bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimating the occurrence of primary ubiquinone deficiency by analysis of large-scale sequencing data
Authors: Hughes Bryan G. , Harrison Paul M. , Hekimi Siegfried 
Published: December 2017

AbstractPrimary ubiquinone (UQ) deficiency is an important subset of mitochondrial disease that is caused by mutations in UQ biosynthesis genes. To guide therapeutic efforts we sought to estimate the number of individuals who are born with pathogenic variants likely to cause this disorder. We used the NCBI ClinVar database and literature reviews to identify pathogenic genetic variants that have been shown to cause primary UQ deficiency, and used the gnomAD database of full genome or exome sequences to estimate the frequency of both homozygous and compound heterozygotes within seven genetically-defined populations. We used known population sizes to estimate the number of afflicted individuals in these populations and in the mixed population of the USA. We then performed the same analysis on predicted pathogenic loss-of-function and missense variants that we identified in gnomAD. When including only known pathogenic variants, our analysis predicts 1,665 affected individuals worldwide and 192 in the USA. Adding predicted pathogenic variants, our estimate grows to 123,789 worldwide and 1,462 in the USA. This analysis predicts that there are many undiagnosed cases of primary UQ deficiency, and that a large proportion of these will be in developing regions of the world.
Heritability of the melatonin synthesis variability in autism spectrum disorders
Authors: Benabou Marion , Rolland Thomas , Leblond Claire S. , Millot Gaël A. , Huguet Guillaume , Delorme Richard , Leboyer Marion , Pagan Cécile , Callebert Jacques , Maronde Erik , Bourgeron Thomas 
Published: December 2017

AbstractAutism Spectrum Disorders (ASD) are heterogeneous neurodevelopmental disorders with a complex genetic architecture. They are characterized by impaired social communication, stereotyped behaviors and restricted interests and are frequently associated with comorbidities such as intellectual disability, epilepsy and severe sleep disorders. Hyperserotonemia and low melatonin levels are among the most replicated endophenotypes reported in ASD, but their genetic causes remain largely unknown. Based on the biochemical profile of 717 individuals including 213 children with ASD, 128 unaffected siblings and 376 parents and other relatives, we estimated the heritability of whole-blood serotonin, platelet N-acetylserotonin (NAS) and plasma melatonin levels, as well as the two enzymes arylalkylamine N-acetyltransferase (AANAT) and acetylserotonin O-methyltransferase (ASMT) activities measured in platelets. Overall, heritability was higher for NAS (0.72 ± 0.091) and ASMT (0.59 ± 0.097) compared with serotonin (0.31 ± 0.078), AANAT (0.34 ± 0.077) and melatonin (0.22 ± 0.071). Bivariate analyses showed high phenotypic and genetic correlations between traits of the second step of the metabolic pathway (NAS, ASMT and melatonin) indicating the contribution of shared genetic factors. A better knowledge of the heritability of the melatonin synthesis variability constitutes an important step to identify the factors that perturb this pathway in individuals with ASD.
Dual direction CRISPR transcriptional regulation screening uncovers gene networks driving drug resistance
Authors: le Sage Carlos , Lawo Steffen , Panicker Prince , Scales Tim M. E. , Rahman Syed Asad , Little Annette S. , McCarthy Nicola J. , Moore Jonathan D. , Cross Benedict C. S. 
Published: December 2017

AbstractPooled CRISPR–Cas9 knock out screens provide a valuable addition to the methods available for novel drug target identification and validation. However, where gene editing is targeted to amplified loci, the resulting multiple DNA cleavage events can be a cause of false positive hit identification. The generation of nuclease deficient versions of Cas9 has enabled the development of two additional techniques – CRISPR interference (CRISPRi) and CRISPR activation (CRISPRa) – that enable the repression or overexpression, respectively, of target genes. Here we report the first direct combination of all three approaches (CRISPRko, CRISPRi and CRISPRa) in the context of genome-wide screens to identify components that influence resistance and sensitivity to the BRAF inhibitor, vemurafenib. The pairing of both loss- and gain-of-function datasets reveals complex gene networks which control drug response and illustrates how such data can add substantial confidence to target identification and validation analyses.
Newborn Screening of Genetic Mutations in Common Deafness Genes With Bloodspot-Based Gene Chip Array
Authors: He Xuehu , Li Xiuzhong , Guo Yaqi , Zhao Yue , Dong Hui , Dong Jie , Zhong Li , Shi Zhiyun , Zhang Yuying , Soliman Mario , Song Chunhua , Zhao Zhijun 
Published: December 2017

Purpose
This study screens for deafness gene mutations in newborns in the Northwest China population.

