bluuebunny/crossref_metadata_2025_split huggingface dataset:
The devil in the tiers1
Authors: Feldman Robin 
Published: October 2020

ABSTRACT
Prescription drug spending in the USA has soared, fueled by rising drug prices. A critical mechanism for restraining drug prices is the formulary tiering system. Although tiering should reflect the cost of a drug—and reward patients who choose less-expensive drugs—something is seriously amiss. Using Medicare claims data from roughly one million patients between 2010 and 2017, this article finds troubling amounts of distorted tiering and wasted cost. Increasingly, generics are shifted to more expensive—and therefore less accessible—tiers. The percentage of generics on the least-expensive tier drops from 73% to 28%; the percentage of drugs on inappropriate tiers rises from 47% to 74%. Considering only costs paid by patients and the federal Low-Income Subsidy Program, tier misplacement cumulatively costs society $13.25 billion over the time period. An unruly problem demands a disruptive solution. This article advances the counterintuitive regulatory reform that tiering should be based on a drug’s list price. Yes, list price—that roundly dismissed figure—should become the touchstone. This would deter incentive-distorting rebate schemes while recognizing that many people already pay list price. It is a remarkably streamlined approach for cutting through a wide swath of perverse incentives and manipulations.
The effects of an experimental drought on the ecophysiology and fruiting phenology of a tropical rainforest palm
Authors: Vogado Nara O , Liddell Michael J , Laurance Susan G W , Campbell Mason J , Cheesman Alexander W , Engert Jayden E , Palma Ana C , Ishida Françoise Y , Cernusak Lucas A 
Published: October 2020

AbstractAimsAnthropogenic climate change is predicted to increase mean temperatures and rainfall seasonality. How tropical rainforest species will respond to this climate change remains uncertain. Here, we analysed the effects of a 4-year experimental throughfall exclusion (TFE) on an Australian endemic palm (Normambya normanbyi) in the Daintree rainforest of North Queensland, Australia. We aimed to understand the impact of a simulated reduction in rainfall on the species’ physiological processes and fruiting phenology.MethodsWe examined the fruiting phenology and ecophysiology of this locally abundant palm to determine the ecological responses of the species to drought. Soil water availability was reduced overall by ~30% under a TFE experiment, established in May 2015. We monitored monthly fruiting activity for 8 years in total (2009–2018), including 4 years prior to the onset of the TFE. In the most recent year of the study, we measured physiological parameters including photosynthetic rate, stomatal conductance and carbon stable isotopes (δ 13C, an integrated measure of water use efficiency) from young and mature leaves in both the dry and wet seasons.Important FindingsWe determined that the monthly fruiting activity of all palms was primarily driven by photoperiod, mean solar radiation and mean temperature. However, individuals exposed to lower soil moisture in the TFE decreased significantly in fruiting activity, photosynthetic rate and stomatal conductance. We found that these measures of physiological performance were affected by the TFE, season and the interaction of the two. Recovery of fruiting activity in the TFE palms was observed in 2018, when there was an increase in shallow soil moisture compared with previous years in the treatment. Our findings suggest that palms, such as the N. normanbyi, will be sensitive to future climate change with long-term monitoring recommended to determine population-scale impacts.
The Polycomb group methyltransferase StE(z)2 and deposition of H3K27me3 and H3K4me3 regulate the expression of tuberization genes in potato
Authors: Kumar Amit , Kondhare Kirtikumar R , Malankar Nilam N , Banerjee Anjan K 
Published: October 2020

AbstractPolycomb repressive complex (PRC) group proteins regulate various developmental processes in plants by repressing target genes via H3K27 trimethylation, and they function antagonistically with H3K4 trimethylation mediated by Trithorax group proteins. Tuberization in potato has been widely studied, but the role of histone modifications in this process is unknown. Recently, we showed that overexpression of StMSI1, a PRC2 member, alters the expression of tuberization genes in potato. As MSI1 lacks histone-modification activity, we hypothesized that this altered expression could be caused by another PRC2 member, StE(z)2, a potential H3K27 methyltransferase in potato. Here, we demonstrate that a short-day photoperiod influences StE(z)2 expression in the leaves and stolons. StE(z)2 overexpression alters plant architecture and reduces tuber yield, whereas its knockdown enhances yield. ChIP-sequencing using stolons induced by short-days indicated that several genes related to tuberization and phytohormones, such as StBEL5/11/29, StSWEET11B, StGA2OX1, and StPIN1 carry H3K4me3 or H3K27me3 marks and/or are StE(z)2 targets. Interestingly, we observed that another important tuberization gene, StSP6A, is targeted by StE(z)2 in leaves and that it has increased deposition of H3K27me3 under long-day (non-induced) conditions compared to short days. Overall, our results show that StE(z)2 and deposition of H3K27me3 and/or H3K4me3 marks might regulate the expression of key tuberization genes in potato.
Complex DNA sequence readout mechanisms of the DNMT3B DNA methyltransferase
Authors: Dukatz Michael , Adam Sabrina , Biswal Mahamaya , Song Jikui , Bashtrykov Pavel , Jeltsch Albert 
Published: October 2020

