Comparative analysis of open government data topics and usability.

This study identifies differences in the content of open public data managed by the central government, local governments, public institutions, and the office of education in Korea through keyword network analysis. Pathfinder network analysis was performed by extracting keywords assigned to 1,200 data cases, open to the Korean Public Data Portals. Subject clusters were derived for each type of government and their utility was compared using download statistics. Eleven clusters were formed for public institutions with specialized information on national issues such as Health care and Real estate, while 15 clusters were formed for the central government with national administrative information, including Crime and Safety policing. Local governments and offices of education were assigned 16 and 11 topic clusters respectively, with data focusing on regional life such as Local factories and manufacturing, Resident registration, and Lifelong education. Usability was higher in public and central governments that deal with national-level specialized information than for regional-level information. It was also confirmed that subject clusters such as Health care, Real estate, and Crime showed high usability. Furthermore, there was a large gap in data utilization because of the existence of popular data that showed extremely high usage. Supplementary Information: The online version contains supplementary material available at 10.1007/s11135-023-01630-x.

Design and Optimization of an α-Helical Bundle Dimer Cell-Penetrating Peptide for In Vivo Drug Delivery.

To deliver membrane-impermeable drugs into eukaryotic cells, a lot of cell-penetrating peptides (CPPs) were discovered. Previously we designed an amphipathic α-helical peptide which dimerizes itself via its two C-residues. This bis-disulfide-linked dimeric bundle, LK-3, has remarkable cell-penetrating ability at nanomolar concentration, which is an essential prerequisite for CPP. In an effort to optimize the sequence of LK-3, we adjusted its length and evaluated changes in the dimerization rate. We found that a 10-amino-acid monomer has the fastest dimerization rate and subsequently modified its hydrophobic and hydrophilic residues to construct a small peptide library. The evaluation of cell permeability of these derivatives showed that their cell-penetrating ability is comparable to that of the LK-3, except V- or H-containing ones. In this library, diLR10 was found to display fast nanomolar cell membrane penetration, low toxicity, and ease of production. The methotrexate (MTX) conjugate of diLR10, MTX-diLR10, has a 19-fold increased efficacy over MTX in MDA-MB-231 cells and efficiently deflates lesions in a rheumatoid arthritis (RA) in vivo mouse model.

Managing Human Subjects Research During a Global Pandemic at an Academic Center: Lessons Learned From COVID-19.

By March 2020, New York City became the early epicenter of the COVID-19 pandemic in the United States. Consequently, Columbia University, with its large portfolio of human subjects research, had to address the challenges of protecting thousands of research participants and research staff from potential exposure to COVID-19 while facilitating essential biomedical research, especially pandemic-related studies. The authors describe, from the perspective of Columbia's research administration leadership, how the University and its primary teaching hospital ramped down-and later ramped up-human subjects research and reflect on lessons learned. As the pandemic unfolded, only studies offering the prospect of direct benefit to subjects were permitted to continue with in-person contact. New in-person participant enrollment ceased, except for COVID-19 prevention or treatment studies. Centralized, frequently updated communication about policies and procedures was disseminated to the Columbia research community. Procedural efficiencies were rapidly developed and implemented for review and oversight of human subjects research and contractual agreements for clinical trials. More frequent institutional review board meetings and 24-hour support markedly reduced turnaround time for COVID-19 studies, without delaying approvals of non-COVID-19 research. Research administration worked closely with relevant principal federal agencies, whose regulatory flexibility facilitated the efficient implementation of COVID-19-related research. Overall, the ramp-down and ramp-up of the majority of human subjects research, with specified priorities and accelerated processes, worked well. Adjustments were made to handle the increase in administrative tasks, the need to respond rapidly to added oversight responsibilities, and the management of the many new COVID-19-related research protocols. Timely, centralized communication, support for staff needs, prioritization, and collaboration were critical to successful research oversight at a large-scale academic setting in the midst of a pandemic. These perspectives may be useful to academic research centers addressing the current and future pandemics.

Ocular Ultrasound Abnormalities and Optic Nerve Sheath Diameter in Dogs and Cats.

