bluuebunny/crossref_metadata_2025_split huggingface dataset:
Secukinumab treatment of plaque psoriasis shows early improvement in DLQI response – results of a phase II regimen‐finding trial
Authors: Augustin M. , Abeysinghe S. , Mallya U. , Qureshi A. , Roskell N. , McBride D. , Papavassillis C. , Gelfand J. 
Published: December 2015

AbstractBackgroundThe social stigma and chronicity of psoriasis significantly affect health‐related quality of life (HRQoL).ObjectiveWe examined the effect of three regimens of secukinumab on HRQoL in moderate to severe psoriasis patients.MethodsTwelve‐week data from a phase II, randomized, double‐blind, placebo‐controlled, regimen‐finding study evaluated HRQoL, measured by the Dermatology Life Quality Index (DLQI). Secukinumab or placebo was administered subcutaneously in three treatment regimens: single (baseline only), monthly (baseline, weeks 4, 8) and early (baseline, weeks 1, 2, 4). Differences among regimens were assessed with logistic regression models and Fisher's exact test.ResultsPatients (n = 404) were randomized to single (baseline) treatment regimen, n = 66; monthly, (baseline, weeks 4 and 8), n = 138; early, (baseline, weeks 1, 2, 4), n = 133; and placebo, n = 67. DLQI response was significantly higher in early, monthly and single regimens than in placebo regimen (40.8%, 33.6% and 13.1% vs. 1.6%, respectively; P < 0.001 for all).ConclusionModerate to severe psoriasis patients receiving monthly and early treatment with secukinumab demonstrated improved HRQoL compared with placebo.
Risk profiles of neurosyphilis in HIV‐negative patients with primary, secondary and latent syphilis: implications for clinical intervention
Authors: Shi M. , Peng R.‐R. , Gao Z. , Zhang S. , Lu H. , Guan Z. , Gao Y. , Wang C. , Zhou P. 
Published: December 2015

AbstractBackgroundNeurosyphilis is one of the most feared complications of syphilis. The question of how to identify patients at higher risk in order for timely intervention whilst avoiding unnecessary lumbar puncture remains.MethodsBetween August 2009 and March 2013, a total of 834 HIV‐negative patients with primary, secondary or latent syphilis were recruited. Venous blood and cerebrospinal fluid specimens were collected for diagnoses of syphilis and/or neurosyphilis and information of socio‐demographic and behavioral characteristics was collected by interviewing with a questionnaire.ResultsThe prevalence of neurosyphilis differed among patients with primary (7.1%), secondary (23.8%) and latent (26.6%) syphilis. Neurosyphilis was more likely in male patients (1.52‐fold). Compared with patients aged <30 years, those aged 45–59 years and ≥60 years old had a 2.51‐fold and 4.98‐fold risk of neurosyphilis respectively. Male gender and age ≥45 years were consistently associated with neurosyphilis both in secondary and latent stage. There was a 2.68‐fold, 2.55‐fold and 3.67‐fold increased risk of neurosyphilis when the serum RPR titer was 1:32, 1:64 and ≥1:128 compared to that of ≤1:16. ).ConclusionsMale gender and age 45years are both correlated risk factors for neurosyphilis in HIV‐negative patients with primary, secondary and latent syphilis.
Older Adults Reporting More Diabetes Mellitus Care Have Greater 9‐Year Survival
Authors: Han Benjamin H. , Blaum Caroline S. , Ferris Rosie E. , Min Lillian C. , Lee Pearl G. 
Published: December 2015

ObjectivesTo determine whether receiving more recommended diabetes mellitus (DM) care processes (tests and screenings) would translate into better 9‐year survival for middle‐aged and older adults.DesignLongitudinal mortality analysis using the Health and Retirement Study Diabetes Mailout Survey.SettingHealth and Retirement Study (HRS).ParticipantsIndividuals aged 51 and older (n = 1,879; mean age 68.8 ± 8.7, 26.5% aged ≥75) with self‐reported DM who completed the Diabetes Mailout Survey and the core 2002 HRS survey.MeasurementsA composite measure of five self‐reported diabetes mellitus care process measures were dichotomized as greater (3–5 processes) versus fewer (0–2 processes) care processes provided. Cox proportional hazards models were used to test relationships between reported measures and mortality, controlling for sociodemographic characteristics, function, comorbidities, geriatric conditions, and insulin use.ResultsPrevalence of self‐reported care processes was 80.1% for glycosylated hemoglobin test, 75.9% for urine test, 67.5% for eye examination, 67.7% for aspirin counseling, and 48.2% for diabetes education. In 9 years, 32.1% respondents died. Greater care correlated with 24% lower risk of dying (adjusted hazard ratio = 0.76, 95% confidence interval = 0.64–0.91) at 9‐year follow up. When respondents were age‐stratified (≥75 vs <75) longer survival was statistically significant only in the older age group.ConclusionAlthough it is not possible to account for differences in adherence to care that may also affect survival, this study demonstrates that monitoring of and counseling about types of DM care processes are associated with long‐term survival benefit even in individuals aged 75 and older with DM.
The definitions of three‐dimensional landmarks on the human face: an interdisciplinary view
Authors: Katina Stanislav , McNeil Kathryn , Ayoub Ashraf , Guilfoyle Brendan , Khambay Balvinder , Siebert Paul , Sukno Federico , Rojas Mario , Vittert Liberty , Waddington John , Whelan Paul F. , Bowman Adrian W. 
Published: December 2015

