment optical coherence tomography after resolution of the corneal edema confirmed the presence of a well-aligned penetrating tract through the posterior stromal bed underneath the LASIK flap. Epithelial ingrowth that developed within the post-operative period further affirmed the initial tract of the penetrating foreign body.

CONCLUSIONS
This case illustrates a novel complication after trauma in a post-LASIK patient, describes possible management, and underscores the care that must be taken when assessing patients with a history of LASIK surgery.
No evidence of widespread mechanical pressure hyperalgesia after experimentally induced central sensitization through skin nociceptors
Authors: Cayrol Timothée , Pitance Laurent , Roussel Nathalie , Mouraux André , van den Broeke Emanuel N. 
Published: October 2018

Abstract

Introduction:
An increasing number of clinical studies involving a range of chronic pain conditions report widespread mechanical pressure pain hypersensitivity, which is commonly interpreted as resulting from central sensitization (CS). Secondary hyperalgesia (increased pinprick sensitivity surrounding the site of injury) is considered to be a manifestation of CS. However, it has not been rigorously tested whether CS induced by peripheral nociceptive input involves widespread mechanical pressure pain hypersensitivity.

Objectives:
The aim of this study was to assess whether high-frequency electrical stimulation (HFS), which induces a robust secondary hyperalgesia, also induces a widespread decrease of pressure pain thresholds (PPTs).

Methods:
We measured PPTs bilaterally on the temples (temporalis muscles), on the legs (tibialis anterior muscles), and on the ventral forearm (flexor carpi radialis muscles) before, 20 minutes after, and 45 minutes after applying HFS on the ventral forearm of sixteen healthy young volunteers. To evaluate the presence of secondary hyperalgesia, mechanical pinprick sensitivity was assessed on the skin surrounding the site where HFS was applied and also on the contralateral arm.

Results:
HFS induced a significant increase in mechanical pinprick sensitivity on the HFS-treated arm. However, HFS did not decrease PPTs neither in the area of increased pinprick sensitivity nor at more distant sites.

Conclusion:
This study provides no evidence for the hypothesis that CS, induced after intense activation of skin nociceptors, involves a widespread decrease of PPTs.
Iodine Quantification Using Dual-Energy Computed Tomography for Differentiating Thymic Tumors
Authors: Yan Wei-Qiang , Xin Yong-Kang , Jing Yong , Li Gang-Feng , Wang Shu-Mei , Rong Wei-Cheng , Xiao Gang , Lei Xue-Bin , Li Bo , Hu Yu-Chuan , Cui Guang-Bin 
Published: October 2018

Purpose
The aim of the study was to explore the efficacy of iodine quantification with dual-energy computed tomography (DECT) in differentiating thymoma, thymic carcinoma, and thymic lymphoma.

Materials and Methods
Fifty-seven patients with pathologically confirmed low-risk thymoma (n = 16), high-risk thymoma (n = 15), thymic carcinoma (n = 14), and thymic lymphoma (n = 12) underwent chest contrast-enhanced DECT scan were enrolled in this study. Tumor DECT parameters including iodine-related Hounsfield unit (IHU), iodine concentration (IC), mixed HU (MHU), and iodine ratio in dual phase, slope of energy spectral HU curve (λ), and virtual noncontrast (VNC) were compared for differences among 4 groups by one-way analysis of variance. Receiver operating characteristic curve was used to determine the efficacy for differentiating the low-risk thymoma from other thymic tumor by defined parameters.

Results
According to quantitative analysis, dual-phase IHU, IC, and MHU values in patients with low-risk thymoma were significantly increased compared with patients with high-risk thymoma, thymic carcinoma, and thymic lymphoma (P < 0.05/4).The venous phase IHU value yielded the highest performance with area under the curve of 0.893, 75.0% sensitivity, and 89.7% specificity for differentiating the low-risk thymomas from high-risk thymomas or thymic carcinoma at the cutoff value of 34.3 HU. When differentiating low-risk thymomas from thymic lymphoma, the venous phase IC value obtained the highest diagnostic efficacy with the area under the curve of 0.969, and sensitivity, specificity, and cutoff value were 87.5%, 100.0%, and 1.25 mg/mL, respectively.

Conclusions
Iodine quantification with DECT may be useful for differentiating the low-risk thymomas from other thymic tumors.
Recapitulation of Unilateral Cleft Lip Nasal Deformity on Normal Nasal Structure: A Finite Element Model Analysis
Authors: Huang Hanyao , Luo Xiangyou , Cheng Xu , Zhang Zihao , Ma Guanqiu , Shi Bing , Li Jingtao 
Published: October 2018