Indications for, technique, and findings for normal and abnormal ocular ultrasound are discussed, with specific sonographic findings, images, differential diagnoses, and other considerations. Because the eye is a fluid-filled structure, ultrasound can be used as a screening test when pathology prevents direct examination. Structural abnormalities, such as lens luxation, retinal detachments, and intraocular and orbital masses, also may be defined better using point-of-care ultrasound. Details on additional ophthalmic diagnostics, treatment, and prognosis are not covered.

Cytokine Levels in Human Vitreous in Proliferative Diabetic Retinopathy.

In this study, we compare the vitreous cytokine profile in patients with proliferative diabetic retinopathy (PDR) to that of patients without PDR. The identification of novel cytokines involved in the pathogenesis of PDR provides candidate therapeutic targets that may stand alone or work synergistically with current therapies in the management of diabetic retinopathy. Undiluted vitreous humor specimens were collected from 74 patients undergoing vitrectomy for various vitreoretinal disorders. Quantitative immunoassay was performed for a panel of 36 neuroinflammatory cytokines in each specimen and assessed to identify differences between PDR (n = 35) and non-PDR (n = 39) patients. Levels of interleukin-8 (IL-8), IL-15, IL-16, vascular endothelial growth factor (VEGF), VEGF-D, c-reactive protein (CRP), serum amyloid-A (SAA), and intracellular adhesion molecule-1 (ICAM1) were significantly increased in the vitreous of PDR patients compared to non-PDR patients (p < 0.05). We report novel increases in IL-15 and IL-16, in addition to the expected VEGF, in the human vitreous humor of patients with PDR. Additionally, we confirm the elevation of ICAM-1, VCAM-1, SAA, IL-8 and CRP in the vitreous of patients with PDR, which has previously been described.

RAPIDLY PROGRESSIVE NEOVASCULAR GLAUCOMA FROM CYTOMEGALOVIRUS RETINITIS IN A NON-HUMAN IMMUNODEFICIENCY VIRUS PATIENT.

PURPOSE: To describe a case of neovascular glaucoma from cytomegalovirus (CMV) retinitis in a human immunodeficiency virus-negative patient with immunosuppression after stem-cell transplant for multiple myeloma. METHODS: Retrospective case report. RESULTS: A 71-year-old man on monthly infusion of daratumumab for multiple myeloma after stem-cell transplant presenting with a 2-week history of floaters, photophobia, and blurry vision was found to have polymerase chain reaction-confirmed CMV retinitis associated with diffuse occlusive vasculitis. The patient was human immunodeficiency virus negative with a CD4 count of 450/mm3. Despite immediate aggressive treatment, the patient developed neovascular glaucoma with poor visual outcome. CONCLUSION: Cytomegalovirus retinitis in human immunodeficiency virus-negative patients is becoming more prevalent with increasing use of systemic immunosuppression therapy for various reasons. Patients with non-human immunodeficiency virus related CMV retinitis can have severe ischemia atypical of the classic CMV retinitis and should be followed closely for neovascularization.

Oligomer Formation Propensities of Dimeric Bundle Peptides Correlate with Cell Penetration Abilities.

LK-3, an amphipathic dimeric peptide linked by two disulfide bonds, and related isomeric bundles were synthesized, and their cell penetrating abilities were investigated. The measurements using size exclusion chromatography and dynamic light scattering show that LK-3 and its isomers form cell penetrating oligomers. Calculations, performed for various types of peptide isomers, elucidate a strong correlation between the amphipathic character of dimers and cell penetration ability. The results suggest that the amphipathicities of LK-3 and related bundle dimers are responsible for their oligomerization propensities which in turn determine their cell penetrating abilities. The observations made in this study provide detailed information about the mechanism of cell uptake of LK-3 and suggest a plausible insight of the early stage of nanoparticle formation of the cell penetrating amphipathic peptides.

Evaluation of Stem Cell Therapies in a Bilateral Patellar Tendon Injury Model in Rats.

