bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experimental Study of Refraction Effects of Nominally Plano Ophthalmic Prisms and Magnifying Lenses
Authors: Atchison David A. , Lu Jianing , Yip Cleo , Suheimat Marwan , Schmid Katrina L. 
Published: December 2018

SIGNIFICANCE
Nominally plano ophthalmic prisms give autorefraction results similar to those predicted on the basis of how effective powers change with pantoscopic tilt, and magnifying lenses give autorefraction results similar to those predicted on the basis of vergence changes. Without appreciation of the optics involved, these effects might wrongly be considered artifacts.

PURPOSE
The purpose of this study was to investigate the interactions of autorefractors with lenses and prisms.

METHODS
There were 15 adult participants across three experiments, with a range of ages and refractions. In experiments 1 and 2, participants wore frames containing base-up and base-down nominally plano prisms. In experiment 3, participants wore a lens that produced either 6.3% magnification or 5.9% minification, depending on which surface faced the eye. Autorefracting instruments with different operating principles were used: Shin-Nippon SRW5000 autorefractor, Grand Seiko 5100K autorefractor, Hoya AR-530 autorefractor, a Complete Ophthalmic Analysis System–High Definition wavefront sensor, and Tomey FC-800 autorefractor. A theory on the likely effects of magnifying lenses was presented.

RESULTS
For ophthalmic prisms, refractions showed results similar to those predicted on the basis of how effective prism powers change with pantoscopic tilt. As tilt increased, base-up prism gave more positive mean refractions and more negative horizontal/vertical astigmatism and vice versa for base-down prisms. In the presence of 10° tilt, 8Δ base-up prisms and 8Δ base-down prisms had different effects by a mean of 0.36 diopters. Magnifying lenses affected refractions similar to those predicted on the basis of vergence changes, with 6% magnification and minification producing mean changes of −11 and +8%, respectively, in absolute mean refraction. There was no strong evidence that different instruments had different effects.

CONCLUSIONS
The results have implications for studies in which prisms and lenses are placed in the front eyes, such as accommodation studies using thick lenses close to the eyes to stimulate accommodation rather than by changing object distance.
Supporting Dry Eye Diagnosis with a New Method for Noninvasive Tear Film Quality Assessment
Authors: Llorens-Quintana Clara , Szczesna-Iskander Dorota , Iskander D. Robert 
Published: December 2018

SIGNIFICANCE
Noninvasive high-speed videokeratoscopy equipped with specific software has shown potential for assessing the homeostasis of tear film, providing clinicians with a fast and consistent tool for supporting dry eye diagnosis and management.

PURPOSE
The purpose of this study was to evaluate the efficacy of a recently proposed method for characterizing tear film dynamics using noninvasive high-speed videokeratoscopy in assessing the loss of homeostasis of tear film.

METHODS
Thirty subjects from a retrospective study, of which 11 were classified as dry eye and 19 as healthy, were included. High-speed videokeratoscopy measurements were performed using E300 videokeratoscope (Medmont Pty., Ltd., Melbourne, Australia). Raw data were analyzed using a recently proposed method to estimate the dynamics of the tear film based on a fractal dimension approach. This method provides three time-varying indicators related to the regularity of the reflected rings: tear film surface quality indicator, breaks feature indicator, and distortions feature indicator. From each indicator, five parameters were extracted and analyzed, including noninvasive breakup time, mean value of the indicator in the stability phase, mean value of the indicator in the whole interblink interval, mean value of the indicator in the leveling phase, and the general trend of the time series. Receiver operating characteristic curves were used to determine the sensitivity and specificity of each parameter in dry eye detection.

RESULTS
The best discrimination performance between dry eye and healthy subjects was achieved with the breaks feature indicator noninvasive breakup time parameter, with an area under the curve of 0.85. For a cutoff value of 10 seconds, the sensitivity was 100% and the specificity was 84%.

