bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Test-and-Not-Treat Strategy for Onchocerciasis Elimination in Loa loa–coendemic Areas: Cost Analysis of a Pilot in the Soa Health District, Cameroon
Authors: Lenk Edeltraud J , Moungui Henri C , Boussinesq Michel , Kamgno Joseph , Nana-Djeunga Hugues C , Fitzpatrick Christopher , Peultier Anne-Claire M M , Klion Amy D , Fletcher Daniel A , Nutman Thomas B , Pion Sébastien D , Niamsi-Emalio Yannick , Redekop William K , Severens Johan L , Stolk Wilma A 
Published: June 2019

Abstract

Background
Severe adverse events after treatment with ivermectin in individuals with high levels of Loa loa microfilariae in the blood preclude onchocerciasis elimination through community-directed treatment with ivermectin (CDTI) in Central Africa. We measured the cost of a community-based pilot using a test-and-not-treat (TaNT) strategy in the Soa health district in Cameroon.

Methods
Based on actual expenditures, we empirically estimated the economic cost of the Soa TaNT campaign, including financial costs and opportunity costs that will likely be borne by control programs and stakeholders in the future. In addition to the empirical analyses, we estimated base-case, less intensive, and more intensive resource use scenarios to explore how costs might differ if TaNT were implemented programmatically.

Results
The total costs of US$283 938 divided by total population, people tested, and people treated with 42% coverage were US$4.0, US$9.2, and US$9.5, respectively. In programmatic implementation, these costs (base-case estimates with less and more intensive scenarios) could be US$2.2 ($1.9–$3.6), US$5.2 ($4.5–$8.3), and US$5.4 ($4.6–$8.6), respectively.

Conclusions
TaNT clearly provides a safe strategy for large-scale ivermectin treatment and overcomes a major obstacle to the elimination of onchocerciasis in areas coendemic for Loa loa. Although it is more expensive than standard CDTI, costs vary depending on the setting, the implementation choices made by the institutions involved, and the community participation rate. Research on the required duration of TaNT is needed to improve the affordability assessment, and more experience is needed to understand how to implement TaNT optimally.
Neutralization of CXCL12 attenuates established pulmonary hypertension in rats
Authors: Bordenave Jennifer , Thuillet Raphaël , Tu Ly , Phan Carole , Cumont Amélie , Marsol Claire , Huertas Alice , Savale Laurent , Hibert Marcel , Galzi Jean-Luc , Bonnet Dominique , Humbert Marc , Frossard Nelly , Guignabert Christophe 
Published: June 2019

Abstract

Aims
The progressive accumulation of cells in pulmonary vascular walls is a key pathological feature of pulmonary arterial hypertension (PAH) that results in narrowing of the vessel lumen, but treatments targeting this mechanism are lacking. The C-X-C motif chemokine 12 (CXCL12) appears to be crucial in these processes. We investigated the activity of two CXCL12 neutraligands on experimental pulmonary hypertension (PH), using two complementary animal models.

Methods and results
Male Wistar rats were injected with monocrotaline (MCT) or were subjected to SU5416 followed by 3-week hypoxia to induce severe PH. After PH establishment, assessed by pulsed-wave Doppler echocardiography, MCT-injected or SU5416 plus chronic hypoxia (SuHx) rats were randomized to receive CXCL12 neutraligands chalcone 4 or LIT-927 (100 mg/kg/day), the C-X-C motif chemokine receptor 4 (CXCR4) antagonist AMD3100 (5 mg/kg/day), or vehicle, for 2 or 3 weeks, respectively. At the end of these treatment periods, echocardiographic and haemodynamic measurements were performed and tissue samples were collected for protein expression and histological analysis. Daily treatment of MCT-injected or SuHx rats with established PH with chalcone 4 or LIT-927 partially reversed established PH, reducing total pulmonary vascular resistance, and remodelling of pulmonary arterioles. Consistent with these observations, we found that neutralization of CXCL12 attenuates right ventricular hypertrophy, pulmonary vascular remodelling, and decreases pulmonary artery smooth muscle cell (PA-SMC) proliferation in lungs of MCT-injected rats and SuHx rats. Importantly, CXCL12 neutralization with either chalcone 4 or LIT-927 inhibited the migration of PA-SMCs and pericytes in vitro with a better efficacy than AMD3100. Finally, we found that CXCL12 neutralization decreases vascular pericyte coverage and macrophage infiltration in lungs of both MCT-injected and SuHx rats.

