bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arterial Destiffening in Previously Untreated Mild Hypertensives After 1 Year of Routine Clinical Management
Authors: Rodilla Enrique , Millasseau Sandrine , Costa Jose Antonio , Pascual Jose Maria 
Published: December 2016

Abstract

BACKGROUND
Arterial stiffness, measured with pulse wave velocity (PWV), is now classified as a marker of target organ damage (TOD) alongside left ventricular hypertrophy and moderately increased albuminuria. Interventional studies on treated hypertensive patients have shown that PWV could be improved. Our aim was to assess changes in arterial stiffness after 1 year of routine clinical practice in never-treated hypertensive patients.

PATIENTS AND METHODS
We studied 356 never-treated patients with suspected hypertension. After standard clinical assessment during which presence of TOD was evaluated, hypertension diagnosis was confirmed in 231 subjects who subsequently received standard routine care. Both hypertensive and the 125 controls came back for a follow-up visit after 1 year.

RESULTS
Hypertensive patients were slightly older (46 ± 12 vs. 50 ± 12 years, P &lt; 0.001), with higher mean arterial pressure (MAP)-adjusted PWV compared to controls (8.6 ± 2.0 vs. 8.0 ± 1.7 m/s, P &lt; 0.001) and 47% of them presented 1 or more TOD. After 1 year of treatment, MAP was similar in both groups (94.9 vs. 96.2 mm Hg; P = ns), but adjusted PWV remained significantly higher in the hypertensive patients (7.8 ± 1.4 vs. 8.3 ± 1.7 m/s, P = 0.004). The prevalence of elevated PWV was reduced from 20% to 12%. All antihypertensive drugs achieved the same blood pressure (BP) and PWV reduction with the exception of vasodilating beta-blockers which gave slightly better results probably due to heart rate reduction.

CONCLUSION
BP reduction in newly diagnosed hypertensive patients improves arterial stiffness within a year of real-life clinical practice. Patients with the highest PWV and the largest reduction of BP “destiffened” the most whatever antihypertensive class was used.
Lineage-specific mutational clustering in protein structures predicts evolutionary shifts in function
Authors: Adams Jeremy , Mansfield Michael J , Richard Daniel J , Doxey Andrew C 
Published: December 2016

AbstractMotivationSpatially clustered mutations within specific regions of protein structure are thought to result from strong positive selection for altered protein functions and are a common feature of oncoproteins in cancer. Although previous studies have used spatial substitution clustering to identify positive selection between pairs of proteins, the ability of this approach to identify functional shifts in protein phylogenies has not been explored.ResultsWe implemented a previous measure of spatial substitution clustering (the P3D statistic) and extended it to detect spatially clustered substitutions at specific branches of phylogenetic trees. We then applied the analysis to 423 690 phylogenetic branches from 9261 vertebrate protein families, and examined its ability to detect historical shifts in protein function. Our analysis identified 19 607 lineages from 5362 protein families in which substitutions were spatially clustered on protein structures at P3D &lt; 0.01. Spatially clustered substitutions were overrepresented among ligand-binding residues and were significantly enriched among particular protein families and functions including C2H2 transcription factors and protein kinases. A small but significant proportion of branches with spatially clustered substitution also were under positive selection according to the branch-site test. Lastly, exploration of the top-scoring candidates revealed historical substitution events in vertebrate protein families that have generated new functions and protein interactions, including ancient adaptations in SLC7A2, PTEN, and SNAP25. Ultimately, our work shows that lineage-specific, spatially clustered substitutions are a useful feature for identifying functional shifts in protein families, and reveal new candidates for future experimental study.Availability and ImplementationSource code and predictions for analyses performed in this study are available at: https://github.com/doxeylab/evoclust3dSupplementary informationSupplementary data are available at Bioinformatics online.
LncRNA/DNA binding analysis reveals losses and gains and lineage specificity of genomic imprinting in mammals
Authors: Liu Haihua , Shang Xiaoxiao , Zhu Hao 
Published: December 2016

Abstract

Motivation
Genomic imprinting is regulated by lncRNAs and is important for embryogenesis, physiology and behaviour in mammals. Aberrant imprinting causes diseases and disorders. Experimental studies have examined genomic imprinting primarily in humans and mice, thus leaving some fundamental issues poorly addressed. The cost of experimentally examining imprinted genes in many tissues in diverse species makes computational analysis of lncRNAs’ DNA binding sites valuable.

