bluuebunny/crossref_metadata_2025 huggingface dataset:
THREE-YEAR OUTCOMES IN A RANDOMIZED SINGLE-BLIND CONTROLLED TRIAL OF INTRAVITREAL RANIBIZUMAB AND ORAL SUPPLEMENTATION WITH DOCOSAHEXAENOIC ACID AND ANTIOXIDANTS FOR DIABETIC MACULAR EDEMA
Authors: Lafuente María , Ortín Lourdes , Argente María , Guindo José L. , López-Bernal María D. , López-Román Francisco J. , Domingo Joan Carles , Lajara Jerónimo
Published: February 2018

Purpose:

To report 3-year results of a randomized single-blind controlled trial of intravitreal ranibizumab combined with oral docosahexaenoic acid (DHA) supplementation versus ranibizumab alone in patients with diabetic macular edema.

Methods:

There were 26 patients (31 eyes) in the DHA group and 29 (38 eyes) in the control group. Ranibizumab (0.5 mg) was administered monthly for the first 4 months followed by a pro re nata (PRN) regimen. In the experimental group, patients received oral DHA supplementation (1,050 mg/day) (Brudyretina 1.5 g).

Results:

At 36 months, mean decrease of central subfield macular thickness was higher in the DHA-supplementation group than in controls (275 ± 50 μm vs. 310 ± 97 μm) with significant differences at Months 25, 30, 33, and 34. Between-group differences in best-corrected visual acuity were not found, but the percentages of ETRDS gains >5 and >10 letters were higher in the DHA-supplementation group. Differences serum HbA1c, plasma total antioxidant capacity values, erythrocyte DHA content, and serum IL-6 levels were all significant in favor of the DHA-supplementation group.

Conclusion:

The addition of a high-rich DHA dietary supplement to intravitreal ranibizumab was effective to achieve better sustained improvement of central subfield macular thickness outcomes after 3 years of follow-up as compared with intravitreal ranibizumab alone.
ASSOCIATION OF OBSTRUCTIVE SLEEP APNEA WITH CENTRAL SEROUS CHORIORETINOPATHY AND CHOROIDAL THICKNESS
Authors: Wu Chris Y. , Riangwiwat Tanawan , Rattanawong Pattara , Nesmith Brooke L. W. , Deobhakta Avnish
Published: February 2018

Purpose:

Obstructive sleep apnea (OSA) has been associated with an array of ocular disorders. This systematic review aims to investigate the association of OSA with central serous chorioretinopathy (CSCR) and subfoveal choroidal thickness changes on enhanced depth imaging optical coherence tomography.

Methods:

Systematic review and meta-analysis of all articles published up to November 2017 examining rate of OSA in patients with CSCR versus controls or examining subfoveal choroidal thickness measurements on enhanced depth imaging optical coherence tomography in patients with OSA versus controls. Pooled odds ratios and weighted mean difference with 95% confidence intervals (CIs) were calculated.

Results:

For the CSCR/OSA analysis, 7,238 patients (1,479 with CSCR and 5,759 controls) from 6 studies were eligible. For the choroidal thickness/OSA analysis, 778 eyes of 778 patients (514 with OSA and 264 controls) from 9 studies were eligible. Patients with CSCR had a 1.56 increased odds of having OSA than controls (odds ratio, 1.56; 95% CI, 1.16–2.10). There was no statistically significant difference in choroidal thickness between mild OSA subjects and controls (weighted mean difference = −3.17; 95% CI, −19.10 to 12.76). Patients with moderate OSA (weighted mean difference = −24.14; 95% CI, −42.16 to −6.12) and severe OSA (weighted mean difference = −51.19; 95% CI, −99.30 to −3.08) had thinner choroidal thickness measurements than controls.

Conclusion:

In summary, our results suggest that patients with CSCR are more likely to have OSA, and that moderate/severe OSA is associated with smaller subfoveal choroidal measurements on enhanced depth imaging optical coherence tomography.
USE OF THE ISCHEMIC INDEX ON WIDEFIELD FLUORESCEIN ANGIOGRAPHY TO CHARACTERIZE A CENTRAL RETINAL VEIN OCCLUSION AS ISCHEMIC OR NONISCHEMIC
Authors: Thomas Akshay S. , Thomas Mridul K. , Finn Avni P. , Fekrat Sharon
Published: February 2018

Purpose:

To understand the relationship between baseline ischemic index (IsI) values on ultra-widefield fluorescein angiography and classification as ischemic central retinal vein occlusion (CRVO).

Methods:

Single-center retrospective cohort study of CRVO patients imaged using ultra-widefield fluorescein angiography from which IsI values were calculated. An ischemic CRVO was defined as those eyes with an afferent pupillary defect and counting fingers acuity or worse or neovascularization during the first year of follow-up. Logistic regression was performed to characterize the relation between the IsI and clinical outcomes.

Results:

Sixty eyes of 60 treatment-naive CRVO patients with baseline ultra-widefield fluorescein angiography and ≥1 year of follow-up were identified. Those with an IsI ≥35% were significantly more likely to have an ischemic CRVO during the first year of follow-up than those with an IsI <35% (83.3 vs. 13.9%, odds ratio 111, P < 0.0001). Baseline and final logarithm of the minimum angle of resolution acuity were worse in eyes with an IsI ≥35% (1.18 vs. 0.46, P < 0.001 and 1.26 vs. 0.45, P < 0.001, respectively) despite similar baseline and final central subfield thickness (P = 0.1–0.23).