CONCLUSIONS
The analyzed method improves the assessment of tear film homeostasis in comparison with previous high-speed videokeratoscopy methods showing higher potential in assisting dry eye diagnosis.
Introducing BREAST-Q Computerized Adaptive Testing: Short and Individualized Patient-Reported Outcome Assessment following Reconstructive Breast Surgery
Authors: Young-Afat Danny A. , Gibbons Christopher , Klassen Anne F. , Vickers Andrew J. , Cano Stefan J. , Pusic Andrea L. 
Published: December 2018

Background:
The BREAST-Q is a widely used patient-reported outcome instrument measuring health-related quality-of-life and patient satisfaction in breast surgery. Shorter assessment potentially increases patients’ willingness to complete scales, but simply offering a shortened version leads to unacceptable loss in measurement precision. The authors aimed to develop a computerized adaptive test (CAT) to shorten the BREAST-Q’s Satisfaction with Breasts scale while maintaining reliability of measurement.

Methods:
The authors created a CAT, which repetitively administered questions from the pool of 16 questions, until prespecified levels of reliability were reached [i.e., standard errors (SE) of 0.32 to 0.55]. In a simulation study, the authors tested the CAT's feasibility for all potential satisfaction scores. In a second study using actual patient data, 5000 breast reconstruction patients who had previously completed the full scale were randomly selected from a large database. Their full-scale satisfaction scores were compared with their CAT-derived scores.

Results:
In both studies, by applying CAT, the Satisfaction with Breasts scale could be reduced to an average of 10 questions when using the minimum level of measurement precision for individual-patient measurement (SE, 0.32), compared with four questions when using the minimum precision level for group-based research (SE, 0.55). Score estimates were highly correlated between the CAT assessment and the full scale (0.91 to 0.98 in the simulation study, and 0.89 to 0.98 in the patient data study).

Conclusions:
Applying computerized adaptive testing to the BREAST-Q’s Satisfaction with Breasts scale facilitates reliable assessment, with 38 to 75 percent fewer questions than the full version. The novel BREAST-Q CAT version may decrease response burden and help overcome barriers to implementation in routine care.
Arterial Wall Penetration Forces in Needles versus Cannulas
Authors: Pavicic Tatjana , Webb Katherine L. , Frank Konstantin , Gotkin Robert H. , Tamura Bhertha , Cotofana Sebastian 
Published: December 2018

Background:
If safety is defined as the diminished ability to penetrate facial arteries, the goal of this study was to investigate whether different-sized cannulas are safer than correspondingly sized needles for the application of facial soft-tissue fillers.

Methods:
Two hundred ninety-four penetration procedures of the facial and superficial temporal arteries were performed in four fresh frozen cephalic specimens using both needles (20-, 22-, 25-, and 27-gauge) and cannulas (22-, 25-, and 27-gauge). Continuously increasing force was applied and measured until intraarterial penetration occurred.

Results:
No statistically significant differences were detected when comparing forces required to penetrate the facial arterial vasculature between different sexes, arteries, or sides of the face (all p > 0.05). Forces needed to penetrate significantly (p < 0.001) decreased with smaller diameter needles (20-gauge, 1.12 ± 0.29 N; 22-gauge, 1.08 ± 0.25 N; 25-gauge, 0.69 ± 0.24 N; and 27-gauge, 0.70 ± 0.29 N) and in cannulas (22-gauge, 1.50 ± 0.31 N; 25-gauge, 1.04 ± 0.36 N; and 27-gauge, 0.78 ± 0.35 N). Comparing 27-gauge injectors, no statistically significant difference was detected between needles and cannulas; an artery could be penetrated with a similar force independent of whether the injector was a needle or a cannula (0.70 ± 0.29 N versus 0.78 ± 0.35 N; p = 0.558).

Conclusions:
Cannulas, in all measured sizes except 27-gauge, required greater forces for intraarterial penetration compared with correspondingly sized needles, confirming the safety of 22- and 25-gauge cannulas; 27-gauge cannulas, however, required similar forces as 27-gauge needles, indicating that 27-gauge cannulas are not safer than 27-gauge needles.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, V.
Low-Dose Perfusion Computed Tomography for Breast Cancer to Quantify Tumor Vascularity
Authors: Park Eun Kyung , Seo Bo Kyoung , Kwon Myoungae , Cho Kyu Ran , Woo Ok Hee , Song Sung Eun , Cha Jaehyung , Lee Hye Yoon 
Published: December 2018

Objectives
The aim of this study was to investigate the feasibility of using low-dose perfusion computed tomography (CT) in breast cancers for quantification of tumor vascularity and to correlate perfusion indexes with prognostic biomarkers.

