bluuebunny/crossref_metadata_2025_split huggingface dataset:
Noncognate DNA damage prevents the formation of the active conformation of the Y‐family DNA polymerases DinB and DNA polymerase κ
Authors: Nevin Philip , Lu Xueguang , Zhang Ke , Engen John R. , Beuning Penny J. 
Published: April 2015

Y‐family DNA polymerases are specialized to copy damaged DNA, and are associated with increased mutagenesis, owing to their low fidelity. It is believed that the mechanism of nucleotide selection by Y‐family DNA polymerases involves conformational changes preceding nucleotidyl transfer, but there is limited experimental evidence for such structural changes. In particular, nucleotide‐induced conformational changes in bacterial or eukaryotic Y‐family DNA polymerases have, to date, not been extensively characterized. Using hydrogen–deuterium exchange mass spectrometry, we demonstrate here that the Escherichia coli Y‐family DNA polymerase DinB and its human ortholog DNA polymerase κ undergo a conserved nucleotide‐induced conformational change in the presence of undamaged DNA and the correct incoming nucleotide. Notably, this holds true for damaged DNA containing N2‐furfuryl‐deoxyguanosine, which is efficiently copied by these two polymerases, but not for damaged DNA containing the major groove modification O6‐methyl‐deoxyguanosine, which is a poor substrate. Our observations suggest that DinB and DNA polymerase κ utilize a common mechanism for nucleotide selection involving a conserved prechemical conformational transition promoted by the correct nucleotide and only preferred DNA substrates.
Headache, Cerebral Aneurysms, and the Use of Triptans and Ergot Derivatives
Authors: Baron Eric P. 
Published: April 2015

BackgroundUncertainty exists regarding the correlation between unruptured cerebral aneurysms and their role in headache etiology. It is also unclear whether surgical endovascular treatment may improve or worsen the headache, and if there are predictable factors for headache outcome such as pre‐existing headache features, aneurysm characteristics, or other medical history. There is debate regarding safe treatment of migraine in patients with aneurysms, both before and after endovascular treatments. Particularly, there is hesitancy to use the triptans and ergot derivatives such as dihydroergotamine because of their vasoconstrictive effects and concern for adverse events related to the aneurysm such as aneurysmal instability and rupture.ObjectiveTo review the literature regarding the anatomy, pathophysiology, and association between headache, untreated vs surgically treated aneurysms, and the use of triptans and ergot derivatives for migraine treatment in this setting.ConclusionAssociations between some headaches and aneurysms may exist. Some chronic headaches may respond to surgical aneurysm repair while others may worsen. These associations are undefined by current literature because of variable results, study methods, and limited data. Prospective studies are needed which incorporate pre‐ and post‐procedure headache character and diagnosis, aneurysm characteristics, type of aneurysm repair, associated risk factors for worsening post‐procedure headache, and ultimately combining all of these data to better predict headache outcome following surgical aneurysm treatment. Lastly, the caution and avoidance of triptan and ergot derivative use for migraine in the setting of aneurysm is not supported by the current evidence, and much of this concern may be excessive and unwarranted, although more evidence confirming safety is needed.
Cutaneous lymphoma misdiagnosed as chronic lymphadenitis
Authors: Munteanu Mircea , Mohor Georgiana S , Baderca Flavia , Solovan Caius 
Published: April 2015

AbstractCutaneous lymphomas (CLs) represent a group of lymphoproliferative disorders that can be difficult to diagnose in the early stage because they could mimic many benign inflammatory dermatoses (chronic eczema, bullous dermatosis, idiopathic erythroderma, psoriasis, lymphadenitis). Primary cutaneous B‐cell lymphomas are a unique and controversial group of skin lymphomas characterised by the absence of extracutaneous manifestations at diagnosis.We present the case of a 60‐year‐old man with 7‐month history of a growing inguinal mass/tumour, which was misdiagnosed as inguinal chronic lymphadenitis.Recognition of the correct entity, primary cutaneous diffuse large B‐cell lymphoma leg type, led to an appropriate therapeutic strategy, knowing that these types of tumours behave more aggressively than other types of primary cutaneous B‐cell lymphomas. The patient was discharged with rituximab + chemotherapy indication and favourable outcome.The aim of the presentation is to describe these common skin manifestations, however seen in a primary cutaneous B‐cell lymphoma, which underlines the necessity of rigorous monitoring/long‐term follow‐up as well as exhaustive histopathological analysis for the diagnosis.
Vibration Assisted Hot‐Press Sintering of AlN Ceramics
Authors: Feng Bin , Zhou Yao , Peng Cheng , Li Xiaoyan , Liu Juying , Wang Yumei , Rao Pinggen , Wu Jianqing 
Published: April 2015

