bluuebunny/crossref_metadata_2025_split huggingface dataset:
Child survival revolutions revisited – lessons learned from Bangladesh, Nicaragua, Rwanda and Vietnam
Authors: Persson Lars Åke , Rahman Anisur , Peña Rodolfo , Perez Wilton , Musafili Aimable , Hoa Dinh Phuong 
Published: March 2017

AbstractAnalysing child mortality may enhance our perspective on global achievements in child survival. We used data from surveillance sites in Bangladesh, Nicaragua and Vietnam and Demographic Health Surveys in Rwanda to explore the development of neonatal and under‐five mortality. The mortality curves showed dramatic reductions over time, but child mortality in the four countries peaked during wars and catastrophes and was rapidly reduced by targeted interventions, multisectorial development efforts and community engagement.Conclusion: Lessons learned from these countries may be useful when tackling future challenges, including persistent neonatal deaths, survival inequalities and the consequences of climate change and migration.
Auditory impairment in infants with neonatal chronic lung disease is alleviated after term
Authors: Jiang Ze D. 
Published: March 2017

AbstractAimVery premature infants with neonatal chronic lung disease (CLD) have been reported to have major auditory impairment at term, and we examined the outcomes in 30 infants after term age.MethodsBrainstem auditory evoked response (BAER) was recorded at a postconceptional age of 46–61 weeks in 13 CLD cases and 14 controls from China and 17 CLD cases and 22 controls from the UK.ResultsThe BAER threshold in the CLD infants was slightly higher. Clicks at the normal hearing level (60 dB) showed no significant differences between the cases and controls in the latencies of BAER waves I, III and V and the I–V interval. However, the CLD infants demonstrated marginal shortening in the I‐III interval and a marginal increase in the III‐V interval. The amplitudes of BAER waves in the CLD infants were all slightly smaller than the controls. At 70 and 40 dB normal hearing level, the BAER findings were similar to those obtained at 60 dB normal hearing level, with only small variations.ConclusionThere were minor BAER abnormalities in the CLD infants, suggesting minor auditory impairment. The auditory impairment previously detected at the term date was later alleviated.
Moderate grazing sustains plant diversity in Afromontane grassland
Authors: Joubert Lize , Pryke James S. , Samways Michael J. 
Published: March 2017

AbstractAimsNatural disturbances drive plant assemblages in Afromontane grassland. Our aim is to assess how intensity of cattle grazing and time since last fire influence plant species richness, dominance and assemblage composition.LocationCentral Midlands, KwaZulu‐Natal province, South Africa.MethodsSites differed in grazing intensity (light, moderate and heavy) and time since last fire: recently burned (RB) vs unburned (UB). We sampled plants in 24 vegetation quadrats (1‐m2) randomly located within each site (~1000 m2). We used linear regression models for species richness and dominance, IndVal to identify indicator species and CCA for assemblage composition. All analyses were conducted at quadrat and site level.ResultsSpecies richness was significantly influenced by time since last fire (RB > UB), grazing intensity (light < moderate > heavy) and the fire–grazing interaction at quadrat level. Dominance reciprocated the response of species richness to time since last fire (UB > RB), but did not respond consistently to grazing intensity (light > moderate > or < heavy). Plant assemblage composition was significantly influenced by time since last fire, grazing intensity and vegetation structure (live vegetation cover and vegetation height). Indicator species of species‐poor, heavily grazed sites included alien species, such as Cirsium vulgare and Conyza bonariensis.ConclusionResponse of species richness to grazing intensity conforms to the predictions of the intermediate disturbance hypothesis. Burning and moderate grazing should be part of grassland management. To prevent species loss and influx of alien species, heavy grazing should be minimized. As development of grassland ecological networks in a timber matrix is being pioneered in South Africa, these findings indicate a way forward for the management of similar systems elsewhere in the world.
CCL20 neutralization by a monoclonal antibody in healthy subjects selectively inhibits recruitment of CCR6+ cells in an experimental suction blister
Authors: Bouma Gerben , Zamuner Stefano , Hicks Kirsty , Want Andrew , Oliveira João , Choudhury Arpita , Brett Sara , Robertson Darren , Felton Leigh , Norris Virginia , Fernando Disala , Herdman Michael , Tarzi Ruth 
Published: March 2017

