bluuebunny/crossref_metadata_2025 huggingface dataset:
Integration of solar plants into energy systems in apartment residential buildings
Authors: Chudinov D M , Kolosov A I , Shchukina T V , Zverkov A P
Published: January 2021

Non-traditional renewable energy resources (solar radiation, wind energy, etc.), alternative thermal and electric generators have incontestable positive qualities in comparison with fossil fuel (natural gas, coal, fuel oil), classical systems: relative environmental friendliness, vast total reserves, low operational costs, reliability, ease of management. The scale of their implementation in the Central Black Earth Region can be limited by high initial capital investments, the value of the energy resource, and low awareness of the population. The article presents the results of modeling solar plants functioning during their integration into traditional energy systems of apartment residential buildings. In the article we demonstrate technical and economic indicators of projected and modernized engineering heating services in the city of Voronezh. The technically viable period of use is spring-summer-autumn. Economic indicators put solar systems into the experimental category.
Widely linewidth tunable lasers through cascaded four-wave mixing based phase modulation amplification
Authors: Vikram B S , Prakash Roopa , Supradeepa V R
Published: January 2021

We demonstrate wide-range linewidth-tuning of a narrow-linewidth laser in the C-band up to 40 GHz through cascaded four-wave mixing (CFWM) based phase modulation amplification. Stimulated Brillouin scattering (SBS) severely limits the power scaling of narrow-linewidth lasers. Continuous tuning of the linewidth or temporal coherence of the laser to mitigate SBS is conventionally achieved through external phase modulation with white noise or other RF waveforms. However, the range of linewidth tuning is limited by the bandwidth and power of the electro-optic modulator. We overcome this through the use of FWM as a linewidth multiplier. To achieve linewidth multiplication, two tunable pumps line-broadened in electro-optic phase modulators with white noise are power scaled and propagated through highly nonlinear fiber. We achieve linewidth tuning up to ∼4 GHz using control of the noise waveform, while CFWM achieves a 10× multiplication of linewidth up to 40 GHz at a fixed wavelength. Linewidth tuning can be further scaled through power scaling or cascading multiple nonlinear stages. The proposed technique would be useful in nonlinearity control in narrow-linewidth laser amplifiers, high-resolution optical imaging, LIDAR, and infrared spectroscopy.
Femtosecond laser fabrication of nanograting-based distributed fiber sensors for extreme environmental applications
Authors: Wang Mohan , Zhao Kehao , Wu Jingyu , Li Yuqi , Yang Yang , Huang Sheng , Zhao Jieru , Tweedle Thomas , Carpenter David , Zheng Guiqiu , Yu Qingxu , Chen Kevin P
Published: January 2021

The femtosecond laser has emerged as a powerful tool for micro- and nanoscale device fabrication. Through nonlinear ionization processes, nanometer-sized material modifications can be inscribed in transparent materials for device fabrication. This paper describes femtosecond precision inscription of nanograting in silica fiber cores to form both distributed and point fiber sensors for sensing applications in extreme environmental conditions. Through the use of scanning electron microscope imaging and laser processing optimization, high-temperature stable, Type II femtosecond laser modifications were continuously inscribed, point by point, with only an insertion loss at 1 dB m−1 or 0.001 dB per point sensor device. High-temperature performance of fiber sensors was tested at 1000 °C, which showed a temperature fluctuation of ±5.5 °C over 5 days. The low laser-induced insertion loss in optical fibers enabled the fabrication of a 1.4 m, radiation-resilient distributed fiber sensor. The in-pile testing of the distributed fiber sensor further showed that fiber sensors can execute stable and distributed temperature measurements in extreme radiation environments. Overall, this paper demonstrates that femtosecond-laser-fabricated fiber sensors are suitable measurement devices for applications in extreme environments.
Autonomous apomixis in Praxelis clematidea (Asteraceae: Eupatorieae), an invasive alien plant
Authors: Zhang Yuhuan , Wu Hairong , Hörandl Elvira , de Oliveira Franca Rafael , Wang LiXin , Hao Jianhua
Published: January 2021

