bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of nifedipine and atosiban on perinatal brain injury: secondary analysis of the APOSTEL‐III trial
Authors: Nijman T. A. J. , Goedhart M. M. , Naaktgeboren C. N. , de Haan T. R. , Vijlbrief D. C. , Mol B. W. , Benders M. J. N. , Franx A. , Oudijk M. A. 
Published: April 2017

ABSTRACTObjectiveBrain injury in neonates born prematurely is associated strongly with poor neurodevelopmental outcome. The aim of this study was to evaluate whether tocolysis with nifedipine or atosiban in women with threatened preterm birth can reduce the incidence of overall brain injury in neonates born prematurely.MethodsThis was a secondary analysis of the APOSTEL‐III trial (Dutch Clinical Trial Registry, no. NTR2947), a randomized clinical trial in which women with threatened preterm labor between 25 and 34 weeks of gestation were allocated to treatment with nifedipine or atosiban. In this secondary analysis, women delivered at ≤ 32 weeks of gestational age in the two main contributing centers were included. Primary outcome was the presence of neonatal brain injury, which was defined as presence of abnormalities on ultrasound investigation and classified into mild and severe. To evaluate type and severity of brain injury, all neonatal ultrasounds performed during neonatal intensive and medium care admission were analyzed. To test the robustness of our results, a sensitivity analysis was performed assessing differences in baseline or known risk factors for brain injury.ResultsA total of 117 neonates (from 102 women) were studied, of which 51 had been exposed to nifedipine and 66 to atosiban. Brain injury was observed in 22 (43.1%) neonates in the nifedipine group compared with 37 (56.1%) in the atosiban group (OR, 0.60; 95% CI, 0.29–1.24). Presence of mild brain injury was comparable between the nifedipine (33.3%) and atosiban (48.5%) groups (OR, 0.53; 95% CI, 0.25–1.13). Severe brain injury was also comparable between the groups, observed in 9.8% of neonates in the nifedipine vs 7.6% of those in the atosiban group (OR, 1.33; 95% CI, 0.36–4.85). Intraventricular hemorrhage (≥ Grade I) was the most frequently seen ultrasound abnormality, observed in 18 (35.3%) neonates in the nifedipine group vs 25 (37.9%) in the atosiban group (OR, 0.90; 95% CI, 0.42–1.91). The sensitivity analysis, with adjustment for maternal age and gestational age at randomization, showed no statistical difference between the groups for presence of brain injury (OR, 0.58; 95% CI, 0.27–1.27).ConclusionIn children born before 32 weeks of gestation after the use of tocolytics, the prevalence of brain injury was high. No significant differences were found with respect to overall brain injury between neonates exposed to nifedipine and those exposed to atosiban. However, as this study was a secondary analysis of the APOSTEL III trial, it was underpowered for brain injury. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
Politics in the Age of Fox, Pitt and Liverpool
Authors: Derry John W. 
Published: April 2017

For many people the late eighteenth century was a period of political corruption, with the political world waiting for the triumph of reform. In this lucidly written study, now in a revised edition, John Derry shows that the traditional political system was more remarkable for its resilience than for its defects, and that it succeeded to an astonishing extent in meeting the challenges of war, the threat from the French Revolution, and the problems caused by unprecedented social and economic change. A vigorous narrative is combined with pungent analysis of the assumptions on which the practice of politics was based and the fashion in which politicians responded to the demands made of them.
Due weight is given to the element of continuity. The king continued to play a significant role in politics and no ministry could survive without the confidence of the crown and the support of the country gentlemen, and Pitt and Liverpool owed their success to their ability to appeal to these two powerful political forces. The importance of the French Revolution is not underplayed, but war is seen as a greater factor than ideology in bringing about a polarisation of opinion and the dominance of a conservatism which rested squarely upon traditional values. But trasnformation was also part of the story, and this study is fascinating in the manner in which it demonstrates the subtle blend of the old and the new which gave politics their unique flavour. The personalities of George III, Fox, Pitt and Liverpool are brought to life with deft and succinct characterisation in a style which will entertain as well as inform.
The Association Between Atherosclerosis and Low Back Pain: A Systematic Review
Authors: Shcherbina Anton , Longacre Mckenna 
Published: April 2017

