bluuebunny/crossref_metadata_2025_split huggingface dataset:
An open-label randomized controlled trial of DMARD withdrawal in RA patients achieving therapeutic response with certolizumab pegol combined with DMARDs
Authors: Pope Janet , Rampakakis Emmanouil , Vaillancourt Julie , Bessette Louis , Lazovskis Juris , Haraoui Boulos , Sampalis John S 
Published: September 2019

Abstract

Objectives
The objective of this trial was to compare effectiveness of certolizumab pegol added to conventional synthetic DMARDs (csDMARDs) in RA patients, followed by continuing vs discontinuing background csDMARDs after treatment response.

Methods
Patients with active RA who had certolizumab pegol added to their existing csDMARD regimen due to inadequate response were eligible. At 3 or 6 months, patients who achieved a change (Δ) in DAS28 of ⩾1.2 were randomized to continue combination therapy (COMBO) or withdraw csDMARD therapy (MONO) (unblinded). The primary outcome was non-inferiority of stopping vs continuing csDMARD(s) in terms of maintaining ΔDAS28 ⩾ 1.2 or achieving DAS28 low disease activity at 18 months (non-inferiority margin: 15 percentile units).

Results
A total of 125 patients were enrolled, 88 randomized to COMBO (n = 43) or MONO (n = 45). No significant differences were observed between groups in baseline age, gender, race, RF status or prior biologics (16% vs 11%). Although the rate of ΔDAS28 ⩾ 1.2 and/or DAS28 low disease activity achievement at 18 months was clinically comparable between the two groups (72% vs 69%), non-inferiority assumptions were not met [absolute risk difference (upper limit of 90% CI): 2.6% (19.1%)]. Similar baseline-adjusted improvements were seen in DAS28 (COMBO vs MONO: −2.3 vs −2.1; P = 0.49) and all endpoints were not statistically different including 59% vs 56% achieved DAS28 low disease activity, 69% vs 59% ΔDAS28 ⩾ 1.2, and 41% each remission.

Conclusion
Among RA patients achieving a therapeutic response on combination therapy with certolizumab pegol and csDMARDs, withdrawing csDMARDs was not non-inferior to maintaining csDMARDs but improvements were sustained in both groups at 18 months.
Towards “Green” Trusteeship: new statutory amendments for occupational pension trustees
Authors: Brown Lloyd 
Published: October 2019

Abstract
This article looks at the amendments to occupational pension schemes that are brought in by the Pension Protection Fund (Pensionable Service) and the Occupational Pension Schemes (Investment and Disclosure) (Amendment and Modification) Regulations 2018. It is respectfully submitted that the named regulations are legally compelling because they amend the regulatory landscape in a manner to enforce greater consideration of Environmental Social Governance risks by UK pension funds. In particular, this article engages with how the amendments are going to increase the pension fund trustees’ appetite to consider environmental risks (including climate-related risks) when exercising their general duty of investment.
Effects of monensin source on in vitro rumen fermentation characteristics and performance of Bos indicus beef bulls offered a high-concentrate diet
Authors: Teixeira Daniel A A , Cappellozza Bruno I , Fernandes Juliano R , Nascimento Kaique S , Bonfim Lorena E L M , Lopes Catarina N , Ehrhardt Jorge A C , Peres José R , Harris Simon A , Simas José M C , Richardson Leo F 
Published: October 2019