Understanding the reproductive mechanisms of invasive alien species can lay the foundation for effective control measures. Praxelis clematidea is a triploid neotropical Asteraceae species that is invasive in China and other countries. However, few studies have focused on its reproductive biology. In this study, flow cytometric seed screening (FCSS) was used to identify and confirm the reproductive mode of the species. The development of ovules, anthers, and mega- and microgametophytes was observed using a clearing method and differential interference contrast microscopy. Pollen viability was measured using the Benzidine test and Alexander’s stain. Pollen morphology was observed via fluorescence microscopy after sectioning the disk florets and staining with water-soluble aniline blue or 4′6-diamidino-2-phenylindole nuclei dyes. Controlled pollination experiments were conducted on four populations in China to examine the breeding system and to confirm autonomous apomixis. The reproductive mode was found to be autonomous apomixis without pseudogamy, according to FCSS. Megaspore mother cells developed directly into eight-nucleate megagametophytes without meiosis, conforming to Antennaria-type diplospory. The unreduced egg cells developed into embryos through parthenogenesis, while the endosperm was formed by the fusion of two unreduced polar nuclei. Pollen viability was very low (0.82 ± 0.57 % and 0.36 ± 0.44 %) as measured by the Benzidine test and Alexander’s stain, respectively. The majority of the pollen grains were empty and had neither cytoplasm nor nuclei. The seed set was >90 % for all treatments of open pollination, bagging and emasculated capitula. Mature cypselae developed in capitula that were emasculated before flowering, which confirmed that the breeding system of P. clematidea was autonomous apomixis. The present study is the first report of autonomous apomixis in P. clematidea in China. Antennaria-type autonomous apomixis in P. clematidea greatly increases the probability of successful colonisation and dispersal of P. clematidea into new areas, which likely contributes to its high invasion potential. Effective control measures should be implemented to prevent autonomous (pollen-independent) seed production.
Knockdown of lncRNA LINC00707 alleviates LPS-induced injury in MRC-5 cells by acting as a ceRNA of miR-223-5p
Authors: Zou Xiequn , Gao Cheng , Shang Rong , Chen Huan , Wang Bing
Published: January 2021

Pneumonia is a common respiratory disease worldwide. Long noncoding RNAs have been implicated in the pathogenesis of pneumonia. However, the effect and mechanism of long intergenic nonprotein-coding RNA (LINC00707) on pneumonia pathogenesis were still unclear. Lipopolysaccharide (LPS) reduced cell viability and promoted apoptosis and inflammation in MRC-5 cells. LINC00707 was increased, and miR-223-5p was decreased in LPS-treated MRC-5 cells. LINC00707 knockdown relieved LPS-triggered injury in MRC-5 cells. LINC00707 directly interacted with miR-223-5p through acting as a miR-223-5p sponge. Moreover, miR-223-5p mediated the regulation of LINC00707 silencing on LPS-stimulated cytotoxicity in MRC-5 cells. p38 mitogen-activated protein kinases and nuclear factor-κB signaling pathways were modulated by the LINC00707/miR-223-5p axis in LPS-induced MRC-5 cells. Our present study indicated that LINC00707 depletion alleviated LPS-induced injury in MRC-5 cells at least partly by acting as a sponge of miR-223-5p, highlighting a new potential therapeutic avenue for pneumonia treatment.
A meta-epidemiological study of bias in randomized clinical trials of open and laparoscopic surgery
Authors: Amer M A , Herbison G P , Grainger S H , Khoo C H , Smith M D , McCall J L
Published: January 2021

Background

Blinding, random sequence generation, and allocation concealment are established strategies to minimize bias in RCTs. Meta-epidemiological studies of drug trials have demonstrated exaggerated treatment effects in RCTs where such methods were not employed. As blinding is more difficult in surgical trials it is important to determine whether this applies to them. The study aimed to investigate this using systematic meta-epidemiological methods.

Method

The Cochrane Database of Systematic Reviews was searched for systematic reviews of RCTs that compared laparoscopic and open abdominal surgical procedures. Each review was then scrutinized to determine whether at least one of the included trials was blinded. Eligible reviews were updated and individual RCTs retrieved. Extracted data included the primary outcomes of interest (length of stay and complications), secondary outcomes and a risk of bias assessment. A multistep meta-regression analysis was then performed to obtain an overall difference in the reported outcome differences between trials that employed each bias-minimization strategy, and those that did not.