Abstract
Cleft lip nasal deformity has been challenging to plastic surgeons. A better understanding of the biomechanical aspect of the cleft nose would contribute to a better correction. In this study, finite element model of a normal nose was constructed and loaded with forces to recapitulate the unilateral cleft lip nasal deformity. Tether at the alar base was simulated by a laterally directed force at the lateral crus, and tether at the columella base by a posteriorly directed force at the medial crus. The equivalent von-Mises stress and the total deformation consequent to different patterns of loading were captured. In accordance with clinical observations, unilaterally loaded forces caused deformation on both sides of the nose. A correlation between the patterns of loading and different cleft lip nasal deformities was documented in detail. When set at the same force magnitude, tether at the columella base led to more extensive changes in the nasal morphology and higher level of stress than at the alar base. Clear identification of major pathological tethers in the nasolabial region might lead to more accurate and stable correction of cleft lip nasal deformities.
Acute Lung Injury in Critically Ill Patients: Actin-Scavenger Gelsolin Signals Prolonged Respiratory Failure
Authors: Holm Freja Stæhr , Sivapalan Pradeesh , Seersholm Niels , Itenov Theis Skovsgaard , Christensen Per Hjort , Jensen Jens-Ulrik Stæhr 
Published: October 2018

ABSTRACT

Background:
Gelsolin is an actin-scavenger controlling the tissue damage from actin in the blood. Gelsolin levels in circulation drops when tissue damage and corresponding actin release is pronounced due to catabolic conditions. The purpose of this study was to determine if low plasma gelsolin independently predicts a reduced chance of weaning from ventilator-demanding respiratory failure in critically ill patients within 28 days from admission.

Results:
This cohort study included 746 critically ill patients with ventilator-demanding respiratory failure from the randomized clinical trial, “Procalcitonin And Survival Study (PASS).” Primary end point was successful weaning from mechanical ventilation within 28 days. We used multivariable Cox regression adjusted for age, sepsis, PaO2/FiO2 ratio and other known and suspected predictors of persistent respiratory failure. Follow-up was complete.
For medical patients, baseline-gelsolin below the 25th percentile independently predicted a 40% lower chance of successful weaning within 28 days (HR 0.60, 95% CI 0.46–0.79, P = 0.0002); among surgical patients this end point was not predicted. Low gelsolin levels predicted chance of being “alive and out of intensive care at day 14” for both medical and surgical patients (HR 0.69, 95% CI 0.54–0.89, P = 0.004). Gelsolin levels did not predict 28 day mortality for surgical or medical patients.

Conclusions:
Low levels of serum gelsolin independently predict a decreased chance of successful weaning from ventilator within 28 days among medical intensive care patients. This finding has implications for identifying patients who need individualized intervention early in intensive care course to prevent unfavorable lung prognosis in acute respiratory failure.

Trial registration:
This is a substudy to the PASS, Clinicaltrials.gov ID: NCT00271752, first registered January 1, 2006.
Sphingosine-1-Phosphate Reduces Hemorrhagic Shock and Resuscitation-Induced Microvascular Leakage by Protecting Endothelial Mitochondrial Integrity
Authors: Alves Natascha G. , Trujillo Andrea N. , Breslin Jerome W. , Yuan Sarah Y. 
Published: October 2018

ABSTRACT
Excessive microvascular permeability is a serious complication following hemorrhagic shock and resuscitation (HSR). S1P has been shown to ameliorate microvascular leakage in a model of combined alcohol intoxication and HSR. In the current study, we tested the hypothesis that S1P reduces HSR-induced microvascular leakage by preserving endothelial cell junctional structure and the endothelial glycocalyx through the protection of mitochondrial function. We used an established in vivo rat model of conscious HSR and assessed microvascular leakage, endothelial glycocalyx integrity, and mitochondrial function by intravital microscopy. Junctional integrity in the mesenteric microcirculation was assessed by confocal microscopy. Cultured rat intestinal microvascular endothelial cells monolayers were used to test the ability of S1P to protect against glycocalyx shedding and endothelial barrier dysfunction caused by direct disruption of mitochondrial integrity due to inhibition of mitochondrial complex III. The results show that in vivo, S1P protects against HSR-induced hyperpermeability, preserves the expression of adherens junctional proteins, and protects against glycocalyx degradation. S1P treatment during HSR also protects against mitochondrial membrane depolarization. S1P also protects against mitochondrial dysfunction-induced endothelial barrier dysfunction and glycocalyx degradation by acting through mitochondrial complex III. Taken together, our data indicate that S1P protects against HSR-induced mitochondrial dysfunction in endothelial cells, which in turn improves the structure of the endothelial glycocalyx after HSR and allows for better junctional integrity to the prevention of excess microvascular permeability.
Liver Transplantation Trends and Outcomes for Hereditary Hemorrhagic Telangiectasia in the United States
Authors: Iyer Vivek N. , Saberi Behnam , Heimbach Julie K. , Larson Joseph J. , Raghavaiah Suresh , Ditah Ivo , Swanson Karen , Kamath Patrick S. , Watt KD , Taner Timucin , Krowka Michael J. , Leise Michael D. 
Published: October 2018

Background.
Liver arteriovenous malformations (AVM) in hereditary hemorrhagic telangiectasia (HHT) can necessitate liver transplantation. There is limited data on HHT patients undergoing liver transplantation (LT) in the United States.