Regenerative medicine provides novel alternatives to conditions that challenge traditional treatments. The prevalence and morbidity of tendinopathy across species, combined with the limited healing properties of this tissue, have prompted the search for cellular therapies and propelled the development of experimental models to study their efficacy. Umbilical cord matrix-derived mesenchymal stem cells (UCM-MSC) are appealing candidates because they are abundant, easy to collect, circumvent the ethical concerns and risk of teratoma formation, yet resemble primitive embryonic stem cells more closely than adult tissue-derived MSCs. Significant interest has focused on chitosan as a strategy to enhance the properties of MSCs through spheroid formation. This paper details techniques to isolate UCM-MSCs, prepare spheroids on chitosan film, and analyze the effect of spheroid formation on surface marker expression. Consequently, creation of a bilateral patellar tendon injury model in rats is described for in vivo implantation of UCM-MSC spheroids formed on chitosan film. No complication was observed in the study with respect to morbidity, stress rising effects, or tissue infection. The total functional score of the operated rats at 7 days was lower than that of normal rats, but returned to normal within 28 days after surgery. Histological scores of tissue-healing confirmed the presence of a clot in treated defects evaluated at 7 days, absence of foreign body reaction, and progressing healing at 28 days. This bilateral patella tendon defect model controls inter-individual variation via creation of an internal control in each rat, was associated with acceptable morbidity, and allowed detection of differences between untreated tendons and treatments.

Influence of hypoxia on the stemness of umbilical cord matrix-derived mesenchymal stem cells cultured on chitosan films.

Chitosan is attractive as a substrate for stem cell expansion because it improves stemness through formation of spheroids. Hypoxia has also been proposed as a strategy to enhance stemness and survival of stem cells after in vivo implantation. This study was therefore designed to evaluate the influence of hypoxia on chitosan-induced behavior of stem cells. Umbilical cord matrix-derived stem cells were cultured on chitosan film or standard plate under normoxia and hypoxia, for 3 and 7 days. Based on immunophenotyping, chitosan strongly suppresses the expression of CD90 and CD105 cell surface markers, changes partially reversed by combined exposure to hypoxia. Hypoxia generally increased the volume and number of spheroids formed on chitosan, but the cellularity of cultures on chitosan films remained lower than that of standard plates. After 7 days of culture, the expression of stemness related genes (Oct4, Sox2, and Nanog) was best stimulated by combined exposure to chitosan and hypoxia. Based on our results, conditioning stem cells for 7 days on chitosan films under hypoxic conditions is recommended to enhance the stemness of stem cells, and minimize cell loss due to lack of attachment on chitosan. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 501-511, 2018.

Modified retroperitoneal lymph node dissection for post-chemotherapy residual tumour: a long-term update.

OBJECTIVE: To update previously reported outcomes of modified-template post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) in appropriately selected patients with metastatic non-seminomatous germ cell tumour (NSGCT), as our previous report was criticised for short follow-up and so we now provide a long-term update on this cohort. PATIENTS AND METHODS: In all, 100 patients with normal serum markers after cisplatin-based chemotherapy and residual retroperitoneal tumour underwent modified PC-RPLND between 1991 and 2004. Using a prospectively managed institutional testicular cancer database, long-term follow-up was obtained. RESULTS: As previously reported, 43 patients underwent a right-modified template, 18 patients underwent a full-left-modified template, and 39 patients underwent a left-modified template. The updated long-term median follow-up for the entire cohort is 125 months. Seven patients developed recurrent disease with a median (range) time to recurrence of 11 (6-102) months, and one patient died from recurrent disease in the chest 4 years after surgery. All recurrences were outside the boundaries of a full-bilateral template RPLND, with the most common location of recurrence being the chest. The 5- and 10-year recurrence-free survival rates were 93% and 92%, respectively. The overall survival at 10 years was 99%. CONCLUSIONS: In appropriately selected patients with low-volume disease before and after chemotherapy, a modified template has durable long-term efficacy without risk of in-field recurrences at a median follow-up of 125 months.

Neoadjuvant chemotherapy in urothelial bladder cancer: impact of regimen and variant histology.

AIM: We compared the efficacy of methotrexate/vinblastine/doxorubicin/cisplatin (MVAC) versus gemcitabine/cisplatin in urothelial cancer and neoadjuvant chemotherapy (NACT) efficacy in variant histology (VH). MATERIALS & METHODS: Radical cystectomy patients were retrospectively compared with those who received NACT. Factors associated with survival, pathologic complete response (pCR) and downstaging (pDS) were evaluated in multivariable models. RESULTS: 9% of radical cystectomy patients (84/919) received NACT, with improved survival, pCR and pDS on both regimens. MVAC lead to higher pDS without an increase in pCR. On multivariable analysis, there was a nonsignificant increase in pDS with MVAC. NACT conferred similar responses in squamous and glandular differentiation VH. CONCLUSION: NACT was associated with improved survival, pCR and pDS. Furthermore, responses to NACT were not dependent on presence of VH.