Results

Some 316 RCTs were included, reporting on eight different procedures. Patient-blinded RCTs reported a smaller difference in length of stay between laparoscopic and open groups (difference of standardized mean differences –0·36 (95 per cent c.i. –0·73 to 0·00)) and complications (ratio of odds ratios 0·76 (95 per cent c.i. 0·61 to 0·93)). Blinding of postoperative carers and outcome assessors had similar effects.

Conclusion

Lack of blinding significantly altered the treatment effect estimates of RCTs comparing laparoscopic and open surgery. Blinding should be implemented in surgical RCTs where possible to avoid systematic bias.
Plant communities in tropical ancient mountains: how are they spatially and evolutionary structured?
Authors: de Mattos Jacqueline S , Morellato Leonor Patrícia C , Batalha Marco Antonio
Published: January 2021

The integration of phylogenetic methods and species distribution can really help in the investigation of biogeographic patterns and to fill gaps in evolutionary ecology. Here we investigated how the vascular flora of the Brazilian ancient Cipó Mountains, an alleged OCBIL (old, climatic buffered infertile landscape) with a high diversity of species and endemism, evolved across that harsh archipelago-like system and altitudinal gradient. We used a node-based analysis of species distributions that follows the concepts of over- and underrepresentation and takes into account the relationship between sister clades, to yield two very statistically tractable metrics: the geographical node divergence and specific over-representation score. We collected and identified plant species along an elevational gradient ranging from 800 to 1400 m a.s.l. We also collected environmental variables such as elevation and soil properties. We found three allopatric nodes, which revealed the major biogeographic shifts in this tropical mountaintop vegetation. We found evidence to support the idea that environmental filtering is significantly shaping the distribution of biological communities and is restraining clades in the phylogeny. We argue that our study offers new insights into the biogeographic history and distributional shifts of the ancient rocky grasslands flora and to mountaintop vegetation systems in general.
Beneficial effects of dipeptidyl peptidase-4 inhibitors in diabetic Parkinson’s disease
Authors: Jeong Seong Ho , Chung Seok Jong , Yoo Han Soo , Hong Namki , Jung Jin Ho , Baik Kyoungwon , Lee Yang Hyun , Sohn Young H , Lee Phil Hyu
Published: January 2021

Dipeptidyl peptidase 4 (DPP4) inhibitors are widely used hypoglycaemic agents and improve glucose metabolism by enhancing the bioavailability of active glucagon-like peptide-1. In this study, we hypothesized that treatment with DPP4 inhibitors may have beneficial effects on nigrostriatal dopamine and longitudinal motor performance in diabetic patients with Parkinson’s disease. We classified 697 drug naive patients with de novo Parkinson’s disease who had undergone dopamine transporter imaging into three groups according to a prior diagnosis of diabetes and use of DPP4 inhibitors: diabetic patients with Parkinson’s disease being treated with (n = 54) or without DPP4 inhibitors (n = 85), and non-diabetic patients with Parkinson’s disease (n = 558). Diabetic patients with Parkinson’s disease being treated with DPP4 inhibitors had a higher baseline dopamine transporter availability in the anterior (2.56 ± 0.74 versus 2.10 ± 0.50; P = 0.016), posterior (1.83 ± 0.69 versus 1.40 ± 0.50; P < 0.001), and ventral putamina (1.72 ± 0.58 versus 1.35 ± 0.37; P = 0.001) than that in diabetic patients with Parkinson’s disease without DPP4 inhibitors. Additionally, diabetic patients with Parkinson’s disease being treated with DPP4 inhibitors had higher dopamine transporter availability in the posterior putamen than that in non-diabetic patients with Parkinson’s disease (1.83 ± 0.69 versus 1.43 ± 0.59; P < 0.001). After adjusting for age, sex, disease duration, and vascular risk factors, linear regression models showed that a prior treatment of DPP4 inhibitors remained independently and significantly associated with dopamine transporter availability in the anterior (β = −0.186, P = 0.012; β = −0.207, P = 0.003), posterior (β = −0.336, P < 0.001; β = −0.286, P < 0.001), and ventral putamina (β = −0.204, P = 0.005; β = −0.250, P < 0.001). A linear mixed model revealed that the diabetic group with Parkinson’s disease being treated with DPP4 inhibitors had a slower longitudinal increase in levodopa-equivalent dose than the other groups (P = 0.003). Survival analyses showed that the rate of levodopa-induced dyskinesia was significantly lower in the diabetic group with a prior treatment with DPP4 inhibitors than the diabetic group without DPP4 inhibitors (hazard ratio = 0.194, P = 0.037). These findings suggest that DPP4 inhibitors may confer beneficial effects on the baseline nigrostriatal dopamine degeneration and long-term motor outcomes in diabetic patients with Parkinson’s disease and may extend its role into non-diabetic patients with Parkinson’s disease.
Distinct microglial response against Alzheimer's amyloid and tau pathologies characterized by P2Y12 receptor
Authors: Maeda Jun , Minamihisamatsu Takeharu , Shimojo Masafumi , Zhou Xiaoyun , Ono Maiko , Matsuba Yukio , Ji Bin , Ishii Hideki , Ogawa Masanao , Akatsu Hiroyasu , Kaneda Daita , Hashizume Yoshio , Robinson John L , Lee Virginia M -Y , Saito Takashi , Saido Takaomi C , Trojanowski John Q , Zhang Ming-Rong , Suhara Tetsuya , Higuchi Makoto , Sahara Naruhiko
Published: January 2021

