bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing Population Trends of New Hampshire Forest Birds: Local vs. Regional Patterns
Authors: Holmes Richard T. , Sherry Thomas W. 
Published: October 2019

Abstract
We examined the changes in abundance between 1969 and 1986 of 19 forest-dwelling, mostly migratory bird species breeding in New Hampshire at 2 different scales: one local (an intensively studied 10-ha plot in unfragmented forest) and the other regional (Breeding Bird Surveys statewide). Twelve of the 19 species exhibited similar trends at both scales. Eight neither increased nor decreased, and 4 (Least Flycatcher, Winter Wren, Wood Thrush, and Swainson's Thrush) declined significantly. Others increased, decreased, or remained steady at one or the other scale. Overall, more species declined than increased both locally (8 vs. 1) and regionally (5 vs. 1). Comparisons of these patterns, combined with results of intensive studies at the local level, suggest that changes in food abundance and in vegetation structure related to forest succession on the breeding grounds, along with other processes that influence bird reproductive success and survivorship, are the most plausible explanations for most of the observed trends. Winter mortality was also identified as affecting breeding abundances, but only in short-distance migrant and permanently resident species. We have no evidence to indicate that the numbers of long-distance migrants were affected by events in their Neotropical wintering areas, although this possibility is difficult to assess from breeding-ground data. We urge caution in attributing declines of breeding forest migrant birds to tropical deforestation or similar causes until we either can eliminate alternate explanations that involve breeding-season events or have available critically needed demographic information on migrant populations in their wintering areas.
A comprehensive evaluation of connectivity methods for L1000 data
Authors: Lin Kequan , Li Lu , Dai Yifei , Wang Huili , Teng Shuaishuai , Bao Xilinqiqige , Lu Zhi John , Wang Dong 
Published: October 2019

Abstract
The methodologies for evaluating similarities between gene expression profiles of different perturbagens are the key to understanding mechanisms of actions (MoAs) of unknown compounds and finding new indications for existing drugs. L1000-based next-generation Connectivity Map (CMap) data is more than a thousand-fold scale-up of the CMap pilot dataset. Although several systematic evaluations have been performed individually to assess the accuracy of the methodologies for the CMap pilot study, the performance of these methodologies needs to be re-evaluated for the L1000 data. Here, using the drug–drug similarities from the Drug Repurposing Hub database as a benchmark standard, we evaluated six popular published methods for the prediction performance of drug–drug relationships based on the partial area under the receiver operating characteristic (ROC) curve at false positive rates of 0.001, 0.005 and 0.01 (AUC0.001, AUC0.005 and AUC0.01). The similarity evaluating algorithm called ZhangScore was generally superior to other methods and exhibited the highest accuracy at the gene signature sizes ranging from 10 to 200. Further, we tested these methods with an experimentally derived gene signature related to estrogen in breast cancer cells, and the results confirmed that ZhangScore was more accurate than other methods. Moreover, based on scoring results of ZhangScore for the gene signature of TOP2A knockdown, in addition to well-known TOP2A inhibitors, we identified a number of potential inhibitors and at least two of them were the subject of previous investigation. Our studies provide potential guidelines for researchers to choose the suitable connectivity method. The six connectivity methods used in this report have been implemented in R package (https://github.com/Jasonlinchina/RCSM).
Regulation of placentation by the transforming growth factor beta superfamily†
Authors: Adu-Gyamfi Enoch Appiah , Ding Yu-Bin , Wang Ying-Xiong 
Published: October 2019

AbstractDuring pregnancy, there is increased expression of some cytokines at the fetal–maternal interface; and the clarification of their roles in trophoblast–endometrium interactions is crucial to understanding the mechanism of placentation. This review addresses the up-to-date reported mechanisms by which the members of the transforming growth factor beta superfamily regulate trophoblast proliferation, differentiation, and invasion of the decidua, which are the main phases of placentation. The available information shows that these cytokines regulate placentation in somehow a synergistic and an antagonistic manner; and that dysregulation of their levels can lead to aberrant placentation. Nevertheless, prospective studies are needed to reconcile some conflicting reports; and identify some unknown mediators involved in the actions of these cytokines before their detailed mechanistic regulation of human placentation could be fully characterized. The TGF beta superfamily are expressed in the placenta, and regulate the process of placentation through the activation of several signaling pathways.
Multisample estimation of bacterial composition matrices in metagenomics data
Authors: Cao Yuanpei , Zhang Anru , Li Hongzhe 
Published: October 2019

