bluuebunny/crossref_metadata_2025_split huggingface dataset:
New NOBOX Mutations Identified in a Large Cohort of Women With Primary Ovarian Insufficiency Decrease KIT-L Expression
Authors: Bouilly Justine , Roucher-Boulez Florence , Gompel Anne , Bry-Gauillard Hélène , Azibi Kemal , Beldjord Cherif , Dodé Catherine , Bouligand Jérôme , Mantel Anne Guiochon , Hécart Annie-Claude , Delemer Brigitte , Young Jacques , Binart Nadine 
Published: December 2014

Context:
Primary ovarian insufficiency (POI) is a major cause of anovulation and infertility in women. This disease affects 1% of women before 40 years, and several genetic causes have been reported.

Objective:
The aim of the study was to evaluate the prevalence of NOBOX mutations in a new large cohort of women with POI and to characterize these variants and identify a NOBOX novel target gene.

Patients and Methods:
A total of 213 unrelated patients with POI were screened for NOBOX mutations, and luciferase reporter assays were performed for the mutations identified.

Results:
We reported 3 novel and 2 recurrent heterozygous missense NOBOX rare variants found in 12 patients but not in 724 alleles from ethnic-matched individual women with occurrence of menopause at a normal age. Their functional impact had been tested on the classic growth differentiation factor-9 (GDF9) promoter and on KIT-L, a new NOBOX target gene. The p.Gly91Thr, p.Gly111Arg, p.Arg117Trp, p.Lys371Thr, and p.Pro619Leu mutations were deleterious for protein function.

Conclusions:
In our series, 5.6% of the patients with POI displayed heterozygous NOBOX mutations. We demonstrate that KIT-L could be now a direct NOBOX target. These findings replicate the high prevalence of the association between the NOBOX rare variants and POI.
The use of orthoses in stroke rehabilitation
Authors: Charlton Paul T 
Published: December 2014

Orthotics is the field of splinting and bracing. This article sets outlines what orthotics are, how they can be used and the underlying biomechanical principles and key areas where orthotic intervention can complement stroke rehabilitation. A common condition in stroke patients is dropped foot; the article explains and illustrates the three-point force system used to correct it. While emphasising the specialist work of the orthotist in helping patients recover from stroke, the role of the whole multidisciplinary team in supplementing that specialist work is stressed. Teaching the patient how to stand and then to walk are dealt with. The article concludes with sections on tuning and problem-solving in orthotics and how they can help with spasticity.
Quantitative Charge-Tags for Sterol and Oxysterol Analysis
Authors: Crick Peter J , William Bentley T , Abdel-Khalik Jonas , Matthews Ian , Clayton Peter T , Morris Andrew A , Bigger Brian W , Zerbinati Chiara , Tritapepe Luigi , Iuliano Luigi , Wang Yuqin , Griffiths William J 
Published: December 2014

Abstract

BACKGROUND
Global sterol analysis is challenging owing to the extreme diversity of sterol natural products, the tendency of cholesterol to dominate in abundance over all other sterols, and the structural lack of a strong chromophore or readily ionized functional group. We developed a method to overcome these challenges by using different isotope-labeled versions of the Girard P reagent (GP) as quantitative charge-tags for the LC-MS analysis of sterols including oxysterols.

METHODS
Sterols/oxysterols in plasma were extracted in ethanol containing deuterated internal standards, separated by C18 solid-phase extraction, and derivatized with GP, with or without prior oxidation of 3β-hydroxy to 3-oxo groups.

RESULTS
By use of different isotope-labeled GPs, it was possible to analyze in a single LC-MS analysis both sterols/oxysterols that naturally possess a 3-oxo group and those with a 3β-hydroxy group. Intra- and interassay CVs were &lt;15%, and recoveries for representative oxysterols and cholestenoic acids were 85%–108%. By adopting a multiplex approach to isotope labeling, we analyzed up to 4 different samples in a single run. Using plasma samples, we could demonstrate the diagnosis of inborn errors of metabolism and also the export of oxysterols from brain via the jugular vein.

