bluuebunny/crossref_metadata_2025_split huggingface dataset:
From genetic gain to economic gain: simulated growth and financial performance of genetically improved Pinus sylvestris and Pinus pinaster planted stands in France, Finland and Sweden
Authors: Serrano-León Hernán , Ahtikoski Anssi , Sonesson Johan , Fady Bruno , Lindner Marcus , Meredieu Céline , Raffin Annie , Perret Sandrine , Perot Thomas , Orazio Christophe 
Published: January 2021

Abstract
The translation of genetic gains into economic gains is important for evaluating the impact of using genetically improved forest reproductive material (FRM) in the forest sector. However, few studies based on European forests have been published to date. Here, we analyse the stand-level wood production and financial performance of planting genetically improved FRM in even-aged planted forests focusing on four European case studies with advanced breeding programme material and different management contexts: Scots pine (Pinus sylvestris L.) in southern Finland, central Sweden and central France, and maritime pine (Pinus pinaster Ait.) in southwestern France. The growth of improved stands was simulated using species-specific growth models by incorporating two levels of expected genetic gains (present and next generations of seed orchards, varying from 7 to 40 per cent depending on the breeding programme) into the estimated mean annual volume increment over a rotation (m3 ha−1 yr−1). For each level of genetic gain, we tested the plantation of improved FRM managed with two silvicultural scenarios (maintaining the standard baseline rotation and thinning regime vs shorter rotation through the earlier achievement of the recommended felling criteria) in comparison with the plantation of the reference unimproved material (absence of genetic gain) managed according to the standard silvicultural regime. The use of improved FRM resulted in a larger financial performance in terms of soil expectation value (SEV € ha−1, discount rate 3 per cent) than planting unimproved reference material in all case studies and silvicultural scenarios for different wood price contexts (SEV gain from +20 to +190 per cent depending on the genetic and silvicultural context). The challenges associated with the economic assessment of realized gains from genetically improved FRM are discussed. We argue that silvicultural guidelines should be adapted to the use of improved FRM in order to gain better financial performance and flexible silvicultural response of planted forests to future environmental and socio-economic changes.
The impact of the reference pricing policy in China on drug procurement and cost
Authors: Jiang Bin , Zhou Ruo Jing , Feng Xing Lin 
Published: January 2021

Abstract
High drug costs are putting pressure on healthcare budgets and posing an obstacle for China to achieve universal health coverage. Policies such as the direct price ceiling and the Essential Medicines Program—with the Zero Markup Drug Policy (ZMDP) one key component—have been implemented, but out with limited evidence of success. As a benchmark of China’s recent health reform, Sanming city initiated the ZMDP in January 2013; and further piloted the first reference pricing (RP) policy in China in September 2014, with the intention to disincentivize the use of costly original drugs. In this study, we used hospital-based drug procurement data of 14 drug substances that were subjected to RP, from four hospitals in Sanming and a neighbouring city Longyan, between 2012 and 2016. Adopting the difference-in-difference (DID) approach, we evaluated the impacts of RP together with the ZMDP. On the one hand, we found that the ZMDP had no impact on drugs’ procurement prices, volumes and costs. While on the other hand, we found that the introduction of RP was not associated with changes in unit prices for the 14 drugs in Sanming. However, the RP pilot was associated with a 25.9% (95% confidence interval (CI), 12.9–37.0%) decrease in monthly drug procurement volumes and a 47.7% (95% CI, 33.7–58.7%) decrease in the total drug costs. In particular, it reduced the procurement volumes of original drugs by 56.8% (95% CI, 47.0–64.7%). Subgroup analyses by hospital level and therapeutic class found similar results. We draw lessons for the Chinese government to experiment with RP on a larger scale, considering the development and effective regulation of the generic market. This is a first report on the effects of RP in China, Asia and middle-income countries.
Genome-wide identification of cis DNA methylation quantitative trait loci in three Southeast Asian Populations
Authors: Kassam Irfahan , Tan Sili , Gan Fei Fei , Saw Woei-Yuh , Tan Linda Wei-Lin , Moong Don Kyin Nwe , Soong Richie , Teo Yik-Ying , Loh Marie 
Published: January 2021