AimsGSK3050002, a humanized IgG1κ antibody with high binding affinity to human CCL20, was administered in a first‐in‐human study to evaluate safety, pharmacokinetics (PK) and pharmacodynamics (PD). An experimental skin suction blister model was employed to assess target engagement and the ability of the compound to inhibit recruitment of inflammatory CCR6 expressing cells.MethodsThis study was a randomized, double‐blind (sponsor open), placebo‐controlled, single‐centre, single ascending intravenous dose escalation trial in 48 healthy male volunteers.ResultsGSK3050002 (0.1–20 mg kg−1) was well tolerated and no safety concerns were identified. The PK was linear over the dose range, with a half‐life of approximately 2 weeks. Complex of GSK3050002/CCL20 increased in serum and blister fluid with increasing doses of GSK3050002. There were dose‐dependent decreases in CCR6+ cell recruitment to skin blisters with maximal effects at doses of 5 mg kg−1 and higher, doses at which GSK3050002/CCL20 complex in serum and blister fluid also appeared to reach maximum levels.ConclusionsThese results indicate a relationship between PK, target engagement and PD, suggesting a selective inhibition of recruitment of CCR6+ cells by GSK3050002 and support further development of GSK3050002 in autoimmune and inflammatory diseases.
A population pharmacokinetic meta‐analysis of custirsen, an antisense oligonucleotide, in oncology patients and healthy subjects
Authors: Edwards Alena Y. , Elgart Anna , Farrell Colm , Barnett‐Griness Ofra , Rabinovich‐Guilatt Laura , Spiegelstein Ofer 
Published: March 2017

AimsCustirsen (OGX‐011/TV‐1011), a second‐generation antisense oligonucleotide that reduces clusterin production, is under investigation with chemotherapy in prostate and lung cancer. This meta‐analysis evaluated the population pharmacokinetics (PK) of custirsen in cancer patients and healthy subjects.MethodsThe population PK analysis used custirsen plasma concentrations from five Phase 1 studies, one Phase 1/2 study, and one Phase 3 study in two stages. Cancer patients received multiple doses of custirsen (40–640 mg intravenously over 120 min) with chemotherapy; healthy subjects received single or multiple doses (320–640 mg). An interim population PK model was developed using a nonlinear mixed‐effect approach incorporating data from four Phase 1 or 1/2 studies, followed by model refinement and inclusion of two Phase 1 and one Phase 3 studies.ResultsThe final model was developed with 5588 concentrations from 631 subjects with doses of 160–640 mg. Custirsen PK was adequately described by a three‐compartment model with first‐order elimination. For a representative 66‐year‐old individual with body weight 82 kg and serum creatinine level 0.933 mg dl−1, the estimated typical (95% CI) parameter values were clearance (CL) = 2.36 (2.30–2.42) l h−1, central volume of distribution (V1) = 6.08 (5.93–6.23) l, peripheral volume of distribution (V2) = 1.13 (1.01–1.25) l, volume of the second peripheral compartment (V3) = 15.8 (14.6–17.0) l, inter‐compartmental clearance Q2 = 0.0755 (0.0689–0.0821) l h−1, and Q3 = 0.0573 (0.0532–0.0614) l h−1. Age, weight and serum creatinine were predictors of CL; age was a predictor of Q3.ConclusionA population PK model for custirsen was successfully developed in cancer patients and healthy subjects, including covariates contributing to variability in custirsen PK.
Potential of bisbenzimidazole‐analogs toward metronidazole‐resistant Trichomonas vaginalis isolates
Authors: Korosh Travis , Bujans Emmanuel , Morada Mary , Karaalioglu Canan , Vanden Eynde Jean Jacques , Mayence Annie , Huang Tien L. , Yarlett Nigel 
Published: March 2017