CONCLUSIONS
This method allows the profiling of the widest range of sterols/oxysterols in a single analytical run and can be used to identify inborn errors of cholesterol synthesis and metabolism.
Polynomial solvability of NP-complete problems
Authors: Panyukov Anatoly 
Published: December 2014

Abstract
A polynomial algorithm for solving the “Hamiltonian circuit” problem is presented in the paper. Computational complexity of the algorithm is equal to

O

(

n
8

log

2
2

n

)

, where n is the cardinality of the observed graph vertex set. Thus, the polynomial solvability for

N
P

-complete problems is proved.
Isolation and preliminary characterization of
cyanobacteria strains from freshwaters of Greece
Authors: Gkelis Spyros , Fernández Tussy Pablo , Zaoutsos Nikos 
Published: December 2014

Abstract
Cyanobacterial harmful algal blooms (or
CyanoHABs) represent one of the most conspicuous
waterborne microbial hazards. The characterization of
the bloom communities remains problematic because
the cyanobacterial taxonomy of certain genera has not
yet been resolved. In this study, 29 planktic and benthic
cyanobacterial strains were isolated from freshwaters
located in Greece. The strains were assigned to the genera Chroococcus, Microcystis, Synechococcus, Jaaginema,
Limnothrix, Pseudanabaena, Anabaena, and Calothrix
and screened for the production of the cyanotoxins
microcystins (MCs), cylindrospermopsins (CYNs), and
saxitoxins (STXs) using molecular (PCR amplification of
seven genes implicated in cyanotoxin biosynthesis) and
immunological (ELISA) methods. This study presents,
for the first time, a cyanobacteria culture collection
from Greece, thus providing missing study material for
the understanding of bloom formation and cyanotoxin
production in the Mediterranean and for the polyphasic
characterization of important components of the
phytoplankton. The combined use of molecular and
immunochemical methods allowed the identification of
MC producing strains, but further data are needed for CYNand
STX-producing cyanobacteria. The high percentage
of MC-producing Microcystis strains in the urban Lakes
Kastoria and Pamvotis, frequently used for agriculture
irrigation, fishing and recreation, highlights the potential
risk for human health.
Constructing a schema: Word-class changing morphology in a usage-based perspective
Authors: Hartmann Stefan 
Published: December 2014

AbstractThis paper discusses how collostructional analysis can be applied to the study of word-formation patterns. Drawing on a diachronic corpus study of German ung-nominalization and Infinitival Nominalization using the GerManC Corpus, it is shown that a cross-tabulation analysis comparing the frequencies of word-formation products to those of their respective bases can give valuable clues to the input language users rely on when abstracting a schema (i.e., a word-formation construction) from a quite heterogeneous array of instantiations.
Virilizing adrenal oncocytoma in a 9-year-old girl: rare neoplasm with an intriguing postoperative course
Authors: Yordanova Galina , Iotova Violeta , Kalchev Kalin , Ivanov Krasimir , Balev Boyan , Kolev Nikola , Tonev Anton , Oosterhuis Wolter 
Published: December 2014

AbstractAdrenal oncocytoma is an extremely rare neoplasm, which is mostly non-functional. Only five cases of childhood adrenal oncocytoma have been described so far, all of which were hormonally active. Currently, guidelines for management and follow-up are not available. We report a 9-year-old girl with benign adrenal oncocytoma, presenting with severe short-term virilization. After diagnostic work-up the patient underwent laparoscopic unilateral adrenalectomy. For the first 2 weeks following surgery she suffered marked mood swings, irritability and fatigue. There were no other clinical and/or laboratory abnormalities except the rapid drop-down of androgen levels to normal values. Follow-up showed no signs of recurrence and in the absence of signs of adrenal insufficiency, we speculate that, the rapid drop of androgen levels after removal of the tumor might be the reason for the deteriorated psychoemotional condition of our patient.
On the strong metric dimension of the strong products of graphs
Authors: Kuziak Dorota , Yero Ismael G. , Rodríguez-Velázquez Juan A. 
Published: December 2014

