bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of epistasis and environment on flowering time in barley reveals a novel flowering-delaying QTL allele
Authors: Afsharyan Nazanin P , Sannemann Wiebke , Léon Jens , Ballvora Agim 
Published: November 2019

AbstractFlowering time is a complex trait and has a key role in crop yield and adaptation to environmental stressors such as heat and drought. This study aimed to better understand the interconnected dynamics of epistasis and environment and look for novel regulators. We investigated 534 spring barley MAGIC DH lines for flowering time at various environments. Analysis of quantitative trait loci (QTLs), epistatic interactions, QTL × environment (Q×E) interactions, and epistasis × environment (E×E) interactions were performed with single SNP and haplotype approaches. In total, 18 QTLs and 2420 epistatic interactions were detected, including intervals harboring major genes such as Ppd-H1, Vrn-H1, Vrn-H3, and denso/sdw1. Epistatic interactions found in field and semi-controlled conditions were distinctive. Q×E and E×E interactions revealed that temperature influenced flowering time by triggering different interactions between known and newly detected regulators. A novel flowering-delaying QTL allele was identified on chromosome 1H (named ‘HvHeading’) and was shown to be engaged in epistatic and environment interactions. Results suggest that investigating epistasis, environment, and their interactions, rather than only single QTLs, is an effective approach for detecting novel regulators. We assume that barley can adapt flowering time to the environment via alternative routes within the pathway.
Modulation of NAC transcription factor NST1 activity by XYLEM NAC DOMAIN1 regulates secondary cell wall formation in Arabidopsis
Authors: Zhang Qian , Luo Fang , Zhong Yu , He Jiajia , Li Laigeng 
Published: November 2019

Abstract
In Arabidopsis, secondary cell walls (SCW) are formed in fiber cells and vessel cells in vascular tissue for providing plants with mechanical strength and channels for the long distance transportation of water and nutrients. NAC SECONDARY WALL THICKENING PROMOTING FACTOR1 (NST1) acts as a key gene for the initiation of SCW formation through a hierarchical transcription network. In this study, we report that NST activity is modulated by the NAC domain transcription factor XYLEM NAC DOMAIN1 (XND1) during plant growth. Using yeast two-hybrid screening and in vivo protein interaction analysis, XND1 was identified as an NST-interacting protein that modulates NST1 activity. XND1 and NST1 were co-localized in the nucleus and the interaction of XND1 with NST1 resulted in inhibition of NST1 transactivation activity. In the process of inflorescence growth, XND1 was expressed with a similar pattern to NST1. Up-regulation of XND1 in fiber cells repressed SCW formation. The study demonstrates that NST1 activity is modulated by XND1 in the regulation of secondary cell walls formation.
Slicing the cool circumgalactic medium along the major axis of a star-forming galaxy at z = 0.7
Authors: Lopez S , Tejos N , Barrientos L F , Ledoux C , Sharon K , Katsianis A , Florian M K , Rivera-Thorsen E , Bayliss M B , Dahle H , Fernandez-Figueroa A , Gladders M D , Gronke M , Hamel M , Pessa I , Rigby J R 
Published: November 2019

ABSTRACT
We present spatially resolved Echelle spectroscopy of an intervening Mg ii–Fe ii–Mg i absorption-line system detected at zabs = 0.73379 towards the giant gravitational arc PSZ1 G311.65–18.48. The absorbing gas is associated with an inclined disc-like star-forming galaxy, whose major axis is aligned with the two arc-segments reported here. We probe in absorption the galaxy’s extended disc continuously, at ≈3 kpc sampling, from its inner region out to 15× the optical radius. We detect strong ($W_0^{2796}\gt 0.3$Å) coherent absorption along 13 independent positions at impact parameters D = 0–29 kpc on one side of the galaxy, and no absorption at D = 28–57 kpc on the opposite side (all de-lensed distances at zabs). We show that (1) the gas distribution is anisotropic; (2) $W_0^{2796}$, $W_0^{2600}$, $W_0^{2852}$, and the ratio $W_0^{2600}\!/W_0^{2796}$, all anticorrelate with D; (3) the $W_0^{2796}$–D relation is not cuspy and exhibits significantly less scatter than the quasar-absorber statistics; (4) the absorbing gas is co-rotating with the galaxy out to D ≲ 20 kpc, resembling a ‘flat’ rotation curve, but at D ≳ 20 kpc velocities decline below the expectations from a 3D disc-model extrapolated from the nebular [O ii] emission. These signatures constitute unambiguous evidence for rotating extra-planar diffuse gas, possibly also undergoing enriched accretion at its edge. Arguably, we are witnessing some of the long-sought processes of the baryon cycle in a single distant galaxy expected to be representative of such phenomena.
A novel 5′-hydroxyl dinucleotide hydrolase activity for the DXO/Rai1 family of enzymes
Authors: Doamekpor Selom K , Gozdek Agnieszka , Kwasnik Aleksandra , Kufel Joanna , Tong Liang 
Published: November 2019

