bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long‐term efficacy and safety results from an open‐label phase III study (UNCOVER‐J) in Japanese plaque psoriasis patients: impact of treatment withdrawal and retreatment of ixekizumab
Authors: Umezawa Y. , Torisu‐Itakura H. , Morisaki Y. , ElMaraghy H. , Nakajo K. , Akashi N. , Saeki H. ,   the Japanese Ixekizumab Study Group
Published: October 2018

AbstractBackgroundLong‐term management of moderate‐to‐severe psoriasis is usually discussed in terms of continuous administration; however, there are many situations in clinical practice where treatment may be withdrawn with subsequent retreatment.ObjectiveTo assess the clinical course after ixekizumab treatment withdrawal and retreatment, as well as the effectiveness of ixekizumab retreatment, in Japanese patients with plaque psoriasis.MethodsThis single‐arm, open‐label study (UNCOVER‐J; NCT01624233) comprised 78 patients with plaque psoriasis. After ixekizumab treatment (160‐mg loading dose, 80 mg every 2 weeks for the first 12 weeks, and then 80 mg every 4 weeks (IXE Q4W) until Week 52), 70 patients achieved a Psoriasis Area Severity Index (PASI)75 response at Week 52. These 70 patients withdrew from ixekizumab treatment from Weeks 52 to 100. Patients who relapsed (PASI ≤50) during the Treatment Withdrawal Period were retreated with IXE Q4W for 192 weeks.ResultsAt Weeks 52, 76 and 100, PASI75 response rates were 100%, 26% and 7%; PASI90 response rates were 87%, 11% and 3%; and PASI100 response rates were 53%, 0% and 0%. After treatment withdrawal, 87% of patients relapsed; median time to relapse was 143 days. After 12 weeks of retreatment with IXE Q4W, 83% of relapsed patients achieved PASI75, 68% achieved PASI90 and 25% achieved PASI100; improvements were maintained up to 120 weeks of retreatment. Treatment‐emergent adverse events and serious adverse events were reported in 56% and 4% of patients during the Treatment Withdrawal Period, and in 88% and 14% of patients during the Retreatment Period.ConclusionIn patients withdrawn from ixekizumab after achieving PASI75, approximately half relapsed within 5 months of withdrawal; however, most patients recaptured response within 12 weeks, and response was maintained for up to 120 weeks of retreatment.
Physical Activity and Association Between Frailty and All‐Cause and Cardiovascular Mortality in Older Adults: Population‐Based Prospective Cohort Study
Authors: Higueras‐Fresnillo Sara , Cabanas‐Sánchez Verónica , Lopez‐Garcia Esther , Esteban‐Cornejo Irene , Banegas José R. , Sadarangani Kabir P. , Rodríguez‐Artalejo Fernando , Martinez‐Gomez David 
Published: October 2018

ObjectivesTo examine the separate and joint association between physical activity and frailty and long‐term all‐cause and cardiovascular disease (CVD) mortality in older adults.DesignPopulation‐based prospective cohort study.SettingCohort representative of the noninstitutionalized Spanish population.ParticipantsIndividuals aged 60 and older (N=3,896) in 2000–01.MeasurementsParticipants reported their physical activity using a validated instrument, and frailty was ascertained using the Fatigue, low Resistance, limitation in Ambulation, Illness and weight Loss (FRAIL) scale. Those with 0 frailty criteria were considered to be robust, with 1 or 2 criteria to be prefrail, and with 3 of more criteria to be frail. Participants were followed until 2014 to identify all‐cause and CVD deaths. Associations were summarized using hazard ratios (HRs) and Cox regression after adjustment for main covariates.ResultsDuring a median 14 years of follow‐up, 1,801 total deaths occurred, 672 from CVD. Compared with being robust, the multivariate hazard ratio (95% confidence interval) for all‐cause mortality was 1.29 (1.14–1.45) in prefrail individuals, and 2.16 (1.82–2.58) in frail individuals (p‐trend <.001). Compared with being physically inactive, being physically active was associated with a statistically significant 18% (1–32%), 28% (16–39%) and 39% (17–55%) lower all‐cause mortality among robust, prefrail, and frail individuals, respectively (all p <.001). Compared with participants who were robust and physically active, those who were frail and inactive showed the highest all‐cause mortality 2.45 (95%CI: 1.95–3.06); however, the hazard ratio (95% confidence interval) for all‐cause mortality in frail individuals who were physically active was comparable to that in pre‐frail and inactive participants: 1.70 (1.32–2.19) and 1.56 (1.34–1.82), respectively. Mortality of prefrail active participants was similar to that of robust inactive participants. Results were similar for CVD mortality.ConclusionPhysical activity might partly compensate for the greater mortality risk associated with frailty in old age. J Am Geriatr Soc 66:2097–2103, 2018.
Likelihood of Sustaining an Injury in the Setting of Multiple Falls
Authors: Gill Thomas M. , Williams Christianna S. 
Published: October 2018