Conclusion
We report here a greater beneficial effect of CXCL12 neutralization vs. the conventional CXCR4 blockade with AMD3100 in the MCT and SuHx rat models of severe PH, supporting a role for CXCL12 in the progression of vascular complications in PH and opening to new therapeutic options.
Silvicultural implications from analyzing light induced height growth development of eight North American juvenile tree species in mixed-conifer forests
Authors: Annighöfer Peter , Seidel Dominik , Ammer Christian , Stephens Scott L , York Robert A 
Published: June 2019

Abstract
Modern silviculture is based on simulating natural disturbance regimes on the one side and reducing their impact on the other side. Disturbances modify light regimes of forests along complex spatial patterns, and species participating in the ecosystem tend to have unique adaptations to the multitude of light conditions found in forests. We studied the height growth reaction of saplings from eight native North American tree species to different light availabilities in a Sierra Nevada mixed conifer forest. Large height growth differences occurred between species. Height growth increased for most species with increasing light availability. However, black oak but also incense cedar and tanoak reached an optimal value or saturation point of light availability at intermediate light levels, above which their growth stayed the same or slightly declined on average. A variety of stand conditions, representing the range from early to late successional stages, are beneficial to maintain tree species diversity across stands. Such a gradient of conditions can be achieved by diversifying silvicultural regimes and using regeneration approaches that mimic a range of disturbance intensities. The results add to knowledge on the species’ ecology by specifying their height growth in dependence of a quantified light environment. The quantification of the light environment can directly be linked to % canopy cover and a range of regeneration methods, respectively. With this, the results may help achieve a more precise and target-oriented management of Sierra Nevada mixed conifer forests.
Exhibiting Work in Germany—From Industrial Labour to (Industrial) Culture*
Authors: Kritter Sabine 
Published: June 2019

Abstract
History museums in old industrial regions are important agents in the current debate on how we perceive work in our society. One of their key issues is how work built the region and how it changed in the context of deindustrialization. The article explores the depictions of work in the Ruhr Museum, which is the central regional history museum of the foremost region of heavy industry in Germany. It shows that with few exceptions the representations of the past in this museum include only images of standardized male industrial work, mainly in the coal and steel industries. Furthermore, it demonstrates that in the sections of the museum dedicated to the present, work has disappeared almost entirely from the representations, to be replaced with representations of culture, including industrial heritage, and lifestyles. In light of these findings the article argues that this way of presenting (and not presenting) work emphasizes the break between the past and the present. It homogenizes the historical narrative of work while making current work forms invisible and downplaying the continuing importance of the world of work. Instead, the museum tells a story of loss that requires compensation by culture.
Concurrent Western Australian telephone surveys highlight the advantages of sampling from a registry of recreational fishers
Authors: Taylor S M , Ryan K L 
Published: June 2019

Abstract
Surveys play an integral role in providing reliable recreational fishing information for the sustainable management of fisheries resources. The selection of a representative sample is an important and often challenging part of designing surveys. Here we compare concurrent telephone surveys conducted in 2016 and 2017 using a telephone directory (White Pages®, WP) and a Recreational Boat Fishing Licence (RBFL) as sampling frames. Information on boat- and shore-based recreational fishing was collected from both surveys. The response rates for the RBFL surveys were more than double those from the WP surveys. The RBFL surveys identified more respondents who had recreationally fished in the previous 12 months compared to the WP surveys. Fishing activity differed markedly between fishers in the WP and RBFL surveys; however, characteristics were consistent for boat-based fishers sampled from the two types of surveys. The high levels of sample loss observed in the WP surveys suggest that other general population lists may provide greater coverage of shore-based fishers. We recommend testing the demographic and behavioural characteristics of recreational fishers sampled in offsite surveys against benchmark data to assist in assessing whether or not the characteristics of the sample are representative of the target population.
Bivalent Human Papillomavirus (HPV) Vaccine Effectiveness Correlates With Phylogenetic Distance From HPV Vaccine Types 16 and 18
Authors: Bogaards Johannes A , van der Weele Pascal , Woestenberg Petra J , van Benthem Birgit H B , King Audrey J 
Published: June 2019

