bluuebunny/crossref_metadata_2025_split huggingface dataset:
Different Materials for Plugging a Dehiscent Superior Semicircular Canal: A Comparative Histologic Study Using a Gerbil Model
Authors: Kwok Pingling , Gleich Otto , Spruss Thilo , Strutz Jürgen 
Published: April 2019

Hypothesis:
The choice of the material for plugging a dehiscence of the superior semicircular canal is based on the ease of use and the success of the procedure to permanently relieve symptoms without adverse side effects.

Background:
Dehiscence of the superior semicircular canal can lead to autophony, conductive hearing loss, and vertigo. Surgical treatment by plugging the canal is a highly effective treatment of the symptoms in many patients, although, the procedure can be associated with some degree of hearing loss in more than or equal to 25% of the patients. The available data indicate that adverse effects may be more frequently observed with bone wax as compared with other materials.

Methods:
In the present study we compare the tissue reactions induced by plugging the superior semicircular canal with autologous bone pate/bone chips, muscle, fat, artificial bone wax, and teflon in the gerbil model in an attempt to identify the material leading to successful plugging with the least adverse tissue reactions.

Results:
Our data show that successful plugging was achieved in 100% of the ears by bone pate/bone chips, teflon, and bone wax while the success rate was significantly lower (<50%) following muscle and fat. The proportion of adverse tissue reactions was significantly more pronounced using bone wax as compared with teflon and bone pate/bone chips.

Conclusion:
The use of teflon or autologous bone as a material for plugging a dehiscent superior semicircular canal should be favored over bone wax, muscle, and fat.
Liver stiffness and fibrosis-4 alone better predict liver events compared with aspartate aminotransferase to platelet ratio index in a cohort of human immunodeficiency virus and hepatitis C virus co-infected patients from ANRS CO13 HEPAVIH cohort
Authors: Chalouni Mathieu , Sogni Philippe , Miailhes Patrick , Lacombe Karine , Poizot-Martin Isabelle , Chas Julie , Vittecoq Daniel , Neau Didier , Aumaitre Hugues , Alric Laurent , Piroth Lionel , Bouchaud Olivier , Katlama Christine , Morlat Philippe , Lascoux-Combe Caroline , Gervais Anne , Naqvi Alissa , Rosenthal Eric , Garipuy Daniel , Barange Karl , Esterle Laure , Salmon Dominique , Wittkop Linda 
Published: April 2019

Objectives
HIV/hepatitis C virus (HCV) co-infection leads to major complications, and noninvasive markers developed to stage liver fibrosis could be used as prognostic markers. We aimed to compare the performances of liver stiffness (LS), fibrosis-4 (FIB-4), and aspartate aminotransferase to platelet ratio index (APRI) to predict liver-related events in HIV/HCV co-infected patients.

Patients and methods
HIV/HCV co-infected patients from the ANRS CO13 HEPAVIH cohort were included if they had LS, FIB-4, and APRI measurements done in a window of 3 months. Primary outcome was the time between inclusion and occurrence of a liver-related event. Univariable and multivariable Fine and Gray models were performed. Predictive performances were compared by the area under the receiver operating characteristic (AUROC) differences after correction of optimistic by bootstrap samples. Best cutoffs to predict liver-related events were estimated by sensitivity and specificity maximization.

Results
A total of 998 patients were included. Overall, 70.7% were men. Their median age was 46.8 years. According to LS value, 204 (20.4%) patients had cirrhosis. Overall, 39 patients experienced at least one liver-related event. In univariable analysis, LS AUROC curve was significantly superior to FIB-4 and APRI AUROC curves, being 87.9, 78.2, and 75.0%, respectively. After adjustment on age, CD4 levels, and insulin resistance, no differences were observed. The best cutoffs to identify patients at low or high risk of liver-related events were below 8.5, 1.00, and 0.35 and above 16.5, 4.00, and 1.75 for LS, FIB-4, and APRI, respectively.