AbstractObjectiveTo assess the evidence of association between atherosclerosis and low back pain (LBP).TypeFocused systematic review.Literature SurveyPubMed, Web of Science, CINAHL, and EMBASE were searched for original research articles, not limited by language, from January 1, 1990, to October 31, 2016.MethodologyTitles and then abstracts were identified using predefined search terms and excluded based on lack of relevancy. This was followed by full‐text reviews. Two authors independently assessed methodological quality based on Cochrane Handbook for Systematic Reviews of Interventions.SynthesisA total of 26 studies met the inclusion criteria. The quality of the studies was low to moderate. There was significant heterogeneity across articles with respect to methodology. There was insufficient evidence to support an association between ischemia and low back pain.ConclusionsThe cause of LBP remains poorly understood. Better insight into how intervertebral disk changes relate to LBP is needed to guide future research. High‐quality prospective studies are needed to answer the question of whether atherosclerosis is a risk factor for LBP.Level of EvidenceII
Radiocarbon Chronology of the DSDDP Core at the Deepest Floor of the Dead Sea
Authors: Kitagawa Hiroyuki , Stein Mordechai , Goldstein Steven L , Nakamura Toshio , Lazar Boaz ,   DSDDP Scientific Party
Published: April 2017

AbstractThis study establishes the chronological framework of the sedimentary sequence deposited Dead Sea, ICDP 5017-1, Radiocarbon chronology during the past 50 ka at the deepest part of the Dead Sea (the ICDP 5017-1 site), which was recovered by the Dead Sea Deep Drilling Project (DSDDP) under the auspices of the International Continental Scientific Drilling Program (ICDP). The age-depth model is constructed using 3814C dates of terrestrial plant remains in a composite 150-m-long profile, generated by anchoring 32 marker layers identified in five cores. The sedimentary records at the ICDP 5017-1 site fills gaps in those obtained from the exposed sections at the high margins of the lake, particularly in times of lake-level retreat, and allows for a high-resolution comparison between the lake’s margins and deepest floor.
Frequent somatic mutations in epigenetic regulators in newly diagnosed chronic myeloid leukemia
Authors: Togasaki E , Takeda J , Yoshida K , Shiozawa Y , Takeuchi M , Oshima M , Saraya A , Iwama A , Yokote K , Sakaida E , Hirase C , Takeshita A , Imai K , Okumura H , Morishita Y , Usui N , Takahashi N , Fujisawa S , Shiraishi Y , Chiba K , Tanaka H , Kiyoi H , Ohnishi K , Ohtake S , Asou N , Kobayashi Y , Miyazaki Y , Miyano S , Ogawa S , Matsumura I , Nakaseko C , Naoe T ,   for the Japan Adult Leukemia Study Group (JALSG)
Published: April 2017

AbstractAlthough tyrosine kinase inhibitors (TKIs) have significantly improved the prognosis of chronic myeloid leukemia (CML), the ability of TKIs to eradicate CML remains uncertain and patients must continue TKI therapy for indefinite periods. In this study, we performed whole-exome sequencing to identify somatic mutations in 24 patients with newly diagnosed chronic phase CML who were registered in the JALSG CML212 study. We identified 191 somatic mutations other than the BCR-ABL1 fusion gene (median 8, range 1–17). Age, hemoglobin concentration and white blood cell counts were correlated with the number of mutations. Patients with mutations ⩾6 showed higher rate of achieving major molecular response than those<6 (P=0.0381). Mutations in epigenetic regulator, ASXL1, TET2, TET3, KDM1A and MSH6 were found in 25% of patients. TET2 or TET3, AKT1 and RUNX1 were mutated in one patient each. ASXL1 was mutated within exon 12 in three cases. Mutated genes were significantly enriched with cell signaling and cell division pathways. Furthermore, DNA copy number analysis showed that 2 of 24 patients had uniparental disomy of chromosome 1p or 3q, which disappeared major molecular response was achieved. These mutations may play significant roles in CML pathogenesis in addition to the strong driver mutation BCR-ABL1.
Optical coherence tomography-based contact indentation for diaphragm mechanics in a mouse model of transforming growth factor alpha induced lung disease
Authors: Wang Kimberley C. W. , Astell Chrissie J. , Wijesinghe Philip , Larcombe Alexander N. , Pinniger Gavin J. , Zosky Graeme R. , Kennedy Brendan F. , Berry Luke J. , Sampson David D. , James Alan L. , Le Cras Timothy D. , Noble Peter B. 
Published: April 2017