Use of the cell cycle progression (CCP) score for predicting systemic disease and response to radiation of biochemical recurrence.

BACKGROUND: Determining the optimal treatment for biochemical recurrence (BCR) after radical prostatectomy (RP) is challenging. OBJECTIVE: We evaluated the ability of CCP score (a prognostic RNA expression signature) to discriminate between systemic disease and local recurrence in patients with BCR after RP. METHODS: Sixty patients with BCR after RP were selected for analysis based on: 1) metastatic disease, 2) non-response to salvage external beam radiotherapy (EBRT), and 3) durable response to salvage EBRT. CCP scores were generated from the RNA expression of 46 genes. Logistic regression assessed the association between CCP score and patient group. RESULTS: Passing CCP scores were generated for 47 patients with complete clinical and pathologic data. CCP score predicted clinical status when comparing patients with metastatic disease or non-responders to salvage therapy to patients with durable response (p = 0.006). CCP score remained significantly predictive of clinical status after accounting for time to BCR, PSA level at BCR, and Gleason score (p = 0.0031). CONCLUSIONS: Elevated CCP score was associated with increased risk of systemic disease, indicating that CCP score may be useful in identifying patients with BCR who are most likely to benefit from salvage radiation therapy.

Technique for office-based, ultrasonography-guided percutaneous biopsy of renal cortical neoplasms using a novel transducer for facilitated ultrasound targeting.

OBJECTIVES: To help clarify which small renal cortical neoplasms (RCNs) require surgery by using office-based, ultrasonography-guided percutaneous renal biopsy. PATIENTS AND METHODS: Biopsies were performed using facilitated ultrasound targeting (FUT) technology, which incorporates a needle guide and onscreen beam-steered technology to permit highly precise needle deployment. Patient and tumour characteristics, procedure time, complications and biopsy efficacy were documented. Wong-Baker pain levels were obtained before, during and 1 h after the procedure. RESULTS: Seven patients underwent biopsy, six for RCNs and one for medical renal disease. The mean (range) patient age was 68.5 (54-79) years, and the mean (range) tumour diameter was 2.55 (2.0-2.9) cm. Mean pain levels before, during and 1 h after the procedure were 0, 1.6 and 0.5, respectively. There were no intra- or post-procedural complications. Biopsy results were diagnostic in five of the six RCN cases and in the single case of medical renal disease. CONCLUSIONS: Our preliminary experience shows that office-based percutaneous renal biopsy using a novel transducer for FUT is safe and effective. An international multicentre study is planned to confirm these preliminary results.

Rapid generation of sub-type, region-specific neurons and neural networks from human pluripotent stem cell-derived neurospheres.

Stem cell-based neuronal differentiation has provided a unique opportunity for disease modeling and regenerative medicine. Neurospheres are the most commonly used neuroprogenitors for neuronal differentiation, but they often clump in culture, which has always represented a challenge for neurodifferentiation. In this study, we report a novel method and defined culture conditions for generating sub-type or region-specific neurons from human embryonic and induced pluripotent stem cells derived neurosphere without any genetic manipulation. Round and bright-edged neurospheres were generated in a supplemented knockout serum replacement medium (SKSRM) with 10% CO2, which doubled the expression of the NESTIN, PAX6 and FOXG1 genes compared with those cultured with 5% CO2. Furthermore, an additional step (AdSTEP) was introduced to fragment the neurospheres and facilitate the formation of a neuroepithelial-type monolayer that we termed the "neurosphederm". The large neural tube-type rosette (NTTR) structure formed from the neurosphederm, and the NTTR expressed higher levels of the PAX6, SOX2 and NESTIN genes compared with the neuroectoderm-derived neuroprogenitors. Different layers of cortical, pyramidal, GABAergic, glutamatergic, cholinergic neurons appeared within 27 days using the neurosphederm, which is a shorter period than in traditional neurodifferentiation-protocols (42-60 days). With additional supplements and timeline dopaminergic and Purkinje neurons were also generated in culture too. Furthermore, our in vivo results indicated that the fragmented neurospheres facilitated significantly better neurogenesis in severe combined immunodeficiency (SCID) mouse brains compared with the non-fragmented neurospheres. Therefore, this neurosphere-based neurodifferentiation protocol is a valuable tool for studies of neurodifferentiation, neuronal transplantation and high throughput screening assays.

