bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Genetics of Age-Related Macular Degeneration: Current Status
Authors: Allikmets R. 
Published: January 2018

Age-related macular degeneration (AMD), a multifactorial human disorder, is the most common cause of acquired visual impairment in people over the age 60. It is estimated to affect millions of individuals worldwide. Prevalence increases with age; among persons 75 years and older, mild, or early forms occur in nearly 30% and advanced forms in about 7% of the population. AMD has been associated both with environmental and genetic factors. However, the clinical heterogeneity, late age at onset, and complex etiology have confounded genetic studies of the disorder. Methods applicable to the study of single-gene and some complex disorders (i.e., linkage analysis, sib-pair analysis, transmission disequilibrium test, etc.) have had limited utility in elucidating the genetic components of the complex AMD trait. Recently, substantial progress has been made in determining the genetic basis of monogenic eye disorders. On a monthly basis mutations are identified in new genes responsible for some form of retinal degeneration. Most, if not all, of these genes become candidates for potential involvement in multifactorial disorders especially if the phenotypes of the early-onset Mendelian diseases they cause resemble later onset complex traits. Unfortunately, to date mutational analyses of the candidate genes in AMD patients to date have not yielded the highly anticipated information: statistically significant association of sequence variants with AMD. Whether this is due to the unsuccessful selection of the right candidate genes for the analysis, or the methods employed, or both, has to be elucidated. This review summarizes current knowledge of genetic research aimed at delineating the molecular genetic basis of age-related macular degeneration. Moreover, it attempts to offer some approaches for the future studies directed towards understanding the genetic components of this complex disorder.
Iris Fluorescein Angiography and Iris Indocyanine Green Videoangiography in Pseudoexfoliation Syndrome
Authors: Battaglia Parodi M. , Bondel E. , Saviano S. , Ravalico G. 
Published: January 2018

Background Precise evaluation of the iris vascular pattern in pseudoexfoliation syndrome (PXS) may be difficult with iris fluorescein angiography (IFA) because of the frequent presence of a heavily pigmented iris and conspicuous late leakage. However, iris indocyanine green videoangiography (IICGV) can precisely visualize details of the iris vascular pattern. This study analyzed the utility of IICGV in detecting microvascular changes in PXS and compared these findings with those of IFA. Methods Twenty-eight patients with PXS in both eyes underwent an ophthalmic examination including IFA and IICGV. IICGV was done with the IMAGEnet system H1024. Results IICGV gave better visualization of iris hypoperfusion and anastomotic vessels whereas iris microneovascularisation was far more clearly visible on IFA. IICGV also detected iris pigment epithelium defects. Conclusions IICGV can be considered a useful tool for evaluation of the iris vascular pattern in PXS. Iris hypoperfusion did not appear to contribute to the development of iris microvascular changes.
Coralline Hydroxyapatite Sphere in Orbit Restoration
Authors: Georgiadis N.S. , Terzidou C.D. , Dimitriadis A. S. 
Published: January 2018

Purpose To restore the anophthalmic socket, primarily or secondarily, using a hydroxy-apatite sphere (HA). Methods We used HA in 33 patients (25 male, 8 female), aged from 4 to 68 years (mean 38.1 years) for 19 primary and 14 secondary implantations. HA spheres measured 16 mm in one patient, 18 mm in 21 and 20 mm in 11. The spheres were wrapped in donor sclera preserved in absolute alcohol. All six extraocular muscles were isolated, in the cases where this was possible. Buccal membrane was grafted in three patients to restore the fornices. Drilling was done on four patients using a 3.8 serrated plastic sheath. Results During follow-up of 7 - 69 months we observed no complications except for slight edema in the immediate postoperative period. All patients gained very good to excellent motility of the implant, acceptable symmetric appearance in the case of primary implantation, and a dramatic improvement of facial appearance in the case of secondary implantation. Conclusions HA spheres are an excellent orbital implant for primary and secondary restoration of the anophthalmic socket causing no serious complications
Estimation of intra-arterial chemotherapy distribution to the retina in pediatric retinoblastoma patients using quantitative digital subtraction angiography
Authors: Kondapavulur Sravani , Cooke Daniel L , Kao Andrew , Amans Matthew R , Alexander Matthew , Darflinger Robert , Dowd Christopher F , Higashida Randall T , Damato Bertil , Halbach Van V , Matthay Katherine K , Hetts Steven W 
Published: January 2018