Results
We performed lncRNA/DNA binding analysis in imprinting clusters from multiple mammalian clades and discovered the following: (i) lncRNAs and imprinting sites show significant losses and gains and distinct lineage-specificity; (ii) binding of lncRNAs to promoters of imprinted genes may occur widely throughout the genome; (iii) a considerable number of imprinting sites occur in only evolutionarily more derived species; and (iv) multiple lncRNAs may bind to the same imprinting sites, and some lncRNAs have multiple DNA binding motifs. These results suggest that the occurrence of abundant lncRNAs in mammalian genomes makes genomic imprinting a mechanism of adaptive evolution at the epigenome level.

Availability and Implementation
The data and program are available at the database LongMan at lncRNA.smu.edu.cn.

Supplementary information
Supplementary data are available at Bioinformatics online.
ProQ3D: improved model quality assessments using deep learning
Authors: Uziela Karolis , Menéndez Hurtado David , Shu Nanjiang , Wallner Björn , Elofsson Arne 
Published: December 2016

Abstract

Summary
Protein quality assessment is a long-standing problem in bioinformatics. For more than a decade we have developed state-of-art predictors by carefully selecting and optimising inputs to a machine learning method. The correlation has increased from 0.60 in ProQ to 0.81 in ProQ2 and 0.85 in ProQ3 mainly by adding a large set of carefully tuned descriptions of a protein. Here, we show that a substantial improvement can be obtained using exactly the same inputs as in ProQ2 or ProQ3 but replacing the support vector machine by a deep neural network. This improves the Pearson correlation to 0.90 (0.85 using ProQ2 input features).

Availability and Implementation
ProQ3D is freely available both as a webserver and a stand-alone program at http://proq3.bioinfo.se/

Supplementary information
Supplementary data are available at Bioinformatics online.
Postoperative Analgesia by a Transversus Abdominis Plane Block Using Different Concentrations of Ropivacaine for Abdominal Surgery
Authors: Sun Ni , Wang Shouyong , Ma Pengpeng , Liu Shuting , Shao Aijie , Xiong Ling 
Published: December 2016

Background:
Transversus abdominis plane block (TAPB) has been proven to be an effective means of postoperative anesthesia, but the optimum effective concentration of ropivacaine warrants further research.

Objective:
This study aimed to identify the optimal ropivacaine concentration of TAPB using a meta-analysis.

Materials and Methods:
This study consisted of a meta-analysis of randomized controlled trials (RCTs). We searched online databases, including PubMed, Embase, the Cochrane Database of Systematic Reviews, and Web of Science. RCTs investigating the 24-hour postoperative opioid consumption and the rest and dynamic pain scores 2, 12, and 24 hours after surgery were included in this analysis. We also assessed opioid-related side-effects and patient satisfaction 24 hours after surgery.

Results:
Nineteen RCTs (1217 patients) were included in this meta-analysis, which showed that only TAPB with 0.375% and 0.5% ropivacaine was able to reduce opioid consumption 24 hours after surgery by weighted mean differences of −6.55 and −4.44 mg (morphine IV equivalents), respectively (P<0.05). A meta-regression analysis did not reveal an association between the local anesthetic dose (in mg), surgery, anesthesia, block timing, and the TAPB effect on opioid consumption. Ropivacaine concentrations of 0.375% and 0.5% reduced the 2-hour postoperative pain score and reduced the incidence of nausea and vomiting, but this analgesic effect disappeared at 12 and 24 hours. Only TAPB with 0.375% ropivacaine improved the degree of satisfaction 24 hours after surgery (weighted mean difference of 0.87 [0.08-1.66], P=0.03).