Does Squamous Differentiation Portend Worse Outcomes in Urothelial Bladder Cancer?

INTRODUCTION: Interest on the impact of variant histology in bladder cancer prognosis is increasing. Although squamous differentiation is the most well characterized, only recently have less common variants gained increased recognition. We assessed whether squamous differentiation conferred a worse prognosis than nonvariant urothelial bladder cancer in a contemporary cohort of patients treated with radical cystectomy given the increased awareness of other less common variants. METHODS: We identified patients with squamous differentiation or nonvariant histology on transurethral resection of bladder tumor and/or cystectomy pathology during a 10-year period. Disease specific and overall survival were evaluated using Kaplan-Meier methodology. Cox regression was used to assess variables associated with mortality. RESULTS: Between 2003 and 2013, 934 patients underwent cystectomy for urothelial bladder cancer. Overall 617 nonvariant and 118 squamous differentiation cases were identified, and the remainder was nonsquamous differentiation variant histology. Overall 75% of patients with squamous differentiation had muscle invasive disease at diagnosis compared with 59% of those with nonvariant histology (p=0.002). Nonorgan confined disease at cystectomy was more common in patients with squamous differentiation (57% vs 44%, p=0.009). Among cases on neoadjuvant chemotherapy 20% (9 of 45) of nonvariant and 13% (1 of 8) of squamous differentiation were pT0N0 (p=0.527). Median followup was 52 months. Adjusted for demographics, pathological stage and chemotherapy, squamous differentiation was not associated with an increased risk of disease specific (HR 1.35, 95% CI 0.90-2.04, p=0.150) or all cause mortality (HR 0.90, 95% CI 0.60-1.25, p=0.515). CONCLUSIONS: In a contemporary cohort of urothelial bladder cancer with recognition and characterization of less commonly described variants, squamous differentiation is not associated with a worse disease specific and all cause mortality when compared to a pure nonvariant cohort.

Severity of hematuria effects resolution in patients treated with hyperbaric oxygen therapy for radiation-induced hematuria.

INTRODUCTION: We investigated the differences between prostate cancer patients with radiation-induced hematuria treated with hyperbaric oxygen (HBO) therapy that did or did not have a resolution of hematuria. MATERIALS AND METHODS: We performed a retrospective review of prostate cancer patients with radiation-induced hematuria who underwent HBO from April 2000 to March 2010. We performed an analysis of demographic data and severity of hematuria in those who had resolution of or persistent hematuria. Additionally, prostate-specific antigen (PSA) data were also obtained during the study period. RESULTS: Overall, 11/22 men had resolution of hematuria after HBO therapy with a median follow-up of 2.2 (0.35-13.6) years. The Radiation Therapy Oncology Group (RTOG) grade of hematuria is predictive of final hematuria outcome (resolution vs. persistent) after HBO (p = 0.026). No significant PSA changes were noted before and after HBO therapy. CONCLUSIONS: The RTOG hematuria grade is associated with the resolution of hematuria after HBO therapy for radiation-induced hematuria in men treated for prostate cancer. This information may be helpful during shared medical decision-making regarding utility of HBO therapy in the context of severity of hematuria.

In vitro comparison of a novel facilitated ultrasound targeting technology vs standard technique for percutaneous renal biopsy.

OBJECTIVE: To improve the understanding of the epidemiology of renal cortical neoplasms through pretreatment biopsy, we evaluated a facilitated ultrasound targeting (FUT) technology. The technology allows a needle to be passed through the transducer probe and guided along a virtual dotted line on the monitor. We compared the FUT with standard percutaneous biopsy (PB) technique. MATERIALS AND METHODS: Forty-eight participants with various levels of training were recruited. Participants performed ultrasound-guided biopsies on phantom models using FUT and the standard biopsy technique in a randomized sequence. The phantom models consisted of pimento olives embedded in an opaque mold of Metamucil and Knox gelatin. Patients were given up to 10 attempts to achieve 3 complete specimens from the olives. Patients rated each biopsy technique. Results were stratified by level of experience. RESULTS: The mean time to obtain 3 complete biopsy specimens was significantly faster for FUT compared with the standard technique (140 seconds vs 246 seconds, P = .0001). The mean number of attempts needed to obtain 3 specimens was significantly less with FUT compared with the standard technique (4.3 vs 5.6 attempts, P = .0007). Patients reported that FUT was significantly easier to use compared with the standard technique (P = .0005). No significant order effect was observed. CONCLUSION: In this in vitro comparison, FUT increased the efficiency and efficacy of PB for users of all experience levels. FUT may allow urologists with limited PB experience to perform the procedure reliably and easily. Clinical evaluation of this technology is actively in progress.