Background and purpose The purpose of this article is to estimate the distribution of superselective intra-arterial chemotherapy (IAC) delivery to ocular target tissue using quantitative digital subtraction angiography (qDSA). Materials and methods From March 2010 to January 2016, 50 ophthalmic artery contrast DSAs obtained immediately prior to IAC infusions in 22 patients were analyzed. This study was conducted under a retrospective review IRB (no. 10-01862). Parametric color-coded DSAs (iFlow, Siemens Medical) were post-processed (MATLAB, The Mathworks Inc.) using two methods: two box regions of interest (pre-retina and globe) and four custom regions of interest (ROIs—ophthalmic artery, choroid, supraclinoid internal carotid artery (ICA), cavernous ICA). Mean interobserver reliability of custom ROI selection is presented as a 95% confidence interval of interclass correlation, and fractional chemotherapy delivery to selected ROIs as means ± standard deviation in this study. Results The estimated fraction of chemotherapy delivered to the globe with the first method was 79.5%. Percentage regional delivery using the second method was as follows: ophthalmic artery, 85.8%; choroid, 60.5%; supraclinoid ICA, 14.2%. The cavernous ICA ROI (encompassing distal catheter and potential reflux) gave a signal equivalent to 9.3% of total delivery. Conclusion Parametric color-coded qDSA can estimate the fraction of IAC delivered to the retina and other orbital structures in ocular retinoblastoma patients. This information can inform delivery location and dosing strategies on a patient-specific basis.
Metabolic Effects of Single-Dose Pamidronate Administration in Prostate Cancer Patients with Bone Metastases
Authors: Berruti A. , Dogliotti L. , Tucci M. , Tarabuzzi R. , Guercio S. , Torta M. , Tampellini M. , Dovio A. , Poggio M. , Scarpa R.M. , Angeli A. 
Published: January 2018

Background Increased osteolysis usually accompanies sclerotic bone metastases from prostate cancer. This provides a rationale for the use of bisphosphonates to treat bone pain and prevent skeletal complications. Methods The fasting urinary levels of calcium, hydroxyproline (OHPRO), pyridinolines (PYD), deoxypyridinolines (DPYD), collagen cross-linked N-telopeptide (NTX) and the serum values of calcium, total alkaline phosphatase and relevant bone isoenzyme, bone gla protein (BGP), carboxy-telopeptide of type I collagen (ICTP) and parathyroid hormone (PTH) were determined at baseline and on the 15th, 30th, 60th and 90th days after single-dose (90 mg) pamidronate administration in 35 consecutive prostate cancer patients with bone metastases. These biochemical indices and serum interleukin 6 (IL-6) were also measured after four days in the last consecutive 17 cases. Results PYD, DPYD and NTX showed a significant decrease lasting four weeks (p<0.01, <0.01 and <0.001, respectively). OHPRO and ICTP did not change significantly. The NTX decline was greater than that of PYD and DPYD (maximum percent decrease: −71.3, −23.1 and −28.2, respectively). Bone formation markers and serum calcium did not change significantly. Serum PTH showed a rapid initial increase followed by a slow decrease (p<0.001). DPYD and NTX patterns did not correlate with changes in bone pain. As observed in the last 17 cases, the maximum osteolysis inhibition after pamidronate occurred on the fourth day after drug infusion. Serum IL-6 levels showed a short-lived decrease preceded by a transient rise on the fourth day. Conclusions Pamidronate is able to induce a decrease in bone resorption without significantly influencing bone formation. The maximum decrease in bone resorption occurs very early. NTX is the most sensitive bone resorption marker in bisphosphonate therapy monitoring. Changes in IL-6 but not bone resorption markers may be useful in the prediction of symptomatic response.
Metalloproteinase-1, Metalloproteinase-7, and p53 Immunoexpression and their Correlation with Clinicopathological Prognostic Factors in Colorectal Adenocarcinoma
Authors: Nunes Benicio L.B.B.P. , Jucá Mário J. , Gomes Edmundo G.A. , Menezes Hunaldo L. , Costa Henrique O. , Matos Delcio , Saad Sarhan S. 
Published: January 2018