Conclusion:

A baseline IsI of ≥35% on ultra-widefield fluorescein angiography in eyes with treatment-naive CRVO was sensitive (90%) and specific (92.5%) for classification as an ischemic CRVO during the first year of follow-up.
Dyadic differences in friendships of adolescents with chronic pain compared with pain-free peers
Authors: Forgeron Paula A. , Chambers Christine T. , Cohen Janice , Dick Bruce D. , Finley G. Allen , Lamontagne Christine
Published: February 2018

A multisite cross-sectional study was conducted to examine dyadic friendship features between adolescents with chronic pain (ACP) and their friends compared with non-pain adolescent friendship dyads and the association of these friendship features with loneliness and depressive symptoms. Participants completed a battery of standardized measures to capture friendship features (friendship quality, closeness, and perceived social support from friends) and indices of social–emotional well-being. Sixty-one same sex friendship dyads (122 adolescents) participated; 30 friendship dyads included an adolescent with chronic pain and 52 dyads were female. Adolescents with chronic pain scored significantly higher on measures of loneliness and depressive symptoms compared with all other participants. Hierarchical Multiple Regression analysis revealed that friendship features predicted loneliness and depressive symptoms. Chronic pain predicted loneliness and depressive symptoms above and beyond friendship features. Actor Partner Interdependence Modeling found perceived social support from friends had differing associations on loneliness and depressive symptoms for dyads with a chronic pain member compared with pain-free control dyads. Friendship features were associated with loneliness and depressive symptoms for adolescents, but friendship features alone did not explain loneliness and depressive symptoms for ACP. Further research is needed to understand whether pain-related social support improves loneliness and depressive symptoms for ACP. Furthermore, a more nuanced understanding of loneliness in this population is warranted. Strategies to help ACP garner needed social support from friends are needed to decrease rates of loneliness to improve long-term outcomes.
Paying for Outcomes in Medicaid
Authors: Roohan Patrick J.
Published: February 2018

Medicaid can improve quality and reduce costs by adopting a transparent quality measurement system based on outcomes that will improve quality and reduce costs.
Identifying Demographic and Preadmission Factors Predictive of Success on the National Physical Therapy Licensure Examination for Graduates of a Public Physical Therapist Education Program
Authors: Coleman-Salgado Bryan , Barakatt Edward
Published: February 2018

Background and Purpose.

A primary outcome of concern to the California State University, Sacramento physical therapy program is the ability of graduates to pass the National Physical Therapy Examination (NPTE) for licensure. The purpose of this case study was to identify the predictive strength of preadmission demographic factors, academic performance, and standardized test scores in graduates' ability to pass the NPTE.

Case Description.

Preadmission data from 11 years of graduates from a single Master of Physical Therapy (MPT) program (n = 320) were analyzed, including prerequisite grade point average (pGPA), analytic Graduate Record Examination (GRE), verbal GRE and quantitative GRE (qGRE) scores, sex, English as a second language (ESL) status, and NPTE test results. The bivariate association of each preadmission variable to NPTE success was assessed, and receiver operating characteristic curve analysis was performed to determine the optimal cutoff score of each continuous variable. Multifactor logistic regression analysis was performed to determine which independent variables were most predictive of NPTE success.

Outcomes.

Of the 320 MPT graduates, 284 (88.7%) passed the NPTE on the first attempt and 305 (95.3%) passed on the first or second attempt. Of all MPT graduates, 182 (57%) were females, and 57 (18%) reported that English was their second language. All three of the GRE subscale average scores, pGPA, and ESL were significantly associated with NPTE outcomes. Persons with ESL were significantly more likely to need more than one attempt to pass the NPTE. The qGRE score was found to be the strongest predictor of NPTE outcomes in the multifactor logistic regression analysis, whether looking at first-time passing rates or second-time pass rates.

Discussion and Conclusion.

The strongest preadmission variable for NPTE success was the qGRE score of ≥29th percentile, and this cutoff score explained the variance predicted by ESL and pGPA. The admission committee used this data to implement an evidence-based admission's minimum threshold for qGRE. This case is an example of how a physical therapist education program can analyze its own data to apply evidence to its admission criteria that best serve the mission of the program.
High Rates of High-Grade Cervical Dysplasia in High-Risk Young Women With Low-Grade Cervical Cytology
Authors: Daily Laura R. , Erickson Britt K. , Pasko Daniel N. , Straughn J. Michael , Huh Warner K. , Leath Charles A.
Published: February 2018

Objective

The aim of the study was to determine rates of cervical intraepithelial neoplasia (CIN) 2 or greater in high-risk, racially diverse, young women with low-grade cytology.

Materials and Methods

After institutional review board approval, a cross-sectional study of 21- to 24-year-old women with low-grade cytology (atypical squamous cells of undetermined significance, high-risk human papillomavirus+, low-grade squamous intraepithelial lesion, or human papillomavirus+ only) managed with colposcopy at our university-based clinic between May 2011 and April 2013 were identified. Demographics and pathologic data were collected including age, race, parity, smoking status, screening history, and histology. Studentttest and χ2tests were used to compare women with and without CIN 2 or 3. Univariate analysis was performed with demographic data.