Abstract
DNA methyltransferases interact with their CpG target sites in the context of variable flanking sequences. We investigated DNA methylation by the human DNMT3B catalytic domain using substrate pools containing CpX target sites in randomized flanking context and identified combined effects of CpG recognition and flanking sequence interaction together with complex contact networks involved in balancing the interaction with different flanking sites. DNA methylation rates were more affected by flanking sequences at non-CpG than at CpG sites. We show that T775 has an essential dynamic role in the catalytic mechanism of DNMT3B. Moreover, we identify six amino acid residues in the DNA-binding interface of DNMT3B (N652, N656, N658, K777, N779, and R823), which are involved in the equalization of methylation rates of CpG sites in favored and disfavored sequence contexts by forming compensatory interactions to the flanking residues including a CpG specific contact to an A at the +1 flanking site. Non-CpG flanking preferences of DNMT3B are highly correlated with non-CpG methylation patterns in human cells. Comparison of the flanking sequence preferences of human and mouse DNMT3B revealed subtle differences suggesting a co-evolution of flanking sequence preferences and cellular DNMT targets.
Arabidopsis ECERIFERUM2-LIKEs Are Mediators of Condensing Enzyme Function
Authors: Haslam Tegan M , Kunst Ljerka 
Published: October 2020

AbstractCondensing enzymes catalyze the committed reaction of fatty acid elongation and determine the chain length of fatty acids accepted and produced by the elongation complex. While necessary for the elongation of very-long-chain fatty acids (VLCFAs), identified plant condensing enzymes cannot efficiently produce VLCFAs longer than 28 carbons, which are precursors for the most abundant cuticular waxes of most plant species that have been surveyed. The eceriferum2 (cer2) mutant of Arabidopsis thaliana has a severe wax-deficient phenotype and specifically lacks waxes longer than 28 carbons, but the CER2 protein does not share sequence similarity with condensing enzymes. Instead, CER2 is homologous to BAHD acyltransferases. Heterologous expression in yeast previously demonstrated that CER2, and a small clade of BAHD acyltransferases with high sequence identity to CER2, can extend the chain-length specificity of the condensing enzyme CER6. This biochemical function is distinct from that of the broader BAHD acyltransferase family. The product specificity and physiological functions of individual CER2-LIKE proteins are unique. Here, we demonstrate that CER2 physically interacts with the fatty acid elongase. We cloned chimeric CER2-LIKE proteins and expressed these in yeast cells to identify the features that define the substrate specificities of CER2-LIKEs. We generated homology-based structural models to compare CER2-LIKEs and BAHD acyltransferases. In addition, based on the current phylogenetic analysis of the CER2-LIKE clade, we describe two further Arabidopsis CER2-LIKE genes, CER2-LIKE3 and CER2-LIKE4. We used yeast expression and mutant analysis to characterize these genes. Collectively, these results expand our knowledge of the functions of CER2-LIKEs, the BAHD acyltransferase family and cuticular wax metabolism.
Gender Differences in Job Search: Trading off COMMUTE AGAINST WAGE*
Authors: Le Barbanchon Thomas , Rathelot Roland , Roulet Alexandra 
Published: October 2020