AbstractThe analysis of shape is a key part of anatomical research and in the large majority of cases landmarks provide a standard starting point. However, while the technology of image capture has developed rapidly and in particular three‐dimensional imaging is widely available, the definitions of anatomical landmarks remain rooted in their two‐dimensional origins. In the important case of the human face, standard definitions often require careful orientation of the subject. This paper considers the definitions of facial landmarks from an interdisciplinary perspective, including biological and clinical motivations, issues associated with imaging and subsequent analysis, and the mathematical definition of surface shape using differential geometry. This last perspective provides a route to definitions of landmarks based on surface curvature, often making use of ridge and valley curves, which is genuinely three‐dimensional and is independent of orientation. Specific definitions based on curvature are proposed. These are evaluated, along with traditional definitions, in a study that uses a hierarchical (random effects) model to estimate the error variation that is present at several different levels within the image capture process. The estimates of variation at these different levels are of interest in their own right but, in addition, evidence is provided that variation is reduced at the observer level when the new landmark definitions are used.
Infrahepatic inferior caval and azygos vein formation in mammals with different degrees of mesonephric development
Authors: Hikspoors Jill P. J. M. , Mekonen Hayelom K. , Mommen Greet M. C. , Cornillie Pieter , Köhler S. Eleonore , Lamers Wouter H. 
Published: December 2015

AbstractControversies regarding the development of the mammalian infrahepatic inferior caval and azygos veins arise from using topography rather than developmental origin as criteria to define venous systems and centre on veins that surround the mesonephros. We compared caudal‐vein development in man with that in rodents and pigs (rudimentary and extensive mesonephric development, respectively), and used Amira 3D reconstruction and Cinema 4D‐remodelling software for visualisation. The caudal cardinal veins (CCVs) were the only contributors to the inferior caval (IVC) and azygos veins. Development was comparable if temporary vessels that drain the large porcine mesonephros were taken into account. The topography of the CCVs changed concomitant with expansion of adjacent organs (lungs, meso‐ and metanephroi). The iliac veins arose by gradual extension of the CCVs into the caudal body region. Irrespective of the degree of mesonephric development, the infrarenal part of the IVC developed from the right CCV and the renal part from vascular sprouts of the CCVs in the mesonephros that formed ‘subcardinal’ veins. The azygos venous system developed from the cranial remnants of the CCVs. Temporary venous collaterals in and around the thoracic sympathetic trunk were interpreted as ‘footprints’ of the dorsolateral‐to‐ventromedial change in the local course of the intersegmental and caudal cardinal veins relative to the sympathetic trunk. Interspecies differences in timing of the same events in IVC and azygos‐vein development appear to allow for proper joining of conduits for caudal venous return, whereas local changes in topography appear to accommodate efficient venous perfusion. These findings demonstrate that new systems, such as the ‘supracardinal’ veins, are not necessary to account for changes in the course of the main venous conduits of the embryo.
Is THEREAN OPTIMAL PENSION FUND SIZE? A SCALE‐ECONOMY ANALYSISOF ADMINISTRATIVE COSTS
Authors: Bikker Jacob A. 
Published: December 2015