Abstract
DNA methylation (DNAm) is an epigenetic modification that acts to regulate gene transcription, is essential for cellular processes and plays an important role in complex traits and disease. Variation in DNAm levels is influenced by both genetic and environmental factors. Several studies have examined the extent to which common genetic variation influences DNAm (i.e. mQTLs), however, an improved understanding of mQTLs across diverse human populations is needed to increase their utility in integrative genomic studies in order to further our understanding of complex trait and disease biology. Here, we systematically examine cis-mQTLs in three Southeast Asian populations in the Singapore Integrative Omics (iOmics) Study, comprised of Chinese (n = 93), Indians (n = 83) and Malays (n = 78). A total of 24 851 cis-mQTL probes were associated with at least one SNP in meta- and ethnicity-specific analyses at a stringent significance level. These cis-mQTL probes show significant differences in local SNP heritability between the ethnicities, enrichment in functionally relevant regions using data from the Roadmap Epigenomics Mapping Consortium and are associated with nearby genes and complex traits due to pleiotropy. Importantly, DNAm prediction performance and the replication of cis-mQTLs both within iOmics and between two independent mQTL studies in European and Bangladeshi individuals is best when the genetic distance between the ethnicities is small, with differences in cis-mQTLs likely due to differences in allele frequency and linkage disequilibrium. This study highlights the importance of, and opportunities from, extending investigation of the genetic control of DNAm to Southeast Asian populations.
The causal effects of serum lipids and apolipoproteins on kidney function: multivariable and bidirectional Mendelian-randomization analyses
Authors: Rasheed Humaira , Zheng Jie , Rees Jessica , Sanderson Eleanor , Thomas Laurent , Richardson Tom G , Fang Si , Bekkevold Ole-Jørgen , Stovner Endre Bakken , Gabrielsen Maiken Elvestad , Skogholt Anne Heidi , Romundstad Solfrid , Brumpton Ben , Hallan Stein , Willer Cristen , Burgess Stephen , Hveem Kristian , Davey Smith George , Gaunt Tom R , Åsvold Bjørn Olav 
Published: January 2021

Abstract

Background
The causal nature of the observed associations between serum lipids and apolipoproteins and kidney function are unclear.

Methods
Using two-sample and multivariable Mendelian randomization (MR), we examined the causal effects of serum lipids and apolipoproteins on kidney function, indicated by the glomerular-filtration rate estimated using creatinine (eGFRcrea) or cystatin C (eGFRcys) and the urinary albumin-to-creatinine ratio (UACR). We obtained lipid- and apolipoprotein-associated genetic variants from the Global Lipids Genetics Consortium (n = 331 368) and UK Biobank (n = 441 016), respectively, and kidney-function markers from the Trøndelag Health Study (HUNT; n = 69 736) and UK Biobank (n = 464 207). The reverse causal direction was examined using variants associated with kidney-function markers selected from recent genome-wide association studies.

Results
There were no strong associations between genetically predicted lipid and apolipoprotein levels with kidney-function markers. Some, but inconsistent, evidence suggested a weak association of higher genetically predicted atherogenic lipid levels [indicated by low-density lipoprotein cholesterol (LDL-C), triglycerides and apolipoprotein B] with increased eGFR and UACR. For high-density lipoprotein cholesterol (HDL-C), results differed between eGFRcrea and eGFRcys, but neither analysis suggested substantial effects. We found no clear evidence of a reverse causal effect of eGFR on lipid or apolipoprotein traits, but higher UACR was associated with higher LDL-C, triglyceride and apolipoprotein B levels.

Conclusion
Our MR estimates suggest that serum lipid and apolipoprotein levels do not cause substantial changes in kidney function. A possible weak effect of higher atherogenic lipids on increased eGFR and UACR warrants further investigation. Processes leading to higher UACR may lead to more atherogenic lipid levels.
Measuring the impact of delayed access to elective cholecystectomy through patient’s cost-utility: an observational cohort study
Authors: Karimuddin Ahmer , Albanese Carmela Melina , Crump Trafford , Liu Guiping , Sutherland Jason M 
Published: January 2021

Abstract

Background
Deferral of surgeries due to COVID-19 has negatively affected access to elective surgery and may have deleterious consequences for patient’s health. Delays in access to elective surgery are not uniform in their impact on patients with different attributes. The objective of this study is to measure the change in patient’s cost utility due to delayed elective cholecystectomy.