ABSTRACTWe relate gender differences in willingness to commute to the gender wage gap. Using French administrative data on job search criteria, we first document that unemployed women have a lower reservation wage and a shorter maximum acceptable commute than their male counterparts. We identify indifference curves between wage and commute using the joint distributions of reservation job attributes and accepted job bundles. Indifference curves are steeper for women, who value commute around 20% more than men. Controlling in particular for the previous job, newly hired women are paid after unemployment 4% less per hour and have a 12% shorter commute than men. Through the lens of a job search model where commuting matters, we estimate that gender differences in commute valuation can account for a 0.5 log point hourly wage deficit for women, that is, 14% of the residualized gender wage gap. Finally, we use job application data to test the robustness of our results and to show that female workers do not receive less demand from far-away employers, confirming that most of the gender gap in commute is supply-side driven.
Changes in the clustering of unhealthy movement behaviors during the COVID-19 quarantine and the association with mental health indicators among Brazilian adults
Authors: Werneck André O , Silva Danilo R , Malta Deborah C , Souza-Júnior Paulo R B , Azevedo Luiz O , Barros Marilisa B A , Szwarcwald Célia L 
Published: October 2020

AbstractOur aim was to analyze the prevalence of unhealthy movement behavior clusters before and during the COVID-19 pandemic, as well as to investigate whether changes in the number of unhealthy behaviors during the COVID-19 pandemic quarantine were associated with mental health indicators. Data of 38,353 Brazilian adults from a nationwide behavior research were used. For movement behaviors, participants reported the frequency and duration of physical activity and daily time on TV viewing and computer/tablet use before and during the pandemic period. Participants also reported the frequency of loneliness, sadness (feeling sad, crestfallen, or depressed), and anxiety feelings (feeling worried, anxious, or nervous) during the pandemic period. Sex, age group, highest academic achievement, working status during quarantine, country region, and time adhering to the quarantine were used as correlates. We used descriptive statistics and logistic regression models for the data analysis. The prevalence of all movement behavior clusters increased during the COVID-19 pandemic. The cluster of all three unhealthy movement behaviors increased from 4.6% (95% confidence interval [CI]: 3.9–5.4) to 26.2% (95% CI: 24.8–27.7). Younger adults, people with higher academic achievement, not working or working at home, and those with higher time in quarantine presented higher clustering. People that increased one and two or three unhealthy movement behaviors were, respectively, more likely to present loneliness (odds ratio [OR] = 1.41 [95% CI: 1.21–1.65] and OR = 1.71 [95% CI: 1.42–2.07]), sadness (OR = 1.25 [95% CI: 1.06–1.48] and OR = 1.73 [95% CI: 1.42–2.10]), and anxiety (OR = 1.34 [95% CI: 1.13–1.57] and OR = 1.78 [95% CI: 1.46–2.17]) during the COVID-19 quarantine. Clustering of unhealthy movement behaviors substantially increased and was associated with poorer mental health during the COVID-19 pandemic.
Microcystin-LR Induces NLRP3 Inflammasome Activation via FOXO1 Phosphorylation, Resulting in Interleukin-1β Secretion and Pyroptosis in Hepatocytes
Authors: Zhang Yali , Zhu Peipei , Wu Xiaofeng , Yuan Tianli , Su Zhangyao , Chen Shiyin , Zhou Yajun , Tao Weiguo Andy 
Published: October 2020

Abstract
Microcystin-LR (MC-LR), the most common and toxic microcystin (MC) present in freshwater, poses a substantial threat to human health, especially hepatotoxicity. Recent evidence reveals that the NLRP3 inflammasome plays an important role in liver injury by activating caspase-1 to promote interleukin-1β (IL-1β) secretion. In this study, we investigated the possible role of NLRP3 inflammasome activation in MC-LR-induced mouse liver inflammatory injury. We found that MC-LR administered to mice by oral gavage mainly accumulated in liver and induced the activation of the NLRP3 inflammasome and production of mature IL-1β. Additionally, we observed an increase in the levels of NLRP3 inflammasome-related proteins and the proportion of pyroptosis in MC-LR-treated AML-12 cells. We also found that inhibition of NLRP3 in mice attenuated MC-LR-induced IL-1β production, indicating an essential role for NLRP3 in MC-LR-induced liver inflammatory injury. In addition, we found that inhibition of FOXO1 by AKT-mediated hyperphosphorylation, due to protein phosphatase 2A (PP2A) inhibition, is required for MC-LR-induced expression of NLRP3. Taken together, our in vivo and in vitro findings suggest a model in which the NLRP3 inflammasome activation, a result of AKT-mediated hyperphosphorylation of FOXO1 through inhibition of PP2A, plays a key role in MC-LR–induced liver inflammatory injury via IL-1β secretion and pyroptotic cell death.
Using ethnographic film in tackling podoconiosis
Authors: Cremers A L , Visser B J , Getahun Z , Borku M , Meskele E , Ahmed J , van Vugt M , Birnie E 
Published: October 2020

Abstract

Background
Ethiopia has one of the worst podoconiosis rates in the world, affecting &gt;1.5 million patients. We present our ethnographic film ‘Tigist, the story of a girl with podoconiosis’ and its potential use in tackling podoconiosis.