Results

One thousand fifty-eight women with a mean (SD) age of 22.5 (1.1) were included. Most patients (59.5%) were parous, 36.1% were smokers, and most (52.9%) were black. These patients were considered high risk because of their lower socioeconomic status, minority status, lack of insurance, or having Medicaid and therefore had limited access to preventative health care. Based on colposcopy, the prevalence of CIN 2+ was 19.1%: 13.9% (95% CI = 11.9–16.1) CIN 2 and 5.1% (95% CI = 3.9–6.6) CIN 3. There was an overall prevalence of 4.7% (95% CI = 3.7%–6.3%) of CIN 3 from excisional pathology from the 157 of 185 patients who returned for a recommended excisional procedure. Smoking (odds ratio = 1.64, 95% CI = 1.2–2.25) and a history of high-grade cytology (odds ratio = 2.06, 95% CI = 1.02–4.01) were associated with CIN 2/3.

Conclusions

High prevalence of CIN 2/3 in young women with low-grade cervical cytology in this population suggests that it may be prudent to consider alternative surveillance such as colposcopy in similar high-risk populations.
Early Treatment Response Predicts Outcome in Paediatric Ulcerative Colitis
Authors: Gasparetto Marco , Wong‐Spracklen Vivien , Torrente Franco , Howell Kate , Brennan Mary , Noble‐Jamieson Gabriele , Heuschkel Robert , Zilbauer Matthias
Published: February 2018

The disease course of children with ulcerative colitis (UC) varies substantially. Published data on predictors of disease outcomes in children remain scarce. We validate clinical predictors of outcomes in 93 children with UC in a single centre (age range: 2–18 years, minimum follow‐up: 18 months). We stratified children into 3 groups according to their disease course, that is, 1 = mild (38/93, 40.9%), 2 = moderate (38/93, 40.9%), 3 = severe (17, 18.2%). Comparison of clinical and biochemical parameters was performed between groups using Chi‐square, Mann‐Whitney, and log‐rank tests. Predictors of a severe disease course included pancolitis (P 0.01), low albumin (P 0.005), low haemoglobin at diagnosis (P 0.04), paediatric ulcerative colitis activity index (PUCAI) at 3 months, and nonresponse to steroids at 3 months (P 0.0001). In our cohort, failure to achieve remission at 3 months implied an 80% likelihood to require biologics or major surgery within 18 months. A specific 3‐month review point is recommended to guide future management.
Characterization of Chemical Constituents of Human Sweat
Authors: Moulvi Aafrinnaz , Minz Pooja , Rath Subrata , Ashma Richa
Published: February 2018

There is a strong evidence in the literature that human odor is unique to an individual; therefore, the focus of this study was to strengthen this evidence through the testing of sweat samples on unrelated individuals with the same ethnicity. Sweat samples were collected from 42 unrelated Indian males and females residing in the same city to determine the chemical constituents in human sweat. The volatile compounds of sweat were subsequently analyzed and identified using gas chromatography–mass spectrometry, and a National Institute of Standards and Technology library was used for individual profiling. A total of 78 compounds were identified in human sweat tested with 22 compounds found to be unique to the individual (frequency of occurrence one). A scent profile, or “chexmotype,” unique to the sweat of each individual was obtained. This is the first extensive study on an Indian population with 36 new compounds detected in human sweat.
Randomized Cross-over Comparison of Icon™ Reusable Underwear to Disposable Pads for the Management of Mild to Moderate Urinary Incontinence
Authors: Alam Pakeeza A. , Burkett Linda S. , Clark Brett A. , White Nicola C. , Tefera Eshetu A. , Richter Lee A.
Published: February 2018

Objective

The objective of this study was to compare disposable pads to Icon™ reusable underwear for the management of urinary incontinence on dimensions of quality of life and product performance.

Methods

This randomized cross-over trial included women with mild to moderate urinary incontinence as defined by baseline responses to the International Consultation on Incontinence Questionnaire—Short Form. Excluded were patients who had fecal incontinence or an active urinary tract infection. Participants were randomized to 2 days of Icon™ underwear or disposable pads use and then completed another 2 days using the alternate product. Outcome measures were responses to Incontinence Quality of Life Instrument (I-QOL) and Product Performance Questionnaire for each product.

Results

Of the 70 women who were randomized, 52 completed the study. There was no significant difference between Icon™ underwear and disposable pads with regards to I-QOL total scores (66.2 ± 23.4 vs 65.5 ± 24.5, P = 0.71) or I-QOL subscores: avoidance and limiting behaviors (62.1 ± 24.4 vs 62.4 ± 25.0, P = 0.88), psychosocial impacts (74.4 ± 25.0 vs 73.4 ± 25.6, P = 0.51), and social embarrassment (57.8 ± 27.8 vs 56.1 ± 29.5, P = 0.43). Icon™ underwear scored significantly better than disposable pads on the Product Performance Questionnaire, with regards to overall impression (P = 0.0002), fit (P < 0.0001), discreteness (P < 0.0001), comfort when dry (P < 0.0001), comfort when wet (P = 0.0008), ability to keep skin dry (P = 0.0034), and kindness to skin (P < 0.0001). There was no difference between products in ability to hold urine without leaking (P = 0.40) or prevent odor when worn (P = 0.41).

Conclusions

There was no difference in quality of life measures between Icon™ underwear and disposable pad users; however, Icon™ underwear was preferred on product performance.
Predicting Pain Levels Following Vaginal Reconstructive Surgery: Who Is at Highest Risk?
Authors: Shatkin-Margolis Abigail , Crisp Catrina C. , Morrison Christopher , Pauls Rachel N.
Published: February 2018

Objectives

An ability to anticipate individuals at increased risk of postoperative pain would improve coordination of care and patient satisfaction. We sought to describe predictive factors of postoperative pain following vaginal reconstructive surgery.