AbstractThis study tested the utility of optical coherence tomography (OCT)-based indentation to assess mechanical properties of respiratory tissues in disease. Using OCT-based indentation, the elastic modulus of mouse diaphragm was measured from changes in diaphragm thickness in response to an applied force provided by an indenter. We used a transgenic mouse model of chronic lung disease induced by the overexpression of transforming growth factor-alpha (TGF-α), established by the presence of pleural and peribronchial fibrosis and impaired lung mechanics determined by the forced oscillation technique and plethysmography. Diaphragm elastic modulus assessed by OCT-based indentation was reduced by TGF-α at both left and right lateral locations (p < 0.05). Diaphragm elastic modulus at left and right lateral locations were correlated within mice (r = 0.67, p < 0.01) suggesting that measurements were representative of tissue beyond the indenter field. Co-localised images of diaphragm after TGF-α overexpression revealed a layered fibrotic appearance. Maximum diaphragm force in conventional organ bath studies was also reduced by TGF-α overexpression (p < 0.01). Results show that OCT-based indentation provided clear delineation of diseased diaphragm, and together with organ bath assessment, provides new evidence suggesting that TGF-α overexpression produces impairment in diaphragm function and, therefore, an increase in the work of breathing in chronic lung disease.
Rationally co-targeting divergent pathways in KRAS wild-type colorectal cancers by CANscript technology reveals tumor dependence on Notch and Erbb2
Authors: Brijwani Nilesh , Jain Misti , Dhandapani Muthu , Zahed Farrah , Mukhopadhyay Pragnashree , Biswas Manjusha , Khatri Deepak , Radhakrishna Vinod D. , Majumder Biswanath , Radhakrishnan Padhma , Thiyagarajan Saravanan 
Published: April 2017

AbstractKRAS mutation status can distinguish between metastatic colorectal carcinoma (mCRC) patients who may benefit from therapies that target the epidermal growth factor receptor (EGFR), such as cetuximab. However, patients whose tumors harbor mutant KRAS (codons 12/13, 61 and 146) are often excluded from EGFR-targeted regimens, while other patients with wild type KRAS will sometimes respond favorably to these same drugs. These conflicting observations suggest that a more robust approach to individualize therapy may enable greater frequency of positive clinical outcome for mCRC patients. Here, we utilized alive tumor tissues in ex-vivo platform termed CANscript, which preserves the native tumor heterogeneity, in order to interrogate the antitumor effects of EGFR-targeted drugs in mCRC (n = 40). We demonstrated that, irrespective of KRAS status, cetuximab did not induce an antitumor response in a majority of patient tumors. In the subset of non-responsive tumors, data showed that expression levels of EGFR ligands contributed to a mechanism of resistance. Transcriptomic and phosphoproteomic profiling revealed deregulation of multiple pathways, significantly the Notch and Erbb2. Targeting these nodes concurrently resulted in antitumor efficacy in a majority of cetuximab-resistant tumors. These findings highlight the importance of integrating molecular profile and functional testing tools for optimization of alternate strategies in resistant population.
Accumulation of multiple neurodegenerative disease-related proteins in familial frontotemporal lobar degeneration associated with granulin mutation
Authors: Hosokawa Masato , Kondo Hiromi , Serrano Geidy E. , Beach Thomas G. , Robinson Andrew C. , Mann David M. , Akiyama Haruhiko , Hasegawa Masato , Arai Tetsuaki 
Published: April 2017

AbstractIn 2006, mutations in the granulin gene were identified in patients with familial Frontotemporal Lobar Degeneration. Granulin transcript haploinsufficiency has been proposed as a disease mechanism that leads to the loss of functional progranulin protein. Granulin mutations were initially found in tau-negative patients, though recent findings indicate that these mutations are associated with other neurodegenerative disorders with tau pathology, including Alzheimer’s disease and corticobasal degeneration. Moreover, a reduction in progranulin in tau transgenic mice is associated with increasing tau accumulation. To investigate the influence of a decline in progranulin protein on other forms of neurodegenerative-related protein accumulation, human granulin mutation cases were investigated by histochemical and biochemical analyses. Results showed a neuronal and glial tau accumulation in granulin mutation cases. Tau staining revealed neuronal pretangle forms and glial tau in both astrocytes and oligodendrocytes. Furthermore, phosphorylated α-synuclein-positive structures were also found in oligodendrocytes and the neuropil. Immunoblot analysis of fresh frozen brain tissues revealed that tau was present in the sarkosyl-insoluble fraction, and composed of three- and four-repeat tau isoforms, resembling Alzheimer’s disease. Our data suggest that progranulin reduction might be the cause of multiple proteinopathies due to the accelerating accumulation of abnormal proteins including TDP-43 proteinopathy, tauopathy and α-synucleinopathy.
Bioinformatic and expression analysis of the Brassica napus L. cyclophilins
Authors: Hanhart Patrizia , Thieß Melanie , Amari Khalid , Bajdzienko Krzysztof , Giavalisco Patrick , Heinlein Manfred , Kehr Julia 
Published: April 2017