Conclusion
To predict HCV-related events, APRI had lower performance than LS and FIB-4. FIB-4 is as good as LS to predict HCV-related events, suggesting that it can be used for the management of HIV/HCV co-infected patients and replace LS.
Hepatocellular carcinoma macroscopic gross appearance on imaging: predictor of outcome after transarterial chemoembolization in a real-life multicenter French cohort
Authors: Adhoute Xavier , Pénaranda Guillaume , Raoul Jean-Luc , Pietri Olivia , Bronowicki Jean-Pierre , Castellani Paul , Perrier Hervé , Monnet Olivier , Bayle Olivier , Oules Valérie , Pol Bernard , Beaurain Patrick , Muller Cyrille , Cassagneau Pierre , Bourlière Marc 
Published: April 2019

Background
Conventional transarterial chemoembolization (cTACE) with lipiodol is widely performed in patients with hepatocellular carcinoma (HCC) unsuitable for curative treatment. Additional tumor parameters such as HCC macroscopic appearance based on imaging might be helpful for transarterial chemoembolization prognostication and management.

Patients and methods
A total of 405 patients with HCC who underwent cTACE between 2008 and 2016 from a real-life multicenter French cohort were retrospectively reviewed. Tumors were classified into two macroscopic types according to HCC gross appearance on imaging: nodular versus non-nodular. The study population was stratified into two groups: derivation and validation cohorts. Independent prognostic factors of survival based on multivariate cox regression models were determined and then assessed in the validation set. Thereafter, time to progression (TTP) and radiological response rate were investigated for each prognostic factors of survival.

Results
Median overall survival (OS) was 35 months for Barcelona Clinic Liver Cancer (BCLC) stage A, 22 months for BCLC stage B and 12 months for BCLC stage C patients (P < 0.0001). The corresponding TTP for these patients was 12 (7–17) months, 5 (3–6) months and 1.2 (1.2–3) months (P < 0.0001). Multivariate analysis revealed that tumors size and number, non-nodular type, alpha-fetoprotein, aspartate aminotransferase serum levels and impairment of performance status-1 were independent predictors of survival among the study groups. Non-nodular type was the most powerful factor that influences OS, TTP and radiological response rate for the recommended transarterial chemoembolization candidates. TTP was consistent with OS within each stage.

Conclusion
HCC macroscopic appearance on imaging is a determinant predictor of outcome after cTACE in a real-life multicenter cohort.
Ex-vivo lung perfusion and ventilation: where to from here?
Authors: Ali Aadil , Cypel Marcelo 
Published: April 2019

Purpose of review
Within the last decade, ex-vivo lung perfusion (EVLP) has become a widespread technology used for organ assessment and reconditioning within clinical transplantation. This review aims to offer insights toward future applications and developments in regards to its utility.

Recent findings
The intervention of EVLP is a well-tolerated method to effectively allow for extended preservation periods. The thoughtful usage of EVLP can therefore be used to optimize operating room logistics and progress lung transplantation toward becoming a more elective procedure. EVLP has also demonstrated itself as an excellent platform for targeted therapies. Prolonged perfusion achieved through further platform stability will allow for time-dependent molecular therapies. Lastly, EVLP allows for the opportunity to perform advanced diagnostics within an isolated setting. Sophistication of point-of-care technologies will allow for accurate predictive measures of transplant outcomes within the platform.

Summary
The future of EVLP involves usage of the system as a preservation modality, utilizing advanced diagnostics to predict transplant outcome, and performing therapeutic interventions to optimize organ quality. The generation of clinical data to facilitate and validate these approaches should be performed by transplant centers, which have acquired significant experience using EVLP within their clinical activity.
Characteristics and Survival Outcomes of Children With Hodgkin Lymphoma Treated Primarily With Chemotherapy
Authors: Ashraf Muhammad S. , Naz Fozia , Yakoob Mohammad Y. 
Published: April 2019

Background:
Hodgkin disease is a malignant tumor of the lymphatic system that comprises ∼6% of childhood cancers. In developing countries, efforts are made to ensure adherence to standard protocol/regimens, study patients’ outcomes, and compare with that in developed world.

Materials and Methods:
We conducted a retrospective medical records’ review of 212 children younger than 20 years presenting to The Indus Hospital in Pakistan with previously untreated Hodgkin lymphoma between August 2000 and December 2012. We collected demographic and other epidemiologic variables such as age, sex, stage, subtype of disease, and survival outcomes.