ObjectivesTo evaluate the relationship between number of falls and risk of injury after a specific fall.DesignProspective cohort study.SettingGreater New Haven, Connecticut.ParticipantsProbability sample of 1,103 community‐living persons aged 72 and older.MeasurementsFalls and fall‐related injuries were ascertained monthly for 3 years using a fall calendar and follow‐up telephone interviews.ResultsOf 606 participants with a fall, 164 (27.0%) had at least 1 fall with a serious injury, and 455 (75.1%) had at least 1 fall with any injury; mean number of falls was 2.6±2.3 (range 1–18), of falls with serious injury was 0.3±0.6 (range 0–4), and of falls with any injury was 1.4±1.4 (range 0–9). On a per‐participant basis, risk of serious injury and any injury increased progressively as the number of falls increased (P < .001). On a per‐fall basis, risk of serious injury and any injury increased from 1 to 2 falls but then decreased from 2 to 3 or 4 falls and from 3 or 4 to 5 or more falls, although these differences were not statistically significant. The results were consistent for women and men and for analyses that evaluated the proportion of falls with injuries.ConclusionIn community‐living older persons, risk of injury from a specific fall did not differ as the number of falls increased. Falls appear to operate independently in terms of conferring risk of injury in the setting of multiple falls. J Am Geriatr Soc 67:119–123, 2019.
Hardness of the habitual diet and its relationship with cognitive function among 70‐year‐old Japanese elderly: Findings from the SONIC Study
Authors: Okubo Hitomi , Murakami Kentaro , Inagaki Hiroki , Gondo Yasuyuki , Ikebe Kazunori , Kamide Kei , Masui Yukie , Arai Yasumichi , Ishizaki Tatsuro , Sasaki Satoshi , Nakagawa Takeshi , Kabayama Mai , Sugimoto Ken , Rakugi Hiromi , Maeda Yoshinobu ,   SONIC Study Group
Published: October 2018

SummaryBackgroundThere is increasing evidence of causal links between poor mastication and cognitive impairment, but possible effects of dietary hardness, which clearly affects mastication, on cognitive function are unknown.ObjectiveWe investigated the hypothesis that hardness of the habitual diet would be associated with cognitive function among older Japanese adults.MethodsThe subjects of this cross‐sectional study were 635 Japanese community‐dwelling people aged 69‐71 years. The masticatory muscle activity required for the habitual diet was used to determine dietary hardness. Consumption of 38 foods was assessed by a validated, brief‐type, self‐administered diet history questionnaire. A published database was then used to estimate the masticatory muscle activity involved in the ingestion of these foods. The Japanese version of the Montreal Cognitive Assessment (MoCA‐J) was used for the measurement of cognitive function.ResultsThe principal contributors to dietary hardness were cooked rice (28.0%), green leafy vegetables (5.1%), dried fish (4.9%), and pork and beef (4.6%). There was a positive association between dietary hardness and MoCA‐J score that was robust to adjustment for potential confounders (MoCA‐J score per 100‐unit increase in dietary hardness: β = 0.83 [95% CI: 0.08, 1.59], P = 0.03). These results did not change materially even after exclusion of subjects who reported substantial changes in their diet for any reason (β = 0.94 [95% CI: 0.02, 1.86], P = 0.04).ConclusionThis preliminary cross‐sectional study suggests that dietary hardness might have a beneficial effect on cognitive function in older Japanese people. Further prospective studies with more accurate measurements are needed to confirm this finding.
Reduced folate carrier-mediated methotrexate transport in human distal lung epithelial NCl-H441 cells
Authors: Kawami Masashi , Honda Natsuko , Miyamoto Mioka , Yumoto Ryoko , Takano Mikihisa 
Published: October 2018

Abstract

Objectives
We had previously found that reduced folate carrier (RFC; SLC19A1) is mainly involved in an influx of transport of methotrexate (MTX), a folate analogue, using alveolar epithelial A549 cells. Therefore, we examined MTX uptake in NCl-H441 (H441) cells, another in vitro alveolar epithelial model, focusing on the localization of RFC in the present study.