Summary
Metagenomics sequencing is routinely applied to quantify bacterial abundances in microbiome studies, where bacterial composition is estimated based on the sequencing read counts. Due to limited sequencing depth and DNA dropouts, many rare bacterial taxa might not be captured in the final sequencing reads, which results in many zero counts. Naive composition estimation using count normalization leads to many zero proportions, which tend to result in inaccurate estimates of bacterial abundance and diversity. This paper takes a multisample approach to estimation of bacterial abundances in order to borrow information across samples and across species. Empirical results from real datasets suggest that the composition matrix over multiple samples is approximately low rank, which motivates a regularized maximum likelihood estimation with a nuclear norm penalty. An efficient optimization algorithm using the generalized accelerated proximal gradient and Euclidean projection onto simplex space is developed. Theoretical upper bounds and the minimax lower bounds of the estimation errors, measured by the Kullback–Leibler divergence and the Frobenius norm, are established. Simulation studies demonstrate that the proposed estimator outperforms the naive estimators. The method is applied to an analysis of a human gut microbiome dataset.
Spectrum and dosing of urate-lowering drugs in a large cohort of chronic kidney disease patients and their effect on serum urate levels: a cross-sectional analysis from the German Chronic Kidney Disease study
Authors: Kielstein Jan T , Heisterkamp Markus , Jing Jiaojiao , Nadal Jennifer , Schmid Matthias , Kronenberg Florian , Busch Martin , Sommerer Claudia , Lorenzen Johan M , Eckardt Kai-Uwe , Köttgen Anna ,   for the GCKD Study Investigators
Published: October 2019

Abstract

Background
Despite a plethora of studies on the effect of urate-lowering therapy (ULT) in patients with chronic kidney disease (CKD), current guidelines on the treatment of hyperuricaemia and gout vary, especially concerning the need for dose adjustment of allopurinol, whose main metabolite is accumulating with declining renal function. Data on allopurinol dosing and its relationship to renal function, co-medication and sex and the resulting urate level in large cohorts are missing.

Methods
We studied a subgroup of 2378 patients of the German Chronic Kidney Disease (GCKD) study to determine prescription patterns of ULT among CKD patients under nephrological care and the relationship of ULT dose to urate levels. Prescription and dosing of ULT were manually abstracted from the patient’s paper charts at the baseline visit, in which all currently used medications and their dosing were recorded.

Results
In this cohort, 39.6% were women, the mean estimated glomerular filtration rate (eGFR) was 51.3 ± 19.3 mL/min/1.73 m2 and the mean age was 59.0 ± 12.4 years. Of the 2378 examined patients, 666 (28.0%) received ULT. The dose of ULT was available for 572 patients. The main ULT agent was allopurinol (94.4%), followed by febuxostat (2.9%) and benzbromarone (2.6%). Of the 540 patients who used allopurinol with a reported daily dose, 480 had an eGFR &lt;60 mL/min/1.73 m2 and 320 had an eGFR &lt;45 mL/min/1.73 m2, 31.5% of the latter (n = 101) received a dose &gt;150 mg/day, the recommended maximal dose for this level of eGFR. The prescribed dose was not related to eGFR: the median eGFR for patients taking 100, 150 and 300 mg/day was 40 [interquartile range (IQR) 32–49], 43 (34–52) and 42 (35–54) mL/min/1.73 m2, respectively. Patients with lower doses of allopurinol had higher serum urate levels than patients with higher (than recommended) allopurinol doses. Sex, alcohol intake, eGFR, use of diuretics and treatment with allopurinol were independent determinants of serum urate levels in multivariate regression analysis.