Results:
The mean±SD age of patients at time of diagnosis was 9.0±3.8 years with a male to female ratio of ∼4.7:1. In total, 44 (20.8%) patients were 5 years of age or above at presentation. Overall, 131 (61.8%) patients presented with B-symptoms and mixed cellularity was the most frequently diagnosed subtype in 65.1% of cases. In total, 170 (80.2%) achieved full remission after completion of chemotherapy. Patients were treated with alternating cycles of ABVD (Adriamycin, Bleomycin, Vincristine, and Dacarbazine) and COPDAC (Cyclophosphamide, Vincristine, Prednisolone, and Dacarbazine). The majority (n=114, 59.1%) received 6 cycles of chemotherapy, 44 (22.8%) received ≤4 cycles followed by 24 (12.4%) receiving 8 cycles. Radiotherapy was administered only to those patients with significant residual disease at the end of chemotherapy (n=20, 10%). The 5-year overall survival and event-free survival in our cohort was 89.6% and 82.1%, respectively.

Conclusion:
Our findings suggest that treatment with 4 to 8 alternating cycles of ABVD/COPDAC has an excellent outcome in childhood Hodgkin disease.
Feasibility of Assessing Sodium-Associated Body Fluid Composition in End-Stage Renal Disease
Authors: Clark-Cutaia Maya N. , Reisinger Nathaniel , Anache Maria Rita , Ramos Kara , Sommers Marilyn S. , Townsend Raymond R. , Yu Gary , Fargo Jamison 
Published: April 2019

Background
Cardiovascular disease accounts for more than half of all deaths in the hemodialysis (HD) population. Although much of this mortality is associated with fluid overload (FO), FO is difficult to measure, and many HD patients have significant pulmonary congestion despite the absence of clinical presentation. Cohort studies have observed that FO, as measured by bioimpedance spectroscopy (BIS), correlates with mortality. Other studies have observed that lower sodium intake is associated with less fluid-related weight gain, improved hypertension, and survival. Whether sodium intake influences FO in HD patients as measured by BIS is not known.

Objective
The aims of the study were to determine the feasibility of assessing the impact of sodium restriction on body fluid composition as measured by BIS among patients with three levels of sodium intake and to determine if there are statistical and/or clinical differences in BIS measures across sodium intake groups.

Methods
We used a double-blinded randomized controlled trial design with three levels of sodium restriction, 2,400 mg per day, 1,500 mg per day, and unrestricted (control group), to test our aims. Forty-two HD patients from a tertiary acute care academic institution associated with three urban DaVita dialysis centers were enrolled. Participants remained in the inpatient center for 5 days and 4 nights and were randomly assigned to sodium intake groups. Body fluid composition was measured with BIS.

Results
Recruitment, enrollment, and retention statistics supported the feasibility of the study design. Regression analyses showed that there were no statistically significant differences among sodium intake groups on any of the outcomes.

Discussion
Our data suggest the need for additional research into the effects of sodium restriction on body fluid composition.
Overcoming Challenges in Multisite Trials
Authors: Smith Laureen , Tan Alai , Stephens Janna D. , Hibler David , Duffy Sonia A. 
Published: April 2019

Background
Conducting multisite studies has many challenges, including determining the geographic distance between sites, ensuring effective communication, monitoring intervention and data integrity, handling institutional policy variations, seeking institutional review board approval with unique site needs or complex subcontracts, and planning for additional costs.

Objectives
This article discusses common challenges in conducting multisite studies and identifies strategies to overcome these challenges using real-world examples from the literature, the authors’ research studies, and their personal experiences.

Methods
A summary of articles on multisite trials conducted within the past 10 years was explored to uncover common challenges in conducting multisite trials. To enrich the context, exemplars from authors’ works are included. Based on literature and experience, strategies to combat challenges are summarized.

Results
Unique issues related to multisite studies include site selection, use of epicenters/coordinating centers, hiring/managing staff, fidelity monitoring, institutional review board approval, statistical considerations, and approaches to authorship.

Conclusion
Addressing challenges a priori can improve scientific rigor, reproducibility, and evidence from multisite studies. Given the benefits to scientific rigor, reproducibility, and design, findings from multisite studies are more likely to provide evidence to transform clinical practice and influence policy.
Predictive Performance of Cardiovascular Disease Risk Prediction Algorithms in People Living With HIV
Authors: van Zoest Rosan A. , Law Matthew , Sabin Caroline A. , Vaartjes Ilonca , van der Valk Marc , Arends Joop E. , Reiss Peter , Wit Ferdinand W. ,   on behalf of the ATHENA National Observational HIV Cohort
Published: April 2019

Background:
People living with HIV (PLWH) experience a higher cardiovascular disease (CVD) risk. Yet, traditional algorithms are often used to estimate CVD risk. We evaluated the performance of 4 commonly used algorithms.