Materials and Methods
This preliminary study was approved by our institutional review board. Signed informed consent was obtained from all 70 enrolled patients with invasive breast cancers. Low-dose perfusion CT was performed with the patient in the prone position using a spectral CT device set at 80 kVp and 30 mAs (1.30–1.40 mSv). Images were analyzed using commercial software applying the maximum slope algorithm. On CT perfusion maps, perfusion (mL/min per 100 mL), blood volume (mL/100 g), time-to-peak enhancement (second), and peak enhancement intensity (HU) were measured in the tumor, normal breast glandular tissues, and fat. Tumor grade, estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), and Ki67 level were evaluated using histopathology. Statistically, CT perfusion indexes of the tumor and normal glandular tissues or fat were compared using the Wilcoxon signed-rank test, and CT indexes were correlated with histological characteristics using the Mann-Whitney U or Kruskal-Wallis tests. We also correlated CT indexes with magnetic resonance imaging enhancement characteristics.

Results
In breast cancers, perfusion, blood volume, and peak enhancement intensity values were significantly higher, and time to peak was shorter than in normal glandular tissues and fat (P < 0.001). Perfusion increased significantly in high-grade, ER–, or HER2+ cancers (P < 0.05). Time to peak decreased in ER–, HER2+, and high-grade cancers or in those with high Ki67 levels (P < 0.05). Peak enhancement intensity significantly increased in high-grade cancers (P < 0.05). HER2 overexpressing cancers showed significantly higher perfusion and shorter time to peak than luminal-type cancers (P < 0.05). Perfusion increased and time to peak decreased significantly in cancers with washout enhancement patterns on magnetic resonance imaging.

Conclusions
Low-dose perfusion CT in the prone position is feasible to quantify tumor vascularity in breast cancers, and CT perfusion indexes are significantly correlated with prognostic biomarkers and molecular subtypes of breast cancer.
Matching and Homogenizing Convolution Kernels for Quantitative Studies in Computed Tomography
Authors: Mackin Dennis , Ger Rachel , Gay Skylar , Dodge Cristina , Zhang Lifei , Yang Jinzhong , Jones Aaron Kyle , Court Laurence 
Published: December 2018

Abstract
The sharpness of the kernels used for image reconstruction in computed tomography affects the values of the quantitative image features. We sought to identify the kernels that produce similar feature values to enable a more effective comparison of images produced using scanners from different manufactures. We also investigated a new image filter designed to change the kernel-related component of the frequency spectrum of a postreconstruction image from that of the initial kernel to that of a preferred kernel. A radiomics texture phantom was imaged using scanners from GE, Philips, Siemens, and Toshiba. Images were reconstructed multiple times, varying the kernel from smooth to sharp. The phantom comprised 10 cartridges of various textures. A semiautomated method was used to produce 8 × 2 × 2 cm3 regions of interest for each cartridge and for all scans. For each region of interest, 38 radiomics features from the categories intensity direct (n = 12), gray-level co-occurrence matrix (n = 21), and neighborhood gray-tone difference matrix (n = 5) were extracted. We then calculated the fractional differences of the features from those of the baseline kernel (GE Standard). To gauge the importance of the differences, we scaled them by the coefficient of variation of the same feature from a cohort of patients with non–small cell lung cancer. The noise power spectra for each kernel were estimated from the phantom's solid acrylic cartridge, and kernel-homogenization filters were developed from these estimates. The Philips C, Siemens B30f, and Toshiba FC24 kernels produced feature values most similar to GE Standard. The kernel homogenization filters reduced the median differences from baseline to less than 1 coefficient of variation in the patient population for all of the GE, Philips, and Siemens kernels except for GE Edge and Toshiba kernels. For prospective computed tomographic radiomics studies, the scanning protocol should specify kernels that have been shown to produce similar feature values. For retrospective studies, kernel homogenization filters can be designed and applied to reduce the kernel-related differences in the feature values.
Precision Oncology in Surgery
Authors: Dreyer Stephan B. , Pinese Mark , Jamieson Nigel B. , Scarlett Christopher J. , Colvin Emily K. , Pajic Marina , Johns Amber L. , Humphris Jeremy L. , Wu Jianmin , Cowley Mark J. , Chou Angela , Nagrial Adnan M. , Chantrill Lorraine , Chin Venessa T. , Jones Marc D. , Moran-Jones Kim , Carter Christopher Ross , Dickson Euan J. , Samra Jaswinder S. , Merrett Neil D. , Gill Anthony J. , Kench James G. , Duthie Fraser , Miller David K. , Cooke Susanna , Aust Daniela , Knösel Thomas , Rümmele Petra , Grützmann Robert , Pilarsky Christian , Nguyen Nam Q. , Musgrove Elizabeth A. , Bailey Peter J. , McKay Colin J. , Biankin Andrew V. , Chang David K. 
Published: December 2018