Conclusions
The most frequently used drug to lower serum urate levels in this CKD cohort was allopurinol. Even in patients regularly seen by nephrologists, the dose of allopurinol is often not adjusted to the current eGFR. Patients with higher ULT doses achieved better control of their serum urate levels. Lowering of serum urate in CKD patients requires balancing potential adverse effects of allopurinol with suboptimal control of serum urate levels.
Colesevelam enhances the beneficial effects of brown fat activation on hyperlipidaemia and atherosclerosis development
Authors: Zhou Enchen , Hoeke Geerte , Li Zhuang , Eibergen Arthur C , Schonk Amber W , Koehorst Martijn , Boverhof Renze , Havinga Rick , Kuipers Folkert , Coskun Tamer , Boon Mariëtte R , Groen Albert K , Rensen Patrick C N , Berbée Jimmy F P , Wang Yanan 
Published: October 2019

Abstract

Aims
Brown fat activation accelerates the uptake of cholesterol-enriched remnants by the liver and thereby lowers plasma cholesterol, consequently protecting against atherosclerosis development. Hepatic cholesterol is then converted into bile acids (BAs) that are secreted into the intestine and largely maintained within the enterohepatic circulation. We now aimed to evaluate the effects of prolonged brown fat activation combined with inhibition of intestinal BA reabsorption on plasma cholesterol metabolism and atherosclerosis development.

Methods and results
APOE*3-Leiden.CETP mice with humanized lipoprotein metabolism were treated for 9 weeks with the selective β3-adrenergic receptor (AR) agonist CL316,243 to substantially activate brown fat. Prolonged β3-AR agonism reduced faecal BA excretion (−31%), while markedly increasing plasma levels of total BAs (+258%), cholic acid-derived BAs (+295%), and chenodeoxycholic acid-derived BAs (+217%), and decreasing the expression of hepatic genes involved in BA production. In subsequent experiments, mice were additionally treated with the BA sequestrant Colesevelam to inhibit BA reabsorption. Concomitant intestinal BA sequestration increased faecal BA excretion, normalized plasma BA levels, and reduced hepatic cholesterol. Moreover, concomitant BA sequestration further reduced plasma total cholesterol (−49%) and non-high-density lipoprotein cholesterol (−56%), tended to further attenuate atherosclerotic lesion area (−54%). Concomitant BA sequestration further increased the proportion of lesion-free valves (+34%) and decreased the relative macrophage area within the lesion (−26%), thereby further increasing the plaque stability index (+44%).

Conclusion
BA sequestration prevents the marked accumulation of plasma BAs as induced by prolonged brown fat activation, thereby further improving cholesterol metabolism and reducing atherosclerosis development. These data suggest that combining brown fat activation with BA sequestration is a promising new therapeutic strategy to reduce hyperlipidaemia and cardiovascular diseases.
3-Hydroxyanthralinic acid metabolism controls the hepatic SREBP/lipoprotein axis, inhibits inflammasome activation in macrophages, and decreases atherosclerosis in Ldlr−/− mice
Authors: Berg Martin , Polyzos Konstantinos A , Agardh Hanna , Baumgartner Roland , Forteza Maria J , Kareinen Ilona , Gisterå Anton , Bottcher Gerhard , Hurt-Camejo Eva , Hansson Göran K , Ketelhuth Daniel F J 
Published: October 2019

AbstractAimsAtherosclerosis is a chronic inflammatory disease involving immunological and metabolic processes. Metabolism of tryptophan (Trp) via the kynurenine pathway has shown immunomodulatory properties and the ability to modulate atherosclerosis. We identified 3-hydroxyanthranilic acid (3-HAA) as a key metabolite of Trp modulating vascular inflammation and lipid metabolism. The molecular mechanisms driven by 3-HAA in atherosclerosis have not been completely elucidated. In this study, we investigated whether two major signalling pathways, activation of SREBPs and inflammasome, are associated with the 3-HAA-dependent regulation of lipoprotein synthesis and inflammation in the atherogenesis process. Moreover, we examined whether inhibition of endogenous 3-HAA degradation affects hyperlipidaemia and plaque formation.Methods and resultsIn vitro, we showed that 3-HAA reduces SREBP-2 expression and nuclear translocation and apolipoprotein B secretion in HepG2 cell cultures, and inhibits inflammasome activation and IL-1β production by macrophages. Using Ldlr−/− mice, we showed that inhibition of 3-HAA 3,4-dioxygenase (HAAO), which increases the endogenous levels of 3-HAA, decreases plasma lipids and atherosclerosis. Notably, HAAO inhibition led to decreased hepatic SREBP-2 mRNA levels and lipid accumulation, and improved liver pathology scores.ConclusionsWe show that the activity of SREBP-2 and the inflammasome can be regulated by 3-HAA metabolism. Moreover, our study highlights that targeting HAAO is a promising strategy to prevent and treat hypercholesterolaemia and atherosclerosis.
Blood flow patterns regulate PCSK9 secretion via MyD88-mediated pro-inflammatory cytokines
Authors: Liu Shijie , Deng Xiaoyan , Zhang Peng , Wang Xianwei , Fan Yubo , Zhou Sichang , Mu Shengyu , Mehta Jawahar L , Ding Zufeng 
Published: October 2019