Aim The aim of this study was to analyze the immunoexpression of metalloproteinase-1, metalloproteinase-7, and p53 in colorectal adenocarcinoma, and to correlate this with clinicopathological prognostic factors. Material and methods Formalin-fixed paraffin-embedded tumor tissue from 82 patients was analyzed by means of immunohistochemistry, using the streptavidin-biotin method and the tissue microarray technique. Protein tissue expression was correlated with the variables of the degree of cell differentiation, stage, relapse-free survival, recurrence, survival, and specific mortality. Results All of the tumors were positive for metalloproteinase-1, while 50 (61%) were positive for metalloproteinase-7, and 32 (39%) were negative for the latter. For p53, 70 (85.4%) of the tumors were positive and 12 (14.6%) were negative. Correlation of the marker expressions separately and in conjunction did not produce any statistically significant data. Conclusion The immunoexpression of metalloproteinase-1, metalloproteinase-7, and p53 did not correlate with recurrence, mortality, relapse-free survival, survival, degree of cell differentiation, or staging of colorectal cancer.
Quantitative DTI metrics in a canine model of Krabbe disease: comparisons versus age-matched controls across multiple ages
Authors: Li Jonathan Y , Middleton Dana M , Chen Steven , White Leonard , Corado Carley R , Vite Charles , Bradbury Allison , Provenzale James M 
Published: January 2018

Purpose The purpose of this study was to compare quantitative diffusion tensor imaging metrics in dogs affected with a model of Krabbe disease to age-matched normal controls. We hypothesized that fractional anisotropy would be decreased and radial diffusivity would be increased in the Krabbe dogs. Methods We used a highly reproducible region-of-interest interrogation technique to measure fractional anisotropy and radial diffusivity in three different white matter regions within the internal capsule and centrum semiovale in four Krabbe affected brains and three age-matched normal control brains. Results Despite all four Krabbe dogs manifesting pelvic limb paralysis at the time of death, age-dependent differences in DTI metrics were observed. In the 9, 12, and 14 week old Krabbe dogs, FA values unexpectedly increased and RD values decreased. FA values were generally higher and RD values generally lower in both regions of the internal capsule in the Krabbe brains during this period. FA values in the brain from the 16 week old Krabbe dog decreased and were lower than in control brains and RD values increased and were higher than in control brain. Conclusion Our findings suggest that FA and RD in the internal capsule and centrum semiovale are affected differently at different ages, despite disease having progressed to pelvic limb paralysis in all dogs evaluated. In 9, 12, and 14 week old Krabbe dogs, higher FA values and lower RD values are seen in the internal capsule. However, in the 16 week old Krabbe dog, lower FA and higher RD values are seen, consistent with previous observations in Krabbe dogs, as well as observations in human Krabbe patients.
The evolving role of traditional birth attendants in maternal health in post-conflict Africa: A qualitative study of Burundi and northern Uganda
Authors: Chi Primus Che , Urdal Henrik 
Published: January 2018

Objectives: Many conflict-affected countries are faced with an acute shortage of health care providers, including skilled birth attendants. As such, during conflicts traditional birth attendants have become the first point of call for many pregnant women, assisting them during pregnancy, labour and birth, and in the postpartum period. This study seeks to explore how the role of traditional birth attendants in maternal health, especially childbirth, has evolved in two post-conflict settings in sub-Saharan Africa (Burundi and northern Uganda) spanning the period of active warfare to the post-conflict era. Methods: A total of 63 individual semi-structured in-depth interviews and 8 focus group discussions were held with women of reproductive age, local health care providers and staff of non-governmental organisations working in the domain of maternal health who experienced the conflict, across urban, semi-urban and rural settings in Burundi and northern Uganda. Discussions focused on the role played by traditional birth attendants in maternal health, especially childbirth during the conflict and how the role has evolved in the post-conflict era. Transcripts from the interviews and focus group discussions were analysed by thematic analysis (framework approach). Results: Traditional birth attendants played a major role in childbirth-related activities in both Burundi and northern Uganda during the conflict, with some receiving training and delivery kits from the local health systems and non-governmental organisations to undertake deliveries. Following the end of the conflict, traditional birth attendants have been prohibited by the government from undertaking deliveries in both Burundi and northern Uganda. In Burundi, the traditional birth attendants have been integrated within the primary health care system, especially in rural areas, and re-assigned the role of ‘birth companions’. In this capacity they undertake maternal health promotion activities within their communities. In northern Uganda, on the other hand, traditional birth attendants have not been integrated within the local health system and still appear to undertake clandestine deliveries in some rural areas. Conclusion: The prominent role of traditional birth attendants in childbirth during the conflicts in Burundi and northern Uganda has been dwindling in the post-conflict era. Traditional birth attendants can still play an important role in facilitating facility and skilled attended births if appropriately integrated with the local health system.
Detection of the intention to grasp during reach movements
Authors: de Vries JC , van Ommeren AL , Prange-Lasonder GP , Rietman JS , Veltink PH 
Published: January 2018