ABSTRACTThis article investigates scale economies and the optimal scale of pension funds, estimating different cost functions with varying assumptions about the shape of the underlying average cost function: U‐shaped versus monotonically declining. Using unique data for Dutch pension funds over 1992–2009, we find that unused scale economies for both administrative activities are indeed large and concave, that is, huge for small pension funds and decreasing with pension fund size. We observe a clear optimal scale of around 40,000 participants during 1992–2000 (pointing to a U‐shaped average cost function), which increases in subsequent years to size above the largest pension fund, pointing to monotonically decreasing average costs. These model‐based outcomes are roughly in line with the results of a survivorship analysis.
THE ROLE OF PREGNANCY IN MICRO HEALTH INSURANCE: EVIDENCE OF ADVERSE SELECTION FROM PAKISTAN
Authors: Yao Yi , Schmit Joan T. , Sydnor Justin R. 
Published: December 2015

ABSTRACTWith increasing interest from commercial players in developing insurance markets to meet the needs of low‐income people, efforts to find sustainable products have expanded rapidly yet remain elusive. This is particularly true in the domain of health insurance, where the general challenges of offering voluntary private health insurance are often exacerbated by poor underlying health services and a lack of public health programs. In an effort to identify new opportunities to expand health insurance protection to underserved markets, we analyze a rich data set from a micro health insurance program in Pakistan. Observing that pregnancy‐related care accounts for 40 percent of all claims and 36 percent of the total claims amount, we focus much of our attention on understanding the role of pregnancy in micro health insurance. We find evidence of extensive adverse selection related to pregnancy claims, both with regard to original coverage purchase and with regard to renewal. In many countries, pregnancy health care is provided by or paid for by the government. We encourage consideration of this possibility, leaving the remaining health care needs for market‐based health insurance.
Comparative quantitative assessment of global small bowel motility using magnetic resonance imaging in chronic intestinal pseudo‐obstruction and healthy controls
Authors: Menys A. , Butt S. , Emmanuel A. , Plumb A. A. , Fikree A. , Knowles C. , Atkinson D. , Zarate N. , Halligan S. , Taylor S. A. 
Published: December 2015

AbstractBackgroundChronic intestinal pseudo‐obstruction (CIPO) is characterized by dilatation of the bowel lumen and abnormal motility. In this study, we aimed to quantify small bowel dysmotility in CIPO using a validated pan‐intestinal motility assessment technique based on motion capture magnetic resonance imaging (MRI) compared to normal controls. In addition, we explored if motility responses of CIPO patients to neostigmine challenge differed from healthy volunteers.MethodsTwenty healthy volunteers (mean age 28, range 22–48) and 11 CIPO patients (mean age 47, range 19–90) underwent MRI enterography to capture global small bowel motility. Eleven controls and seven CIPO patients further underwent a randomized placebo‐controlled crossover study of either intravenous neostigmine (0.5 mg) or saline with motility MRI repeated at a mean of 3 weeks. Motility was quantified in regions of interest placed to encompass the whole small bowel volume using a validated, postprocessing technique to give a global motility index in arbitrary units (AU). Baseline and stimulated motility was compared using Wilcoxon rank–sum paired T‐tests.Key ResultsBaseline global small bowel motility was significantly lower in CIPO patients compared to controls (mean 0.25 AU vs 0.35 AU, p < 0.001). Motility in both groups increased significantly after neostigmine (0.06 AU increase, p = 0.016 in CIPO and 0.06 AU increase, p = 0.002 in controls). Three patients with scleroderma had a reduced response to neostigmine.Conclusions & InferencesGlobal small bowel motility in CIPO patients is significantly lower than controls and response to the pro‐kinetic agent neostigmine may differ according to disease phenotype. Software‐quantified bowel motility using cine MRI has potential as a future tool to investigate enteric dysmotility.
First report of an Asian family with hemoglobin Evans [α2 62 (E11) Val → Met]
Authors: Ishimaru Sae , Saito Yuya , Yokokawa Yuichi , Yuza Yuki , Kaneko Takashi 
Published: December 2015

AbstractHemoglobin Evans is an unstable variant caused by a single nucleotide mutation that produces a valine‐to‐methionine substitution at residue 62 of the α‐globin chain. It has not been reported in the Asian population and only three cases have been reported worldwide. We diagnosed a Japanese boy with chronic hemolytic anemia with hemoglobin Evans after genetic testing. This is the first familial case of hemoglobin Evans in an Asian population.
Long‐term UVA eye irradiation causes decreased learning ability in mice
Authors: Hiramoto Keiichi , Kasahara Emiko 
Published: December 2015