Methods

This institutional review board–approved, retrospective study used previously collected data from research performed at 1 center from 2009 to 2015. Eligible trials enrolled subjects undergoing vaginal reconstructive surgery for pelvic organ prolapse. All studies used a validated visual analog scale (VAS) for pain on postoperative day 1. Other information collected included pain medication use, medical and surgical history, and demographics. Linear regression analyses, multiple regression analyses, Mann-Whitney U, and Kruskal-Wallis tests were used to analyze the relationship between VAS scores and other variables.

Results

Six studies were analyzed with a total of 364 patients. The median age was 60 years (interquartile range, 16 years), and the median pain score on postoperative day 1 was 35 mm on a 100-mm VAS. Patients younger than 60 years (P < 0.001), those who used tobacco (P = 0.014), those who used pain medication prior to surgery (P = 0.007), and those who did not have a concomitant midurethral sling (P = 0.018) had significantly higher pain scores postoperatively. A trend was also noted with operating times greater than 210 minutes (P = 0.057) and preexisting history of depression (P = 0.065). Multiple regression was performed, and age, depression, tobacco use, and concomitant sling were found to be independent factors predictive of postoperative pain scores.

Conclusions

Age, depression, tobacco use, and concomitant midurethral sling are significant independent factors predictive of postoperative pain following vaginal reconstructive surgery.
Optic Nerve Head and Macular Optical Coherence Tomography Measurements in Papilledema Compared With Pseudopapilledema
Authors: Aghsaei Fard Masoud , Okhravi Sara , Moghimi Sasan , Subramanian Prem S.
Published: February 2018

Background:

To compare macular and optic nerve head optical coherence tomography (OCT) measurements in mild to moderate papilledema and pseudopapilledema.

Methods:

One hundred nineteen eyes of 61 patients with mild to moderate papilledema, 84 eyes of 48 patients with pseudopapilledema, and 60 eyes of 60 healthy normal individuals were enrolled in this cross-sectional study. Using Spectralis SD-OCT, macular scans with macular ganglion cell–inner plexiform layer (GCIPL) and macular retinal nerve fiber layer (RNFL) segmentation were performed and divided into 2 regions (inner and outer, with a diameter of 3 and 6 mm, respectively); in addition, Bruch membrane opening (BMO) area and peripapillary RNFL thickness were obtained.

Results:

BMO area was similar in papilledema (1.83 ± 0.34 mm2), pseudopapilledema (1.85 ± 0.37 mm2), and controls (1.85 ± 0.32 mm2). Average inner region macular GCIPL thickness in the papilledema, pseudopapilledema, and control groups was 87.2 ± 14.4 μm, 90.8 ± 6.1 μm, and 91.2 ± 9.8 μm, respectively (P > 0.05). Outer temporal region macular GCIPL was significantly thinner in the papilledema group compared with control group (P = 0.01). By contrast, outer inferior and outer nasal macular RNFL sectors were significantly thicker in the papilledema group compared with control groups (P = 0.01 and P < 0.01, respectively). Those measures were not different between pseudopapilledema and control eyes.

Conclusions:

In papilledema eyes, outer temporal region macular GCIPL thickness decreased and outer inferior and outer nasal macular RNFL sectors thickness increased compared with the control group. These changes were not observed in the pseudopapilledema group.
The effects of haploid selection on Y chromosome evolution in two closely related dioecious plants
Authors: Sandler George , Beaudry Felix E.G. , Barrett Spencer C.H. , Wright Stephen I.
Published: February 2018

The evolution of sex chromosomes is usually considered to be driven by sexually antagonistic selection in the diploid phase. However, selection during the haploid gametic phase of the lifecycle has recently received theoretical attention as possibly playing a central role in sex chromosome evolution, especially in plants where gene expression in the haploid phase is extensive. In particular, male-specific haploid selection might favour the linkage of pollen beneficial alleles to male sex determining regions on incipient Y chromosomes. This linkage might then allow such alleles to further specialise for the haploid phase. Purifying haploid selection is also expected to slow the degeneration of Y-linked genes expressed in the haploid phase. Here, we examine the evolution of gene expression in flower buds and pollen of two species ofRumexto test for signatures of haploid selection acting during plant sex chromosome evolution. We find that genes with high ancestral pollen expression bias occur more often on sex chromosomes than autosomes and that genes on the Y chromosome are more likely to become enriched for pollen expression bias. We also find that genes with low expression in pollen are more likely to be lost from the Y chromosome. Our results suggest that sex-specific haploid selection during the gametophytic stage of the lifecycle may be a major contributor to several features of plant sex chromosome evolution.
Dissociable contributions of the amygdala to the immediate and delayed effects of emotional arousal on memory
Authors: Schümann Dirk , Sommer Tobias
Published: February 2018