Microglia are the resident phagocytes of the central nervous system, and microglial activation is considered to play an important role in the pathogenesis of neurodegenerative diseases. Recent studies with single-cell RNA analysis of CNS cells in Alzheimer’s disease and diverse other neurodegenerative conditions revealed that the transition from homeostatic microglia to disease-associated microglia was defined by changes of gene expression levels, including down-regulation of the P2Y12 receptor gene (P2Y12R). However, it is yet to be clarified in Alzheimer’s disease brains whether and when this down-regulation occurs in response to amyloid-β and tau depositions, which are core pathological processes in the disease etiology. To further evaluate the significance of P2Y12 receptor alterations in the neurodegenerative pathway of Alzheimer’s disease and allied disorders, we generated an anti-P2Y12 receptor antibody and examined P2Y12 receptor expressions in the brains of humans and model mice bearing amyloid-β and tau pathologies. We observed that the brains of both Alzheimer’s disease and non-Alzheimer’s disease tauopathy patients and tauopathy model mice (rTg4510 and PS19 mouse lines) displayed declined microglial P2Y12 receptor levels in regions enriched with tau inclusions, despite an increase in the total microglial population. Notably, diminution of microglial immunoreactivity with P2Y12 receptor was noticeable prior to massive accumulations of phosphorylated tau aggregates and neurodegeneration in rTg4510 mouse brains, despite a progressive increase of total microglial population. On the other hand, Iba1-positive microglia encompassing compact and dense-cored amyloid-β plaques expressed P2Y12 receptor at varying levels in amyloid precursor protein (APP) mouse models (APP23 and AppNL-F/NL-F mice). By contrast, neuritic plaques in Alzheimer’s disease brains were associated with P2Y12 receptor-negative microglia. These data suggest that the down-regulation of microglia P2Y12 receptor, which is characteristic of disease-associated microglia, is intimately associated with tau rather than amyloid-β pathologies from an early stage and could be a sensitive index for neuroinflammatory responses to Alzheimer’s disease-related neurodegenerative processes.
Are Mycoplasma hominis, Ureaplasma urealyticum and Ureaplasma parvum Associated With Specific Genital Symptoms and Clinical Signs in Nonpregnant Women?
Authors: Plummer Erica L , Vodstrcil Lenka A , Bodiyabadu Kaveesha , Murray Gerald L , Doyle Michelle , Latimer Rosie L , Fairley Christopher K , Payne Matthew , Chow Eric P F , Garland Suzanne M , Bradshaw Catriona S
Published: January 2021

Background

There is limited evidence supporting an association between Mycoplasma hominis, Ureaplasma urealyticum, and Ureaplasma parvum with symptoms or disease in nonpregnant women. However, testing and reporting of these organisms frequently occurs, in part due to their inclusion in multiplex-PCR assays for sexually transmitted infection (STI) detection. We investigated if M. hominis, U. urealyticum, and U. parvum were associated with symptoms and/or signs in nonpregnant women attending a sexual health service.