Abstract
Modifications at the 5′-end of RNAs play a pivotal role in determining their fate. In eukaryotes, the DXO/Rai1 family of enzymes removes numerous 5′-end RNA modifications, thereby regulating RNA turnover. Mouse DXO catalyzes the elimination of incomplete 5′-end caps (including pyrophosphate) and the non-canonical NAD+ cap on mRNAs, and possesses distributive 5′-3′ exoribonuclease activity toward 5′-monophosphate (5′-PO4) RNA. Here, we demonstrate that DXO also catalyzes the hydrolysis of RNAs bearing a 5′-hydroxyl group (5′-OH RNA). The crystal structure of DXO in complex with a 5′-OH RNA substrate mimic at 2.0 Å resolution provides elegant insight into the molecular mechanism of this activity. More importantly, the structure predicts that DXO first removes a dinucleotide from 5′-OH RNA. Our nuclease assays confirm this prediction and demonstrate that this 5′-hydroxyl dinucleotide hydrolase (HDH) activity for DXO is higher than the subsequent 5′-3′ exoribonuclease activity for selected substrates. Fission yeast Rai1 also has HDH activity although it does not have 5′-3′ exonuclease activity, and the Rat1-Rai1 complex can completely degrade 5′-OH RNA. An Arabidopsis DXO1 variant is active toward 5′-OH RNA but prefers 5′-PO4 RNA. Collectively, these studies demonstrate the diverse activities of DXO/Rai1 and expands the collection of RNA substrates that can undergo 5′-3′ mediated decay.
Different class IIa HDACs repressive complexes regulate specific epigenetic responses related to cell survival in leiomyosarcoma cells
Authors: Di Giorgio Eros , Dalla Emiliano , Franforte Elisa , Paluvai Harikrishnareddy , Minisini Martina , Trevisanut Matteo , Picco Raffaella , Brancolini Claudio 
Published: November 2019

Abstract
Transcriptional networks supervising class IIa HDAC expression are poorly defined. Here we demonstrate that MEF2D is the key factor controlling HDAC9 transcription. This control, which is part of a negative feed-back loop during muscle differentiation, is hijacked in cancer. In leiomyosarcomas the MEF2D/HDAC9 vicious circuit sustains proliferation and cell survival, through the repression of the death receptor FAS. Comprehensive genome-wide studies demonstrate that HDAC4 and HDAC9 control different genetic programs and show both specific and common genomic binding sites. Although the number of MEF2-target genes commonly regulated is similar, only HDAC4 represses many additional genes that are not MEF2D targets. As expected, HDAC4−/− and HDAC9−/− cells increase H3K27ac levels around the TSS of the respective repressed genes. However, these genes rarely show binding of the HDACs at their promoters. Frequently HDAC4 and HDAC9 bind intergenic regions. We demonstrate that these regions, recognized by MEF2D/HDAC4/HDAC9 repressive complexes, show the features of active enhancers. In these regions HDAC4 and HDAC9 can differentially influence H3K27 acetylation. Our studies describe new layers of class IIa HDACs regulation, including a dominant positional effect, and can contribute to explain the pleiotropic actions of MEF2 TFs.
Impact of an antimicrobial stewardship bundle for uncomplicated gram-negative bacteremia
Authors: Erickson Reaghan M , Tritle Brandon J , Spivak Emily S , Timbrook Tristan T 
Published: November 2019

Abstract

Background
Recent studies in gram-negative bacteremia (GNB) suggest intravenous (IV) to oral (PO) switch and short treatment durations yield similar clinical outcomes and fewer adverse events. Antimicrobial stewardship program (ASP) bundled initiatives have been associated with improved clinical outcomes for blood stream infections.

Methods
This single-center retrospective cohort evaluation included inpatient adults from 11/2014-10/2015 and 10/2017-9/2018 with GNB. The pre-ASP period was prior to the establishment of an ASP program. In the post-period, the ASP promoted IV to PO switches, avoidance of repeat blood cultures, and short treatment durations for patients with uncomplicated GNB. The primary outcome was duration of antibiotic therapy. Secondary outcomes included associated process measures with the bundle and clinical outcomes.