Abstract

Aims
Blood flow patterns play an important role in the localization of atherosclerosis in the sense that low-flow state is pro-atherogenic, and helical flow is protective against atherosclerosis. Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates cholesterol metabolism via low-density lipoprotein receptor (LDLr) degradation and is highly expressed in the atherosclerotic tissues. This study was designed to investigate the role of different blood flow patterns in the regulation of PCSK9 expression.

Methods and results
We designed an experimental model guider to generate stable helical flow. Our data showed that compared with normal flow, low-flow state induces whereas helical flow inhibits PCSK9 expression in the rabbit thoracic aorta in an inflammatory state. Our data also identified that TLR4-MyD88-NF-κB signalling plays an important role in PCSK9 expression. On the other hand, TRIF pathway had almost no effect. Further studies showed that the signals downstream of NF-κB, such as pro-inflammatory cytokines (IL-1β, IL-18, MCP-1, IL-6, TNF-α, IL-12, IFNγ, and GM-CSF) directly influence PCSK9 expression. Interestingly, high fat diet further enhanced PCSK9 expression in an inflammatory milieu.

Conclusions
These observations suggest a link between abnormal flow patterns and PCSK9 expression in inflammatory states, which may qualify helical flow and pro-inflammatory cytokines as potential targets to treat PCSK9-related cardiovascular diseases.
Reactome and ORCID—fine-grained credit attribution for community curation
Authors: Viteri Guilherme , Matthews Lisa , Varusai Thawfeek , Gillespie Marc , Milacic Marija , Cook Justin , Weiser Joel , Shorser Solomon , Sidiropoulos Konstantinos , Fabregat Antonio , Haw Robin , Wu Guanming , Stein Lincoln , D’Eustachio Peter , Hermjakob Henning 
Published: October 2019

Abstract
Reactome is a manually curated, open-source, open-data knowledge base of biomolecular pathways. Reactome has always provided clear credit attribution for authors, curators and reviewers through fine-grained annotation of all three roles at the reaction and pathway level. These data are visible in the web interface and provided through the various data download formats. To enhance visibility and credit attribution for the work of authors, curators and reviewers, and to provide additional opportunities for Reactome community engagement, we have implemented key changes to Reactome: contributor names are now fully searchable in the web interface, and contributors can ‘claim’ their contributions to their ORCID profile with a few clicks. In addition, we are reaching out to domain experts to request their help in reviewing and editing Reactome pathways through a new ‘Contribution’ section, highlighting pathways which are awaiting community review.
Database URL: https://reactome.org
Preoperative versus intraoperative image-guided localization of multiple ipsilateral lung nodules
Authors: Chao Yin-Kai , Fang Hsin-Yueh , Pan Kuang-Tse , Wen Chih-Tsung , Hsieh Ming-Ju 
Published: October 2019

Abstract

OBJECTIVES
Computed tomography (CT)-guided localization of multiple ipsilateral pulmonary nodules remains challenging. Hybrid operating rooms equipped with cone-beam CT and laser navigation systems have the potential for improving clinical workflows and patient outcomes.

METHODS
Patients with multiple ipsilateral pulmonary nodules requiring localization were divided according to the localization method [preoperative CT-guided (POCT group) localization versus intraoperative CT-guided (IOCT group) localization]. The 2 groups were compared in terms of procedural efficacy, safety and radiation exposure.