Abstract
To substantiate cross-protection reported across AS04-adjuvanted bivalent human papillomavirus (HPV) vaccine (2vHPV) studies, we reevaluated vaccine effectiveness against type-specific HPV positivity as a function of phylogenetic distance to vaccine target types HPV-16 and -18. We provide evidence of sustained cross-protection up to 8 years postvaccination in a high-risk population in the Netherlands. Moreover, our findings suggest that genomic distance better explains cross-protection than distance measures based on capsid antigens only. Taken together, 2vHPV is predicted to provide partial cross-protection against HPV-31, -33, -35, -45, -52, and possibly -58, that is, acknowledged oncogenic types with close phylogenetic relationships to HPV-16 or -18.
Leisure-Time Music Groups and Their Localities: Exploring the Commercial, Educational, and Reciprocal Relationships of Amateur Music-Making
Authors: Pitts Stephanie E 
Published: June 2019

Abstract
Membership of an amateur musical group is typically understood in relation to members’ experiences: the research undertaken for this article poses new questions about the ways in which those groups connect with other people, organizations, and venues in their locality to build a broader sense of culturally engaged citizenship. The networks built by amateur musicians are often rendered invisible in the research literature and in policy-making in ways that limit the understanding and recognition of their contribution to contemporary society. Through a collaboration with the national network Making Music, the commercial, educational, and reciprocal relationships of a particular variety of amateur music-making are revealed. This article presents a new framework for understanding organized amateur musical engagement as part of a cultural ecology, and considers the implications for recognizing and supporting leisure-time music groups.
CRISPR/Cas9-targeted removal of unwanted sequences from small-RNA sequencing libraries
Authors: Hardigan Andrew A , Roberts Brian S , Moore Dianna E , Ramaker Ryne C , Jones Angela L , Myers Richard M 
Published: June 2019

Abstract
In small RNA (smRNA) sequencing studies, highly abundant molecules such as adapter dimer products and tissue-specific microRNAs (miRNAs) inhibit accurate quantification of lowly expressed species. We previously developed a method to selectively deplete highly abundant miRNAs. However, this method does not deplete adapter dimer ligation products that, unless removed by gel-separation, comprise most of the library. Here, we have adapted and modified recently described methods for CRISPR/Cas9–based Depletion of Abundant Species by Hybridization (‘DASH’) to smRNA-seq, which we have termed miRNA and Adapter Dimer—DASH (MAD-DASH). In MAD-DASH, Cas9 is complexed with single guide RNAs (sgRNAs) targeting adapter dimer ligation products, alongside highly expressed tissue-specific smRNAs, for cleavage in vitro. This process dramatically reduces adapter dimer and targeted smRNA sequences, can be multiplexed, shows minimal off-target effects, improves the quantification of lowly expressed miRNAs from human plasma and tissue derived RNA, and obviates the need for gel-separation, greatly increasing sample throughput. Additionally, the method is fully customizable to other smRNA-seq preparation methods. Like depletion of ribosomal RNA for mRNA-seq and mitochondrial DNA for ATAC-seq, our method allows for greater proportional read-depth of non-targeted sequences.
MTR-Viewer: identifying regions within genes under purifying selection
Authors: Silk Michael , Petrovski Slavé , Ascher David B 
Published: June 2019