Methods
This study is based on retrospective analysis of a longitudinal sample of participants who have had elective cholecystectomy and completed the EQ-5D(3L) measuring health status preoperatively and postoperatively. Emergent cases were excluded. Patients younger than 19 years of age, unable to communicate in English or residing in a long-term care facility were ineligible. Quality-adjusted life years attributable to cholecystectomy were calculated by comparing health state utility values between the pre- and postoperative time points. The loss in quality-adjusted life years due to delayed access was calculated under four assumed scenarios regarding the length of the delay. The mean cost per quality-adjusted life years are shown for the overall sample and by sex and age categories.

Results
Among the 646 eligible patients, 30.1% of participants (N = 195) completed their preoperative and postoperative EQ-5D(3L). A delay of 12 months resulted in a mean loss of 6.4%, or 0.117, of the quality-adjusted life years expected without the delay. Among patients older than 70 years of age, a 12-month delay in their surgery corresponded with a 25.1% increase in the cost per quality-adjusted life years, from $10 758 to $13 463.

Conclusions
There is a need to focus on minimizing loss of quality of life for patients affected by delayed surgeries. Faced with equal delayed access to elective surgery, triage may need to prioritize older patients to maximize their health over their remaining life years.
Oxidative stress and inflammatory response of ghrelin on myocardial and aortic tissues in insulin-resistant rats
Authors: Coskun Zeynep Mine , Beydogan Alisa Bahar , Yanar Karolin , Atukeren Pınar , Bolkent Sema 
Published: January 2021

Abstract

Objectives
This study was designed to clarify the effects of ghrelin on myocardial and aortic tissues in insulin-resistant rats.

Methods
Sprague-Dawley rats were divided into the following groups: control (Group 1), insulin resistance (IR, Group 2), ghrelin (Group 3) and IR+Ghrelin (Group 4) groups. Levels of HOMA-IR, fibronectin, hydroxyproline, collagen-1, collagen-3, matrix metalloproteinase-3, and matrix metalloproteinase-9, and tissue inhibitor of metalloproteinase-1, and oxidative stress parameters as protein carbonyl (PCO), lipid hydroperoxides (LHPs), malondialdehyde, total thiol were determined in myocardial tissue. Expressions of IL-6, NF-κB and TNF-α mRNAs were detected by RT-qPCR. Aorta tissue was stained Masson trichrome.

Key findings
The HOMA-IR level decreased in the IR+Ghrelin group compared with the IR group (P &lt; 0.001). The PCO and LHP concentrations were higher in the IR group compared with control rats (P &lt; 0.05). The PCO level was reduced by ghrelin in the IR+Ghrelin group compared with the IR group (P &lt; 0.001). Ghrelin treatment reduced the mRNA expression levels of IL-6, NF-κB and TNF-α in the IR+Ghrelin group compared with the IR group (P &lt; 0.001). There was no difference among the groups in the histology of aortic tissue.

Conclusions
Ghrelin, a regulator of appetite and energy homeostasis, may be effective in regulating oxidative stress and the inflammatory response when impaired by IR. Therefore, ghrelin may reduce the risks of myocardial dysfunction in IR.
An atypical presentation of a bilateral nasolabial cyst: a case report
Authors: Bijou Walid , Laababsi Rabii , Mennouni Mohamed Amine , Oukessou Youssef , Rouadi Sami , Abada Reda , Roubal Mohamed , Mahtar Mohamed 
Published: January 2021

Abstract
The nasolabial cyst is a rare, non-odontogenic, soft tissue cyst that develops submucosally in the anterior nasal floor. This cyst accounts for 0.7% of all non-odontogenic cysts. Bilateral nasolabial cyst represents only 10% of the cases. This cyst originates from the remnants of embryonic nasolacrimal duct tissue. Generally, patients present with swelling and facial deformity and rarely local pain. The definite diagnosis should be based on clinical, radiological and above all histopathologic findings. The treatment is enucleation of the cystic tissue. Following is a case report of a bilateral nasolabial cyst in a 40-year-old woman who presented with a chronic nasal obstruction.
Kinematics and multiband period–luminosity–metallicity relation of RR Lyrae stars via statistical parallax
Authors: Muhie T D , Dambis A K , Berdnikov L N , Kniazev A Y , Grebel E K 
Published: January 2021