AbstractCyclophilins (CYPs) are a group of ubiquitous proteins characterized by their ability to bind to the immunosuppressive drug cyclosporin A. The CYP family occurs in a wide range of organisms and contains a conserved peptidyl-prolyl cis/trans isomerase domain. In addition to fulfilling a basic role in protein folding, CYPs may also play diverse important roles, e.g. in protein degradation, mRNA processing, development, and stress responses. We performed a genome-wide database survey and identified a total of 94 CYP genes encoding 91 distinct proteins. Sequence alignment analysis of the putative BnCYP cyclophilin-like domains revealed highly conserved motifs. By using RNA-Seq, we could verify the presence of 77 BnCYP genes under control conditions. To identify phloem-specific BnCYP proteins in a complementary approach, we used LC-MS/MS to determine protein abundances in leaf and phloem extracts. We detected 26 BnCYPs in total with 12 being unique to phloem sap. Our analysis provides the basis for future studies concentrating on the functional characterization of individual members of this gene family in a plant of dual importance: as a crop and a model system for polyploidization and long-distance signalling.
Device performance enhancement via a Si-rich silicon oxynitride buffer layer for the organic photodetecting device
Authors: Heo Sung , lee Jooho , Kim Seong Heon , Yun Dong-Jin , Park Jong-Bong , Kim Kihong , Kim NamJeong , Kim Yongsung , Lee Dongwook , Kim Kyu-Sik , Kang Hee Jae 
Published: April 2017

AbstractAn advanced organic photodetector (OPD) with a butter layer of Si-rich silicon oxynitride (SiOxNy) was fabricated. The detector structure is as follows: Indium tin oxide (ITO) coated glass substrate/SiOxNy(10 nm)/naphthalene-based donor:C60(1:1)/ITO. Values of x and y in SiOxNy were carefully controlled and the detector performances such as dark current and thermal stability were investigated. When the values of x and y are 0.16 and 0.66, the detector illustrates low dark current as well as excellent thermal stability. In the OPD, silicon oxynitride layer works as electron barrier under reverse bias, leading to the decrease of dark current and increase of detectivity. Since the band gap of silicon oxynitride unlike conventional buffer layers can also be controlled by adjusting x and y values, it can be adapted into various photodiode applications.
Vegetation Controls on the Spatio-Temporal Heterogeneity of Deep Moisture in the Unsaturated Zone: A Hydrogeophysical Evaluation
Authors: Acharya Bharat S. , Halihan Todd , Zou Chris B. , Will Rodney E. 
Published: April 2017

AbstractInformation on the spatio-temporal variability of soil moisture in the vadose zone is important to assess groundwater recharge and solute transport in unconsolidated substrate as influenced by biological processes. Time-lapse electrical resistivity imaging (ERI) was used to monitor soil moisture dynamics to a depth of 9 m in a grassland, a grassland encroached by a juniper species (eastern redcedar,Juniperus virginiana), a juniper woodland and an oak forest in the south-central Great Plains, Oklahoma, USA. A site-specific relationship between moisture content and electrical conductivity data was developed for the soil zone, and a perched water zone was monitored at two of the sites. Results showed that (a) change in soil moisture content was linearly correlated to change in electric conductivity in the soil zone; (b) vegetation cover type induced differences in vertical bulk electrical resistivity (ER) profiles and influenced the temporal evolution of soil moisture profiles; and (c) juniper encroachment lowered the water level in the perched groundwater aquifer. Our results suggest land use and vegetation cover type, as opposed to rock properties, controls deep water drainage for the vegetation transition zone. Methods used to measure hydrogeophysical changes, such as ERI, can be used for broader understanding of geological, physical, and biological processes and their links in Earth’s critical zones.
Pluronic based β-cyclodextrin polyrotaxanes for treatment of Niemann-Pick Type C disease
Authors: Collins Christopher J. , Loren Bradley P. , Alam Md Suhail , Mondjinou Yawo , Skulsky Joseph L. , Chaplain Cheyenne R. , Haldar Kasturi , Thompson David H. 
Published: April 2017