Methods.
Two sources of data were used: (1) Scientific Registry of Transplant Recipients (SRTR) database (1998-2016) (2) Single center liver transplant database (Mayo Clinic Rochester, MN). The aims of this study were (1) to determine trends in LT for HHT-related liver involvement in the United States using the SRTR database; (2) to identify clinical characteristics, indications, and outcomes for LT in HHT.

Results.
Thirty-nine HHT patients were listed for LT in the SRTR database from 1998-2016 to 1998-2001 (n = 1); 2002-2005 (n = 4); 2006-2010 (n = 10), and 2011-2016 (n = 24). Twenty-four underwent LT at a median age of 47.5 years (interquartile range, 37.0-58.5 years). Median calculated MELD score at time of LT was 8.0 (interquartile range, 7.0-9.5), and 75% received an exception MELD score. Two status-1 patients died during transplant surgery. Nineteen (86%) patients were alive after a median post-LT follow-up of 48 months, whereas 2 patients were lost to follow-up. Five of the aforementioned HHT patients underwent LT at Mayo Clinic, 4 with high output cardiac failure, and 1 with biliary ischemia. All 5 were alive at the time of last follow-up with good graft function and resolution of heart failure.

Conclusions.
Outcomes after LT for HHT patients are excellent with 86% survival after a median follow-up of 48 months and resolution of heart failure. LT listing for HHT has increased in substantially in more recent eras.
Epigenome priming dictates transcription response and white matter fate upon perinatal inflammation
Authors: Schang Anne-Laure , van Steenwinckel Juliette , Lipecki Julia , Rich-Griffin Charlotte , Woolley-Allen Kate , Dyer Nigel , Charpentier Tifenn Le , Schäfer Patrick , Fleiss Bobbi , Ott Sascha , SabéRan-Djoneidi Délara , Mezger Valérie , Gressens Pierre 
Published: October 2018

SummaryInflammatory insults accompanying prematurity provokes diffuse white matter injury (DWMI) which is associated with increased risk of neurodevelopmental disorders: pre-term infants have a 10 to 18-fold increased risk of developing autism spectrum disorders, compared to term infants. DWMI is due to maturation arrest in oligodendrocyte precursor cells (OPCs). Using integrated genome-wide approaches in a validated mouse perinatal model of DWMI, induced by systemic- and neuro-inflammation based on repeated interleukin-1B administrations, we show that neuroinflammation induces limited epigenomic disturbances in OPCs. In contrast, we unravel marked transcriptomic alterations of genes of the immune/inflammatory pathways, which are expressed in unstressed OPCs and physiologically downregulated along OPC maturation. Consistently, we observe that transcription factors of the inflammatory pathways occupy DNA both in unstressed and inflamed OPCs. Thus, rather than altering genome-wide chromatin accessibility, neuroinflammation takes advantage of open chromatin regions and deeply counteracts the stage-dependent downregulation of these active transcriptional programs. Therefore, our study opens new avenues for the future development of targeted approaches to protect preterm brains.Highlights∘Limited epigenomic impact of inflammation on OPC maturation blockade∘Major transcriptomic disturbances take advantage of a primed epigenetic landscape∘Proinflammatory genes are active in OPCs and downregulated upon maturation∘Neuroinflammation counteracts both this downregulation and maturation in OPCs
GRID – Genomics of Rare Immune Disorders: a highly sensitive and specific diagnostic gene panel for patients with primary immunodeficiencies
Authors: Simeoni Ilenia , Shamardina Olga , Deevi Sri VV , Thomas Moira , Megy Karyn , Staples Emily , Whitehorn Deborah , Duarte Daniel , Mapeta Rutendo , Ouwehand Willem H , Penkett Christopher J , Rayner-Matthews Paula , Stark Hannah , Stephens Jonathan C , Stirrups Kathleen E , Turro Ernest ,   NIHR BioResource, Thrasher Adrian , Kuijpers Taco W , Smith Kenneth GC , Savic Sinisa , Burns Siobhan O , Thaventhiran James E , Allen Hana Lango 
Published: October 2018

AbstractPrimary Immune disorders affect 15,000 new patients every year in Europe. Genetic tests are usually performed on a single or very limited number of genes leaving the majority of patients without a genetic diagnosis. We designed, optimised and validated a new clinical diagnostic platform called GRID, Genomics of Rare Immune Disorders, to screen in parallel 279 genes, including 2015 IUIS genes, known to be causative of Primary Immune disorders (PID). Validation to clinical standard using more than 58,000 variants in 176 PID patients shows an excellent sensitivity, specificity. The customised and automated bioinformatics pipeline prioritises and reports pertinent Single Nucleotide Variants (SNVs), INsertions and DELetions (INDELs) as well as Copy Number Variants (CNVs). An example of the clinical utility of the GRID panel, is represented by a patient initially diagnosed with X-linked agammaglobulinemia due to a missense variant in the BTK gene with severe inflammatory bowel disease. GRID results identified two additional compound heterozygous variants in IL17RC, potentially driving the altered phenotype.