Emotionally arousal enhances memory encoding and consolidation leading to better immediate and delayed memory. Although the central noradrenergic system and the amygdala play critical roles in both effects of emotional arousal, we have recently shown that these effects are at least partly independent of each other, suggesting distinct underlying neural mechanisms. Here we aim to dissociate the neural substrates of both effects in 70 female participants using an emotional memory paradigm to investigate how neural activity, as measured by fMRI, and a polymorphism in the α2B-noradrenoceptor vary for these effects. To also test whether the immediate and delayed effects of emotional arousal on memory are stable traits, we invited back participants who were a part of a large-scale behavioral memory study about 3.5 years ago. We replicated the low correlation of the immediate and delayed emotional enhancement of memory across participants (r = 0.16) and observed, moreover, that only the delayed effect was, to some degree, stable over time (r = 0.23). Bilateral amygdala activity, as well as its coupling with the visual cortex and the fusiform gyrus, was related to the preferential encoding of emotional stimuli, which is consistent with affect-biased attention. Moreover, the adrenoceptor genotype modulated the bilateral amygdala activity associated with this effect. The left amygdala and its coupling with the hippocampus was specifically associated with the more efficient consolidation of emotional stimuli, which is consistent with amygdalar modulation of hippocampal consolidation.
Reading Profiles in Multi-site Data with Missingness
Authors: Eckert Mark A. , Vaden Kenneth I. , Gebregziabher Mulugeta ,   Dyslexia Data Consortium
Published: February 2018

Children with reading disability exhibit varied deficits in reading and cognitive abilities that contribute to their reading comprehension problems. Some children exhibit primary deficits in phonological processing, while others can exhibit deficits in oral language and executive functions that affect comprehension. This behavioral heterogeneity is problematic when missing data prevent the characterization of different reading profiles, which often occurs in retrospective data sharing initiatives without coordinated data collection. Here we show that reading profiles can be reliably identified based on Random Forest classification of incomplete behavioral datasets, after the missForest method is used to multiply impute missing values. Results from simulation analyses showed that reading profiles could be accurately classified across degrees of missingness (e.g., ~5% classification error for 30% missingness across the sample). The application of missForest to a real multi-site dataset (n = 924) showed that reading disability profiles significantly and consistently differed in reading and cognitive abilities for cases with and without missing data. The results of validation analyses indicated that the reading profiles (cases with and without missing data) exhibited significant differences for an independent set of behavioral variables that were not used to classify reading profiles. Together, the results show how multiple imputation can be applied to the classification of cases with missing data and can increase the integrity of results from multi-site open access datasets.
FERONIA’s sensing of cell wall pectin activates ROP GTPase signaling in Arabidopsis
Authors: Lin Wenwei , Tang Wenxin , Anderson Charles T. , Yang Zhenbiao
Published: February 2018

Plant cells need to monitor the cell wall dynamic to control the wall homeostasis required for a myriad of processes in plants, but the mechanisms underpinning cell wall sensing and signaling in regulating these processes remain largely elusive. Here, we demonstrate that receptor-like kinase FERONIA senses the cell wall pectin polymer to directly activate the ROP6 GTPase signaling pathway that regulates the formation of the cell shape in the Arabidopsis leaf epidermis. The extracellular malectin domain of FER directly interacts with de-methylesterified pectin in vivo and in vitro. Both loss-of-FER mutations and defects in the pectin biosynthesis and de-methylesterification caused changes in pavement cell shape and ROP6 signaling. FER is required for the activation of ROP6 by de-methylesterified pectin, and physically and genetically interacts with the ROP6 activator, RopGEF14. Thus, our findings elucidate a cell wall sensing and signaling mechanism that connects the cell wall to cellular morphogenesis via the cell surface receptor FER.
Controlling insulin resistance through modulation of interplay between mediators of cellular senescence: A mathematical study
Authors: Arora Chakit
Published: February 2018

Obesity, metabolic syndrome and premature ageing form a hugely researched and discussed area of interest these days. In the pathology of this cluster of conditions, adipose tissue is gaining attention as a major playground for the interplay between metabolic stress, inflammation and accelerated ageing, and not merely being an energy storage tank. Drastic elevation in the levels of reactive oxygen species, due to lipid overload and excessive lipolysis, causes genotoxic damage such as shortening of telomeres (an indicator of accelerated cell ageing), increased mRNA and protein expression for p53, p21, TNF−α, IL-6 (interleukin 6), impaired insulin-mediated glucose uptake, and decreased TERT mRNA expression. The increase of p53 in adipocytes is deleterious since elevated p53 results in pre-mature ageing of fat tissues which secrete pro-inflammatory cytokines thereby contributing to insulin resistance. But inhibition of p53 as a therapeutic target, as suggested by many previous studies, could result in developing high risks of cancer. The association between hyperlipidemic/hyperglycaemic stress, premature growth arrest and insulin resistance, thus, forms an interesting premise for searching targets and designing interventions for therapy of metabolic syndrome, type 2 diabetes mellitus etc. We developed a mathematical study involving a 5D ODE model, which revealed crucial parametric conditions governing p53 dynamics in the case of metabolic stress-induced cellular senescence and shed light on potential strategies to reduce pro-inflammatory cytokine levels which exacerbate insulin resistance through premature cellular ageing.
High affinity interactions and signal transduction between Aβ oligomers and TREM2
Authors: Lessard Christian B. , Malnik Samuel L. , Zhou Yingyue , Ladd Thomas B. , Cruz Pedro E. , Ran Yong , Chakrabaty Paramita , Mahan Thomas E. , Holtzman David M. , Ulrich Jason D , Colonna Marco , Golde Todd E.
Published: February 2018