Method

The 9 sites of 4 common deafness genes (
GJB2, GJB3, SLC26A
4,
and
mt 12S rRNA
) were detected by bloodspot-based gene chip array in 2,500 newborns.

Results

We detected mutations of the 4 genes in 101 (4.04%) newborns; particularly, 0.20% detected the double mutations. In the Hui population, 4.58% of the newborns tested positive for mutations, whereas 4.01% of Han newborns tested positive for mutations. The detective rates are as follows: 1.44% for
GJB2
235delC, 1.08% for
SLC26A4
IVS7-2A>G, 0.48% for
GJB2 299
_300delAT, 0.28% for
SLC26A4
2168A>G, 0.2% for
mt 12S rRNA
1555A>G, and 0.16% for
GJB3
538C>T. The 31.25% (5/16) of infants with
GJB2
235delC, 50% (3/6) with
GJB2
299_300delAT, and 25% (3/12) with
SLC26A4
IVS7-2A>G showed abnormal hearing when tested; only 1 double mutation case received the hearing test, and this infant showed abnormality in both ears on the hearing test.

Conclusions
High mutation rates in the common deafness genes were detected in newborns in Northwest China. Our study is helpful in understanding the deafness genomic epidemiology and also provides evidence for prenatal and postnatal care as well as policy making on population health in the region.
Monte Carlo simulation of biological shielding parameters in PGNAA
Authors: Yang Jianbo , Peng Kexin , Qiao Yujie , Zhang Can , Li Rui , Li Zhe 
Published: December 2017

A prompt γ neutron activation analysis (PGNAA) facility based on a 252 Cf spontaneous fission neutron was performed with the final goal of obtaining various optimised radiation protection design parameters. MCNP Monte Carlo code was used to simulate the lead (Pb) shield thickness on two sides of the sample chamber, and B4 C, B2O3, LiOH, LiF, and borax were selected as neutron‐absorbing materials that were simulated to determine optimal parameters for the optimal design of a biological multilayer composite shield. A series of calculations performed with the MCNP code indicated that the 5 cm thick Pb innermost layer of a biological shield rapidly reduced fast neutrons, and a moderation layer of 25 cm thick paraffin, 20 mm thick borax, and 2 mm thick B4 C were selected as neutron‐absorbing materials. The calculated biological shield protection parameters satisfied the requirements of the PGNAA facility used in the experiment.
Shifting of the resonance location for planets embedded in circumstellar disks
Authors: Marzari F. 
Published: December 2017

Context. In the early evolution of a planetary system, a pair of planets may be captured in a mean motion resonance while still embedded in their nesting circumstellar disk.
Aims. The goal is to estimate the direction and amount of shift in the semimajor axis of the resonance location due to the disk gravity as a function of the gas density and mass of the planets. The stability of the resonance lock when the disk dissipates is also tested.
Methods. The orbital evolution of a large number of systems is numerically integrated within a three-body problem in which the disk potential is computed as a series of expansion. This is a good approximation, at least over a limited amount of time.
Results. Two different resonances are studied: the 2:1 and the 3:2. In both cases the shift is inwards, even if by a different amount, when the planets are massive and carve a gap in the disk. For super-Earths, the shift is instead outwards. Different disk densities, Σ, are considered and the resonance shift depends almost linearly on Σ. The gas dissipation leads to destabilization of a significant number of resonant systems, in particular if it is fast.
Conclusions. The presence of a massive circumstellar disk may significantly affect the resonant behavior of a pair of planets by shifting the resonant location and by decreasing the size of the stability region. The disk dissipation may explain some systems found close to a resonance but not locked in it.
Primary or Redo Posterior Sagittal Anorectoplasty without a Stoma: To Feed or Not to Feed?
Authors: Skerrit Clare , Dingemans Alexander , Lane Victoria , Sanchez Alejandra , Weaver Laura , Wagner Andrea , Jenkins Nicole , Wood Richard , Levitt Marc , Reck-Burneo Carlos 
Published: December 2017