Abstract
Let G be a connected graph. A vertex w ∈ V.G/ strongly resolves two vertices u,v ∈ V.G/ if there
exists some shortest u-w path containing v or some shortest v-w path containing u. A set S of vertices is a strong
resolving set for G if every pair of vertices of G is strongly resolved by some vertex of S. The smallest cardinality
of a strong resolving set for G is called the strong metric dimension of G. It is well known that the problem of
computing this invariant is NP-hard. In this paper we study the problem of finding exact values or sharp bounds for
the strong metric dimension of strong product graphs and express these in terms of invariants of the factor graphs.
Invariance groups of finite functions and orbit equivalence of permutation groups
Authors: Horváth Eszter K. , Makay Géza , Pöschel Reinhard , Waldhauser Tamás 
Published: December 2014

Abstract
Which subgroups of the symmetric group Sn arise as invariance groups of n-variable functions defined on a k-element domain? It appears that the higher the difference n-k, the more difficult it is to answer this question. For k ≤ n, the answer is easy: all subgroups of Sn are invariance groups. We give a complete answer in the cases k = n-1 and k = n-2, and we also give a partial answer in the general case: we describe invariance groups when n is much larger than n-k. The proof utilizes Galois connections and the corresponding closure operators on Sn, which turn out to provide a generalization of orbit equivalence of permutation groups. We also present some computational results, which show that all primitive groups except for the alternating groups arise as invariance groups of functions defined on a three-element domain.
Dynamics of differentiation operators on generalized weighted Bergman spaces
Authors: Zhang Liang , Zhou Ze-Hua 
Published: December 2014

Abstract
The chaos of the differentiation operator on generalized weighted Bergman spaces of entire functions has
been characterized recently by Bonet and Bonilla in [CAOT 2013], when the differentiation operator is continuous.
Motivated by those, we investigate conditions to ensure that finite many powers of differentiation operators are
disjoint hypercyclic on generalized weighted Bergman spaces of entire functions.
Tensile properties of polyformaldehyde blends and nanocomposites
Authors: Liang Ji-Zhao , Wang Fang 
Published: December 2014

Abstract
The effects of the compositions and tensile rates on the tensile properties of the polyformaldehyde (POM)/ethylene-vinyl acetate copolymer (EVA)/high-density polyethylene (HDPE) blends and POM/EVA/HDPE composites filled with nanometer calcium carbonate were investigated by means of a tensile test machine at room temperature. The results showed that the Young’s modulus, tensile yield strength, and tensile elongation at break of the blends and the composites decreased nonlinearly with increase in the HDPE weight fraction; it should be attributed to the low stiffness and strength of the HDPE resin; the difference in the Young’s modulus and tensile yield strength between the blends and the composites was insignificant under the same experimental conditions. Both the Young’s modulus and tensile yield strength of the blends and the composites increased nonlinearly with increase in the tensile rate in the case of low tensile rate level. Moreover, the predictions of the Young’s modulus and tensile strength were roughly close to the measured data from the blends.
HMGB1 facilitates repair of mitochondrialDNAdamage and extends the lifespan of mutant ataxin‐1 knock‐in mice
Authors: Ito Hikaru , Fujita Kyota , Tagawa Kazuhiko , Chen Xigui , Homma Hidenori , Sasabe Toshikazu , Shimizu Jun , Shimizu Shigeomi , Tamura Takuya , Muramatsu Shin‐ichi , Okazawa Hitoshi 
Published: December 2014

AbstractMutant ataxin‐1 (Atxn1), which causes spinocerebellar ataxia type 1 (SCA1), binds to and impairs the function of high‐mobility group box 1 (HMGB1), a crucial nuclear protein that regulatesDNAarchitectural changes essential forDNAdamage repair and transcription. In this study, we established that transgenic or virus vector‐mediated complementation withHMGB1 ameliorates motor dysfunction and prolongs lifespan in mutant Atxn1 knock‐in (Atxn1‐KI) mice. We identified mitochondrialDNAdamage repair byHMGB1 as a novel molecular basis for this effect, in addition to the mechanisms already associated withHMGB1 function, such as nuclearDNAdamage repair and nuclear transcription. The dysfunction and the improvement of mitochondrialDNAdamage repair functions are tightly associated with the exacerbation and rescue, respectively, of symptoms, supporting the involvement of mitochondrialDNAquality control byHMGB1 inSCA1 pathology. Moreover, we show that the rescue of Purkinje cell dendrites and dendritic spines byHMGB1 could be downstream effects. Although extracellularHMGB1 triggers inflammation mediated by Toll‐like receptor and receptor for advanced glycation end products, upregulation of intracellularHMGB1 does not induce such side effects. Thus, viral delivery ofHMGB1 is a candidate approach by which to modify the disease progression ofSCA1 even after the onset.
Off-Label Prescribing in Pediatric Outpatients
Authors: Palmaro Aurore , Bissuel Raphael , Renaud Nicholas , Durrieu Geneviève , Escourrou Brigitte , Oustric Stephane , Montastruc Jean-Louis , Lapeyre-Mestre Maryse 
Published: December 2014