SummaryBackgroundLong‐term eye radiation with ultraviolet A (UVA) denatures the cells of the cerebral hippocampus. However, the influence on memory and learning ability in mice is not known.MethodsHR‐1 mice were used. We irradiated the eyes or dorsal skin of the mice with UVA at a dose of 110 kJ/m2 using an FL20SBLB‐A lamp for 6, 12, and 24 months.ResultsThe mean escape latency in the water maze was significantly increased in the UVA‐irradiated mice in comparison with that seen in the controls. In the mice in which UVA eye irradiation was performed for 24 months, the depression of memory and learning ability was remarkable. The acetylcholinesterase activity, choline acetyltransferase activity, and acetylcholine content in the brain in the UVA eye‐irradiated mice were significantly less than those observed in the control mice. Furthermore, during UVA eye irradiation, the levels of β‐amyloid (Aβ), γ‐secretase, which produces Aβ peptide, and advanced glycation end products increased. Moreover, the effects of UVA eye irradiation increased with the duration of irradiation (or aging), and the introduction of glucose into the brain also decreased with UVA eye irradiation.ConclusionsThese results indicate that UVA eye irradiation induces a decreased memory and learning ability in mice.
ABCB19‐mediated polar auxin transport modulates Arabidopsis hypocotyl elongation and the endoreplication variant of the cell cycle
Authors: Wu Guosheng , Carville Jacqueline S. , Spalding Edgar P. 
Published: December 2015

SummaryElongation of the Arabidopsis hypocotyl pushes the shoot‐producing meristem out of the soil by rapid expansion of cells already present in the embryo. This elongation process is shown here to be impaired by as much as 35% in mutants lacking ABCB19, an ATP‐binding cassette membrane protein required for polar auxin transport, during a limited time of fast growth in dim white light beginning 2.5 days after germination. The discovery of high ectopic expression of a cyclin B1;1‐based reporter of mitosis throughout abcb19 hypocotyls without an equivalent effect on mitosis prompted investigations of the endoreplication variant of the cell cycle. Flow cytometry performed on nuclei isolated from upper (growing) regions of 3‐day‐old hypocotyls showed ploidy levels to be lower in abcb19 mutants compared with wild type. CCS52A2 messenger RNA encoding a nuclear protein that promotes a shift from mitosis to endoreplication was lower in abcb19 hypocotyls, and fluorescence microscopy showed the CCS52A2 protein to be lower in the nuclei of abcb19 hypocotyls compared with wild type. Providing abcb19 seedlings with nanomolar auxin rescued their low CCS52A2 levels, endocycle defects, aberrant cyclin B1;1 expression, and growth rate defect. The abcb19‐like growth rate of ccs52a2 mutants was not rescued by auxin, placing CCS52A2 after ABCB19‐dependent polar auxin transport in a pathway responsible for a component of ploidy‐related hypocotyl growth. A ccs52A2 mutation did not affect the level or pattern of cyclin B1;1 expression, indicating that CCS52A2 does not mediate the effect of auxin on cyclin B1;1.
SUMOylation represses SnRK1 signaling in Arabidopsis
Authors: Crozet Pierre , Margalha Leonor , Butowt Rafal , Fernandes Noémia , Elias Carlos A. , Orosa Beatriz , Tomanov Konstantin , Teige Markus , Bachmair Andreas , Sadanandom Ari , Baena‐González Elena 
Published: December 2015

SummaryThe SnRK1 protein kinase balances cellular energy levels in accordance with extracellular conditions and is thereby key for plant stress tolerance. In addition, SnRK1 has been implicated in numerous growth and developmental processes from seed filling and maturation to flowering and senescence. Despite its importance, the mechanisms that regulate SnRK1 activity are poorly understood. Here, we demonstrate that the SnRK1 complex is SUMOylated on multiple subunits and identify SIZ1 as the E3 Small Ubiquitin‐like Modifier (SUMO) ligase responsible for this modification. We further show that SnRK1 is ubiquitinated in a SIZ1‐dependent manner, causing its degradation through the proteasome. In consequence, SnRK1 degradation is deficient in siz1‐2 mutants, leading to its accumulation and hyperactivation of SnRK1 signaling. Finally, SnRK1 degradation is strictly dependent on its activity, as inactive SnRK1 variants are aberrantly stable but recover normal degradation when expressed as SUMO mimetics. Altogether, our data suggest that active SnRK1 triggers its own SUMOylation and degradation, establishing a negative feedback loop that attenuates SnRK1 signaling and prevents detrimental hyperactivation of stress responses.
A comparative study of epidermal tight junction proteins in a dog model of atopic dermatitis
Authors: Kim Ha‐Jung , Cronin Megan , Ahrens Kim , Papastavros Vassi , Santoro Domenico , Marsella Rosanna 
Published: December 2015