RESULTS
Patients in the IOCT (n = 12) and POCT (n = 42) groups did not differ in terms of demographic and tumour characteristics. Moreover, the success and complication rates were similar. Notably, the IOCT approach allowed multiple nodules to be almost simultaneously localized—resulting in a shorter procedural time [mean difference (MD) −15.83 min, 95% confidence interval (CI) −7.97 to −23.69 min] and lower radiation exposure (MD −15.59 mSv, 95% CI −7.76 to −23.42 mSv) compared with the POCT approach. However, the total time under general anaesthesia was significantly longer in the IOCT group (MD 34.96 min, 95% CI 1.48–68.42 min), despite a similar operating time. The excess time under anaesthesia in the IOCT group can be attributed not only to the procedure per se but also to a longer surgical preparation time (MD 21.63 min, 95% CI 10.07–33.19 min).

CONCLUSIONS
Compared with the POCT approach, IOCT-guided localization performed in a hybrid operating room is associated with a shorter procedural time and less radiation exposure, albeit at the expense of an increased time under general anaesthesia.
Two-dimensional versus three-dimensional Frӓnkel Manoeuvre: a reproducibility study
Authors: Rongo Roberto , Bucci Rosaria , Adaimo Raffaella , Amato Massimo , Martina Stefano , Valletta Rosa , D’antò Vincenzo 
Published: October 2019

SummaryBackground/ObjectivesTo assess intra- and inter-observer reproducibility of the evaluation of the Frӓnkel Manoeuvre (FM) on three-dimensional (3D) scans and to compare it to the assessment on two-dimensional (2D) pictures.Materials/MethodsThis study included 44 individuals with a skeletal Class II malocclusion [9–16-years old mean age ± standard deviation: 13.5 ± 2.01 years]. All patients had a full Class II molar relationship, overjet ≥6 mm and point A, Nasion, point B angle (ANB) ≥5 degrees. During the FM, each patient was invited to bite in centric occlusion and then to posture the mandible forward to reach a Class I molar relationship. The FM was recorded both by a normal camera and a 3D scanner (3dMD system). Six examiners divided into two groups according to their orthodontic clinical experience (&lt;5 and &gt;10 years), and one gold standard in the evaluation of FM, commented twice (every 15 days) on both 2D photographs (T0 and T2) and 3D scans (T1 and T3). The intra-observer agreement and the inter-observer agreement compared to the gold standard were evaluated by computing the Cohen’s K.ResultsThe agreement between observations for each examiner ranged from 0.36 to 1 on 2D pictures (T0 versus T2), and from 0.22 to 0.69 on 3D scans (T1 versus T3). The overall agreement was 0.63 (95 per cent CI = 0.35–0.91) in 2D analysis and 0.5 (95 per cent CI = 0.35–0.64) in 3D analysis.Conclusions/ImplicationsThe FM was less reproducible when performed on 3D records than on 2D pictures.
Night work and risk of ischaemic heart disease and anti-hypertensive drug use: a cohort study of 145 861 Danish employees
Authors: Larsen Ann D , Rugulies Reiner , Hansen Johnni , Kolstad Henrik A , Hansen Åse Marie , Hannerz Harald , Garde Anne Helene 
Published: October 2019

Abstract

Background
Ischaemic heart disease (IHD) and hypertension are leading causes of mortality and night work has been suspected as a risk factor. Meta-analyses and previous studies are often limited by power and various definitions of exposure and outcomes. This study aimed to investigate if night work increases the risk of IHD or anti-hypertensive drug usage in a large cohort of Danish employees.

Methods
Individual participant data on night work were drawn from the Danish Labour Force Survey (1999–2013). We included 145 861 participants (53% men) 21–59 years of age working 32 h or more per week. Participants with diagnosis or drug use in the year prior to baseline were excluded. Data on outcomes were obtained from nationwide health registers. Using Poisson regression we analyzed incidence rates of the outcomes as functions of night work adjusted for relevant covariates.

Results
We observed 3635 cases of IHD and 20 648 cases used anti-hypertensive drugs. When examining main effects the association of night work with drug use was estimated at rate ratio (RR): 1.05 (95% CI: 1.01–1.09). A sensitivity analysis suggested a dose-response association. The association of night work with IHD was estimated at RR: 1.08 (95% CI: 0.98–1.19). Overall likelihood ratio test showed no statistically significant associations between night work and IHD or drug use when including interactions with sex and socioeconomic status.

Conclusions
Night work was associated with an increased risk of anti-hypertensive drug use. Small estimates suggested a dose-response association. No statistically significant association between night work and IHD were found.