Objective:
We aimed to define preoperative clinical and molecular characteristics that would allow better patient selection for operative resection.

Background:
Although we use molecular selection methods for systemic targeted therapies, these principles are not applied to surgical oncology. Improving patient selection is of vital importance for the operative treatment of pancreatic cancer (pancreatic ductal adenocarcinoma). Although surgery is the only chance of long-term survival, 80% still succumb to the disease and approximately 30% die within 1 year, often sooner than those that have unresected local disease.

Method:
In 3 independent pancreatic ductal adenocarcinoma cohorts (total participants = 1184) the relationship between aberrant expression of prometastatic proteins S100A2 and S100A4 and survival was assessed. A preoperative nomogram based on clinical variables available before surgery and expression of these proteins was constructed and compared to traditional measures, and a postoperative nomogram.

Results:
High expression of either S100A2 or S100A4 was independent poor prognostic factors in a training cohort of 518 participants. These results were validated in 2 independent patient cohorts (Glasgow, n = 198; Germany, n = 468). Aberrant biomarker expression stratified the cohorts into 3 distinct prognostic groups. A preoperative nomogram incorporating S100A2 and S100A4 expression predicted survival and nomograms derived using postoperative clinicopathological variables.

Conclusions:
Of those patients with a poor preoperative nomogram score, approximately 50% of patients died within a year of resection. Nomograms have the potential to improve selection for surgery and neoadjuvant therapy, avoiding surgery in aggressive disease, and justifying more extensive resections in biologically favorable disease.
Metastatic Potential and Survival of Duodenal and Pancreatic Tumors in Multiple Endocrine Neoplasia Type 1
Authors: Vinault Sandrine , Mariet Anne-Sophie , Le Bras Maëlle , Mirallié Eric , Cardot-Bauters Catherine , Pattou François , Ruszniewski Philippe , Sauvanet Alain , Chanson Philippe , Baudin Eric , Elias Dominique , Menegaux Fabrice , Gaujoux Sébastien , Borson-Chazot Françoise , Lifante Jean-Christophe , Caron Philippe , Carrère Nicolas , Tabarin Antoine , Laurent Christophe , Klein Marc , Brunaud Laurent , Niccoli Patricia , Sebag Frédéric , Cadiot Guillaume , Kianmanesh Reza , Luu Maxime , Binquet Christine , Goudet Pierre 
Published: December 2018

Objective:
To assess the distant metastatic potential of duodeno-pancreatic neuroendocrine tumors (DP-NETs) in patients with MEN1, according to functional status and size.

Summary Background Data:
DP-NETs, with their numerous lesions and endocrine secretion-related symptoms, continue to be a medical challenge; unfortunately they can become aggressive tumors associated with distant metastasis, shortening survival. The survival of patients with large nonfunctional DP-NETs is known to be poor, but the overall contribution of DP-NETs to metastatic spread is poorly known.

Methods:
The study population included patients with DP-NETs diagnosed after 1990 and followed in the MEN1 cohort of the Groupe d’étude des Tumeurs Endocrines (GTE). A multistate Markov piecewise constant intensities model was applied to separate the effects of prognostic factors on 1) metastasis, and 2) metastasis-free death or 3) death after appearance of metastases.