Interobserver reliability and reproducibility of s.T.o.N.e. Nephrolithometry for renal calculi.

PURPOSE: To assess the reliability of the S.T.O.N.E. (stone size [S], tract length [T], obstruction [O], number of involved calices [N], and essence or stone density [E]) nephrolithometry scoring system by testing its reproducibility between different observers. PATIENTS AND METHODS: Preoperative images of 58 patients who underwent percutaneous nephrolithotomy (PCNL) were reviewed. Medical students, urology residents, one fellow, and a urology attending independently reviewed all images and scored the renal stones. Interobserver reliabilities of the total score for all categories and each component were evaluated by the intraclass correlation (ICC) and a κ coefficient. RESULTS: The interobserver reliability for the total score demonstrated high correlations for all components and total score (ICC=S, T, O, N, E and total 0.80, 0.97, 0.89, 0.84, 0.91, and 0.87, respectively). κ rates for individual components between two medical students were 0.36, 1, 0.31, 0.45, 0.33, and 0.30 for the S, T, O, N, E components and total score, respectively. κ values between the two urology residents were 0.71, 1, 0.92, 0.79, 0.93, and 0.67 for S, T, O, N, E components and total score, respectively. κ values between the urology fellow and an attending physician were 0.95, 1, 0.88, 0.94, 0.89, and 0.87 for S, T, O, N, E components and total score, respectively. P value for all the scoring components was <0.05, indicating that the estimated κ was not a result of chance. CONCLUSIONS: The S.T.O.N.E. nephrolithometry has excellent interobserver reliability. Quantifying the S and N metrics was the most challenging and least reliable. Standardized protocols to measure these components should be considered to improve accuracy and reproducibility of the scoring system.

In vitro randomized comparison of a standard and novel echogenic needle for ultrasonography-guided renal targeting.

BACKGROUND AND PURPOSE: Urologists are becoming increasingly aware of the importance of pretreatment percutaneous renal biopsy of small renal cortical neoplasms. A barrier to the routine performance of ultrasonography-guided percutaneous renal biopsy has been the technical challenges associated with the procedure. We evaluated a new modified needle, which incorporates an echogenic needle tip designed to improve the needle tip's visibility under ultrasonographic visualization. We evaluated and compared the ultrasonographic imaging quality of the echogenic needle (EN) and a standard needle (SN). METHODS: Forty-eight participants were recruited to perform ultrasonography-guided needle targeting and drainage of a simulated cyst within a phantom model. The simulated cysts were embedded in an opaque gel mold. Each participant was blinded to the type of needle being deployed and was asked to identify and aspirate the simulated cyst with each needle under ultrasonography guidance. Each needle was tested at three ultrasound-aiming angles, (0, 15, and 30 degrees). The quality of needle visibility under ultrasonographic imaging was assessed via a questionnaire, including needle preference and a visibility score (1-10) at each aiming angle. Participants were stratified by level of ultrasound experience. RESULTS: For each angle tested, the EN received higher visibility ratings. The mean visibility scores for the EN vs the SN were 6.44 vs 5.52 at 0 degrees (P=0.001), 7.77 vs 6.96 at 15 degrees (P=0.0004) and 8.33 vs 7.54 at 30 degrees (P=0.0001). Participants reported significantly greater comfort using the EN needle compared with the SN (P=0.001). These results held true regardless of the sequence of needle tested first. Also, there was a significant difference in visibility scores by angle (P=0.0001). Larger angles (30>15>0) resulted in higher scores. CONCLUSIONS: In this in vitro trial, the application of the EN improved needle visibility for users of all levels of experience. Clinical correlation is pending.