Methods
Transport function of RFC in H441 cells was studied using [3H]MTX.

Key findings
The uptake of MTX was increased remarkably after pretreatment of the cell monolayer with ethylenediaminetetraacetic acid (EDTA) in H441 cells but not in A549 cells, indicating the contribution of the basolaterally located transporter. In addition, folic acid and thiamine monophosphate, RFC inhibitors, inhibited the uptake of MTX from the basolateral side of the H441 cells. In order to compare the function of RFC on the apical and basolateral sides of the cells, the uptake of MTX from each side was examined using a Transwell chamber. Intracellular MTX amounts from the basolateral side were found to be significantly higher than those from the apical side.

Conclusions
These findings suggest that the distribution of MTX in the lung alveolar epithelial cells may be mediated by basolaterally located RFC in alveolar epithelial cells.
Flavonoid composition, cellular antioxidant activity and (myelo)peroxidase inhibition of a Bryonia alba L. (Cucurbitaceae) leaves extract
Authors: Ielciu Irina , Mouithys-Mickalad Ange , Franck Thierry , Angenot Luc , Ledoux Allison , Păltinean Ramona , Cieckiewicz Ewa , Etienne Delphine , Tits Monique , Crişan Gianina , Frédérich Michel 
Published: October 2018

Abstract

Objectives
The aim of the present study consisted in the isolation of flavonoids from the leaves of Bryonia alba L. and evaluation of their antioxidant activity and inhibition on peroxidase-catalysed reactions.

Methods
Flavonoids were isolated by preparative HPLC-DAD and their structures were elucidated by MS and NMR. Inhibitory effect was tested by the horseradish peroxidase and the myeloperoxidase assays. Cellular antioxidant assays consisted in testing the inhibitory activity on the reactive oxygen species released upon activation of neutrophils freshly isolated ex vivo from equine blood and of human monocytes-derived macrophages in vitro. Whole organism toxicity was assessed on zebrafish larvae.

Key findings
Four flavonoids (lutonarin, saponarin, isoorientin and isovitexin) were isolated. The performed assays showed significant antioxidant activity and inhibition for the peroxidase-catalysed reactions. Absence of cellular and zebrafish toxicity was confirmed.

Conclusions
Bryonia alba L. leaves are particularly interesting for their flavonoids content and showed significant inhibitory effect on peroxidase-catalysed oxidation of substrates (Amplex Red and L012), as well as antioxidant/antiradical activity, proving that this species has a medicinal potential. Moreover, the present study highlights the absence of the toxicity of these leaves and offers though a novel perspective on the species, previously known as being toxic.
Minimally invasive treatment of sino‐nasal aspergillosis in dogs
Authors: Ballber Clara , Hill Tracy L. , Bommer Nick X. 
Published: October 2018

Background:Sino‐nasal aspergillosis is a common nasal disease in dogs. Recommended treatment protocols typically involve trephination of the frontal sinuses or the use of an antifungal solution instilled into the frontal sinus under anesthesia, both of which have associated morbidity and complications.Objectives: To assess a minimally‐invasive topical treatment protocol for sino‐nasal aspergillosis in dogs.Animals:Twelve client‐owned dogs diagnosed with sino‐nasal aspergillosis that completed recommended treatment.Methods:Medical records were retrospectively reviewed to identify dogs with sino‐nasal aspergillosis that received treatment. Fungal plaques were manually debrided and irrigated via frontal sinuscopy in 12 dogs that then were treated topically with 1% topical clotrimazole cream. Irrigation and topical medication application was achieved using a catheter placed retrograde directly into the frontal sinuses using the Seldinger technique over a guidewire, thereby avoiding the need for frontal sinus trephination. Invasion into the calvarium was recorded before treatment but was not considered a criterion for exclusion. Debridement and cream deposition was repeated every 2 weeks as needed until negative culture and histopathologic findings were obtained.Results:All dogs were cured (negative results forAspergilluson endoscopy, fungal culture, and histopathology) with a median of 2 treatments. Treatments were well tolerated, with minimal adverse effects reported. Three dogs had evidence of erosion into the calvarium on computed tomography imaging.Conclusions and Clinical Importance:This protocol appears to be an effective and well‐tolerated minimally invasive treatment for sino‐nasal aspergillosis, including in dogs with erosion into the calvarium. Only mild adverse effects were noted.
Coordinated regulation of nitrogen fixation and molybdate transport by molybdenum
Authors: Demtröder Lisa , Narberhaus Franz , Masepohl Bernd 
Published: October 2018