AbstractNiemann-Pick Type C disease (NPC) is a rare metabolic disorder characterized by disruption of normal cholesterol trafficking within the cells of the body. There are no FDA approved treatments available for NPC patients. Recently, the cycloheptaglucoside 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) has shown efficacy as a potential NPC therapeutic by extending lifetime in NPC mice, delaying neurodegeneration, and decreasing visceral and neurological cholesterol burden. Although promising, systemic HP-β-CD treatment is limited by a pharmacokinetic profile characterized by rapid loss through renal filtration. To address these shortcomings, we sought to design a family of HP-β-CD pro-drug delivery vehicles, known as polyrotaxanes (PR), capable of increasing the efficacy of a given injected dose by improving both pharmacokinetic profile and bioavailability of the HP-β-CD agent. PR can effectively diminish the cholesterol pool within the liver, spleen, and kidney at molar concentrations 10-to-100-fold lower than monomeric HP-β-CD. In addition to this proof-of-concept, use of PR scaffolds with differing physiochemical properties reveal structure-activity relationships in which PR characteristics, including hydrophobicity, threading efficiency and surface charge, were found to both decisively and subtly effect therapeutic efficacy. PR scaffolds exhibit absorption, pharmacokinetics, and biodistribution patterns that are significantly altered from monomeric HP-β-CD. In all, PR scaffolds hold great promise as potential treatments for visceral disease in NPC patients.
Leadership in Pediatric Surgery from a Senior's Perspective
Authors: Tovar Juan 
Published: April 2017

AbstractManagement of a pediatric surgical group involves organization, coordination, and direction of human resources in an attempt to achieve the best results in an efficient way. However, true leadership of such group should also involve inspiring it with a purpose. The superior interest of the patients and their families will be better served by achieving excellence at all levels of care, research, teaching, and diffusion of the results. These values are the core of the leader's action and may be difficult to develop in a hospital framework in which the main decisions are not always into his/her hands.This review summarizes a theory on leadership at large and then analyzes in detail the peculiarities that distinguish surgical and pediatric surgical departments from a corporation in an attempt to extend the application of the principles of leadership to these structures.Finally, the steps possibly taken by prospective leaders toward achieving that condition and some tips for the candidates based on the personal experience of the author are advanced.
Belastungen von Fachkräften in stationären Einrichtungen für Kinder und Jugendliche
Authors: Rau Thea , Ohlert Jeannine , Seidler Corinna , Fegert Jörg , Allroggen Marc 
Published: April 2017

ZusammenfassungPsychische Belastungen von Fachkräften werden als zunehmend wichtiges Thema in stationären Einrichtungen für Kinder und Jugendliche betrachtet. Demgegenüber liegen nur wenige Studien vor, die Belastungserleben von pädagogischen Fachkräften allgemein und speziell in Jugendhilfeeinrichtungen untersuchen. Ziel der vorliegenden Studie war, Belastungserleben bei Fachkräften mittels des „Perceived Stress Questionnaire“ (PSQ) in Einrichtungen der Jugendhilfe zu erheben sowie dessen Zusammenhang mit Alter, Dauer der Tätigkeit im Arbeitsfeld und Geschlecht zu untersuchen. Insgesamt nahmen 426 Fachkräfte aus Jugendhilfeeinrichtungen an der Online-Studie teil. Die Ergebnisse zeigen tendenziell höhere Belastungswerte bei jüngeren Fachkräften und signifikant höhere Werte bei Anspannung im Vergleich zu älteren Mitarbeitenden, jedoch keinen Effekt von Geschlecht. Weiterhin besteht kein Zusammenhang zwischen Belastungserleben und Dauer der Tätigkeit im Arbeitsfeld, jedoch ein signifikanter Zusammenhang zwischen einem Gefühl von Sicherheit vor Gewalt in der Einrichtung und Belastung. Der Gesamtscore für Belastungserleben bei Fachkräften ist vergleichbar mit dem von gesunden Erwachsenen, während sich in den Subskalen im Vergleich zur Normstichprobe höhere Werte bei Anforderungen im Sinne von Termin- und Zeitdruck sowie bei Anspannung zeigen. Die Ergebnisse weisen auf eine hohe Vulnerabilität von jungen Fachkräften hin, der möglicherweise mit institutionellen Maßnahmen begegnet werden kann. Zur Klärung kausaler Zusammenhänge sind weitere Studien notwendig.