Setting:
The Netherlands.

Methods:
We used data from 16,070 PLWH aged ≥18 years, who were in care between 2000 and 2016, had no pre-existing CVD, had initiated first combination antiretroviral therapy >1 year ago, and had available data on CD4 count, smoking status, cholesterol, and blood pressure. Predictive performance of 4 algorithms [Data Collection on Adverse Effects of Anti-HIV Drugs Study (D:A:D); Systematic COronary Risk Evaluation adjusted for national data (SCORE-NL); Framingham CVD Risk Score (FRS); and American College of Cardiology and American Heart Association Pooled Cohort Equations (PCE)] was evaluated using a Kaplan–Meier approach. Model discrimination was assessed using Harrell's C-statistic. Calibration was assessed using observed-versus-expected ratios, calibration plots, and Greenwood-Nam-D'Agostino goodness-of-fit tests.

Results:
All algorithms showed acceptable discrimination (Harrell's C-statistic 0.73–0.79). On a population level, D:A:D, SCORE-NL, and PCE slightly underestimated, whereas FRS slightly overestimated CVD risk (observed-versus-expected ratios 1.35, 1.38, 1.14, and 0.92, respectively). D:A:D, FRS, and PCE best fitted our data but still yielded a statistically significant lack of fit (Greenwood-Nam-D'Agostino χ2 ranged from 24.57 to 34.22, P < 0.05). Underestimation of CVD risk was particularly observed in low-predicted CVD risk groups.

Conclusions:
All algorithms perform reasonably well in PLWH, with SCORE-NL performing poorest. Prediction algorithms are useful for clinical practice, but clinicians should be aware of their limitations (ie, lack of fit and slight underestimation of CVD risk in low-risk groups).
Comprehensive Treatment of Facial Deformity Due to Radiotherapy in Rhabdomyosarcoma Patients: Distraction Osteogenesis and Free Flaps Surgical Technique
Authors: Bianchi Alberto , Crimi Salvatore , Cipriani Riccardo , De Ponte Francesco Saverio , Cicciù Marco , Marchetti Claudio 
Published: April 2019

Abstract
Radiotherapy is essential for achieving and maintaining local control in head and neck rhabdomyosarcoma patients. However, radiotherapy may cause outgrowth disturbances of facial bone and soft tissue, resulting in facial asymmetry.
Several studies have shown that the management of irradiated bones still remains challenging. The possibility of obtaining functional and aesthetic results when managing facial deformities due to radiation therapy with distraction osteogenesis combined with free flaps reconstruction is not common and not well documented in recent literature.
In this report, we present the long-term results of distraction osteogenesis and soft tissue reconstruction via microvascular free flap to correct the facial hypoplasia of a young patient who underwent radiation therapy for rhabdomyosarcoma.
This is the first presentation of 26 years long-term results in a patient who also underwent free flaps reconstruction as ancillary surgery for esthetic good results.
National Stop the Bleed Day: The impact of a social media campaign on the Stop the Bleed program
Authors: Fisher Andrew D. , Carius Brandon M. , Lacroix John , Dodge P. Max , Dodd Jimm , Soderlund Eric , Thompson Dominic , Loos Paul , Fannin Jacob , Montgomery Harold R. , Gestring Mark L. 
Published: April 2019

BACKGROUND
National Stop the Bleed Day (NSTBD) was created to increase public awareness of the official Stop-the-Bleed initiative and the Bleeding Control Basic course. The goal was to develop and employ an effective national social media strategy that would encourage and support efforts already in place to train the public in basic bleeding control techniques.

METHODS
March 31, 2018, was designated as NSTBD. Analysis focused on a 2-week window centered on NSTBD. The number of courses offered, number of instructors registered and total number of students trained overall during this period was derived from the American College of Surgeons (ACS) website bleedingcontrol.org. Courses not registered with the ACS were not included. Data on overall website activity were also included for analysis.