OBJECTIVE:
To study the characteristics of off-label prescribing and adverse drug reaction (ADR) occurrence in a sample of pediatric outpatients treated by general practitioners.

METHODS:
A survey on pediatric drug prescribing was implemented in 46 general practices in southwestern France. All consecutive patients aged 0 to 16 years were included. Patient characteristics, reasons for consultation, and drug prescribed (including indications) were collected. ADRs occurring ≤10 days after the date of consultation were recorded by the general practitioners (spontaneous notification). Off-label prescription was defined as prescribing outside the specifications of the Summary of Product Characteristics.

RESULTS:
Among the 2313 children seen between March 8, 2011 and July 31, 2011, 1960 were exposed to ≥1 prescribed drug. Mean age was 5.6 years, with a gender ratio of 1.1. Among children with prescriptions, 37.6% (n = 736) were exposed to ≥1 off-label prescription and 6.7% (n = 132) to ≥1 unlicensed drug. Off-label prescribing involved an unapproved indication in 56.4% of cases (n = 416), a lower dosage (26.5%, n = 195) or higher dosage (19.5%, n = 144) than specified, age not labeled (7.2%, n = 53), incorrect route of administration (3.5%, n = 26), and contraindication (0.3%, n = 2). A total of 23 ADRs were reported (1.5% of patients with off-label prescriptions). ADR occurrence was not significantly related to off-label drug prescribing.

CONCLUSIONS:
Despite the numerous initiatives implemented for promoting rational medicine use in children, the prevalence of off-label prescription in outpatient pediatric practice remains high.
Rapid Normalization of Vitamin D Levels: A Meta-Analysis
Authors: McNally J. Dayre , Iliriani Klevis , Pojsupap Supichaya , Sampson Margaret , O’Hearn Katie , McIntyre Lauralyn , Fergusson Dean , Menon Kusum 
Published: December 2014

BACKGROUND:Vitamin D deficiency may represent a modifiable risk factor to improve outcome in severe illness. The efficacy of high-dose regimens in rapid normalization of vitamin D levels is uncertain.METHODS:We conducted a systematic review of pediatric clinical trials administering high-dose vitamin D to evaluate 25-hydroxyvitamin D (25[OH]D) response and characteristics associated with final 25(OH)D levels by using Medline, Embase, and the Cochrane Central Register of Controlled Trials, including reference lists of systematic reviews and eligible publications. Uncontrolled and controlled trials reporting 25(OH)D levels after high-dose (≥1000 IU) ergocalciferol or cholecalciferol were selected. Two reviewers independently extracted and verified predefined data fields.RESULTS:We identified 88 eligible full-text articles. Two of 6 studies that administered daily doses approximating the Institute of Medicine’s Tolerable Upper Intake Level (1000–4000 IU) to vitamin D–deficient populations achieved group 25(OH)D levels &gt;75 nmol/L within 1 month. Nine of 10 studies evaluating loading therapy (&gt;50 000 IU) achieved group 25(OH)D levels &gt;75 nmol/L. In meta-regression, baseline 25(OH)D, regimen type, dose, age, and time factors were associated with final 25(OH)D levels. Adverse event analysis identified increased hypercalcemia risk with doses &gt;400 000 IU, but no increased hypercalcemia or hypercalciuria with loading doses &lt;400 000 IU (or 10 000 IU/kg). Few studies in adolescents evaluated loading dose regimens &gt;300 000 IU.CONCLUSIONS:Rapid normalization of vitamin D levels is best achieved by using loading therapy that considers disease status, baseline 25(OH)D, and age (or weight). Loading doses &gt;300 000 IU should be avoided until trials are conducted to better evaluate risk and benefit.
Methylphenidate and the Risk of Trauma
Authors: Man Kenneth K.C. , Chan Esther W. , Coghill David , Douglas Ian , Ip Patrick , Leung Ling-pong , Tsui Matthew S.H. , Wong Wilfred H.S. , Wong Ian C.K. 
Published: December 2014