Abstract
In Exp. 1, Brachiaria ruziziensis (11.1 % CP) was inoculated or not with two sources of monensin, resulting in three treatments: 1) no monensin inoculation (CONT), 2) 20 mg of monensin sodium-A/kg of DM (Elanco Animal Health; MON-A), and 3) 20 mg of monensin sodium-B/kg of DM (Shandong Qilu King-Phar Pharmaceutical Co. Ltd.; MON-B). Three rumen-fistulated Jersey steers were offered a cool-season forage-based diet and were used as the rumen inoculum donors. Volatile fatty acids concentrations were evaluated at 0, 6, 12, 24, 30, and 48 h after treatment inoculation. Overall, acetate and butyrate concentrations were reduced in MON-A vs. CONT (P ≤ 0.02), whereas both monensin products reduced Ac:Pr ratio vs. CONT (P ≤ 0.01); however, MON-A also (P = 0.05) reduced the Ac:Pr ratio vs. MON-B. A treatment × hour interaction was detected for rumen propionate concentration (P = 0.01), primarily because MON-A resulted in greater propionate than CONT and MON-B at 24 and 48 h (P ≤ 0.03), but no differences were observed between CONT vs. MON-B (P ≥ 0.27). In Exp. 2, 240 Nellore bulls (initial BW = 363.2 ± 40.9 kg) were ranked and blocked according to initial BW, and within blocks animals were allotted into pens (n = 10 pens/treatment). Pens were randomly assigned into one of three treatments: 1) corn-based diet with no monensin (CONT), 2) CONT plus 28 mg of MON-A/kg of DM, and 3) CONT plus 28 mg of MON-B/kg of DM. The CONT diet was composed of sugarcane bagasse, ground corn, DDGS, urea, and a mineral-vitamin mix. The experimental period lasted 106 d and was divided into a 21-d adaptation period and an 85-d finishing phase. During the adaptation phase, both monensin sources increased (P ≤ 0.01) BW change, ADG, and F:G, as well as reduced DMI variation (P = 0.02). When the entire experimental period was evaluated, no treatment effects were detected for final BW, DMI, and ADG (P ≥ 0.26). Nonetheless, DMI variation was reduced as monensin was included (P = 0.01) and only MON-A improved the efficiency by reducing F:G vs. CONT (P = 0.05) and biological efficiency vs. MON-B (P = 0.05). Additionally, carcass ADG tended (P = 0.10) to be greater for MON-A vs. MON-B, whereas no other differences in the carcass characteristics were observed (P ≥ 0.53). In summary, the source of monensin inoculated in vitro and offered to Nellore bulls during the feedlot phase significantly affected the energetic efficiency and the performance of the animals.
Maternal Education in Early Life and Risk of Metabolic Syndrome in Young Adult American Females and Males
Authors: Huang Jonathan Yinhao , Gariépy Geneviève , Gavin Amelia R. , Rowhani-Rahbar Ali , Siscovick David S. , Enquobahrie Daniel A. 
Published: October 2019

Background:
Maternal education in a child’s early life may directly affect the child’s adult cardiometabolic health, but this is difficult to disentangle from biological, social, and behavioral life course processes that are associated with maternal education. These processes may also differ between males and females.

Methods:
Using data from the National Longitudinal Study of Adolescent to Adult Health (1995–2009) (N = 4,026 females and 3,192 males), we estimated sex-stratified associations between maternal attainment of less than high school (<HS), high school diploma (HS), or college degree (CD) at the respondent’s birth and respondent’s risk of metabolic syndrome (MetS); we used marginal structural models (MSM) to account for the influence of major life course risk factors, such as childhood maltreatment, adolescent overweight, adult education, household income, smoking, and physical activity, in mediating associations between maternal education and offspring MetS risk.

Results:
Each higher level of maternal education was associated with a 36% (Relative Risk = 0.64 [95% Confidence Interval (CI): 0.50-0.82]) reduced risk of MetS among females, but only 19% (RR = 0.81 [95% CI: 0.64-1.01]) reduction among males (P-value interaction < 0.05). Stronger inverse associations were also observed for waist circumference and glycated hemoglobin (HbA1c) among females compared with males (−5 cm vs. −2.4 cm and −1.5% vs. −1.0%, respectively).

Conclusion:
High maternal education in early life was associated with a lower risk of MetS in young adulthood even after accounting for life course risk factors, particularly among females. Results were robust to altered model specifications.
Diagnosis of infective endocarditis using echocardiography
Authors: Yuan Xin-chun , Liu Ming , Hu Jia , Zeng Xi , Zhou Ai-yun , Chen Li 
Published: October 2019