Rare coding variant in the Triggering receptor expressed on myeloid cells 2 (TREM2) are associated with increased risk for Alzheimer’s disease (AD), but how they confer this risk remains uncertain. We assessed binding of TREM2, AD associated TREM2 variants to various forms of Aβ and APOE in multiple assays. TREM2 interacts directly with various forms of Aβ, with highest affinity interactions observed between TREM2 and soluble Aβ42 oligomers. We confirm the previous interaction between APOE3 and APOE4 and TREM2. High affinity binding of TREM2 to Aβ oligomers is characterized by very slow dissociation. Pre-incubation with Aβ is shown to block the interaction of APOE. In cellular assays, AD-associated variants of TREM2 reduced the amount of Aβ42 internalized, and in NFAT assay the R47H variant decreased NFAT signaling activity in response to Aβ42. These studies demonstrate i) a high affinity interaction between TREM2 and Aβ oligomers that can block interaction with another ligand and ii) that AD-associated TREM2 variants bind Aβ with equivalent affinity but show loss of function in terms of signaling and Aβ internalization.
A systematic approach for identifying shared mechanisms in epilepsy and its comorbidities
Authors: Hoyt Charles Tapley , Domingo-Fernández Daniel , Balzer Nora , Güldenpfennig Anka , Hofmann-Apitius Martin
Published: February 2018

Cross-sectional epidemiological studies have shown that the incidence of several nervous system diseases is more frequent in epilepsy patients than in the general population. Some comorbidities (e.g., Alzheimer’s disease and Parkinson’s disease) are also risk factors for the development of seizures; suggesting they may share pathophysiological mechanisms with epilepsy.

A literature-based approach was used to identify gene overlap between epilepsy and its comorbidities as a proxy for a shared genetic basis for disease, or genetic pleiotropy, as a first effort to identify shared mechanisms. While the results identified neurological disorders as the group of diseases with the highest gene overlap, this analysis was insufficient for identifying putative common mechanisms shared across epilepsy and its comorbidities. This motivated the use of a dedicated literature mining and knowledge assembly approach in which a cause-and-effect model of epilepsy was captured with Biological Expression Language.

After enriching the knowledge assembly with information surrounding epilepsy, its risk factors, its comorbidities, and antiepileptic drugs, a novel comparative mechanism enrichment approach was used to propose several downstream effectors (including the GABA receptor, GABAergic pathways, etc.) that could explain the therapeutic effects carbamazepine in both the contexts of epilepsy and AD.

We have made the Epilepsy Knowledge Assembly available at https://www.scai.fraunhofer.de/content/dam/scai/de/downloads/bioinformatik/epilepsy.bel and queryable through NeuroMMSig at http://neurommsig.scai.fraunhofer.de. The source code used for analysis and tutorials for reproduction are available on GitHub at https://github.com/cthoyt/epicom.
Simultaneous detection of DNA and RNA virus species involved in bovine respiratory disease by PCR-free rapid tagmentation-based library preparation and MinION nanopore sequencing
Authors: McCabe Matthew S. , Cormican Paul , Johnston Dayle , Earley Bernadette
Published: February 2018

Abstact

The Oxford Nanopore MinION Mk1B is a portable 90 g device that sequences DNA directly at 450 bases/second generating sequence reads in excess of 400 kb. Recent improvements in error rate and speed of library preparation mean that this device has considerable potential for rapid molecular bovine pathogen diagnostics. We tested the MinION for rapid untargeted detection of viral pathogens associated with bovine respiratory disease (BRD), an economically important disease often involving primary infection of the lung by one or more of a number of DNA and/or RNA viruses. We combined three foetal lung cell cultures which were infected with either Bovine Respiratory Syncytial Virus (BRSV), Bovine Herpes Virus 1 (BoHV1) or Bovine Parainfluenza Virus 3 (BPI-3). BoHV1 is a DNA virus and BPI-3 and BRSV are RNA viruses. The cell cultures were treated with DNase and RNase to deplete bovine nucleic acid prior to viral nucleic acid extraction and double-stranded cDNA synthesis. Sequencing libraries were generated by PCR-free tagmentation in under 10 minutes and loaded onto a MinION sequencer. Approximately 7,000 sequencing reads were generated and analysed using high-throughput local BLAST against the NCBI nr/nt database. The top BLAST hit for 2,937 of these reads was identified as a virus. Of these, 2,926 (99.6%) were correctly identified either as BoHV1, BRSV or BPI-3.
CTD-dependent and - independent mechanisms govern co-transcriptional capping of Pol II transcripts
Authors: Gonzalez Melvin Noe , Sato Shigeo , Tomomori-Sato Chieri , Conaway Joan W. , Conaway Ronald C.
Published: February 2018

Co-transcriptional capping of RNA polymerase II (Pol II) transcripts by capping enzyme proceeds orders of magnitude more efficiently than capping of free RNA. Previous studies brought to light a role for the phosphorylated Pol II CTD in activation of co-transcriptional capping; however, CTD phosphorylation alone could not account for the observed magnitude of activation. Here, we exploit a defined Pol II transcription system that supports both CTD phosphorylation and robust activation of capping to dissect the mechanism of co-transcriptional capping. Taken together, our findings identify a novel CTD-independent, but Pol II-mediated, mechanism that functions in parallel with CTD-dependent processes to ensure optimal capping, and they support a “tethering” model for the mechanism of activation.
Tandem tyrosine residues in the EPEC multicargo chaperone CesT support differential type III effector translocation and early host colonization
Authors: Runte Cameron , Jain Umang , Getz Landon J. , Secord Sabrina , Kuwae Asaomi , Abe Akio , LeBlanc Jason J. , Stadnyk Andrew W. , Kaper James B. , Hansen Anne-Marie , Thomas Nikhil A.
Published: February 2018