RESULTS
Forty-three states and 18 countries participated in NSTBD. During the study period, there were 1884 courses registered on bleedingcontrol.org. Comparatively, over a 4-month period from August to November 2017, the mean number of registered courses per month was 834. There were 34,699 students trained during the two-week study period as opposed to August to November 2017, the mean number of people trained per month was 9,626. In addition, 576 new B-Con instructors were certified during this time window. Additionally, the international coordinators reported 1500 students were trained during the study period. During this time, the ACS reported a significant increase in website activity. This included 10,530 new visitors, 12,772 visitors overall and 35,342 page views recorded during the study period.

CONCLUSION
The NSTBD effort was successful in generating widespread interest for the Stop-the-Bleed initiative. The use of a targeted social media campaign in this context was successful in driving people to available training opportunities while also increasing awareness of the overall effort. While only in its early stages, the NSTBD concept is a good one and should be developed further in coming years.

LEVEL OF EVIDENCE
Retrospective, Level V.
Separating distinct structures of multiple macromolecular assemblies from cryo-EM projections
Authors: Verbeke Eric J. , Zhou Yi , Horton Andrew P. , Mallam Anna L. , Taylor David W. , Marcotte Edward M. 
Published: April 2019

AbstractCryo-electron microscopy is traditionally applied to samples purified to near homogeneity as current reconstruction algorithms are unable to handle heterogeneous mixtures of structures from many macromolecular complexes. We extend on long established methods and demonstrate that relating two-dimensional projection images by their common lines in a graphical framework is sufficient for partitioning distinct protein and multiprotein complexes within the same data set. Using this approach, we first group a large set of synthetic reprojections from 35 unique macromolecular structures ranging from ∼30 – 3000 kDa into individual homogenous classes. We then apply our algorithm on cryo-EM data collected from a mixture of five protein complexes and use existing reconstruction methods to solve multiple three-dimensional structuresab initio. Incorporating methods to sort cryo-EM data from heterogeneous mixtures will alleviate the need for stringent purification and pave the way toward investigation of samples containing many unique structures.
Quantitative Structural Assessment of Graded Receptor Agonism
Authors: Shang Jinsai , Brust Richard , Griffin Patrick R. , Kamenecka Theodore M. , Kojetin Douglas J. 
Published: April 2019

ABSTRACTLigand-receptor interactions, which are ubiquitous in physiology, are described by theoretical models of receptor pharmacology. Structural evidence for graded-efficacy receptor conformations predicted by receptor theory has been limited, but is critical to fully validate theoretical models. We applied quantitative structure-function approaches to characterize the effects of structurally similar and structurally diverse agonists on the conformational ensemble of nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ). For all ligands, agonist efficacy is correlated to a shift in the conformational ensemble equilibrium from a ground state towards an active state, which is detected by NMR spectroscopy but not observed in crystal structures. For the structurally similar ligands, ligand potency is also correlated to efficacy and conformation, indicating ligand residence times among related analogs can influence receptor conformation and function. Our results derived from quantitative graded activity-conformation correlations provide new experimental evidence and a platform with which to extend and test theoretical models of receptor pharmacology to more accurately describe and predict ligand-dependent receptor activity.
Polyubiquitin-dependent recruitment of NEMO/IKKγ into T cell receptor signaling microclusters
Authors: DeRiso Elizabeth A. , Szymczak-Workman Andrea L. , Montecalvo Angela , Murphy Joanne M. , Seminario Maria-Cristina , Kane Lawrence P. , Bunnell Stephen C. 
Published: April 2019

AbstractThe NF-κB essential modulator protein (NEMO) is required for activation of canonical NF-κB by the T cell antigen receptor (TCR). However, the subcellular localization of NEMO during this process is not well understood. By dynamically imaging fluorescent NEMO chimeras in live human T cells, we demonstrate that NEMO is rapidly recruited into TCR microclusters via domains previously implicated in the recognition of linear and K63-linked polyubiquitin. The recruitment of NEMO into TCR microclusters requires the activities of the tyrosine kinases Lck and ZAP-70, but not the adaptor proteins LAT or SLP-76. Thus, our findings reveal that the pathways leading from TCR to NF-κB bifurcate downstream of ZAP-70 to independently control the recruitment and activation of NEMO.