SummaryBiological nitrogen fixation, the reduction of chemically inert dinitrogen to bioavailable ammonia, is a central process in the global nitrogen cycle highly relevant for life on earth. N2 reduction to NH3 is catalyzed by nitrogenases exclusively synthesized by diazotrophic prokaryotes. All diazotrophs have a molybdenum nitrogenase containing the unique iron‐molybdenum cofactor FeMoco. In addition, some diazotrophs encode one or two alternative Mo‐free nitrogenases that are less efficient at reducing N2 than Mo‐nitrogenase. To permit biogenesis of Mo‐nitrogenase and other molybdoenzymes when Mo is scarce, bacteria synthesize the high‐affinity molybdate transporter ModABC. Generally, Mo supports expression of Mo‐nitrogenase genes, while it represses production of Mo‐free nitrogenases and ModABC. Since all three nitrogenases and ModABC can reach very high levels at suitable Mo concentrations, tight Mo‐mediated control saves considerable resources and energy. This review outlines the similarities and differences in Mo‐responsive regulation of nitrogen fixation and molybdate transport in diverse diazotrophs.
Exploring Connections Between First and Second Language Fluency: A Mixed Methods Approach
Authors: PELTONEN PAULIINA 
Published: October 2018

AbstractMany factors influencing second language (L2) speech fluency have been widely studied, but the effects of first language (L1) fluency on L2 speech fluency are still relatively poorly understood. In contrast to mostly quantitative previous studies, the present study adopted a mixed methods approach to examining the connections between L1 fluency and L2 fluency. Monologue speech samples in L1 and L2 were obtained from 42 Finnish learners of English at 2 school levels (9th grade and upper secondary school). The samples were examined for 13 measures capturing different aspects of fluency: temporal fluency, including speed and pausing, and stalling mechanisms. The results indicated positive correlations between the majority of temporal L1 and L2 fluency measures. Regression analyses further demonstrated that most temporal L2 fluency measures could be predicted from L1 fluency measures to a certain extent, although the predictive power varied across the measures. Regarding stalling mechanisms, a complementary qualitative analysis provided insights to idiosyncratic patterns in their use in L1 and L2. Together, the findings suggest that L1 fluency is an important factor in explaining L2 fluency and should be more widely acknowledged in L2 fluency research, assessment, and teaching.
Do nurse‐led critical care outreach services impact inpatient mortality rates?
Authors: Garry Louise , Rohan Niamh , O'Connor Tom , Patton Declan , Moore Zena 
Published: October 2018

ABSTRACTBackgroundPrevious systematic reviews have assessed the effect of critical care outreach services, but none have focused solely on nurse‐led services.AimTo perform a systematic review examining the impact of nurse‐led critical care outreach services on inpatient mortality rates as the primary outcome. Secondary outcomes include arrest call rates and patient length of stay.MethodsA comprehensive search of several electronic databases was carried out, including the Cumulative Index to Nursing and Allied Health Literature and Medline. Non‐catalogued literature was searched, and contact was made by e‐mail with expert authors. All studies were in the English language, and although heterogeneous in design, only quantitative data were extracted for analysis. All included studies were assessed for quality using recognized quality appraisal tools. Meta‐analysis was not possible because of heterogeneity.ResultsTen studies involving almost 72 000 participants were identified. The reduction in mortality rates with nurse‐led critical care outreach services was reported to be 80%, but the statistical significance was low – four studies showed reductions ranging from 0·1% to 0·22%. Greater statistical significance was reported in arrest call rates, with two studies claiming decreased rates of 58·7% and 29·6%. Two studies reported a decrease in patient length of stay – the findings of a third study were equivocal. Half of the included studies scored poorly in terms of quality and validity, and all were single‐centre studies, thereby limiting generalisability.ConclusionNurse‐led critical care outreach services demonstrate benefits in terms of patient care and reduction in adverse events. Higher‐quality research, including multicentre randomized controlled trials, with meta‐analysis is recommended.Relevance to clinical practiceNurse‐led critical care outreach services have the potential to improve patient outcomes. Uniformity of team composition and nomenclature would benefit data collection and reporting.
Couplings in cell differentiation kinetics mitigate air temperature influence on conifer wood anatomy
Authors: Cuny Henri E. , Fonti Patrick , Rathgeber Cyrille B.K. , von Arx Georg , Peters Richard L. , Frank David C. 
Published: October 2018