Enteropathogenic Escherichia coli (EPEC) are worldwide human enteric pathogens inflicting significant morbidity and causing large economic losses. A type 3 secretion system (T3SS) is critical for EPEC intestinal colonization, and injection of effectors into host cells contributes to cellular subversion and innate immune evasion. Here, we demonstrate that two strictly conserved C-terminal tyrosine residues, Y152 and Y153, within the multicargo T3SS chaperone CesT serve differential roles in regulating effector secretion in EPEC. Conservative substitution of both tyrosine residues to phenylalanine attenuated EPEC type 3 effector injection into host cells, and significantly limited Tir effector mediated intimate adherence, a key feature of attaching and effacing pathogenesis. Whereas CesT Y153 supported normal levels of Tir translocation, CesT Y152 was strictly required for the effector NleA to be expressed and subsequently translocated into host cells during infection. Other effectors were observed to be dependent on CesT Y152 for maximal translocation efficiency. Unexpectedly, EPEC expressing a CesT Y152, Y153F variant exhibited significantly enhanced effector translocation of many CesT-interacting effectors, further implicating Y152 in CesT functionality. A mouse infection model of EPEC intestinal disease using Citrobacter rodentium revealed that CesT tyrosine substitution variants displayed delayed colonization and were more rapidly cleared from the intestine. These data demonstrate genetically separable functions for strictly conserved tandem tyrosine residues within CesT. Tyrosine 152 of CesT is implicated in NleA expression, providing functional relevance for localized amino acid conservation. Therefore, CesT via its novel C-terminal domain, has relevant roles beyond typical T3SC that interact and stabilize effector proteins.
Spinal stretch reflexes exploit musculoskeletal redundancy to support postural hand control
Authors: Weiler Jeffrey , Gribble Paul L , Pruszynski J. Andrew
Published: February 2018

Motor behaviour is most efficiently controlled by only correcting disturbances or deviations that influence task success. It is currently thought that such sophisticated control is computed within a transcortical feedback pathway. Here we show that even the fastest spinal feedback pathway can produce corrective responses that adhere to this control scheme. We first applied small mechanical perturbations that flexed the elbow joint – stretching the triceps muscle – and simultaneously flexed or extended the wrist joint, displacing the hand various distances away from a central target. We then changed the arm’s orientation and applied the same joint perturbations, which reversed the mapping between joint motion and hand displacement. In all cases, we found that the triceps’ spinal stretch reflex was tuned to the hand’s displacement relative to the target, and not how the triceps muscle was stretched. Our findings reveal that the fastest spinal feedback pathway is capable of integrating and modulating feedback from multiple muscles to produce efficient corrective responses, forcing a re-evaluation of the how the nervous system derives the sophisticated control laws that support natural motor behaviour.
Inhibition and late errors in the antisaccade task: Influence of task design
Authors: Aponte Eduardo A. , Tschan Dominic G. , Stephan Klaas E. , Heinzle Jakob
Published: February 2018

In the antisaccade task, subjects are instructed to saccade in the opposite direction of a peripheral visual cue (PVC). Importantly, several psychiatric disorders are associated with increased error rates in this paradigm. Despite this observation, there is no consensus about the mechanism behind antisaccade errors: while often explained as inhibition failures, some studies have suggested that errors are caused by deficits in the ability to initiate voluntary saccades. Using a computational model, we recently showed that under some conditions high latency or late errors can be explained by a race process between voluntary pro- and antisaccades. A limitation of our findings is that in our previous experiment the PVC signaled the trial type, whereas in most studies, subjects are informed about the trial type before the PVC is presented. We refer to these task designs as asynchronous (AC) and synchronous cues (SC) conditions. Here, we investigated to which extent differences in design affect the type and frequency of errors in the antisaccade task. Twenty-four subjects participated in mixed blocks of pro- and antisaccade trials in both conditions. Our results demonstrate that error rates were highly correlated across task designs and a non-negligible fraction of them were classified as late errors in both conditions. In summary, our findings indicate that errors in the AC task are the result of both inhibition failures and inaccurate voluntary action initiation.
A comprehensive assessment of benign genetic variability for neurodegenerative disorders
Authors: Guerreiro Rita , Sassi Celeste , Raphael Gibbs Jesse , Edsall Connor , Hernandez Dena , Brown Kristelle , Lupton Michelle K , Parkinnen Laura , Ansorge Olaf , Hodges Angela , Ryten Mina ,   for the UK Brain Expression Consortium, Tienari Pentti J. , Van Deerlin Vivanna M. , Trojanowski John Q , Morgan Kevin , Powell John , Singleton Andrew , Hardy John , Bras Jose
Published: February 2018

1

Abstract

Over the last few years, as more and more sequencing studies have been performed, it has become apparent that the identification of pathogenic mutations is, more often than not, a complex issue. Here, with a focus on neurodegenerative diseases, we have performed a survey of coding genetic variability that is unlikely to be pathogenic.