BACKGROUND AND OBJECTIVE:
Children and adolescents with attention-deficit/hyperactivity disorder (ADHD) are prone to sustaining trauma that requires emergency department (ED) admission. Methylphenidate (MPH) can reduce ADHD symptoms and may thus theoretically reduce the risk of trauma-related ED admission, but previous studies do not make this association clear. This study examines this association.

METHODS:
A total of 17 381 patients aged 6 to 19 years who received MPH prescriptions were identified by using the Clinical Data Analysis & Reporting System (2001–2013). Using a self-controlled case series study design, the relative incidence of trauma-related ED admissions was compared with periods of patient exposure and nonexposure to MPH.

RESULTS:
Among 17 381 patients prescribed MPH, 4934 had at least 1 trauma-related ED admission. The rate of trauma-related ED admission was lower during exposed periods compared with nonexposed periods (incidence rate ratio [IRR]: 0.91 [95% confidence interval (CI): 0.86–0.97]). The findings were similar only when the incident trauma episode was assessed (IRR: 0.89 [95% CI: 0.82–0.96]). A similar protective association was found in both genders. In validation analysis using nontrauma-related ED admissions as a negative control outcome, no statistically significant association was found (IRR: 0.99 [95% CI: 0.95–1.02]). All sensitivity analyses demonstrated consistent results.

CONCLUSIONS:
This study supports the hypothesis that MPH is associated with a reduced risk of trauma-related ED admission in children and adolescents. A similar protective association was found in both male and female patients. This protective association should be considered in clinical practice.
Potential Drug−Drug Interactions in Infant, Child, and Adolescent Patients in Children’s Hospitals
Authors: Feinstein James , Dai Dingwei , Zhong Wenjun , Freedman Jason , Feudtner Chris 
Published: December 2014

BACKGROUND AND OBJECTIVES:
Hospitalized infants, children, and adolescents are typically exposed to numerous distinct medications during inpatient admissions, increasing their risk of potential drug−drug interactions (PDDIs). We assessed the prevalence and characteristics of PDDI exposure of pediatric patients treated in children’s hospitals.

METHODS:
This retrospective cohort study included patients &lt;21 years old hospitalized in children’s hospitals throughout the United States. PDDIs were identified by using the MicroMedex DRUG-REAX system. We calculated the patients exposed to PDDIs, stratified according to the seriousness of the interaction; daily and cumulative counts of PDDI exposures; and characterization of the cited potential adverse effects.

RESULTS:
Of 498 956 hospitalizations in 2011, 49% were associated with ≥1 PDDI, with a “contraindicated” PDDI occurring in 5% of all hospitalizations, a “major” PDDI present in 41%, a “moderate” PDDI in 28%, and a “minor” PDDI in 11%. Opioids were involved in 25% of all PDDIs, followed by antiinfective agents (17%), neurologic agents (15%), gastrointestinal agents (13%), and cardiovascular agents (13%). One-half of all PDDI exposures were due to specific drug pairs occurring in ≤3% of patients per hospital day. The most common potential adverse drug events included additive respiratory depression (in 21% of PDDIs), bleeding risk (5%), QT interval prolongation (4%), reduced iron absorption/availability (4%), central nervous system depression (4%), hyperkalemia (3%), and altered diuretic effectiveness (3%).

CONCLUSIONS:
Exposure to PDDIs is common among hospitalized children. Empirical data are needed to determine the probability and magnitude of the actual harm for each specific PDDI, particularly for less common drug pairs.