Results
137 patients met criteria for inclusion, with 51 patients in the pre- group, and 86 patients in the post- group. Background characteristics were similar between groups. The median duration of therapy was 14 days (IQR = 10-16) in the pre- group and 10 days (7-14) in the post- group (p<0.001). The median day of IV to PO switch was on day 5 (4-6) in the pre- group versus day 4 (3-5) in the post- group (p=0.046). Average total hospital cost per case decreased by 27% in the post- group (p=0.19). Mortality rates and bacteremia recurrence were not significantly different between groups.

Conclusions
An ASP bundle for uncomplicated GNB was associated with reduced durations of therapy and earlier PO switch. These findings highlight the synergistic role of ASPs in optimizing antibiotic use and promoting patient safety.
Flipping the Pain Care Model: A Sociopsychobiological Approach to High-Value Chronic Pain Care
Authors: Mardian Aram S , Hanson Eric R , Villarroel Lisa , Karnik Anita D , Sollenberger John G , Okvat Heather A , Dhanjal-Reddy Amrita , Rehman Shakaib 
Published: November 2019

Abstract

Objective
Much of the pain care in the United States is costly and associated with limited benefits and significant harms, representing a crisis of value. We explore the current factors that lead to low-value pain care within the United States and provide an alternate model for pain care, as well as an implementation example for this model that is expected to produce high-value pain care.

Methods
From the perspective of aiming for high-value care (defined as care that maximizes clinical benefit while minimizing harm and cost), we describe the current evidence practice gap (EPG) for pain care in the United States, which has developed as current clinical care diverges from existing evidence. A discussion of the biomedical, biopsychosocial, and sociopsychobiological (SPB) models of pain care is used to elucidate the origins of the current EPG and the unconscious factors that perpetuate pain care systems despite poor results.

Results
An interprofessional pain team within the Veterans Health Administration is described as an example of a pain care system that has been designed to deliver high-value pain care and close the EPG by implementing the SPB model.

Conclusions
Adopting and implementing a sociopsychobiological model may be an effective approach to address the current evidence practice gap and deliver high-value pain care in the United States. The Phoenix VA Health Care System’s Chronic Pain Wellness Center may serve as a template for providing high-value, evidence-based pain care for patients with high-impact chronic pain who also have medical, mental health, and opioid use disorder comorbidities.
miR-214 stimulated by IL-17A regulates bone loss in patients with ankylosing spondylitis
Authors: Liu Zizhong , Huang Feng , Luo Gui , Wang Yiwen , Du Ruikai , Sun Weijia , Li Jianwei , Yuan Xinxin , Cao Dengchao , Li Yuheng , Liu Caizhi , Liang Shuai , Jin Xiaoyan , Ling Shukuan  , Wang Deqing , Li Yingxian 
Published: November 2019

Abstract

Objective
Bone loss is common in AS, and miR-214 plays an important role in regulating bone formation. The aim of this study was to investigate the effect of miR-214, the production of which is stimulated by IL-17A, on bone loss in AS.

Methods
Peripheral blood was obtained from 32 patients with AS and 24 healthy controls. Levels of IL-17A, soluble RANK ligand (RANKL) and osteoprotegerin in serum were evaluated by ELISA, and the relative level of miR-214 in serum was detected by real-time quantitative PCR. In addition, we assessed the relationship between levels of miR-214, IL-17A and bone loss in primary murine osteoblasts and mouse bone marrow cells.

Results
The expression of RANKL and miR-214 in osteoblasts was increased following stimulation by IL-17A, and osteoblasts stimulated by IL-17A promoted the expression of miR-214 in osteoclasts and the activity of osteoclasts. We showed that osteoblast-derived miR-214 could be transferred to osteoclasts and could then regulate their activity. The levels of IL-17A and miR-214 were much higher in the serum of patients with AS than in that of healthy controls, and the relative level of miR-214 was positively correlated with the level of IL-17A in the serum and synovial fluid of the patients with AS, not healthy controls. The level of miR-214 in the serum of AS patients has potential diagnostic value.