Conclusion:
In terms of efficacy and safety, the use of 0.375% ropivacaine for TAPB is preferred in the clinical work.
Children With Cochlear Implants and Their Parents: Relations Between Parenting Style and Children’s Social-Emotional Functioning
Authors: Ketelaar Lizet , Wiefferink Carin H. , Frijns Johan H. M. , Rieffe Carolien 
Published: December 2016

Objectives:
Parenting a child who has a severe or profound hearing loss can be challenging and at times stressful, and might cause parents to use more adverse parenting styles compared with parents of hearing children. Parenting styles are known to impact children’s social-emotional development. Children with a severe to profound hearing loss may be more reliant on their parents in terms of their social-emotional development when compared with their hearing peers who typically have greater opportunities to interact with and learn from others outside their family environment. Identifying the impact which parenting styles pertain on the social-emotional development of children who have cochlear implants (CIs) could help advance these children’s well-being. Therefore, the authors compared parenting styles of parents with hearing children and of parents with children who have a CI, and examined the relations between parenting styles and two key aspects of children’s social-emotional functioning: emotion regulation and empathy.

Design:
Ninety-two hearing parents and their children (aged 1 to 5 years old), who were either hearing (n = 46) or had a CI (n = 46), participated in this cross-sectional study. Parents completed questionnaires concerning their parenting styles (i.e., positive, negative and uninvolved), and regarding the extent to which their children expressed negative emotions (i.e., anger and sadness) and empathy. Furthermore, an emotion-regulation task measuring negative emotionality was administered to the children.

Results:
No differences in reported parenting styles were observed between parents of hearing children and parents of children with a CI. In addition, negative and uninvolved parenting styles were related to higher levels of negative emotionality in both groups of children. No relation was found between positive parenting and children’s social-emotional functioning. Hearing status did not moderate these relationships. Language mediated the relationship between parenting styles and children’s social-emotional functioning.

Conclusions:
Children’s hearing status did not impact parenting styles. This may be a result of the support that parents of children with a CI receive during their enrollment in the rehabilitation program preceding and after implantation. Rehabilitation programs should dedicate more attention to informing parents about the impact of parenting behaviors on children’s social-emotional functioning. Offering parenting courses as part of the program could promote children’s well-being. Future longitudinal research should address the directionality of the relations between parenting styles and children’s social-emotional functioning.
Updates on the role of receptor activator of nuclear factor κB/receptor activator of nuclear factor κB ligand/osteoprotegerin pathway in breast cancer risk and treatment
Authors: Bayer Christian M. , Beckmann Matthias W. , Fasching Peter A. 
Published: December 2016

Purpose of review
Treatment with bisphosphonates and denosumab is the standard of care in bone metastatic disease. In addition, the adjuvant therapy of denosumab or bisphosphonates is very effective to prevent loss of bone mineral density, for example in osteoporosis. However, it is still unclear if this therapy has an influence on preventing cancer.

Recent findings
Since the identification of novel genes in the 1980s, it took about 30 years until denosumab, as a fully human mAb against receptor activator of nuclear factor (NF)-κB ligand (RANKL), could be introduced to clinical practice. The discovery of the receptor activator of NF-κB/RANKL/osteoprotegerin pathway in the 1990s is an example of how modern databases of genes were utilized to discover new pathways relevant to a variety of diseases. The essential role of this pathway for the function, differentiation and survival of osteoclasts, and the influence on the bone microenvironment helped to understand the vicious circle of bone resorption and destruction in many skeletal diseases.

Summary
In the following review, we discuss the important role of rational targeting concerning receptor activator of NF-κB/RANKL/osteoprotegerin and the bisphosphonate therapy and provide an update for the related treatment of patients suffering from breast cancer and further implications for clinical practice and research using denosumab as a potential chemoprevention in BRCA1-related breast cancer.
TX-004HR vaginal estradiol has negligible to very low systemic absorption of estradiol
Authors: Archer David F. , Constantine Ginger D. , Simon James A. , Kushner Harvey , Mayer Philip , Bernick Brian , Graham Shelli , Mirkin Sebastian 
Published: December 2016

Abstract

Objective:
To evaluate the pharmacokinetics of TX-004HR vaginal estradiol softgel capsules when used for treating moderate-to-severe dyspareunia in postmenopausal women with vulvar and vaginal atrophy.