Results:
Among the 603 patients included, 39 had metastasis at diagnosis of DP-NET, 50 developed metastases during follow-up, and 69 died. The Markov model showed that Zollinger-Ellison-related tumors (regardless of tumor size and thymic tumor pejorative impact), large tumors over 2 cm, and age over 40 years were independently associated with an increased risk of metastases. Men, patients over 40 years old and patients with tumors larger than 2 cm, also had an increased risk of death once metastasis appeared.

Conclusions:
DP-NETs of 2 cm in size or more, regardless of the associated secretion, should be removed to prevent metastasis and increase survival. Surgery for gastrinoma remains debatable.
Resistance to targeted therapies as a multifactorial, gradual adaptation to inhibitor specific selective pressures
Authors: Velde Robert Vander , Yoon Nara , Marusyk Viktoriya , Durmaz Arda , Dhawan Andrew , Myroshnychenko Daria , Lozano-Peral Diego , Desai Bina , Balynska Olena , Poleszhuk Jan , Kenian Liu , Abazeed Mohamed , Mian Omar , Tan Aik Choon , Haura Eric , Scott Jacob , Marusyk Andriy 
Published: December 2018

ABSTRACTDespite high initial efficacy, therapies that target oncogenic kinases eventually fail in advanced, metastatic cancers. This failure in initially responsive tumors is the direct result of the evolution of drug resistance under therapy-imposed selective pressures. In contrast to the massive body of experimental research on the molecular mechanisms of resistance, understanding of its evolutionary origins and dynamics remains fragmented. Using a combination of experimental studies and mathematical modeling, we sought to dissect the evolution of resistance to different clinical ALK inhibitors in an experimental model of ALK positive NSCLC. We found that resistance can originate from heterogeneous, weakly resistant, sub-populations with variable sensitivity to different ALK inhibitors. Instead of the commonly assumed stochastic single hit (epi) mutational transition, or drug-induced reprogramming, we found evidence of a hybrid scenario, of gradual, multifactorial development through acquisition of multiple cooperating genetic and epigenetic adaptive changes, amplified by selection. Additionally, we found that intermediate resistance phenotypes might present unique, temporally restricted collateral sensitivities, absent in therapy naïve or fully resistant cells, suggesting new opportunities for therapeutic interference.
The mutational features of aristolochic acid-induced mouse and human liver cancers
Authors: Lu Zhao-Ning , Luo Qing , Zhao Li-Nan , Shi Yi , Su Xian-Bin , Han Ze-Guang 
Published: December 2018

AbstractAristolochic acid (AA) derived from traditional Chinese herbal remedies has recently been statistically associated with human liver cancer; however, the causal relationships between AA and liver cancer and the underlying evolutionary process of AA-mediated mutagenesis during tumorigenesis are obscure. Here, we subjected mice, including Pten-deficient ones, to aristolochic acid I (AAI) alone or a combination of AAI and carbon tetrachloride (CCl4), which may induce liver injury. Significantly, AAI promoted the development of liver cancer, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma, in a dose-dependent manner, and it increased the incidence of liver cancer, together with CCl4 or Pten deficiency. AAI could lead to DNA damage and AAI-DNA adducts that initiate liver cancer via characteristic A>T transversions, as indicated by the comprehensive genomic analysis, which revealed recurrent mutations in Hras and some genes encoding components of the Ras/Raf, PI3K, Notch, Hippo, Wnt, DNA polymerase family and the SWI/SNF complex, some of which are also often found in human liver cancer. Mutational signature analysis across human cancer types revealed that the AA-related dominant signature was especially implicated in liver cancer in China, based on very stringent criteria derived from the animal cancer form, in which mutations of TP53 and JAK1 are prone to be significantly enriched. Interestingly, AAI-mediated characteristic A>T mutations were the earliest genetic event driving malignant subclonal evolution in mouse and human liver cancer. In general, this study provides documented evidence for AA-induced liver cancer with featured mutational processes during malignant clonal evolution, laying a solid foundation for the prevention and diagnosis of AA-associated human cancers, especially liver cancer.