Conclusion
The production of miR-214 in osteoblasts is stimulated by IL-17A. It is an important inhibitor of bone formation in AS, and the serum level of miR-214 might be of potential diagnostic value for AS.
Second-harmonic generation in focused beam fields of phased-array transducers in a nonlinear solid with a stress-free boundary
Authors: Jeong Hyunjo , Zhang Shu-zeng , Li Xiong-bing 
Published: November 2019

Abstract
In nonlinear acoustic harmonic generation in solids with stress-free boundaries, such a boundary is known to destructively change the second harmonic generation, and the pulse-echo method is not practically applicable. Focused beams have often been used for fluid nonlinearity and biomechanical imaging in pulse-echo test setups. This paper considers the focused beam fields of linear phased-array transducers to ensure that pulse-echo harmonic generation can be applied to solids with stress-free boundaries. The fundamental and second-harmonic beam fields that are focused and reflected at the stress-free and rigid boundaries are calculated and their properties are investigated in terms of the received average fields. The phase difference between the two second-harmonic components after reflection from the boundary—that is, the reflected and the newly generated second harmonic—is emphasized. The phase difference is used to explain the improved and accumulated second harmonic observed in the simulation results.
A comparison of the Functional Movement ScreenTM and the Landing Error Scoring System: A cohort study
Authors: Tran Andrew A. , Shen Jennifer , Wernecke Chloe , Gatewood Corey T. , Harris Alex H.S. , Dragoo Jason L. 
Published: November 2019

Background:
The Functional Movement Screen (FMSTM) is a nonspecific movement pattern assessment while the Landing Error Scoring System (LESS) is a screen for movement patterns associated with lower extremity injury. The purpose of this study was to determine if the LESS and FMSTM are correlated or if they can be used as complementary assessments of preseason injury risk for anterior cruciate ligament injury.

Methods:
FMSTM and LESS were used to conduct a cohort study of 126 male National Collegiate Athletic Association Division IA football players. One hundred and eleven players met the criteria for inclusion during data review. At risk and not at risk LESS scores of players and FMSTM exercise score status were compared using Welch’s t-test. Associations between FMSTM composites and LESS scores were evaluated using linear regression.

Results:
The average LESS score was 5.51±1.34, and the average composite FMSTM score was 11.77±2.13 (max=15). A poor FMSTM squat score (≤1 or asymmetry present) was associated with a higher LESS score (P<0.001). No other FMSTM individual exercise score was associated with an at-risk LESS score (P>0.05). Composite FMSTM score was loosely associated with the LESS score (R-squared=0.0677, P=0.006). Prior history of an ACL injury and player position were not associated with LESS score on multivariate regression (P>0.05).

Conclusions:
The LESS and FMSTM are not well correlated and may serve as complementary assessments for preseason injury risk.

Level of Evidence:
Level III.
The gut microbiome-joint connection: implications in osteoarthritis
Authors: Favazzo Lacey J. , Hendesi Honey , Villani David A. , Soniwala Sarah , Dar Qurratul-Ain , Schott Eric M. , Gill Steven R. , Zuscik Michael J. 
Published: November 2019

Purpose of review
Osteoarthritis is a debilitating disease leading to joint degeneration, inflammation, pain, and disability. Despite efforts to develop a disease modifying treatment, the only accepted and available clinical approaches involve palliation. Although many factors contribute to the development of osteoarthritis, the gut microbiome has recently emerged as an important pathogenic factor in osteoarthritis initiation and progression. This review examines the literature to date regarding the link between the gut microbiome and osteoarthritis.

Recent findings
Studies showing correlations between serum levels of bacterial metabolites and joint degeneration were the first links connecting a dysbiosis of the gut microbiome with osteoarthritis. Further investigations have demonstrated that microbial community shifts induced by antibiotics, a germ-free environment or high-fat are important underlying factors in joint homeostasis and osteoarthritis. It follows that strategies to manipulate the microbiome have demonstrated efficacy in mitigating joint degeneration in osteoarthritis. Moreover, we have observed that dietary supplementation with nutraceuticals that are joint protective may exert their influence via shifts in the gut microbiome.

Summary
Although role of the microbiome in osteoarthritis is an area of intense study, no clear mechanism of action has been determined. Increased understanding of how the two factors interact may provide mechanistic insight into osteoarthritis and lead to disease modifying treatments.
Critical Role of p38 in Spinal Cord Injury by Regulating Inflammation and Apoptosis in a Rat Model
Authors: Zhang Heng-Wei , Ding Jian-Dong , Zhang Zeng-Shan , Zhao Si-shun , Duan Kang-ying , Zhu Bao-qi , Zhao Wen-Feng , Chai Zong-Tao , Liu Xiao-Wei 
Published: November 2019

Study Design.
To evaluate the effect of p38 pathway on spinal cord injury (SCI), a rat model of SCI was performed.