Introduction Soft-robotic gloves have been developed to enhance grip to support stroke patients during daily life tasks. Studies showed that users perform tasks faster without the glove as compared to with the glove. It was investigated whether it is possible to detect grasp intention earlier than using force sensors to enhance the performance of the glove. Methods This was studied by distinguishing reach-to-grasp movements from reach movements without the intention to grasp, using minimal inertial sensing and machine learning. Both single-user and multi-user support vector machine classifiers were investigated. Data were gathered during an experiment with healthy subjects, in which they were asked to perform grasp and reach movements. Results Experimental results show a mean accuracy of 98.2% for single-user and of 91.4% for multi-user classification, both using only two sensors: one on the hand and one on the middle finger. Furthermore, it was found that using only 40% of the trial length, an accuracy of 85.3% was achieved, which would allow for an earlier prediction of grasp during the reach movement by 1200 ms. Conclusions Based on these promising results, further research will be done to investigate the possibility to use classification of the movements in stroke patients.
AHRRhypomethylation, lung function, lung function decline and respiratory symptoms
Authors: Kodal Jakob B. , Kobylecki Camilla J. , Vedel-Krogh Signe , Nordestgaard Børge G. , Bojesen Stig E. 
Published: January 2018

Epigenome-wide association studies have shown a consistent association between smoking exposure and hypomethylation in the aryl hydrocarbon receptor repressor (AHRR) gene (cg05575921). We tested the hypothesis thatAHRRhypomethylation is associated with low lung function, steeper lung function decline, and respiratory symptoms in the general population.AHRRmethylation extent was measured in 9113 individuals from the 1991–1994 examination of the Copenhagen City Heart Study, using bisulfite-treated leukocyte DNA. Spirometry at the time of blood sampling was available for all individuals. Lung function was measured again for 4532 of these individuals in 2001–2003.Cross-sectionally, a 10% lower methylation extent was associated with a 0.2 z-score (95% CI 0.1–0.2) lower forced expiratory volume in 1 s (FEV1) after multivariable adjustment including smoking. Hypomethylation was also associated with a lower z-score for both forced vital capacity (FVC) and FEV1/FVC. In prospective analyses, individuals in the lowestversushighest tertile of methylation extent had a steeper decline in FEV1/height3(p for examination×methylation interaction=0.003) and FVC/height3(p=0.01), but not FEV1/FVC (p=0.08). Multivariable-adjusted odds ratios per 10% lower methylation extent were 1.31 (95% CI 1.18–1.45) for chronic bronchitis and 1.21 (95% CI 1.13–1.30) for any respiratory symptoms.AHRRhypomethylation was associated with low lung function, steeper lung function decline, and respiratory symptoms.
Window detection in facade images for risk assessment in tunneling
Authors: Neuhausen Marcel , Obel Markus , Martin Alexander , Mark Peter , König Markus 
Published: January 2018

Abstract
Background
Settlements induced by tunneling in inner urban areas can easily damage above ground structures. This already has to be considered in early planning of tunneling routes. Assessing the risk of damages to structures on hypothetical tunneling routes inflicted by such settlements beforehand enables routes’ comparability. Hereby, it facilitates the choice of the optimal tunneling route in terms of potential damages and of suitable countermeasures. Risk analyses of structures establishing the assessment obtain relevant data from various sources. Some data even has to be gathered manually. Virtual building models could ease this process and facilitate analyses for entire districts as they combine several required information in a single data set. Commonly, these are yet modelled very coarse. Relevant details like facade openings, which highly affect a structures stiffness, are not included.

Methods
In this paper, we propose a system which detects windows in facade images. This is used to subsequently enrich existing virtual building models allowing for a precise risk assessment. For this, we apply a sliding window detector which employs a cascaded classifier to obtain windows in images patches.