Abstract
The aim of this study was to evaluate the application of transthoracic echocardiography for the diagnosis of infective endocarditis (IE) to provide a basis for the better treatment of IE. From October 2016 to October 2018, 87 consecutive patients with IE at our hospital were selected for this study. All the patients were subjected to transthoracic echocardiography. The morphology, structure, activity, and closure of the patients’ heart valves were observed for vegetation identification, and the size, number, location, morphology, and echo intensity of vegetation, as well as degree of valve involvement, were determined.
The 87 patients investigated in this study included 38 cases of congenital heart disease, 27 cases of nonrheumatic valvular heart disease, 12 patients who underwent valve surgery, 5 cases of rheumatic valvular heart disease, and 5 patients with no obvious signs of heart disease. The most common clinical manifestations were heart murmur in 80 cases and fever in 60 cases. The most common complications were heart failure in 35 cases, followed by organ embolism in 12 cases. There were 36 cases of positive blood cultures, including 26 cases of Gram-positive cocci and 10 cases of Gram-negative bacilli. Echocardiography showed aortic valve involvement in 37 cases, mitral valve involvement in 34 cases, tricuspid valve involvement in 10 cases, pulmonary valve involvement in 2 cases, and the involvement of an artificial valve in 5 cases. Twenty-six of these cases showed multiple valve involvement, and 20 patients exhibited serious complications. No significant differences were found between echocardiography and actual surgical observations with respect to their accuracy in detecting the size, number, and location of vegetation in the 69 patients who underwent surgery (P > .05). Echocardiography could detect the occurrence of severe complications, namely, the rupture of chordae tendineae, valve prolapse, valve perforation, and paravalvular abscess, and no significant difference in diagnostic accuracy was found between echocardiography and surgical observations (P > .05).
Transthoracic echocardiography can rapidly and accurately detect IE vegetation and its complications and has important clinical value for guiding clinical treatment and determining prognosis.
The efficacy and safety of long-term add-on treatment of azithromycin in asthma
Authors: Wang Xiaohu , Luo Jian , Wang Dan , Liu Bicui , Liu Chuntao 
Published: October 2019

Abstract

Aim:
Effects of azithromycin on asthma reported in clinical trials are less consistent. We aimed to further clarify the efficacy and safety of azithromycin in treatment of asthma.

Methods:
The protocol registration number was CRD42017074318 (http://www.crd.york.ac.uk/Prospero). We searched PubMed, EMBASE, Cochrane databases, China National Knowledge Internet (CNKI), and Wanfang databases for the randomized controlled trials (RCTs) with prolonged treatment of azithromycin for more than 3 weeks. Random-effects or fixed-effects model was applied to calculate risk ratio (RR) and mean difference (MD) for dichotomous and continuous data respectively.

Results:
A total of eight studies were included for analysis. The pooled result of adjunctive azithromycin therapy in asthma showed a small, but statistically significant increase in forced expiratory volume in one second (FEV1) (MD = 0.06, 95% confidence interval [CI]: 0.01–0.12, P = .02), but no significant differences in exacerbation frequency (MD = −0.42, 95%CI: −1.13 to 0.30, P = .25) and peak expiratory flow (PEF) (MD = 0.20, 95% CI: −0.05 to 0.44, P = .12), fractional exhaled nitric oxide (FeNO) (MD = 4.12, 95% CI: −2.06 to 10.30, P = .19), asthma quality of life questionnaire (AQLQ) (MD: 0.05, 95% CI: −0.17 to 0.28, P = .65), asthma control questionnaire (ACQ) (MD: −0.03, 95% CI: −0.21 to 0.15, P = .75). The subgroup analysis revealed that azithromycin could decrease FeNO among Asian asthma (MD = 15.04, 95% CI: 6.18–23.90, P = .0009).

Conclusions:
Add-on therapy of azithromycin in asthma patients could improve the FEV1, but failed to improve asthma exacerbations, PEF, ACQ, AQLQ, and FeNO. Subgroup analysis indicated that azithromycin could improve FeNO in Asian group asthmatics.
Comparative evaluation of a website for drug incompatibility
Authors: Suzuki Shinya , Mochizuki Nobuo , Iwamoto Aya Ikeuchi , Yoshida Mikinori , Murakami Akio , Ikegawa Kiwako , Yamaguchi Masakazu , Vigneron Jean 
Published: October 2019

Abstract

Background:
This study was conducted to evaluate the benefit of Stabilis through a survey of the listings of incompatibility data.

Methods:
The review was performed in December 2014 to compare the number of incompatible drugs cited by the Stabilis website, “Injectable Drug Audit Manual, 4th edition” (AM) and “Handbook on Injectable Drugs, 17th edition” (ID). We used the data on incompatible drugs to compare each database. We selected 10 frequently used anticancer medicines to compare the drugs cited in Stabilis, AM and ID. In addition, we compared Stabilis and AM in 23 frequently used antibiotics as an additional evaluation.