We have performed whole-exome sequencing in 478 samples derived from several brain banks in the United Kingdom and the United States of America. Samples were included when subjects were, at death, over 60 years of age, had no signs of neurological disease and were subjected to a neuropathological examination, which revealed no evidence of neurodegeneration. This information will be valuable to studies of genetic variability as a causal factor for neurodegenerative syndromes. We envisage it will be particularly relevant for diagnostic laboratories as a filter step to the results being produced by either genome-wide or gene-panel sequencing. We have made this data publicly available at www.alzforum.org/exomes/hex.
First data-driven approach to using individual cattle weights to estimate mean adult dairy cattle weight in the UK
Authors: Schubert Hannah E. , Wood Sarah , Reyher Kristen K. , Mills Harriet L.
Published: February 2018

Introduction

Knowledge of accurate weights of cattle is crucial for effective dosing of individual animals with medicine and for reporting antimicrobial usage metrics, amongst other uses. The most common weight for dairy cattle presented in current literature is 600 kg, but this is not evidenced by data. For the first time, we provide an evidence-based estimate of the average weight of UK dairy cattle to better inform decisions by farmers, veterinarians and the scientific community.

Methods

We collected data for 2,747 dairy cattle from 20 farms in the UK, 19 using Lely Automatic Milking Systems with weigh floors and 1 using a crush with weigh scales. These data covered farms with different breed types, including Holstein, Friesian, Holstein-Friesian and Jersey, as well as farms with dual purpose breeds and cross-breeds. Data were used to calculate a mean weight for dairy cattle by breed, and a UK-specific mean weight was generated by scaling to UK-specific breed proportions. Trends in weight by lactation number, DIM and production level were also explored using individual cattle-level data.

Results

Mean weight for adult dairy cattle included in this study was 617 kg (standard deviation (sd) 85.6 kg). Mean weight varied across breeds, with a range of 466 kg (sd=56.0 kg, Jersey) to 636 kg (sd=84.1, Holsteins). When scaled to UK breed proportions, the estimated mean UK dairy cattle weight was 620 kg. Overall, first-lactation heifers weighed 9% less than cows. Mean weight declined for the first 30 days post-calving, before steadily increasing. For cattle at peak production, mean weight increased with production level.

Conclusions

This study is the first to calculate a mean weight of adult dairy cattle in the UK based on on-farm data. Overall mean weight was higher than that most often proposed in the literature (600 kg). Evidence-informed weights are crucial as the UK works to better monitor and report metrics to monitor antimicrobial use and are useful to farmers and veterinarians to inform dosing decisions.
Temperature measurements in the cutting zone, mass, chip fragmentation and analysis of chip metallography images during AZ31 and AZ91HP magnesium alloy milling
Authors: Zagórski Ireneusz , Kuczmaszewski Jozef
Published: February 2018

Purpose

This paper presents the results of mean unit weight of chips and their time to ignition measured on a test stand specially designed for this purpose. In addition, the temperature of chips in the cutting area and the morphology of chips produced in HSM milling (as a temperature indicator in the cutting area) are investigated. Also, different fractions of chips produced in the dry milling of Mg alloys AZ31 and AZ91HP by a PCD end mill are examined. Finally, the paper presents conclusions and recommendations with regard to safety and efficiency of dry milling processes for the aforementioned magnesium alloys.

Design/methodology/approach

Milling can be used as a finishing operation, particularly when using PCD end mills. The application of this mill type isparticularly important when producing different machine and device components, especially in the aircraft industry. What can occur in dry machining operations is self-ignition. It is therefore justified to investigate chip temperature in the cutting zone, to classify produced chip fractions and to determine their mass. Safe ranges of technological parameters can be additionally determined based on metallographic analysis of chip edge partial-melting.

Findings

The experimental results helped determine the effect of technological parameters of milling on chip temperature in the cutting zone, chip mass and fragmentation and chip morphology images.

Practical implications

The results reported in this work are innovative in both cognitive and practical aspect. The authors are convinced that this work can contribute to overcoming the mistrust of industrial practitioners toward dry milling of Mg alloys, and also with respect to the application of relatively higher cutting speeds in dry milling of these alloys than it is common practice in industry today. The study investigates the problem of safety in dry milling of Mg alloys. The study was motivated by the milling process itself and the formation of broken chip, which causes a significant change in the character of heat transfer.

Originality/value

The paper presents a method for multi-criteria safety assessment in dry milling operations. Safe and effective parameter ranges are defined with respect to chip temperature in the cutting zone, fraction number and chip mass.
Formal and informal governance mechanisms in state-owned enterprises
Authors: Wasowska Aleksandra , Postula Igor
Published: February 2018

Purpose

The purpose of this paper is to shed light on the formal and informal governance mechanisms of state-owned enterprises operating in a post-transitional economy of Poland.

Design/methodology/approach

The study combines legal analysis of Polish regulations in force, review of literature on the Poland’s institutional legacy, and a statistical analysis, based on a data set of 204 management board members, 180 external supervisory board members, and 114 state officials supervising Polish SOEs in 2011.

Findings

Legally designed relationships among the management board, supervisory board, and the state treasury, represented by the minister and ministry officials, constitute the key formal governance mechanisms in Polish SOEs. They are, however, complemented by relationships between SOEs and their stakeholders and distorted by other informal phenomena, including informal noninstitutional behavior, mechanisms grounded in cognitive and normative institutions, and perception of the relationship structure by the actors themselves. As a result, key corporate governance actors differ in their perception of governance influences upon SOEs.

Practical implications

This study contributes to policymaking by helping authorities gain a better understanding of the governance challenges in SOEs.

Originality/value

This paper is one of the first and few empirical studies investigating the issue of formal and informal governance mechanisms in SOEs in post-transitional economies of CEE.