AlN ceramics is very difficult to be sintered due to its strong covalent bonds and low self‐diffusion. In this work, a new hot‐press sintering system assisted by vibration was used to densify AlN ceramics. During hot‐pressing process an additional vibration caused by pressure fluctuation is imposed on the sample. The well‐densified AlN ceramics had been obtained at 1750°C under 15 MPa, or at 1800°C under 10 MPa which were much milder than traditional hot‐press conditions and would be beneficial to prolong working life of the graphite mold. The samples made by this method have a bending strength about 320 MPa. After annealing, it shows a thermal conductivity of 217 W/mK.
The Legal and Political Accountability Structure of ‘Post‐Crisis’ EU Economic Governance
Authors: Dawson Mark 
Published: April 2015

AbstractHow should decision‐making under EU economic governance be understood following the euro‐crisis? This article argues, contra existing depictions, that the post‐crisis EU has increasingly adopted methods of decision‐making in the economic field which marry the decision‐making structure of inter‐governmentalism with the supervisory and implementation framework of the Community Method. While this ‘post‐crisis’ method has arisen for clear reasons – to achieve economic convergence between eurozone states in an environment where previous models of decision‐making were unsuitable or unwanted – it also carries important normative implications. Post‐crisis governance departs from the mechanisms of legal and political accountability present in previous forms of EU decision‐making without substituting new models of accountability in their place. Providing appropriate channels of political and legal control in the EU's ‘new’ economic governance should be seen as a crucial task for the coming decade.
Distinct trajectories of separation anxiety in the preschool years: persistence at school entry and early‐life associated factors
Authors: Battaglia Marco , Touchette Évelyne , Garon‐Carrier Gabrielle , Dionne Ginette , Côté Sylvana M. , Vitaro Frank , Tremblay Richard E. , Boivin Michel 
Published: April 2015

BackgroundLittle is known about how children differ in the onset and evolution of separation anxiety (SA) symptoms during the preschool years, and how SA develops into separation anxiety disorder. In a large, representative population‐based sample, we investigated the developmental trajectories of SA symptoms from infancy to school entry, their early associated risk factors, and their associations with teachers' ratings of SA in kindergarten.MethodsLongitudinal assessment of SA trajectories and risk factors in a cohort of 1,933 families between the ages of 1.5 and 6 years.ResultsAnalyses revealed a best‐fitting, 4‐trajectory solution, including a prevailing, unaffected Low‐Persistent group (60.2%), and three smaller groups of distinct developmental course: a High‐Increasing (6.9%), a High‐Decreasing (10.8%), and a Low‐Increasing group (22.1%). The High‐Increasing group remained high throughout the preschool years and was the only trajectory to predict teacher‐assessed SA at age 6 years. Except for the High‐Increasing, all trajectories showed substantial reduction in symptoms by age 6 years. The High‐Increasing and High‐Decreasing groups shared several early risk factors, but the former was uniquely associated with higher maternal depression, maternal smoking during pregnancy, and parental unemployment.ConclusionsMost children with high SA profile at age 1.5 years are expected to progressively recover by age 4–5. High SA at age 1.5 that persists over time deserves special attention, and may predict separation anxiety disorder. A host of child perinatal, parental and family‐contextual risk factors were associated with the onset and developmental course of SA across the preschool years.
Liraglutide is effective and well tolerated in combination with an oral antidiabetic drug in Japanese patients with type 2 diabetes: A randomized, 52‐week, open‐label, parallel‐group trial
Authors: Kaku Kohei , Kiyosue Arihiro , Ono Yuri , Shiraiwa Toshihiko , Kaneko Shizuka , Nishijima Keiji , Bosch‐Traberg Heidrun , Seino Yutaka 
Published: April 2015