Methods:
A substudy of the REJOICE trial (multicenter, double-blind, placebo-controlled, phase 3) evaluated the pharmacokinetics of 4, 10, and 25-μg TX-004HR doses once/d for 2 weeks, followed by twice/wk for 10 weeks. Serum samples obtained at 2, 4, 6, 10, and 24 hours postdose on days 1 and 14, and once on day 84, were analyzed for area under the serum concentration-time curve, t
max, C
min, C
avg, and C
max for estradiol, estrone, and estrone conjugates.

Results:
Seventy-two women (mean 59 y) participated. TX-004HR 4 μg showed no statistical differences from placebo in estradiol pharmacokinetic (PK) parameters. At 10 μg, estradiol C
max was statistically higher than placebo on day 1, but was not different from placebo on day 14. With 25 μg, estradiol PK parameters were statistically higher than placebo. Estradiol C
avg values for 25 μg were 9.1 pg/mL on day 1 and 7.1 pg/mL on day 14. Estrone and estrone conjugate PK parameters with TX-004HR were lower than or similar to placebo across all doses. No drug accumulation was observed.

Conclusions:
Vaginal TX-004HR resulted in negligible to very low systemic absorption of estradiol. No statistical differences in estradiol PK parameters were observed on day 14 with 4 and 10 μg, and only minor increases were observed with 25 μg (within the normal postmenopausal range). This PK substudy, in conjunction with the primary efficacy results, demonstrated that TX-004HR provided local benefits of estradiol with limited systemic exposure.
CRYSTALLINE RETINOPATHY AND RETINAL VASCULOPATHY IN CALCIFIC UREMIC ARTERIOLOPATHY (CALCIPHYLAXIS)
Authors: Naysan Jonathan , Dansingani Kunal K. , Balaratnasingam Chandrakumar , Mrejen Sarah , Levasseur Steven , Merkur Andrew , Yannuzzi Lawrence A. 
Published: December 2016

Purpose:
To report the posterior segment and retinal vascular manifestations of calcific uremic arteriolopathy (calciphylaxis). Clinical findings are correlated with multimodal imaging results.

Methods:
Observational case report.

Results:
A 65-year-old white woman on hemodialysis was referred for assessment of poor vision bilaterally. Clinical examination demonstrated a crystalline retinopathy with stigma of previous retinal arterial occlusion. Fluorescein angiography revealed delayed retinal arterial filling bilaterally, sheathing of vessels, and peripheral nonperfusion. The crystals were hyperautofluorescent. Spectral domain and enhanced depth imaging optical coherence tomography localized the crystals within the retina with a predilection for the retinal arterial vasculature. The choriocapillaris was not involved. Two years prior, the patient developed necrotic skin lesions which were biopsied and confirmed the diagnosis of calciphylaxis.

Conclusion:
Calcific uremic arteriolopathy is an extremely rare cause of thrombogenic microangiopathy in end-stage renal disease patients. Retinal arterial occlusion appears to be a rare but significant cause of visual loss in this disease and is likely to be consequent to crystalline deposition in the retinal vasculature.
NEW OBSERVATIONS REGARDING THE RETINOPATHY OF GENETICALLY CONFIRMED KEARNS–SAYRE SYNDROME
Authors: Kozak Igor , Oystreck Darren T. , Abu-Amero Khaled K. , Nowilaty Sawsan R. , Alkhalidi Hisham , Elkhamary Sahar M. , Mohamed Sarar , Hamad Muddathir H. A. , Salih Mustafa A. , Blakely Emma L. , Taylor Robert W. , Bosley Thomas M. 
Published: December 2016

Purpose:
To report novel retinal findings in Kearns–Sayre syndrome and correlate degree of retinopathy with other clinical findings.

Methods:
Observational case series of patients from Saudi Arabia with retinal and neuroophthalmologic examinations, medical chart review, and mitochondrial genetic evaluation.

Results:
The three unrelated patients had progressive external ophthalmoplegia and pigmentary retinopathy bilaterally. Muscle biopsy in two of the cases revealed mitochondrial myopathy. All three had abnormal findings on neuroimaging and modestly reduced visual acuity in both eyes with a variable pigmentary retinopathy. One of the patients had bilateral subretinal fibrosis with a full-thickness macular hole in the right eye. All three patients had single, large-scale mitochondrial DNA (mtDNA) deletions (5.0–7.6 kb in size) with blood mtDNA heteroplasmy levels ranging from below 20% to 57%. Severity of pigmentary retinopathy did not correlate with severity of progressive external ophthalmoplegia, but did correspond grossly with electroretinographic abnormalities, just as the degree of ocular motility restriction and ptosis in each patient correlated with the size of their extraocular muscles on neuroimaging. In addition, the size of the single, large-scale mtDNA deletion and level of mtDNA heteroplasmy corresponded with degree of ocular motility restriction but not with severity of retinopathy.