Methods

Eligible women attending the Melbourne Sexual Health Centre completed a questionnaire regarding sexual practices and symptoms. Symptomatic women underwent examination. Women were assessed for bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC), and tested for M. hominis, U. urealyticum, and U. parvum, and 4 nonviral STIs using a commercial multiplex-PCR.

Results

1272 women were analyzed. After adjusting for STIs and VVC, M. hominis was associated with abnormal vaginal discharge (aOR = 2.70, 95%CI:1.92–3.79), vaginal malodor (aOR = 4.27, 95%CI:3.08–5.91), vaginal pH > 4.5 (aOR = 4.27, 95%CI:3.22–5.66), and presence of clue cells (aOR = 8.08, 95%CI:5.68–11.48). Ureaplasma spp. were not associated with symptoms/signs. Bacterial vaginosis was strongly associated with M. hominis (aOR = 8.01, 95%CI:5.99–10.71), but was not associated with either Ureaplasma spp. In stratified analyses, M. hominis was associated with self-reported vaginal malodor and clinician-recorded vaginal discharge in women with BV, but not with symptoms/signs in women without BV.

Conclusions

Only M. hominis was associated with symptoms/signs, and these were manifestations of BV. Importantly, M. hominis was not associated with symptoms/signs in women without BV. These findings do not support routine testing for M. hominis, U. urealyticum, and U. parvum in nonpregnant women.
Epidemiology of Pertussis in Individuals of All Ages Hospitalized With Respiratory Illness in South Africa, January 2013—December 2018
Authors: Wolter Nicole , Cohen Cheryl , Tempia Stefano , Walaza Sibongile , Moosa Fahima , du Plessis Mignon , McMorrow Meredith L , Treurnicht Florette K , Hellferscee Orienka , Dawood Halima , Variava Ebrahim , von Gottberg Anne
Published: January 2021

Background

Policy recommendations on pertussis vaccination need to be guided by data, which are limited from low- and middle-income countries. We aimed to describe the epidemiology of pertussis in South Africa, a country with high human immunodeficiency virus (HIV) prevalence and routine pertussis vaccination for 6 decades including the acellular vaccine since 2009.

Methods

Hospitalized patients of all ages were enrolled at 5 sentinel sites as part of a pneumonia surveillance program from January 2013 through December 2018. Nasopharyngeal specimens and induced sputum were tested by polymerase chain reaction (PCR) for Bordetella pertussis. In addition, demographic and clinical information were collected. Incidence rates were calculated for 2013–2016, and multivariable logistic regression performed to identify factors associated with pertussis.

Results

Over the 6-year period 19 429 individuals were enrolled, of which 239 (1.2%) tested positive for B. pertussis. Detection rate was highest in infants aged <6 months (2.8%, 155/5524). Mean annual incidence was 17 cases per 100 000 population, with the highest incidence in children <1 year of age (228 per 100 000). Age-adjusted incidence was 65.9 per 100 000 in HIV-infected individuals compared to 8.5 per 100 000 in HIV-uninfected individuals (risk ratio 30.4, 95% confidence interval: 23.0–40.2). Ten individuals (4.2%) with pertussis died; of which 7 were infants aged <6 months and 3 were immunocompromised adults.