Introduction Repair of anorectal malformations (ARMs), primarily or with a reoperation, may be performed in certain circumstances without a diverting stoma. Postoperatively, the passage of bulky stool can cause wound dehiscence and anastomotic disruption. To avoid this, some surgeons keep patients NPO (nothing by mouth) for a prolonged period. Here, we report the results of a change to our routine from NPO for 7 days to clear fluids or breast milk.
Materials and Methods After primary or redo ARM surgery, patients given clear liquids were compared to those who were kept strictly NPO. Age, indication for surgery, incision type, use of a peripherally inserted central catheter (PICC) line, and wound complications were recorded.
Results There were 52 patients, including 15 primary and 37 redo cases. Group 1 comprised 11 female and 15 male patients. The mean age at surgery was 4.9 years (standard deviation [SD]: 2.3). There were 8 primary cases and 18 redo cases. Twelve (46.6%) received a PICC line. The average start of clear liquids was on day 5.3 (SD: 2.2) after examination of the wound, and the diet advanced as tolerated. The first stool passage was recorded on average on day 2.3 (SD: 1.3). Four minor wound complications and no major wound complications occurred.Group 2 comprised 14 females and 12 male patients. The mean age at surgery was 3.5 (SD: 2.4) years. There were 7 primary and 19 redo cases. One (3.8%) patient required a PICC line. A clear liquid diet was started within 24 hours after surgery. A regular diet was started on average on day 5.8 (SD: 1.3). The first stool passage was recorded on an average of day 1.6 (SD: 0.9). Three minor wound complications occurred; however, there was no significant difference between the two groups (SD: 0.71). One major wound complication occurred. However, there was no significant difference in major wound complications between the groups (SD: 0.33).
Conclusion No increase in wound problems was noted in children receiving clear liquids or breast milk compared with the strict NPO group, and PICC line use was reduced. We believe this change in practice simplifies postoperative care without increasing the risk of wound complications.
Impact of Surgery on Growth, Pulmonary Functions, and Acute Pulmonary Exacerbations in Children with Non-Cystic Fibrosis Bronchiectasis
Authors: Dogru Deniz , Yalcin Songul , Tugcu Gokcen , Yalcin Ebru , Ozcelik Ugur , Ekinci Saniye , Kiper Nural , Emiralioglu Nagehan 
Published: December 2017

Background Treatment decisions for the management of bronchiectasis include medical treatment, such as antibiotics, chest physiotherapy, and surgical procedures. Here, we aimed to review the effect of lung resection on longitudinal growth, clinical course of patients depending on annual exacerbation rates, and pulmonary function tests (PFTs) and compare them with the results of only medically treated children with non-cystic fibrosis (non-CF) bronchiectasis.
Methods The medical records of patients with non-CF bronchiectasis were retrospectively analyzed. Patients who underwent lobectomy/segmentectomy/pneumonectomy were categorized as “surgery group” (n = 29). Age- and gender-matched patients who were only medically treated were selected as “medical group” (n = 33). Annual data of patients were included till the end of postoperative second year in the surgery group and third year of medical treatment in the medical group.
Results Mean baseline height z-score was lower in the surgery group, and mean baseline PFT values were all lower in the surgery group than those in the medical group (p < 0.05). In the surgery group, mean values of height z-score were –1.68 ± 0.92 at the time of surgery and improved to –1.42 ± 1.22 and –1.34 ± 1.05 in the first and second postoperative years, respectively, and annual intravenous antibiotic requirements decreased significantly (p < 0.05); however, mean body mass index (BMI) z-score values and PFT parameters did not change significantly. In the medical group, height z-score mean values and PFT parameters showed nonsignificant improvement but annual exacerbation frequency, annual intravenous, and oral antibiotic requirements decreased significantly.
Conclusion Surgical management of non-CF bronchiectasis has no significant effect on BMI z-scores, annual exacerbation frequencies, oral antibiotic requirements and lung function tests; but can lead to significant improvement on height z-scores and decrease need of annual intravenous antibiotic requirements for acute severe exacerbations despite small number of patients in this study.
Kunsttherapie in der Palliativversorgung. Ein narratives Review. Teil I: Forschungsstand
Authors: Kortum Ria , Koch Sabine , Gruber Harald 
Published: December 2017