Methods
We conducted visual ethnography, consisting of video-recorded participant observations and interviews with seven patients, three healthcare workers and two podoconiosis experts.

Results
We acquired video recordings of social moments, the state of podoconiosis patients’ bodies and minds, their emotions and the impact of poverty.

Conclusions
Our film allows for an intensified understanding of patients’ daily experiences with podoconiosis, potentially impacting care, awareness and medical teaching programs.
Genome Sequencing of Ciboria shiraiana Provides Insights into the Pathogenic Mechanisms of Hypertrophy Sorosis Scleroteniosis
Authors: Zhu Panpan , Kou Min , Liu Changying , Zhang Shuai , Lü Ruihua , Xia Zhongqiang , Yu Maode , Zhao Aichun 
Published: October 2020

Ciboria shiraiana causes hypertrophy sorosis scleroteniosis in mulberry trees, resulting in huge economic losses, and exploring its pathogenic mechanism at a genomic level is important for developing new control methods. Here, genome sequencing of C. shiraiana based on PacBio RSII and Illumina HiSeq 2500 platform as well as manual gap filling was performed. Synteny analysis with Sclerotinia sclerotiorum revealed 16 putative chromosomes corresponding to 16 chromosomes of C. shiraiana. Screening of rapid-evolution genes revealed that 97 and 2.4% of genes had undergone purifying selection and positive selection, respectively. When compared with S. sclerotiorum, fewer secreted effector proteins were found in C. shiraiana. The number of genes involved in pathogenicity, including secondary metabolites, carbohydrate active enzymes, and P450s, in the C. shiraiana genome was comparable with that of other necrotrophs but higher than that of biotrophs and saprotrophs. The growth-related genes and plant cell-wall-degradation-related genes in C. shiraiana were expressed in different developmental and infection stages, and may be potential targets for prevention and control of this pathogen. These results provide new insights into C. shiraiana pathogenic mechanisms, especially host range and necrotrophy features, and lay the foundation for further study of the underlying molecular mechanisms. [Formula: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 “No Rights Reserved” license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.
Integrated mRNA and Small RNA Sequencing for Analyzing Leaf Spot Pathogen Didymella segeticola and Its Host, Tea (Camellia sinensis), During Infection
Authors: Yang Rui , Jiang Silong , Li Dongxue , Yin Qiaoxiu , Wu Xian , Wang Yong , Wang Delu , Chen Zhuo 
Published: October 2020

Leaf spot on tea plants (Camellia sinensis [L.] Kuntze), caused by the fungus Didymella segeticola (Q. Chen) Q. Chen, Crous & L. Cai (syn. Phoma segeticola), negatively affects the productivity and quality of tea leaves in Guizhou Province, China. Although the genome sequence of D. segeticola has been published, no data on the transcriptome or microRNAs (miRNAs) of the pathogen or host during infection are available. Here, we report on the high-quality transcriptome and miRNA sequences of both D. segeticola and tea during infection, using the Illumina HiSeq 4000 or HiSeq 2500 platforms. Comprehensive expression profiling of the fungal pathogen and its host will provide a resource for future research into trait-specific genes of the pathogen and the host as well as on host-pathogen interactions and on disease resistance mechanisms. [Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Complete Genome Sequences of Trifolium spp. Inoculant Strains Rhizobium leguminosarum sv. trifolii TA1 and CC275e: Resources for Genomic Study of the Rhizobium-Trifolium Symbiosis
Authors: Perry Benjamin J. , Ferguson Shaun , Laugraud Aurelie , Wakelin Steve A. , Reeve Wayne , Ronson Clive W. 
Published: October 2020