Objective.
We determined the effect of p38 on SCI and SCI related inflammation, apoptosis, and autophagy.

Summary of Background Data.
SCI is a severe clinical problem worldwide. It is difficult to prevent cell necroptosis and promote the survival of residual neurons after SCI. p38, a class of mitogen-activated protein kinases, its effect on SCI and SCI related inflammation, apoptosis, and autophagy have not been studied very well.

Methods.
The rats were randomly divided into the following four groups: the sham-operated (sham) group, the SCI group, the SCI + vehicle group, and the SCI + SB203580 (10 mg/kg) group. The p38 inhibitor SB203580 was administered by oral (10 mg/kg/d) gavage once per day for 14 days. Neurological recovery was assessed using the Basso, Beattie, and Bresnahan locomotion rating scale. Apoptosis, autophagy, and inflammation related proteins were measured by enzyme-linked immunosorbent assay kits or western blotting.

Results.
Our results showed that p38 was upregulated after SCI from day 3, which was paralleled with the levels of its proteins ATF-2, suggesting an increase in p38 activity. Our results showed administration of SB203580 attenuated histopathology and promoted locomotion recovery in rats after SCI. SB203580 administration significantly inhibited inflammatory cytokines levels as well as the inflammation signaling pathway. SB203580 administration also modulated the apoptosis and autophagy signaling pathway.

Conclusion.
Our findings suggest that p38 inhibitor SB203580 treatment alleviates secondary SCI by inhibiting inflammation and apoptosis, thereby promoting neurological and locomoter functional recovery, thus suggest the important role of p38 in neuronal protection after SCI.

Level of Evidence: N/A
Bacterial Reservoirs in the Middle Ear of Otitis-prone Children Are Associated With Repeat Ventilation Tube Insertion
Authors: Seppanen Elke J. , Thornton Ruth B. , North Hannah JD , Corscadden Karli J. , Wiertsema Selma P. , Vijayasekaran Shyan , Coates Harvey L. , Jacoby Peter , Richmond Peter C. , Kirkham Lea-Ann S. 
Published: November 2019

Background:
Repeat ventilation tube insertion (VTI) is common in children with recurrent acute otitis media (rAOM). Identifying risk factors associated with repeat surgery will improve clinical management and prevent repeat VTI.

Methods:
Surgical records were assessed at 8 years following VTI surgery for rAOM in children 6–36 months of age. Children were grouped according to detection of bacterial otopathogen in their middle ear effusion (MEE) at the time of VTI, and outcomes for future otorhinolaryngology surgery compared.

Results:
Age, gender, pneumococcal vaccination status, antibiotic usage, day-care attendance, number of siblings and number of AOM episodes were similar between groups. Of the 63 children who had PCR +ve MEE, 58.7% required repeat VTI compared with 31.4% of the 51 children with no otopathogen detected in their MEE (odds ratio = 3.1, 95% confidence interval [1.4–6.8]; P = 0.004). Nontypeable Haemophilus influenzae (NTHi) was the predominant otopathogen in MEE (79% of all PCR +ve MEE). Respiratory virus detection was not associated with repeat VTI.

Conclusions:
Presence of bacterial otopathogen, specifically nontypeable H. influenzae, in the middle ear during VTI was a predictor of children at-risk of repeat VTI. Here, we identify a modifiable microbiologic factor for repeat VTI that can be targeted to improve clinical management of rAOM.
Using Lean Performance Improvement for Patient-Centered Medical Home Transformation at an Academic Public Hospital
Authors: Wu Shirley , Brown Christopher , Black Susan , Garcia Michael , Harrington Darrell W. 
Published: November 2019

ABSTRACT
Although Lean performance improvement (PI) has been used in health care for more than 15 years, little is known about how Lean has been used in Patient-Centered Medical Home (PCMH) transformation. We describe our experience implementing Lean in our safety-net, primary care teaching clinic. To advance high value care, a culture of systematic, sustainable PI methods needed to be integrated into primary care and taught to resident physicians. Clinic leadership were trained in Lean methods, protected time was dedicated to PI for a stable, interdisciplinary team, then visual management was introduced, and resident physicians were integrated into the clinic's PI initiatives. Self-assessment using the PCMH Assessment tool demonstrated improvement in core features of the PCMH model. Process outcomes also revealed successful, sustainable integration of Lean into our primary care clinic and resident training, and early findings show improvements in clinical quality outcomes. Patient survey outcomes demonstrate improvement in patient experience. Lean can be used successfully to promote PCMH transformation and create a culture of continuous PI in an academic, safety-net primary care setting.