ABSTRACT
This paper presents results from photometric and statistical-parallax analysis of a sample of 850 field RR Lyrae (RRL) variables. The photometric and spectroscopic data for our sample of RRLs are obtained from (1) our new spectroscopic observations (for 448 RRLs) carried out with the Southern African Large Telescope; (2) our photometric observations using the 1.0-m telescope of the South African Astronomical Observatory, and (3) literature. These are combined with accurate proper motion data from the second data release of the Gaia mission (DR2). This study primarily determines the velocity distribution of solar neighbourhood RRLs, and it also calibrates the zero-points of the RRLs’ visual V-band luminosity–metallicity (LZ or MV–[Fe/H]) relation and their period–luminosity–metallicity (PLZ) relations in the Wide-field Infrared Survey ExplorerW1 and Two-Micron All-Sky Survey Ks bands. We find the bulk velocity of the halo RRLs relative to the Sun to be (U0, V0, W0)Halo =(− 16 ± 7, −219 ± 7, −6 ± 5) km s−1 in the direction of Galactic centre, Galactic rotation, and North Galactic pole, respectively, with velocity-dispersion ellipsoids (σVR, σVϕ, σVθ)Halo = (153 ± 7, 106 ± 4, 101 ± 4) km s−1. The corresponding parameters for the disc component are found to be (U0, V0, W0)Disc = (− 19 ± 5, −46 ± 5, −14 ± 3) km s−1 and (σVR, σVϕ, σVθ)Disc =(49 ± 4, 38 ± 4, 25 ± 3) km s−1. The calibrated PLZ in W1-, Ks-, and V-band LZ relations are $\langle \, M_{W1}\rangle =$ $-0.824+0.124[\mathrm{ Fe/H}]-2.381\log \, P_F$, 〈MKs〉 = $-0.804+0.101[\mathrm{ Fe/H}]-2.33\log \, P_F$, and $\langle \, M_V\rangle =1.041+0.232[\mathrm{ Fe/H}]$, respectively. The calibrated PLZ and LZ relations are used to estimate the Galactic Centre distance and the distance modulus of the Large Magellanic Cloud (LMC), which are found to be 7.99 ± 0.49 kpc and 18.46 ± 0.09  mag, respectively. All our results are in excellent agreement with available literature based on statistical-parallax analysis, but are considerably more accurate and precise. Moreover, the zero-points of our calibrated PLZ and LZ relations are quite consistent with current results found by other techniques and yield an LMC distance modulus that is within 0.04 mag of the current most precise estimate.
Parameter estimation of a two-component neutron star model with spin wandering
Authors: Meyers Patrick M , Melatos Andrew , O’Neill Nicholas J 
Published: January 2021

ABSTRACT
It is an open challenge to estimate systematically the physical parameters of neutron star interiors from pulsar timing data while separating spin wandering intrinsic to the pulsar (achromatic timing noise) from measurement noise and chromatic timing noise (due to propagation effects). In this paper, we formulate the classic two-component, crust-superfluid model of neutron star interiors as a noise-driven, linear dynamical system and use a state-space-based expectation–maximization method to estimate the system parameters using gravitational-wave and electromagnetic timing data. Monte Carlo simulations show that we can accurately estimate all six parameters of the two-component model provided that electromagnetic measurements of the crust angular velocity and gravitational-wave measurements of the core angular velocity are both available. When only electromagnetic data are available, we can recover the overall relaxation time-scale, the ensemble-averaged spin-down rate, and the strength of the white-noise torque on the crust. However, the estimates of the secular torques on the two components and white-noise torque on the superfluid are biased significantly.
The morphology of average solar flare time profiles from observations of the Sun’s lower atmosphere
Authors: Kashapova Larisa K , Broomhall Anne-Marie , Larionova Alena I , Kupriyanova Elena G , Motyk Ilya D 
Published: January 2021