Rhizobium leguminosarum symbiovar trifolii strains TA1 and CC275e are nitrogen-fixing microsymbionts of Trifolium spp. and have been used as commercial inoculant strains for clovers in pastoral agriculture in Australia and New Zealand. Here we present the complete genome sequences of both strains, resolving their multipartite genome structures and allowing for future studies using genomic approaches. [Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Who Did the Arthroplasty? Hip Fracture Surgery Reoperation Rates are Not Affected by Type of Training—An Analysis of the HEALTH Database
Authors: DeAngelis Ryan D. , Minutillo Gregory T. , Stein Matthew K. , Schemitsch Emil H. , Bzovsky Sofia , Sprague Sheila , Bhandari Mohit , Donegan Derek J. , Mehta Samir ,   on behalf of the HEALTH Investigators
Published: October 2020

Objectives:
This study compares outcomes for patients with displaced femoral neck fractures undergoing hemiarthroplasty (HA) or total hip arthroplasty (THA) by surgeons of different fellowship training.

Design:
Retrospective review of HEALTH trial data.

Setting:
Eighty clinical sites across 10 countries.

Patients/Participants:
One thousand four hundred forty-one patients ≥50 years with low-energy hip fractures requiring surgical intervention.

Intervention:
Patients were randomized to either HA or THA groups in the initial data set. Surgeons' fellowship training was ascertained retrospectively, and outcomes were compared.

Main Outcome Measurements:
The main outcome was an unplanned secondary procedure at 24 months. Secondary outcomes included death, serious adverse events, prosthetic joint infection (PJI), dislocation, discharge disposition, and use of ambulatory devices postoperatively.

Results:
There was a significantly higher risk of PJI in patients treated by surgeons without fellowship training in arthroplasty (P = 0.01), surgeons with unknown fellowship training (P = 0.03), and surgeons with no fellowship training (P = 0.02) than those treated by an arthroplasty-trained surgeon. There were significantly higher odds of being discharged to a facility rather than home in patients who underwent surgery by a surgeon with no fellowship training compared with arthroplasty–fellowship-trained surgeons (P = 0.03).

Conclusions:
Arthroplasty for hip fracture can be performed by all orthopaedic surgeons with equivalent reoperation rates. Infection prevention strategies and use of “care pathways” by arthroplasty-fellowship-trained surgeons may account for the lower risk of PJI and higher rate of discharge to home. The authors advocate for the use of evidence-based infection prevention initiatives and standardized care pathways in this patient population.

Level of Evidence:
Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.
Is Total Hip Arthroplasty a Cost-Effective Option for Management of Displaced Femoral Neck Fractures? A Trial-Based Analysis of the HEALTH Study
Authors: Axelrod Daniel , Tarride Jean-Éric , Ekhtiari Seper , Blackhouse Gordon , Johal Herman , Bzovsky Sofia , Schemitsch Emil H. , Heels-Ansdell Diane , Bhandari Mohit , Sprague Sheila ,   on behalf of the HEALTH Investigators
Published: October 2020

Background:
Displaced femoral neck fractures are a significant source of morbidity and mortality and can be treated with either hemiarthroplasty (HA) or total hip arthroplasty (THA). Proponents of THA have argued THA offers lower risk of revision, with improved functional outcomes when compared to HA. To evaluate cost effectiveness of THA compared with HA, a trial-based economic analysis of the HEALTH study was undertaken.

Methods:
Health care resource utilization (HRU) and health-related quality of life (HRQoL) data were collected postoperatively and costed using publicly available databases. Using EuroQol-5 Dimensions (EQ-5D) scores, we derived quality adjusted life years (QALYs). A 1.5% discount rate to both costs and QALYs was applied. Age analyses per age group were conducted. All costs are reported in 2019 Canadian dollars.

Results:
When compared with HA, THA was not cost-effective for all patients with displaced femoral neck fractures ($150,000/QALY gained). If decision makers were willing to spend $50,000 or $100,000 to gain one QALY, the probability of THA being cost-effective was 12.8% and 32.8%, respectively. In a subgroup of patients younger than 73 (first quartile), THA was both more effective and less costly. Otherwise, THA was more expensive and yielded marginal HRQoL gains.

Conclusions:
Our results suggest that for most patients, THA is not a cost-effective treatment for displaced femoral neck fracture management versus HA. However, THA may be cost effective for younger patients. These patients experience more meaningful improvements in quality of life with less associated cost because of shorter hospital stay and fewer postoperative complications.

Level of Evidence:
Economic Level II. See Instructions for Authors for a complete description of levels of evidence.