Results
Our system yields sufficient results on facade images of several countries showing its general applicability despite regional and architectural variation in the facades’ and windows’ appearance. In an ensuing case study, we assess the risk of damages to structures based on detections of our system using different analysis methods.

Conclusions
We contrast these results to assessments using manually gathered data. Hereby, we show that the detection rate of our proposed system is sufficient for a reliable estimation of a structure’s damage class.
Badges for sharing data and code at Biostatistics: an observational study
Authors: Rowhani-Farid Anisa , Barnett Adrian G. 
Published: January 2018

Background: Reproducible research includes sharing data and code. The reproducibility policy at the journal Biostatistics rewards articles with badges for data and code sharing. This study investigates the effect of badges at increasing reproducible research, specifically, data and code sharing, at Biostatistics. Methods: The setting of this observational study is the Biostatistics and Statistics in Medicine (control journal) online research archives. The data consisted of 240 randomly sampled articles from 2006 to 2013 (30 articles per year) per journal, a total sample of 480 articles. Data analyses included: plotting probability of data and code sharing by article submission date, and Bayesian logistic regression modelling to test for a difference in the probability of making data and code available after the introduction of badges at Biostatistics. Results: The probability of data sharing was higher at Biostatistics than the control journal but the probability of code sharing was comparable for both journals. The probability of data sharing increased by 3.5 times (95% credible interval: 1.4 to 7.4 times, p-value probability that sharing increased: 0.996) after badges were introduced at Biostatistics. On an absolute scale, however, this difference was only a 7.3% increase in data sharing (95% CI: 2 to 14%, p-value: 0.996). Badges did not have an impact on code sharing at the journal (mean increase: 1.1 times, 95% credible interval: 0.45 to 2.14 times, p-value probability that sharing increased: 0.549). Conclusions: The effect of badges at Biostatistics was a 7.3% increase in the data sharing rate, 5 times less than the effect of badges on data sharing at Psychological Science (37.9% badge effect). Though the effect of badges at Biostatistics did not impact code sharing, and was associated with only a moderate effect on data sharing, badges are an interesting step that journals are taking to incentivise and promote reproducible research.
Resolution of Spurious Immunonephelometric IgG Subclass Measurement Discrepancies by LC-MS/MS
Authors: van der Gugten Grace , DeMarco Mari L , Chen Luke Y C , Chin Alex , Carruthers Mollie , Holmes Daniel T , Mattman Andre 
Published: January 2018

Abstract

BACKGROUND
The Binding Site immunonephelometric (IN) IgG subclass reagents (IgG1, IgG2, IgG3, IgG, BSIN) are used for assessment of both immunodeficiency and IgG4-related disease (IgG4-RD). In our laboratory, suspected analytic errors were noted in patients with increases in IgG4: The sum of the individual IgG subclasses was substantially greater than the measured total IgG concentrations (unlike samples with normal IgG4), and the IgG4 concentration was always less than the IgG2 concentration.

METHODS
We developed a tryptic digest LC-MS/MS method to quantify IgG1, IgG2, IgG3, and IgG4 in serum. Samples with IgG4 concentrations ranging from &lt;0.03 g/L to 32 g/L were reanalyzed by LC-MS/MS, and a subset was also reanalyzed by Siemens IN (SIN) subclass measurements.

RESULTS
Multivariate linear regression identified 3 subclass tests with multiple predictors of the measured subclass concentration. For these 3 subclasses, the predominant predictors were (in terms of LC-MS/MS IgG subclass measurement coefficients) BSIN IgG1 = 0.89·IgG1 + 0.4·IgG4; BSIN IgG2 = 0.94·IgG4 + 0.89·IgG2; and SIN IgG2 = 0.72·IgG2 + 0.24·IgG4.

CONCLUSIONS
There is apparent IgG4 cross-reactivity with select IN subclass measurements affecting tests from both vendors tested. These findings can be explained either by direct cross-reactivity of the IN reagents with the IgG4 subclass or unique physicochemical properties of IgG4 that permit nonspecific binding of IgG4 heavy chain to other IgG immunoglobulin heavy chains. Irrespective of the mechanism, the observed intermethod discrepancies support the use of LC-MS/MS as the preferred method for measurement of IgG subclasses when testing patients with suspected IgG4-RD.