A bisoxyphenylene‐bisbenzimidazole series with increasing aliphatic chain length (CH2 to C10H20) containing a meta‐ (m) or para (p)‐benzimidazole linkage to the phenylene ring was tested for ability to inhibit the growth of metronidazole‐susceptible (C1) and metronidazole‐refractory (085) Trichomonas vaginalis isolates under aerobic and anaerobic conditions. Compound 3m, 2,2′‐[α,ω‐propanediylbis(oxy‐1,3‐phenylene)]bis‐1H‐benzimidazole, displayed a 5.5‐fold lower minimum inhibitory concentration (MIC) toward T. vaginalis isolate 085 than metronidazole under aerobic growth conditions, (26 μm compared to 145 μm). A dose of 25 mg/kg per day for four days of compound 3m cured a subcutaneous mouse model infection using T. vaginalis isolates 286 (metronidazole susceptible) and 085 (metronidazole refractory). Compound 3m was weakly reduced by pyruvate:ferredoxin oxidoreductase, but unlike metronidazole was not dependent upon added ferredoxin. It is concluded from structure‐activity relationships that there was no obvious trend based on the length of the central aliphatic chain, or the steric position of the bisbenzimidazole enabling prediction of biological activity. The compounds generally fulfill Lipinski's rile of five, indicating their potential as drug leads.
Pharmacokinetics of prolonged‐release tacrolimus versus immediate‐release tacrolimus in de novo liver transplantation: A randomized phase III substudy
Authors: Ericzon Bo‐Göran , Varo Evaristo , Trunečka Pavel , Fischer Lutz , Colledan Michele , Gridelli Bruno , Valdivieso Andrés , O'Grady John , Dickinson James , Undre Nasrullah 
Published: March 2017

AbstractBackgroundWith the same dose of tacrolimus, lower systemic exposure on the first day of dosing has been reported for prolonged‐release tacrolimus compared with immediate‐release tacrolimus, prompting investigation of differing initial doses.MethodsThis substudy of a double‐blind, randomized, phase III trial in de novo liver transplant recipients compared the pharmacokinetics of once‐daily prolonged‐release tacrolimus (initial dose: 0.2 mg/kg/day) versus twice‐daily immediate‐release tacrolimus (initial dose: 0.1 mg/kg/day) during the first 2 weeks post‐transplant.ResultsPharmacokinetic data were analyzed from patients receiving prolonged‐release tacrolimus (n=13) and immediate‐release tacrolimus (n=12). Mean systemic exposure (AUC0‐24) was higher with prolonged‐release versus immediate‐release tacrolimus. Dose‐normalized AUC0‐24 (normalized to 0.1 mg/kg/day) showed generally lower exposure with prolonged‐release tacrolimus versus immediate‐release tacrolimus. There was good correlation between AUC0‐24 and concentration at 24 hours after the morning dose (r=.96 and r=.86, respectively), and the slope of the line of best fit was similar for both formulations.ConclusionsDoubling the initial starting dose of prolonged‐release tacrolimus compared with immediate‐release tacrolimus overcompensated for lower exposure on Day 1. A 50% higher starting dose of prolonged‐release tacrolimus than immediate‐release tacrolimus may be required for similar systemic exposure. However, doses of both formulations can be optimized using the same trough‐level monitoring system. (ClinicalTrials.gov number: NCT00189826).
Factors determining uptake of diabetic retinopathy screening in Oxfordshire
Authors: Moreton R. B. R. , Stratton I. M. , Chave S. J. , Lipinski H. , Scanlon P. H. 
Published: March 2017

AbstractAimsTo investigate variables at the demographic and primary care practice levels that influence the uptake of diabetic retinopathy screening.MethodsData were extracted from the management software of one screening programme for 21 797 people registered with 79 general practices. Uptake was examined by gender, age group, modality of screening (mobile unit at general practice versus high‐street optometrist), and by general practice. A telephone survey of high‐street optometrists provided information on the availability of screening appointments.ResultsUptake was 82.4% during the study period, and was higher for men (83.2%) than for women (81.5%) (P = 0.001). Uptake varied by age group (P < 0.001), being lowest in those aged 12–39 years (67%). Uptake was higher for people invited to a general practice for screening by a mobile unit (83.5%) than for those invited for screening by a high‐street optometrist (82%) (P = 0.006). After adjusting for these factors and for socio‐economic deprivation score at the location of the general practice, heterogeneity in uptake rate was still observed between some practices. Our survey of optometrists indicated wide variation in the availability of time slots for screening during the week and of screening appointment provision.ConclusionsDiabetic retinopathy screening services do not achieve high uptake among the youngest or oldest age groups. Practices in the least deprived areas had the highest uptake. Variation in uptake between general practices after adjustment for individual‐level variables and deprivation suggests that practice‐level factors may have an important role in determining rates of screening attendance.
Effects of quantitative and qualitative differences in volatiles from host‐ and non‐host‐infested maize on the attraction of the larval parasitoid Cotesia kariyai
Authors: Thanikkul Ploypilin , Piyasaengthong Narisara , Menezes‐Netto Alexandre Carlos , Taylor DeMar , Kainoh Yooichi 
Published: March 2017