Abstract
Advances in genomic sequencing have enormous potential to revolutionize personalized medicine, however distinguishing disease-causing from benign variants remains a challenge. The increasing number of human genome and exome sequences available has revealed areas where unfavourable variation is removed through purifying selection. Here, we present the MTR-Viewer, a web-server enabling easy visualization at the gene or variant level of the Missense Tolerance Ratio (MTR), a measure of regional intolerance to missense variation calculated using variation from 240 000 exome and genome sequences. The MTR-Viewer enables exploration of MTR calculations, using different sliding windows, for over 18 000 human protein-coding genes and 85 000 alternative transcripts. Users can also view MTR scores calculated for specific ethnicities, to enable easy exploration of regions that may be under different selective pressure. The spatial distribution of population and known disease variants is also displayed on the protein's domain structure. Intolerant regions were found to be highly enriched for ClinVar pathogenic and COSMIC somatic missense variants (Mann–Whitney U test P < 2.2 × 10−16). As the MTR is not biased by known domains and protein features, it can highlight functionally important regions within genes overlooked or inaccessible by traditional methods. MTR-Viewer is freely available via a user friendly web-server at http://biosig.unimelb.edu.au/mtr-viewer/.
Crystal structures of a natural DNA polymerase that functions as an XNA reverse transcriptase
Authors: Jackson Lynnette N , Chim Nicholas , Shi Changhua , Chaput John C 
Published: June 2019

Abstract
Replicative DNA polymerases are highly efficient enzymes that maintain stringent geometric control over shape and orientation of the template and incoming nucleoside triphosphate. In a surprising twist to this paradigm, a naturally occurring bacterial DNA polymerase I member isolated from Geobacillus stearothermophilus (Bst) exhibits an innate ability to reverse transcribe RNA and other synthetic congeners (XNAs) into DNA. This observation raises the interesting question of how a replicative DNA polymerase is able to recognize templates of diverse chemical composition. Here, we present crystal structures of natural Bst DNA polymerase that capture the post-translocated product of DNA synthesis on templates composed entirely of 2′-deoxy-2′-fluoro-β-d-arabino nucleic acid (FANA) and α-l-threofuranosyl nucleic acid (TNA). Analysis of the enzyme active site reveals the importance of structural plasticity as a possible mechanism for XNA-dependent DNA synthesis and provides insights into the construction of variants with improved activity.
Study of conformational transitions of i-motif DNA using time-resolved fluorescence and multivariate analysis methods
Authors: Benabou Sanae , Ruckebusch Cyril , Sliwa Michel , Aviñó Anna , Eritja Ramon , Gargallo Raimundo , de Juan Anna 
Published: June 2019

Abstract
Recently, the presence of i-motif structures at C-rich sequences in human cells and their regulatory functions have been demonstrated. Despite numerous steady-state studies on i-motif at neutral and slightly acidic pH, the number and nature of conformation of this biological structure are still controversial. In this work, the fluorescence lifetime of labelled molecular beacon i-motif-forming DNA sequences at different pH values is studied. The influence of the nature of bases at the lateral loops and the presence of a Watson–Crick-stabilized hairpin are studied by means of time-correlated single-photon counting technique. This allows characterizing the existence of several conformers for which the fluorophore has lifetimes ranging from picosecond to nanosecond. The information on the existence of different i-motif structures at different pH values has been obtained by the combination of classical global decay fitting of fluorescence traces, which provides lifetimes associated with the events defined by the decay of each sequence and multivariate analysis, such as principal component analysis or multivariate curve resolution based on alternating least squares. Multivariate analysis, which is seldom used for this kind of data, was crucial to explore similarities and differences of behaviour amongst the different DNA sequences and to model the presence and identity of the conformations involved in the pH range of interest. The results point that, for i-motif, the intrachain contact formation and its dissociation show lifetimes ten times faster than for the open form of DNA sequences. They also highlight that the presence of more than one i-motif species for certain DNA sequences according to the length of the sequence and the composition of the bases in the lateral loop.
Flights to Safety
Authors: Baele Lieven , Bekaert Geert , Inghelbrecht Koen , Wei Min 
Published: June 2019