SummaryKunsttherapie (Therapie mit bildnerischen Medien) wird in der Palliativversorgung seit über 30 Jahren angeboten und im Rahmen der palliativen Komplexbehandlung (OPS 9–982) neben anderen begleitenden Therapiemaßnahmen empfohlen. Entgegen einer breiten praktischen Erfahrung ist ihre Wirkung bisher jedoch wissenschaftlich kaum untersucht. Auf Basis einer systematischen Datenbankrecherche wurde der aktuelle Forschungs- und Erfahrungsstand ermittelt und in 2 Übersichtsarbeiten aufgeteilt. In dieser Publikation liegt der Schwerpunkt auf der Methodik zur Erstellung des Reviews und der Darstellung des Forschungsstands. Unter insgesamt 82 internationalen Artikeln konnten 5 an größeren Stichproben durchgeführte Studien gefunden werden, in denen sich positive Effekte von Kunsttherapie auf Depression, Traurigkeit, Ängste, Müdigkeit, Fatigue, Wohlbefinden, Krankheitsgefühl und Schmerz aufzeigen ließen. Eine Validierung dieser Befunde durch Kontrollgruppenstudien steht in der Mehrzahl der Fälle noch aus. Als erste positive Befunde sind diese Ergebnisse jedoch eine wichtige Grundlage für weitere Studien und damit zur Evidenzbasierung der Kunsttherapie in der Palliativversorgung.
Reiserückkehrer mit Denguefieber: Diagnostik und Therapieoptionen
Authors: Kroidl Inge 
Published: December 2017

ZUSAMMENFASSUNGAn eine Dengueinfektion sollte bei allen Symptomen, die 3–14 Tage nach einer Reise in die endemischen Länder auftreten, gedacht werden. Auch Symptome, die zunächst nicht an Dengue denken lassen, wie zum Beispiel ophthalmologische Beschwerden oder Enzephalopathien, kommen vor. Hingegen sind andere, im Allgemeinen als typisch geltende Zeichen für die Infektion, wie zum Beispiel das Dengueexanthem oft kaum sichtbar und auch bei anderen viralen Erkrankungen vorhanden. Die erhöhte transiente kapillare Durchlässigkeit während der kritischen Phase führt zu Organvergrößerungen und Verdickung von Schleimhäuten. Die hierbei auftretenden Symptome wie abdomineller Schmerz, Abwehrspannung, Erbrechen sowie Befunde wie Hepatomegalie, Aszites und Pleuraergüsse sind typisch für die kritische Phase der Dengueinfektion, können aber leicht an andere Krankheiten denken lassen. Die Entwicklungen einer Schocksymptomatik und weitere Komplikationen können durch die rechtzeitige Erkennung von Warnzeichen und eine adäquate Therapie verhindert beziehungsweise in der Häufigkeit reduziert werden. Die Zahl der schweren Verläufe des Denguefiebers ist bei Touristen gering, aus den Epidemieländern werden höhere Zahlen gemeldet, insbesondere bei Kindern.
Auswirkungen des altersbezogenen kornealen Elastizitätsmoduls auf die Applanationstonometrie
Authors: Sperlich Karsten , Reiß Stephan , Bohn Sebastian , Stolz Heinrich , Guthoff Rudolf , Jünemann Anselm , Stachs Oliver 
Published: December 2017

ZusammenfassungDer intraokulare Druck (IOP) wird als wichtigster modifizierbarer Risikofaktor für eine Glaukomerkrankung angesehen. Die IOP-Bestimmung durch eine Applanationstonometrie wird aufgrund der individuellen Variation der zentralen Hornhautdicke (CCT) mittels entsprechender Korrekturtabellen korrigiert. Dagegen werden andere Fehler, beispielsweise hervorgerufen durch altersabhängige Veränderung des Elastizitätsmoduls (EM) der Kornea, ignoriert. Ausgehend von Formeln der experimentellen Physik wird im Rahmen dieser Arbeit ein numerisches analytisches Modell entwickelt, welches die Wirkung bekannter Einflussgrößen auf die IOP-Bestimmung insbesondere unter Einbeziehung der elastischen Eigenschaften berücksichtigt. Dabei werden die für die Modellentwicklung notwendigen erforderlichen Annahmen eingeführt und begründet sowie die für eine korrekte IOP-Bestimmung notwendigen Korrekturwerte berechnet. Unsere Korrekturwerte stimmen für CCT-Werte bis 650 µm und einem mittleren kornealen Elastizitätsmodul von 0,29 MPa gut mit der Dresdner Tabelle überein. Eine Variation des EM von 0,2 – 0,5 MPa, was einem EM vom Kindesalter bis zum Alter von 90 Jahren entspricht, verursacht eine Abweichung des IOP von bis zu 10 mmHg. Eine Variation des Krümmungsradius der Hornhaut von 7,4 – 8,0 mm entspricht dagegen einer IOP-Änderung von nur 3 mmHg und kann vernachlässigt werden. Das entwickelte Modell zeigt, dass etablierte Korrekturformeln für eine zuverlässige Bestimmung des IOP unzureichend sein können. In vielen Fällen ist die gängige Praxis der IOP-Bestimmung zuverlässig, aber die durch CCT und EM möglicherweise induzierten Messunsicherheiten liegen etwa im gleichen Größenbereich. Den IOP durch Applanationsmethoden unter Nutzung von etablierten Korrekturformeln zu bestimmen, sollte daher nicht überbewertet werden, ohne den EM der Kornea zu berücksichtigen.
Simultaneous Determination of Rosuvastatin, Rosuvastatin-5 S-lactone, and N-desmethyl Rosuvastatin in Human Plasma by UPLC-MS/MS and Its Application to Clinical Study
Authors: Bai Xue , Wang Xi-Pei , He Guo-Dong , Zhang Bin , Huang Min , Li Jia-Li , Zhong Shi-Long 
Published: December 2017