ABSTRACT
We study the decay phase of solar flares in several spectral bands using a method based on that successfully applied to white light flares observed on an M4 dwarf. We selected and processed 102 events detected in the Sun-as-a-star flux obtained with SDO/AIA images in the 1600 and 304 Å channels and 54 events detected in the 1700 Å channel. The main criterion for the selection of time profiles was a slow, continuous flux decay without significant new bursts. The obtained averaged time profiles were fitted with analytical templates, using different time intervals, that consisted of a combination of two independent exponents or a broken power law. The average flare profile observed in the 1700 Å channel decayed more slowly than the average flare profile observed on the M4 dwarf. As the 1700 Å emission is associated with a similar temperature to that usually ascribed to M dwarf flares, this implies that the M dwarf flare emission comes from a more dense layer than solar flare emission in the 1700 Å band. The cooling processes in solar flares were best described by the two exponents model, fitted over the intervals t1 = [0, 0.5]t1/2 and t2 = [3, 10]t1/2, where t1/2 is time taken for the profile to decay to half the maximum value. The broken power-law model provided a good fit to the first decay phase, as it was able to account for the impact of chromospheric plasma evaporation, but it did not successfully fit the second decay phase.
Hamster PIWI proteins bind to piRNAs with stage-specific size variations during oocyte maturation
Authors: Ishino Kyoko , Hasuwa Hidetoshi , Yoshimura Jun , Iwasaki Yuka W , Nishihara Hidenori , Seki Naomi M , Hirano Takamasa , Tsuchiya Marie , Ishizaki Hinako , Masuda Harumi , Kuramoto Tae , Saito Kuniaki , Sakakibara Yasubumi , Toyoda Atsushi , Itoh Takehiko , Siomi Mikiko C , Morishita Shinichi , Siomi Haruhiko 
Published: January 2021

Abstract
In animal gonads, transposable elements are actively repressed to preserve genome integrity through the PIWI-interacting RNA (piRNA) pathway. In mice, piRNAs are abundantly expressed in male germ cells, and form effector complexes with three distinct PIWIs. The depletion of individual Piwi genes causes male-specific sterility with no discernible phenotype in female mice. Unlike mice, most other mammals have four PIWI genes, some of which are expressed in the ovary. Here, purification of PIWI complexes from oocytes of the golden hamster revealed that the size of the PIWIL1-associated piRNAs changed during oocyte maturation. In contrast, PIWIL3, an ovary-specific PIWI in most mammals, associates with short piRNAs only in metaphase II oocytes, which coincides with intense phosphorylation of the protein. An improved high-quality genome assembly and annotation revealed that PIWIL1- and PIWIL3-associated piRNAs appear to share the 5′-ends of common piRNA precursors and are mostly derived from unannotated sequences with a diminished contribution from TE-derived sequences, most of which correspond to endogenous retroviruses. Our findings show the complex and dynamic nature of biogenesis of piRNAs in hamster oocytes, and together with the new genome sequence generated, serve as the foundation for developing useful models to study the piRNA pathway in mammalian oocytes.
In silicoanalysis of DNA re-replication across a complete genome reveals cell-to-cell heterogeneity and genome plasticity
Authors: Rapsomaniki Maria Anna , Maxouri Stella , Nathanailidou Patroula , Garrastacho Manuel Ramirez , Giakoumakis Nickolaos Nikiforos , Taraviras Stavros , Lygeros John , Lygerou Zoi 
Published: January 2021

AbstractDNA replication is a complex and remarkably robust process: despite its inherent uncertainty, manifested through stochastic replication timing at a single-cell level, multiple control mechanisms ensure its accurate and timely completion across a population. Disruptions in these mechanisms lead to DNA re-replication, closely connected to genomic instability and oncogenesis. Here, we present a stochastic hybrid model of DNA re-replication that accurately portrays the interplay between discrete dynamics, continuous dynamics and uncertainty. Using experimental data on the fission yeast genome, model simulations show how different regions respond to re-replication and permit insight into the key mechanisms affecting re-replication dynamics. Simulated and experimental population-level profiles exhibit a good correlation along the genome, robust to model parameters, validating our approach. At a single-cell level, copy numbers of individual loci are affected by intrinsic properties of each locus, in cis effects from adjoining loci and in trans effects from distant loci. In silico analysis and single-cell imaging reveal that cell-to-cell heterogeneity is inherent in re-replication and can lead to genome plasticity and a plethora of genotypic variations.