AbstractIntroductionThe safety and efficacy of liraglutide in combination with an oral antidiabetic drug (OAD) compared with combination of two OADs were assessed in Japanese patients with type 2 diabetes.Materials and MethodsThis was a 52‐week, open‐label, parallel‐group trial in which patients whose type 2 diabetes was inadequately controlled with a single OAD (glinide, metformin, α‐glucosidase inhibitor or thiazolidinedione) were randomized 2:1 to either pretrial OAD in combination with liraglutide 0.9 mg/day (liraglutide group; n = 240) or pretrial OAD in combination with an additional OAD (additional OAD group; n = 120). The primary outcome measure was the incidence of adverse events (AEs).ResultsOverall, 86.3% of patients in the liraglutide group and 85.0% of patients in the additional OAD group experienced AEs; these were similar in nature and severity. Adverse event rates were 361 and 331 per 100 patient‐years of exposure, respectively. Confirmed hypoglycemia was rare (seven episodes in two patients on liraglutide, and two in two patients on additional OAD). There were no reported pancreatitis events, and no unexpected safety signals were identified. Mean reductions in glycosylated hemoglobin were significantly greater in the liraglutide group than the additional OAD group [estimated mean treatment difference −0.27% (95% confidence interval (CI) −0.44, −0.09; P = 0.0026)]; reductions in mean fasting plasma glucose levels were also greater with liraglutide [estimated mean difference −5.47 mg/dL (−0.30 mmol/L; 95% CI: −10.83, −0.10; P = 0.0458)].ConclusionsLiraglutide was well tolerated and effective as combination therapy with an OAD in Japanese patients with type 2 diabetes.
A simulation study of the interception of prescribing errors by clinical pharmacists in an acute hospital setting
Authors: Caruba Thibaut , Boussadi Abdelali , Lenain Emilie , Korb‐Savoldelli Virginie , Gillaizeau Florence , Durieux Pierre , Sabatier Brigitte 
Published: April 2015

AbstractRationale, aims and objectivesTo evaluate the performance of several pharmacists in the same department who analysed the same prescriptions in a simulation study.MethodsOne hundred prescriptions were retrospectively extracted from the prospective database of our hospital. Five clinical pharmacists working in the same department were asked to analyse individually the order lines of each prescription as if it were part of their routine daily practice. Afterward, an independent committee of five other clinical pharmacists reviewed the same 100 prescriptions. We calculated the sensitivity and the specificity of error detection in a line order by using the results of the committee as the gold standard.ResultsA total of 908 order lines were analysed (mean 9 ± 3 order lines per prescription). Fifty‐one medication errors were identified by the committee (5.6%), including 23 related to laboratory test results: renal failure, or therapeutic concentrations being too low or too high. The sensitivity of the five pharmacists ranged between 19.6% and 56.9% and the specificity between 92.8% and 98.7%. The rates of agreement between each pharmacist and the committee, assessed using kappa coefficient, were between 0.20 and 0.39. The main factors affecting sensitivity and/or specificity in univariate analysis were the number of drugs per prescription, type of drug prescribed (ATC classification) and the glomerular filtration rate.ConclusionDiscrepancies between the performances of pharmacists exist, as there are between other health care professionals. Pharmacist training, standardization of the pharmaceutical analysis of drug prescription, and implementation of a clinical decision support system allowing biological values to be linked to drug prescriptions could improve individual performance.
Conference report: interdisciplinary workshop in the philosophy of medicine: parentalism and trust
Authors: Bullock Emma , Gergel Tania , Kingma Elselijn 
Published: April 2015

AbstractOn 13 June 2014, the Centre for the Humanities and Health at King's College London hosted a 1‐day workshop on ‘parentalism and trust’. This workshop was the sixth in a series of workshops whose aim is to provide a new model for high‐quality open interdisciplinary engagement between medical professionals and philosophers. This report briefly describes the workshop methodology and the discussions on the day.
Does teledermatology reduces secondary care referrals and is it acceptable to patients and doctors?: a service evaluation
Authors: Ford John A. , Pereira Augustine 
Published: April 2015