Abstract
Objective A rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay was developed and validated for the simultaneous quantification of rosuvastatin (RST), rosuvastatin-5 S-lactone (RSTL), and N-desmethyl rosuvastatin (DM-RST) in human plasma.
Methods Sample was prepared by liquid-liquid extraction with ethyl acetate from 100 μL acidulated buffered plasma. Then analytes were chromatographically separated using an Acquity UPLC HSS T3 column (3.0 mm×100 mm, 1.8 µm) by 0.1% formic acid and gradient acetonitrile at a flow rate of 0.30 mL/min. Three analytes and internal standards (carbamazepine) were eluted in 3.5 min. Mass spectrometry detection was performed through positive ion electrospray ionization (ESI).
Results The calibration curves for three analytes were linear (R≥0.9987, n=3) within the concentration range of 0.1–50 ng/mL for RST and RSTL, and 0.2–100 ng/mL for DM-RST. Mean extraction recoveries were enhanced by means of acidulated plasma using ammonium acetate of pH 4.0, which ranged within 75.3–98.8% for three analytes. Intra- and inter precision and accuracy were 88.2–96.4%.
Conclusions This present method was lower LLOQ, less time consuming (3.5 min), less plasma consuming (100 µL) and simpler sample preparation. And it was successfully applied to determine steady state concentrations of RST, RSTL and DM-RST in a clinical study of RST for patients with coronary artery disease (CAD).
Insights from ‘policy learning’ on how to enhance the use of evidence by policymakers
Authors: Witting Antje 
Published: December 2017

AbstractThis article uses the policy-oriented learning literature to provide practical insights on how to enhance the use of evidence by policymakers. After a short introduction to the field, this article presents four steps to understanding and responding to policy learning. First, all people interpret the world through the lens of their beliefs, and learn by combining heuristics and analytical processing. Second, people learn in different ways according to their roles. A novice would not be advised to learn about a specialist isue in the same way as a scientist. Instead, a modified communication strategy would be used to ensure understanding and uptake of evidence. Third, learning is a political process: we interact with our social environment and some actors—including entrepreneurs and brokers—influence the process more than others. Therefore, to encourage learning from scientific evidence we need to move beyond communication towards entrepreneurship and brokerage roles. In other words, policy-oriented learning is as much about interaction and leadership as information.
Bipartite Talus: Arthroscopic Resection – Case Report
Authors: de Oliveira Junior Adilson Sanches , Moreira Mendes Alberto A. , Saito Guilherme H. , Prado Marcelo P. 
Published: December 2017

Background:
Bipartite talus is a rare entity. The etiology is uncertain. The definition is a large bone fragment that occupies the posterior portion of the talus and reaches the posterior subtalar joint.

Case Report:
We report a symptomatic bipartite talus in a female patient, 41 years old, treated with arthroscopic resection.

Discussion:
Posterior hindfoot arthroscopy has gained more popularity in the treatment of foot and ankle pathologies. Indeed, this is a secure and useful tool for the surgeon. In this report, we described the use of this technique for resection of a large bone fragment (bipartite talus).

Conclusions:
We present in detail the arthroscopic resection of a bipartite talus. This is an unusual pathology and a differential diagnosis for posterior impingement. We believe that arthroscopic resection of the bone fragment of the bipartite talus is a safe procedure, with less morbidity for the patient, compared with open resections.

Level of Evidence:
Level V—technique description.