Conclusions

Pertussis continues to be a significant cause of illness and hospitalization in South Africa, despite routine vaccination. The highest burden of disease and death occurred in infants; however, HIV-infected adults were also identified as an important group at risk of B. pertussis infection.
One hundred research questions in conservation physiology for generating actionable evidence to inform conservation policy and practice
Authors: Cooke Steven J , Bergman Jordanna N , Madliger Christine L , Cramp Rebecca L , Beardall John , Burness Gary , Clark Timothy D , Dantzer Ben , de la Barrera Erick , Fangue Nann A , Franklin Craig E , Fuller Andrea , Hawkes Lucy A , Hultine Kevin R , Hunt Kathleen E , Love Oliver P , MacMillan Heath A , Mandelman John W , Mark Felix C , Martin Lynn B , Newman Amy E M , Nicotra Adrienne B , Raby Graham D , Robinson Sharon A , Ropert-Coudert Yan , Rummer Jodie L , Seebacher Frank , Todgham Anne E , Tomlinson Sean , Chown Steven L
Published: January 2021

Environmental change and biodiversity loss are but two of the complex challenges facing conservation practitioners and policy makers. Relevant and robust scientific knowledge is critical for providing decision-makers with the actionable evidence needed to inform conservation decisions. In the Anthropocene, science that leads to meaningful improvements in biodiversity conservation, restoration and management is desperately needed. Conservation Physiology has emerged as a discipline that is well-positioned to identify the mechanisms underpinning population declines, predict responses to environmental change and test different in situ and ex situ conservation interventions for diverse taxa and ecosystems. Here we present a consensus list of 10 priority research themes. Within each theme we identify specific research questions (100 in total), answers to which will address conservation problems and should improve the management of biological resources. The themes frame a set of research questions related to the following: (i) adaptation and phenotypic plasticity; (ii) human–induced environmental change; (iii) human–wildlife interactions; (iv) invasive species; (v) methods, biomarkers and monitoring; (vi) policy, engagement and communication; (vii) pollution; (viii) restoration actions; (ix) threatened species; and (x) urban systems. The themes and questions will hopefully guide and inspire researchers while also helping to demonstrate to practitioners and policy makers the many ways in which physiology can help to support their decisions.
Cardiac symptom burden and arrhythmia recurrence drives digital health use: results from the iHEART randomized controlled trial
Authors: Masterson Creber Ruth M , Reading Turchioe Meghan , Biviano Angelo , Caceres Billy , Garan Hasan , Goldenthal Isaac , Koleck Theresa , Mitha Shazia , Hickey Kathleen , Bakken Suzanne
Published: January 2021

Aims

Digital health can transform the management of atrial fibrillation (AF) and enable patients to take a central role in detecting symptoms and self-managing AF. There is a gap in understanding factors that support sustained use of digital health tools for patients with AF. This study identified predictors of Alivecor® KardiaMobile ECG monitor usage among patients with AF enrolled in the iPhone®Helping Evaluate Atrial fibrillation Rhythm through Technology (iHEART) randomized controlled trial.

Methods and results

We analysed data from 105 English and Spanish-speaking adults with AF enrolled in the intervention arm of the iHEART trial. The iHEART intervention included smartphone-based electrocardiogram self-monitoring with Alivecor® KardiaMobile and triweekly text messages for 6 months. The primary outcome was use of Alivecor® categorized as: infrequent (≤5 times/week), moderate (>5 times and ≤11 times/week), and frequent (>11 times/week). We applied multinomial logistic regression modelling to characterize frequency and predictors of use. Of the 105 participants, 25% were female, 75% were White, and 45% were ≥65 years of age. Premature atrial contractions (PACs) [adjusted odds ratio (OR): 1.23, 1.08–1.40, P = 0.002] predicted frequent as compared to infrequent use. PACs (adjusted OR: 1.17, 95% confidence interval 1.06–1.30, P = 0.003), lower symptom burden (adjusted OR: 1.06, 1.01–1.11, P = 0.02), and less treatment concern (adjusted OR: 0.96, 0.93–0.99, P = 0.02) predicted moderate as compared to infrequent use.

Conclusions

Frequent use of AliveCor® is associated with AF symptoms and potentially symptomatic cardiac events. Symptom burden and frequency should be measured and incorporated into analyses of future digital health trials for AF management.
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

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

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

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

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

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

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 < 0.001). The PCO and LHP concentrations were higher in the IR group compared with control rats (P < 0.05). The PCO level was reduced by ghrelin in the IR+Ghrelin group compared with the IR group (P < 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 < 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

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

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

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

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

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

DNA 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.