AbstractCotesia kariyai Watanabe (Hymenoptera: Braconidae) is a specialist larval parasitoid of Mythimna separata Walker (Lepidoptera: Noctuidae). Cotesia kariyai wasps use herbivore‐induced plant volatiles (HIPVs) to locate hosts. However, complex natural habitats are full of volatiles released by both herbivorous host‐ and non‐host‐infested plants at various levels of intensity. Therefore, the presence of non‐hosts may affect parasitoid decisions while foraging. Here, the host‐finding efficiency of naive C. kariyai from HIPVs influenced by host‐ and non‐host‐infested maize [Zea mays L. (Poaceae)] plants was investigated with a four‐arm olfactometer. Ostrinia furnacalis Guenée (Lepidoptera: Crambidae) was selected as a non‐host species. One unit (1 U) of host‐ or non‐host‐infested plant was prepared by infesting a potted plant with five host or seven non‐host larvae. In two‐choice bioassays, host‐infested plants fed upon by different numbers of larvae, and various units of host‐ and non‐host‐infested plants (infestation units; 1 U, 2 U, and 3 U) were arranged to examine the effects of differences in volatile quantity and quality on the olfactory responses of C. kariyai with the assumption that volatile quantity and quality changes with differences in numbers of insects and plants. Cotesia kariyai was found to perceive quantitative differences in volatiles from host‐infested plants, preferring larger quantities of volatiles from larger numbers of larvae or plants. Also, the parasitoids discriminated between healthy plants, host‐infested plants, and non‐host‐infested plants by recognising volatiles released from those plants. Cotesia kariyai showed a reduced preference for host‐induced volatiles, when larger numbers of non‐host‐infested plants were present. Therefore, quantitative and qualitative differences in volatiles from host‐ and non‐host‐infested plants appear to affect the decision of C. kariyai during host‐habitat searching in multiple tritrophic systems.
Carfilzomib‐containing combinations as frontline therapy for multiple myeloma: A meta‐analysis of 13 trials
Authors: Sheng Zhixin , Li Guifang , Li Bin , Liu Yanju , Wang Lida 
Published: March 2017

AbstractObjectiveTo investigate the activity and safety of carfilzomib‐containing combinations as frontline therapy for multiple myeloma.MethodsWe searched published carfilzomib reports for newly diagnosed multiple myeloma.ResultsThirteen trials were identified, covering 704 subjects. Pooled analysis showed that carfilzomib combinations as frontline therapy for multiple myeloma attained an impressive at least complete response (≥CR) rate of 21%, at least very good partial response (≥VGPR) rate of 68%, overall response rate (ORR) of 94%. The ≥CR rates of 18% pre‐SCT were increased to 43% of post‐ASCT, and 64% of postconsolidation (P<.001). For those patients receiving carfilzomib therapy, response quality improved further over time (≥CR rates of 10% after 2nd cycle, 20% after 4th cycle, 43% after 8th cycle; ≥VGPR of 29% after 2nd cycle, 68% after 4th cycle, 88% after 8th cycle). ≥CR rates of 49% from CFZ‐LEN‐DEX triplet regimen were higher than 18% from CFZ‐CYC‐DEX triplet regimen and 21% from CFZ‐THA‐DEX triplet regimen (P=.03).ConclusionsCarfilzomib combinations could produce clinical benefits in newly diagnosed patients with multiple myeloma. High‐quality response rate could be further improved through ASCT, consolidation therapy, and more cycles of chemotherapy even in the era of carfilzomib. CFZ‐LEN‐DEX could be a good combination regimen.
Multidirectional abundance shifts among North American birds and the relative influence of multifaceted climate factors
Authors: Huang Qiongyu , Sauer John R. , Dubayah Ralph O. 
Published: March 2017