AbstractConifer trees possess a typical anatomical tree‐ring structure characterized by a transition from large and thin‐walled earlywood tracheids to narrow and thick‐walled latewood tracheids. However, little is known on how this characteristic structure is maintained across contrasting environmental conditions, due to its crucial role to ensure sap ascent and mechanical support. In this study, we monitored weekly wood cell formation for up to 7 years in two temperate conifer species (i.e., Picea abies (L.) Karst and Larix decidua Mill.) across an 8°C thermal gradient from 800 to 2,200 m a.s.l. in central Europe to investigate the impact of air temperature on rate and duration of wood cell formation. Results indicated that towards colder sites, forming tracheids compensate a decreased rate of differentiation (cell enlarging and wall thickening) by an extended duration, except for the last cells of the latewood in the wall‐thickening phase. This compensation allows conifer trees to mitigate the influence of air temperature on the final tree‐ring structure, with important implications for the functioning and resilience of the xylem to varying environmental conditions. The disappearing compensation in the thickening latewood cells might also explain the higher climatic sensitivity usually found in maximum latewood density.
Clinical efficacy of intrauterine cephapirin benzathine administration on clearance of uterine bacteria and subclinical endometritis in postpartum buffaloes
Authors: Nehru Dawoud A. , Dhaliwal Gurcharan. S. , Jan Mustafa. H. , Cheema Ranjna S. , Kumar Sanjay 
Published: October 2018

ContentsThis study examined the effect of single IU administration of cephapirin on clinical recovery, clearance of uterine bacteria and reproductive performance of postpartum buffaloes with subclinical endometritis (SCE). Buffaloes (n = 86) at 35 days postpartum (DPP) with >10% polymorphonuclear (PMN) cells in endometrial cytosmears were designated as positive (SCEP,n = 29), and buffaloes with ≤10% PMN cell were designated as negative (SCEN,n = 57) for SCE. Out of 29 positive buffaloes, 15 were administered a single intrauterine dose of cephapirin benzathine on 40 DPP (SCEP‐CB), while the remaining 14 animals were kept as untreated control (SCEP‐C). All animals were observed regularly for oestrous signs and were again subjected to cytobrush sampling on the first postpartum (FPP) oestrus. Buffaloes positive for SCE at 35 DPP were later considered “recovered” if their PMN cells dropped to ≤5% on the FPP oestrus. Presence ofEscherichia coli, Arcanobacterium pyogenesandFusobacterium necrophorumin uterus was detected based upon PCR amplification of genes related to bacteria‐specific virulence factors. A total of 66.7% of SCEP‐CB group buffaloes recovered as compared to 28.6% in SCEP‐C (χ2 = 4.21;p < 0.05). Rate of bacterial clearance did not differ between treated (38.5%) and untreated buffaloes (8.3%) (χ2 = 1.67;p > 0.05). The median days to first service did not differ significantly (p > 0.05) among the three groups, whereas cephapirin administration reduced (p < 0.05) the days open by 14 days in SCEP‐CB compared to SCEP‐C buffaloes. SCEP‐CB buffaloes were as likely to conceive as SCEN, whereas SCEP‐C had 0.28 hazard ratio for pregnancy. In conclusion, a single treatment with cephapirin benzathine at 40 DPP improved the reproductive performance of buffaloes with subclinical endometritis.
Creating a shared past: The representation of Medici–Habsburg relations in the wedding celebrations for Eleonora de Toledo and Cosimo I de’ Medici
Authors: Baker Nicholas Scott 
Published: October 2018

AbstractIn the summer of 1539, an elaborate, ephemeral programme of decoration was constructed in Florence to celebrate the wedding of Cosimo I de' Medici and Eleonora Álvarez de Toledo. Through an interplay of painting, sculpture, heraldry, and classical allusions, the programme constructed a narrative of the marriage as the culmination of a history of mutual support between the Medici family and the Spanish monarchy. In so doing, this article argues, it revealed the dynamic by which the network of political alliances and exchanges that made Spanish hegemony on the Italian peninsula possible operated. The narrative re‐presented the distant and recent history of Medici–Spanish relations and re‐created Florence as a middle ground between Spanish imperialism and Italian resistance and autonomy. It revealed the way in which Spanish Habsburg hegemony in Italy relied on dialogue, accommodation, mutual reciprocity, and a creative interpretation of the past and present.