AbstractRationale, aims and objectivesReferrals to dermatology for skin lesions is increasing. Teledermatology allows patients to obtain specialist advice remotely. The aim of this study is to assess if teledermatology reduces secondary care dermatology referrals and evaluate its acceptability to patients and clinicians.MethodsA 24‐month before and after comparative evaluation of a teledermatology service was undertaken involving four non‐randomly allocated intervention practices and 18 control practices. Referral data for 12 months before and after the introduction of teledermatology was compared in intervention and control practices. Patient questionnaires explored their satisfaction and structured user dialogues explored the usefulness and benefits to clinicians. Time series analysis, adjusted for age and sex, was undertaken to assess the impact on secondary care referrals.ResultsThere were 195 Telederm referrals during the 12‐month pilot period. Seborrhoeic keratosis was the commonest diagnosis. No action was required in 86 patients. Urgent referral to secondary care was recommended in 64 patients and routine referral in 19. The difference in referral rate before and after was +2.11 referrals per 1000 practice population in the teledermatology group and +1.39 in the control group. This was statistically significant in the adjusted, but not unadjusted, analysis. There was a 14% response rate for the questionnaire. The service was very popular with patients and clinicians. Clinicians highlighted the significant educational benefit.ConclusionWe did not find any evidence that teledermatology reduced secondary care referral rates but in this small pilot, we found that it increased referrals in the short term. It was very popular among patients and clinicians, especially for its educational value.
Molecular cloning of Salmo salar Toll‐like receptors (TLR1, TLR22, TLR5M and TLR5S) and expression analysis in SHK‐1 cells during Piscirickettsia salmonis infection
Authors: Salazar C , Haussmann D , Kausel G , Figueroa J 
Published: April 2015

AbstractIn fish, the innate immune system is the primary response against infection. Toll‐like receptors (TLRs) recognize pathogens through pathogen‐associated molecular patterns (PAMPs), and some target molecules of TLRs are homologous between fish and mammals. Piscirickettsia salmonis is one of the main pathogens affecting the salmon industry in Chile. Better knowledge of mechanisms underlying its invasive capacity and recognition of target cells is crucial for vaccine development. Therefore, Salmo salar L. TLR1, TLR22, membrane TLR5M and soluble TLR5S sequences were cloned, and expression kinetics were analysed by RT‐qPCR in salmon head kidney cells (SHK‐1) infected with three different P. salmonis preparations: alive, formaldehyde treated, extract. Clearly, all analysed TLRs were expressed and transcription level changes were revealed at 2 hpi, 12 or 16 hpi and 24 hpi depending on P. salmonis infection scheme. Increased IL1‐beta expression confirmed TLR pathway response. Furthermore, significant expression modulations of several members of the TLR pathway in this in vitro model suggest that P. salmonis extract rather than formaldehyde‐inactivated bacteria might strengthen the salmon immune system.
Analysis of the amyloid precursor protein role in neuritogenesis reveals a biphasic SH‐SY5Y neuronal cell differentiation model
Authors: da Rocha Joana Fernandes , da Cruz e Silva Odete A. B. , Vieira Sandra Isabel 
Published: April 2015