BackgroundTight junctions (TJ) are important for skin barrier function and could be relevant in modulating allergen penetration in atopic dermatitis (AD). Humans with AD have been described to have decreased expressions of some TJ proteins in the skin.Hypothesis/ObjectivesThis study aimed to investigate TJ protein expression using an experimental AD model in dogs.MethodsSkin biopsies from six atopic (nonlesional skin) and five normal beagle dogs were stained for TJ proteins [zonula occludens 1 (ZO‐1), occludin, claudin‐1] by immunohistochemistry. Staining intensity was evaluated both objectively using imaging software and subjectively. Six images/sections were randomized and blindly scored by six investigators for intensity, distribution, integrity and staining pattern.ResultsThe intensity of ZO‐1 was significantly decreased in the atopic group objectively (P = 0.010) and subjectively (P = 0.002) relative to the normal group. Occludin was decreased significantly subjectively (P = 0.027) but not objectively. Claudin was not significantly different between groups by either quantification. Additionally, only ZO‐1 demonstrated a significantly patchier staining pattern in the atopic group. There was no consistent staining pattern in this study.Conclusions and clinical importanceZO‐1 and occludin, which have not been described to be associated with the development of AD in humans, could play a role in this atopic dog model. Further investigation on the expression and modulation of TJ proteins and their clinical relevance is needed.
Repeated oral dose tolerance in dogs treated concomitantly with ciclosporin and oclacitinib for three weeks
Authors: Panteri Alessandro , Strehlau Günther , Helbig Rainer , Prost Christine , Doucette Kelly 
Published: December 2015

BackgroundCiclosporin and oclacitinib are immunomodulators approved for the treatment of canine atopic dermatitis. The administration of a short course of prednisolone at the beginning of ciclosporin therapy hastens the efficacy of this drug; oclacitinib has a rapid antipruritic effect similar to that of prednisolone.ObjectivesTo evaluate the oral tolerance of oclacitinib and ciclosporin given concurrently for three weeks.AnimalsTwo groups of eight beagles.MethodsDogs were randomized to receive oclacitinib alone (0.4–0.6 mg/kg twice daily for 14 days then once daily for seven days) or in combination with ciclosporin (5 mg/kg once daily) for three weeks. They were examined every day and adverse events were recorded. Blood samples were collected during the acclimatization phase, weekly during treatment and at the end of the study for haematology, clinical chemistry and coagulation evaluation.ResultsThere were no abnormal clinical observations following treatment with oclacitinib given alone or concomitantly with ciclosporin, with the exception of diarrhoea in two dogs receiving both drugs. Three dogs from each group experienced transient inappetence; three dogs treated with oclacitinib had mild weight loss. Clinical pathology parameters remained within the reference range for beagle dogs at that facility.Conclusions and clinical importanceThe concomitant administration of ciclosporin and oclacitinib for three weeks to beagles was well tolerated and was not associated with an increase in the number of adverse events or laboratory abnormalities beyond those associated with oclacitinib given alone.
Comparison of Three Biochemical Tests for Rapid Detection of Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae
Authors: Poirel Laurent , Fernández Javier , Nordmann Patrice 
Published: December 2015

ABSTRACT

Enterobacterial isolates producing clavulanic-inhibited extended-spectrum β-lactamases (ESBLs) are increasingly spreading in the community and are often responsible for nosocomial infections. Rapid biochemical tests have been developed recently for their detection. Three tests, namely, the Rapid ESBL NDP test, the β-Lacta test, and the Rapid ESBL Screen, have been evaluated with a collection of 108 well-characterized strains, including wild-type strains, strains producing ESBLs, overexpressed cephalosporinases, and carbapenemases. The ESBL NDP test and the Rapid ESBL Screen (a copy of the ESBL NDP test) are aimed at detecting ESBL producers, while the β-Lacta test is aimed at detecting not only ESBL producers but also cephalosporinase and carbapenemase producers. The sensitivity and specificity for detecting ESBL producers (
n
= 60) were 95% and 100% for the Rapid ESBL NDP test, 80% and 87% (after 30 min) and 92% and 83% (after 2 h) for the Rapid ESBL Screen, and 88% and 71% for the β-Lacta test, respectively. Varied and time-consuming detection (up to 2 h) of ESBLs by the Rapid ESBL Screen and concomitant and varied detection of producers of AmpC and several types of carbapenemases correspond to significant shortcomings of using the Rapid Screen ESBL and β-Lacta tests, respectively.