Results:
Stabilis had 678 drugs including 456 injectable drugs, AM had 496 injectable drugs and ID had 332 injectable drugs, as of December 2014. Compared with the fact that most references in AM were unofficial data from manufacturers, Stabilis cited 1722 references and ID cited 2830 references. For the 10 selected anticancer drugs, the total number of listed drugs was 118 in Stabilis, compared to 51 in AM and 82 in ID. Overall, mean and median duplication rates were 4.5% and 0% in AM and 60.7% and 59.0% in ID, respectively. For the 23 selected antibiotics, the total number of listed drugs was 463 in Stabilis, compared to 238 in AM. Overall, mean and median duplication rates were 20.1% and 16.0% in Stabilis and 10.3% and 8.0% in AM, respectively.

Conclusions:
Stabilis offers a beneficial database for checking drug incompatibilities in a manner similar to ID.
Cortical RORβ is required for layer 4 transcriptional identity and barrel integrity
Authors: Clark Erin A. , Rutlin Michael , Capano Lucia , Aviles Samuel , Saadon Jordan R. , Taneja Praveen , Zhang Qiyu , Bullis James , Lauer Timothy , Myers Emma , Schulmann Anton , Forrest Douglas , Nelson Sacha 
Published: September 2019

AbstractRetinoic Acid-Related Orphan Receptor Beta (RORβ) is a transcription factor (TF) and marker of layer 4 (L4) neurons, which are distinctive both in transcriptional identity and the ability to form aggregates such as barrels in rodent somatosensory cortex. However, the relationship between transcriptional identity and L4 cytoarchitecture is largely unknown. We find RORβ is required in the cortex for L4 aggregation into barrels and thalamocortical afferent (TCA) segregation. Interestingly, barrel organization also degrades with age. Loss of RORβ delays excitatory input and disrupts gene expression and chromatin accessibility, with downregulation of L4 and upregulation of L5 genes, suggesting a shift in cellular identity. Expression and binding site accessibility change for many other TFs, including closure of neurodevelopmental TF binding sites and increased expression and binding capacity of activity-regulated TFs. Lastly, a putative target of RORβ,Thsd7a, is downregulated without RORβ, andThsd7aknockout alone disrupts TCA organization in adult barrels.
GWAS-Flow: A GPU accelerated framework for efficient permutation based genome-wide association studies
Authors: Freudenthal Jan A. , Ankenbrand Markus J. , Grimm Dominik G. , Korte Arthur 
Published: September 2019

AbstractMotivationGenome-wide association studies (GWAS) are one of the most commonly used methods to detect associations between complex traits and genomic polymorphisms. As both genotyping and phenotyping of large populations has become easier, typical modern GWAS have to cope with massive amounts of data. Thus, the computational demand for these analyses grew remarkably during the last decades. This is especially true, if one wants to implement permutation-based significance thresholds, instead of using the naïve Bonferroni threshold. Permutation-based methods have the advantage to provide an adjusted multiple hypothesis correction threshold that takes the underlying phenotypic distribution into account and will thus remove the need to find the correct transformation for non Gaussian phenotypes. To enable efficient analyses of large datasets and the possibility to compute permutation-based significance thresholds, we used the machine learning framework TensorFlow to develop a linear mixed model (GWAS-Flow) that can make use of the available CPU or GPU infrastructure to decrease the time of the analyses especially for large datasets.ResultsWe were able to show that our applicationGWAS-Flowoutperforms custom GWAS scripts in terms of speed without loosing accuracy. Apart from p-values,GWAS-Flowalso computes summary statistics, such as the effect size and its standard error for each individual marker. The CPU-based version is the default choice for small data, while the GPU-based version ofGWAS-Flowis especially suited for the analyses of big data.AvailabilityGWAS-Flowis freely available on GitHub (https://github.com/Joyvalley/GWAS_Flow) and is released under the terms of the MIT-License.
Panmixia across elevation in thermally sensitive Andean dung beetles
Authors: Linck Ethan , Celi Jorge E. , Sheldon Kimberly S. 
Published: September 2019

AbstractJanzen’s seasonality hypothesis predicts that organisms inhabiting environments with limited climatic variability will evolve a reduced thermal tolerance breadth compared with organisms experiencing greater climatic variability. In turn, narrow tolerance breadth may select against dispersal across strong temperature gradients, such as those found across elevation. This can result in narrow elevational ranges and generate a pattern of isolation-by-environment, or neutral genetic differentiation correlated with environmental variables that is independent of geographic distance. We tested for signatures of isolation-by-environment across elevation using genome-wide SNP data from five species of Andean dung beetles (subfamily Scarabaeinae) with well-characterized, narrow thermal physiologies and narrow elevational distributions. Contrary to our expectations, we found no evidence of population genetic structure associated with elevation and little signal of isolation- by-environment. Further, elevational ranges for four of five species appear to be at equilibrium and show no evidence of demographic constraints at range limits. Taken together, these results suggest physiological constraints on dispersal may primarily operate outside of a stable realized niche.Abstract Figure
Interfering with a memory without erasing its trace
Authors: Lange Gesa , Senden Mario , Radermacher Alexandra , De Weerd Peter 
Published: September 2019