AbstractThe existence of an intrinsic programme controlling neuritogenesis and activated during early neuronal differentiation and regeneration stages is well established. However, the identity and role of each molecular player and event, as well as how such a programme is modified by environmental signals, remain a focus of research. The amyloid precursor protein (APP) is a neuromodulator of the developing and mature nervous system, although in a highly complex manner which is far from clear. To study APP‐induced neuritogenesis, the retinoic acid (RA)‐induced SH‐SY5Y cell differentiation model was first minutely characterized in terms of RA dose, morphological outputs and relevant biochemical markers. The findings reported here unveiled two differentiation phases for the 10 μM RA dose: 1–4 (4 days excluded) and 4–8 days, clearly defined by fold increases in the ratio between APP and acetylated Tubulin. Moreover, we describe, for the first time, a unique peak of secreted APP (sAPP)/APP ratio in the first phase. Subsequent APP and sAPP modulations confirmed that a high sAPP/APP ratio potentiates the elongation of smaller processes at the earlier neuritogenic phase. This sAPP/APP ratio drops in the second phase, as holoAPP levels increase to assist the maintenance of the longer neurites, potentially via their stabilization.
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We show that SH‐SY5Y cells differentiation (‘Diff.’) induced by 10 µM retinoic acid (RA) is biphasic, and describe the behaviour of the Alzheimer's amyloid precursor protein APP and its secreted sAPP fragment in this model. This includes a unique sAPP/APP peak in the first phase, and a plateau for holoAPP in the second phase, both related to APP neuritogenic functions.
7T MRI‐Histologic Correlation Study of Low Specific Absorption Rate T2‐Weighted GRASE Sequences in the Detection of White Matter Involvement in Multiple Sclerosis
Authors: Bagnato Francesca , Hametner Simon , Pennell David , Dortch Richard , Dula Adrienne N. , Pawate Siddharama , Smith Seth A. , Lassmann Hans , Gore John C. , Welch Edward B. 
Published: April 2015

ABSTRACTBACKGROUNDThe high value of the specific absorption rate (SAR) of radio‐frequency (RF) energy arising from the series of RF refocusing pulses in T2‐weighted (T2‐w) turbo spin echo (TSE) MRI hampers its clinical application at 7.0 Tesla (7T). T2‐w gradient and spin echo (GRASE) uses the speed from gradient refocusing in combination with the chemical‐shift/static magnetic field (B0) inhomogeneity insensitivity from spin‐echo refocusing to acquire T2‐w images with a limited number of refocusing RF pulses, thus reducing SAR.OBJECTIVESTo investigate whether low SAR T2‐w GRASE could replace T2‐w TSE in detecting white matter (WM) disease in MS patients imaged at 7T.METHODSThe .7 mm3 isotropic T2‐w TSE and T2‐w GRASE images with variable echo times (TEs) and echo planar imaging (EPI) factors were obtained on a 7T scanner from postmortem samples of MS brains. These samples were derived from brains of 3 female MS patients. WM lesions (WM‐Ls) and normal‐appearing WM (NAWM) signal intensity, WM‐Ls/NAWM contrast‐to‐noise ratio (CNR) and MRI/myelin staining sections comparisons were obtained.RESULTSGRASE sequences with EPI factor/TE = 3/50 and 3/75 ms were comparable to the SE technique for measures of CNR in WM‐Ls and NAWM and for detection of WM‐Ls. In all sequences, however, identification of areas with remyelination, Wallerian degeneration, and gray matter demyelination, as depicted by myelin staining, was not possible.CONCLUSIONST2‐w GRASE images may replace T2‐w TSE for clinical use. However, even at 7T, both sequences fail in detecting and characterizing MS disease beyond visible WM‐Ls.
Types and Causes of Injuries of Carers of Adults With Intellectual Disabilities: Observational Study
Authors: Finlayson Janet , Jackson Alison , Mantry Dipali , Morrison Jillian , Cooper Sally‐Ann 
Published: April 2015

AbstractThe aim of this research was to investigate the incidence, types, and causes of injury experienced by a community‐based cohort of family and paid carers of adults with ID (n = 446) in Scotland over a 12‐month period, compared with the age and sex‐matched general population in the same geographical area (n = 1,225). We hypothesized that they would be at an increased risk of injury due to their caring/support role, and particularly as a consequence of caring for adults with ID who present physical aggression. Young and middle‐aged female and older‐aged male carers experienced more injuries in the previous 12 months than did the matched general population, but not significantly so. Contrary to our hypothesis, young and middle‐aged male and older female carers experienced fewer injuries, but this was also not significant. Carers were significantly less likely to experience injury from the use of a tool, implement or equipment (p = .045), and, contrary to our expectations, the carers were not more likely to experience injury from another person's physical aggression (p = .065). Types and causes differed between the carers and the general population. Injuries occur commonly among carers of adults with ID. While carers were not more likely to experience harmful injury from another person's physical aggression, we speculate that the underlying causes of injury are likely to differ between carers and the general population, with the carers being injured due to their carer role. This requires further in‐depth study.