AbstractWe identify flight-to-safety (FTS) days for twenty-three countries using only stock and bond returns and a model averaging approach. FTS days comprise less than 2% of the sample and are associated with a 2.7% average bond-equity return differential and significant flows out of equity funds and into government bond and money market funds. FTS represents flights to both quality and liquidity in international equity markets, but mainly a flight to quality in the U.S. corporate bond market. Emerging markets, endowment funds, and hedge funds perform poorly during FTS, whereas hedge funds appear to vary their systematic exposures prior to an FTS.Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
THE DETERMINATION OF NEUTRON FLUENCE TO ABSORBED DOSE CONVERSION COEFFICIENTS AND RELATIVE BIOLOGICAL EFFECT BASED ON MICRODOSIMETRY MEASUREMENTS
Authors: Zhang Weihua , Li Chunjuan , Zou Yisheng , Liu Yina , Luo Hailong 
Published: June 2019

Abstract
A tissue-equivalent proportional counter (TEPC) is a reference detector to measure microdosimetric quantities. A conventional spherical TEPC and a novel TEPC based on a ceramic thick gas electron multiplier (THGEM) foil were developed to carry out microdosimetric measurements of lineal energy spectra in monoenergetic and 252Cf/241Am-Be neutron radiation fields, and the absorbed dose values had been derived. In order to go further in radiobiology and therapy, the fluence to absorbed dose conversion coefficients in neutron fields were also determined. According to the dose distribution in lineal energy, the neutron relative biological effect (RBE) values were also calculated using an empirical procedure applying biological weighting functions.
Total Health Care Expenditure in Patients With a Herniated Lumbar Disk That Ultimately Require Surgery
Authors: Davison Mark A. , Lilly Daniel T. , Moreno Jessica , Bagley Carlos , Adogwa Owoicho 
Published: June 2019

Study Design:
A retrospective cohort study.

Objective:
To compare the cost of maximum nonoperative therapy (MNT) in patients diagnosed with a herniated lumbar disk undergoing primary (1–3 mo) versus prolonged (4–6 mo) conservative management before microdiscectomy.

Summary of Background Data:
Patients diagnosed with a herniated lumbar disk often attempt a 3-month trial of conservative management before microdiscectomy. A paucity of data exists characterizing the cost of a subsequent round of nonoperative therapies in patients who fail their initial trial, rather than undergo surgery.

Methods:
Clinical records from patients diagnosed with a herniated lumbar disk undergoing index microdiscectomy surgery from 2007 to 2017 were gathered from a large insurance database. Records were searchable by International Classification of Diseases diagnosis/procedure codes, Current Procedural Terminology codes, and generic drug codes. Two cohorts were established: patients undergoing primary (1–3 mo) versus prolonged (4–6 mo) courses of conservative management. Nonoperative therapy utilization was documented from initial herniation diagnosis to microdiscectomy surgery. “Utilization” encompassed cost billed to patients, prescriptions written, and quantity of units dispensed.

Results:
The 3-month MNT cohort included 4587 patients and the 6-month MNT cohort contained 1506 patients. A greater percentage of 6-month cohort patients utilized opioids (P=0.0052), muscle relaxants (P=0.0061), and lumbar steroid injections (P<0.0001). When considering the average amount spent on conservative management, 6-month patients ($1824/patient) spent 1.55 times more than 3-month patients ($1178/patient). The 6-month:3-month average spending ratio was <2.0 for all of the nonoperative therapies except nonsteroidal anti-inflammatory drugs (2.66) and epidural steroid injections (2.25). When normalized by the number of opioid users, the number of opioid medications dispensed was proportionally less in 3-month patients compared with 6-month patients, with a 6-month:3-month ratio of 1.52.

Conclusions:
The costs associated with a subsequent course of nonoperative therapies for symptomatic lumbar disk herniation seem to be slightly less than that of the primary trial. Assuming a minimal clinical benefit after the initial trial of nonsurgical therapies, the incremental cost-effectiveness ratio of a subsequent trial versus surgery may be unfavorable. Future studies identifying patients likely to benefit from surgery earlier in the treatment course is required.

Level of Evidence:
Level III.