Conclusion:
Subretinal fibrosis and macular hole are novel retinal observations which expand clinical profile in Kearns–Sayre syndrome. Genetic testing for mtDNA deletions and heteroplasmy in blood, muscle biopsy, careful ocular and retinal examination including electroretinography, and imaging are indispensable tests for this condition.
Is There a Role for Inflammation in Contact Lens Discomfort?
Authors: Willcox Mark D. P. 
Published: December 2016

Purpose:The aim of this study was to examine the literature with respect to inflammation of the ocular surface and the presence of inflammatory mediators in the tear film during contact lens wear.Methods:The literature on contact lens discomfort that relates to signs of inflammation was searched. Reference was paid to the cardinal signs of inflammation (pain, heat, redness, and swelling) as well as the appearance of inflammatory mediators in the tear film during contact lens wear.Results:Contact lens wear does induce discomfort, which is a mild form of pain, and wearing of lenses can induce increases in limbal and conjunctival redness. However, there is little evidence for a direct relationship between limbal or conjunctival redness and contact lens discomfort. Contact lenses may increase the temperature of the ocular surface by a small amount (≤2.1°C). Corneal or conjunctival swelling has not been associated with contact lens discomfort. Complement or kinin breakdown products or histamine in tears are not associated with contact lens discomfort. Cytokines are generally not related to discomfort, although nerve growth factor levels were increased in tears of symptomatics in one report. The presence of degraded lipids, leukotriene B4and peroxidation products, and the enzyme secretory phospholipase A2 in tears has been associated with contact lens discomfort, and this area is worthy of further research.Conclusions:There have been only a few studies that have investigated a role for inflammation in contact lens–induced discomfort, and the strongest associations have been found with lipid degradation processes.
Long-term Outcomes and Complications of Pars Plana Baerveldt Implantation in Children
Authors: Vinod Kateki , Panarelli Joseph F. , Gentile Ronald C. , Sidoti Paul A. 
Published: December 2016

Purpose of the Study:
The purpose of the study was to report long-term outcomes and complications of Baerveldt glaucoma implant (BGI) surgery with pars plana tube insertion in children.

Materials and Methods:
The medical records of consecutive aphakic and pseudophakic children (<16 y of age) who underwent BGI surgery with pars plana tube insertion between 1990 and 2013 were retrospectively reviewed. Main outcome measures were intraocular pressure and number of glaucoma medications. Postoperative complications were recorded. Failure was defined as an intraocular pressure <5 or ≥21 mm Hg (with or without glaucoma medications), loss of light perception, or need for additional glaucoma surgery.

Results:
Thirty-seven children were identified with a mean age of 6.0±4.7 years (range, 4 mo to 14.5 y). Mean follow-up after pars plana BGI surgery was 6.5±3.4 years (range, 9 mo to 12.8 y) for patients who met success criteria. Mean intraocular pressure and mean number of glaucoma medications at most recent follow-up for patients with successful intraocular pressure control were 13.8±4.1 and 2.3±1.9 mm Hg, respectively. The Kaplan-Meier survival analysis revealed 1-, 3-, 5-, and 7-year success rates of 94.5%, 74.6%, 65.0%, and 45.8%, respectively. Complications included tube exposure in 1 patient (2.7%), tube obstruction in 8 patients (21.6%), and retinal detachment in 9 patients (24.3%). Seventeen patients (45.9%) failed due to inadequate intraocular pressure control, of whom 9 (24.3%) required additional glaucoma surgery.

Conclusions:
Although pars plana BGI surgery is a reasonable option for managing refractory glaucoma in aphakic and pseudophakic children, surgeons must be aware of the potential need for additional glaucoma surgery and/or posterior segment complications with extended follow-up.