AbstractShifts in species distributions are major fingerprint of climate change. Examining changes in species abundance structures at a continental scale enables robust evaluation of climate change influences, but few studies have conducted these evaluations due to limited data and methodological constraints. In this study, we estimate temporal changes in abundance from North American Breeding Bird Survey data at the scale of physiographic strata to examine the relative influence of different components of climatic factors and evaluate the hypothesis that shifting species distributions are multidirectional in resident bird species in North America. We quantify the direction and velocity of the abundance shifts of 57 permanent resident birds over 44 years using a centroid analysis. For species with significant abundance shifts in the centroid analysis, we conduct a more intensive correlative analysis to identify climate components most strongly associated with composite change of abundance within strata. Our analysis focus on two contrasts: the relative importance of climate extremes vs. averages, and of temperature vs. precipitation in strength of association with abundance change. Our study shows that 36 species had significant abundance shifts over the study period. The average velocity of the centroid is 5.89 km·yr−1. The shifted distance on average covers 259 km, 9% of range extent. Our results strongly suggest that the climate change fingerprint in studied avian distributions is multidirectional. Among 6 directions with significant abundance shifts, the northwestward shift was observed in the largest number of species (n = 13). The temperature/average climate model consistently has greater predictive ability than the precipitation/extreme climate model in explaining strata‐level abundance change. Our study shows heterogeneous avian responses to recent environmental changes. It highlights needs for more species‐specific approaches to examine contributing factors to recent distributional changes and for comprehensive conservation planning for climate change adaptation.
Ureteroenteric anastomotic revision as initial management of stricture after urinary diversion
Authors: Gin Greg E , Ruel Nora H , Parihar Jaspreet S , Warner Jonathan N , Yuh Bertram E , Yamzon Jonathan , Wilson Timothy G , Lau Clayton S , Chan Kevin G 
Published: March 2017

ObjectiveTo report our experience with ureteroenteric anastomotic revision as initial treatment of stricture after urinary diversion.MethodsAn institutional review board‐approved retrospective study was carried out. A total of 41 patients who underwent primary ureteroenteric anastamotic revision were identified between 2007 and 2015. Data analyzed included patient characteristics, type of diversion, estimated blood loss, operative time, change in renal function, length of stay, postoperative complications and time with nephrostomy/stent. Success of revision was defined as an improvement in hydronephrosis on radiographic imaging and/or reflux during pouchogram. Predictors of length of stay and complications were analyzed using analysis of covariance.ResultsA total of 50 renal units were revised with a success rate of 100%. The median length of stay was 6 days (2–16 days). There were a total of 15 complications (one major, 14 minor) in 14 patients (33% 30‐day complication rate). The most common were wound infection (n = 4) and arrhythmia (n = 4). Robotic revision (n = 5) had a median length of stay of 3 days (2–4) with no complications.ConclusionsPrimary ureteroenteric anastomotic revisions have an excellent success rate at an experienced center and might obviate the need for multiple interventions. Open revision is associated with mostly minor complications. Robotic revision might reduce the morbidity of open revision in select cases.
PAI1: a novel PP1‐interacting protein that mediates human plasma's anti‐apoptotic effect in endothelial cells
Authors: Yao Hui , He Guangchun , Chen Chao , Yan Shichao , Lu Lu , Song Liujiang , Vijayan K. Vinod , Li Qinglong , Xiong Li , Miao Xiongying , Deng Xiyun 
Published: March 2017

AbstractActivation of apoptotic signalling in endothelial cells contributes to the detrimental effects of a variety of pathological stimuli. In investigating the molecular events underlying the anti‐apoptotic effect of human plasma in cultured human endothelial cells, we unexpectedly uncovered a novel mechanism of apoptosis suppression by human plasma through an interaction between two previously unrelated proteins. Human plasma inhibited hypoxia–serum deprivation‐induced apoptosis and stimulated BADS136 and AktS473 phosphorylation. Akt1 silencing reversed part (~52%) of the anti‐apoptotic effect of human plasma, suggesting the existence of additional mechanisms mediating the anti‐apoptotic effect other than Akt signalling. Human plasma disrupted the interaction of BAD with protein phosphatase 1 (PP1). Mass spectrometry identified fourteen PP1‐interacting proteins induced by human plasma. Notably, a group of serine protease inhibitors including plasminogen activator inhibitor 1 (PAI1), a major inhibitor of fibrinolysis, were involved. Silencing of PAI1 attenuated the anti‐apoptotic effect of human plasma. Furthermore, combined Akt1 and PAI1 silencing attenuated the majority of the anti‐apoptotic effect of human plasma. We conclude that human plasma protects against endothelial cell apoptosis through sustained BAD phosphorylation, which is achieved by, at least in part, a novel interaction between PP1 with PAI1.