AbstractPrevious research has shown that performance of a novice skill can be easily interfered with by subsequent training of another skill. We address the open questions whether extensively trained skills show the same vulnerability to interference as novice skills and which memory mechanism regulates interference between expert skills. We developed a recurrent neural network model of V1 able to learn from feedback experienced over the course of a long-term orientation discrimination experiment. After first exposing the model to one discrimination task for 3480 consecutive trials, we assessed how its performance was affected by subsequent training in a second, similar task. Training the second task strongly interfered with the first (highly trained) discrimination skill. The magnitude of interference depended on the relative amounts of training devoted to the different tasks. We used these and other model outcomes as predictions for a perceptual learning experiment in which human participants underwent the same training protocol as our model. Specifically, over the course of three months participants underwent baseline training in one orientation discrimination task for 15 sessions before being trained for 15 sessions on a similar task and finally undergoing another 15 sessions of training on the first task (to assess interference). Across all conditions, the pattern of interference observed empirically closely matched model predictions. According to our model, behavioral interference can be explained by antagonistic changes in neuronal tuning induced by the two tasks. Remarkably, this did not stem from erasing connections due to earlier learning but rather from a reweighting of lateral inhibition.
Safeguarding the genetic integrity of native pollinators requires stronger regulations on commercial lines
Authors: Bartomeus Ignasi , Molina Francisco P. , Hidalgo-Galiana Amparo , Ortego Joaquín 
Published: September 2019

AbstractEvery year more than one million commercial bumblebee colonies are deployed in greenhouses worldwide for its pollination services to several commercially important crops such as tomato and different species of berries. While commercial pollinators have been an enormous benefit for the production of essential food crops and for achieving higher yields and better fruit quality at a low cost, their use is emerging also as an important threat to wild pollinators. Commercial pollinators have been linked to pathogen spillover to wild species, and its introduction outside its native area have had devastating effects on native pollinator populations. However, a more pervasive, but underappreciated threat is their potential impact on the genetic integrity of native pollinators. Here, we show clear evidence of generalized hybridization between native and introduced commercial bumblebee lineages in southern Spain. The signal of genetic introgression is widespread and already expands up to 60 km from main commercial bumblebee release areas. As pollination services demand is predicted to increase in the coming years, only a more restrictive regulation of commercial lines could mitigate their negative impacts on the genetic integrity of native pollinators and prevent the disruption of local adaptations.
Human gut microbiota networks disturbance by parasites in indigenous communities: Effect on bacteria genera related to depression incidence subnetworks
Authors: Ramírez-Carrillo Elvia , Gaona Osiris , Nieto Javier , Sánchez-Quinto Andrés , Cerqueda-García Daniel , Falcon Luisa I. , Rojas-Ramos Olga , González-Santoyo Isaac 
Published: September 2019

ABSTRACTIf you think you are in control of your behavior, think again. Evidence suggests that behavioral modifications, as development and persistence of depression, may be the consequence of a complex network of communication between macro (i.e. parasites) and micro-organisms capable of modifying the physiological axis of the host. Some parasites cause significant nutritional deficiencies for the host and impair the effectiveness of cognitive processes such as memory, teaching or non-verbal intelligence. Bacterial communities mediate the establishment of parasites and vice versa but this complexity approach remains little explored. We study the gut microbiota-parasite interactions using novel techniques of network analysis using data of individuals from two indigenous communities in the state of Guerrero, Mexico. Our results suggest that A. Lumbricoides, induce a gut microbiota perturbation affecting subnetworks of key species related to depression, consisting in the loss of network features such as path length, heterogeneity, number of nodes and neighbors; and especially by the loss of information emergence. Emergence is related with adaptability that has been linked to the concept of health as a critical balance between (adaptability) and self-organization (robustness). In this way, the loss of emergence means a depart from criticality and ultimately loss of health.