bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a Putative DNA-Binding Protein in Arabidopsis That Acts as a Susceptibility Hub and Interacts With Multiple Pseudomonas syringae Effectors
Authors: Schreiber Karl J. , Lewis Jennifer D. 
Published: December 2020

Phytopathogens use secreted effector proteins to suppress host immunity and promote pathogen virulence, and there is increasing evidence that the host-pathogen interactome comprises a complex network. To identify novel interactors of the Pseudomonas syringae effector HopZ1a, we performed a yeast two-hybrid screen that identified a previously uncharacterized Arabidopsis protein that we designate HopZ1a interactor 1 (ZIN1). Additional analyses in yeast and in planta revealed that ZIN1 also interacts with several other P. syringae effectors. We show that an Arabidopsis loss-of-function zin1 mutant is less susceptible to infection by certain strains of P. syringae, while overexpression of ZIN1 results in enhanced susceptibility. Functionally, ZIN1 exhibits topoisomerase-like activity in vitro. Transcriptional profiling of wild-type and zin1 Arabidopsis plants inoculated with P. syringae indicated that while ZIN1 regulates a wide range of pathogen-responsive biological processes, the list of genes more highly expressed in zin1 versus wild-type plants is particularly enriched for ribosomal protein genes. Altogether, these data illuminate ZIN1 as a potential susceptibility hub that interacts with multiple effectors to influence the outcome of plant-microbe interactions. [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 .
Perineural Liposomal Bupivacaine Is Not Superior to Nonliposomal Bupivacaine for Peripheral Nerve Block Analgesia
Authors: Hussain Nasir , Brull Richard , Sheehy Brendan , Essandoh Michael K. , Stahl David L. , Weaver Tristan E. , Abdallah Faraj W. 
Published: December 2020

Background
Liposomal bupivacaine is purported to extend analgesia of peripheral nerve blocks when administered perineurally. However, evidence of the clinical effectiveness of perineural liposomal bupivacaine is mixed. This meta-analysis seeks to evaluate the effectiveness of perineural liposomal bupivacaine in improving peripheral nerve block analgesia as compared with nonliposomal local anesthetics.

Methods
The authors identified randomized trials evaluating the effectiveness of peripheral nerve block analgesic that compared liposomal bupivacaine with nonliposomal local anesthetics. The primary outcome was the difference in area under the receiver operating characteristics curve (AUC) of the pooled 24- to 72-h rest pain severity scores. Secondary outcomes included postoperative analgesic consumption, time to first analgesic request, incidence of opioid-related side effects, patient satisfaction, length of hospital stay, liposomal bupivacaine side effects, and functional recovery. AUC pain scores were interpreted in light of a minimal clinically important difference of 2.0 cm · h.

Results
Nine trials (619 patients) were analyzed. When all trials were pooled, AUC pain scores ± SD at 24 to 72 h were 7.6 ± 4.9 cm · h and 6.6 ± 4.6 cm · h for nonliposomal and liposomal bupivacaine, respectively. As such, perineural liposomal bupivacaine provided a clinically unimportant benefit by improving the AUC (95% CI) of 24- to 72-h pain scores by 1.0 cm · h (0.5 to 1.6; P = 0.003) compared with nonliposomal bupivacaine. Excluding an industry-sponsored trial rendered the difference between the groups nonsignificant (0.7 cm · h [−0.1 to 1.5]; P = 0.100). Secondary outcome analysis did not uncover any additional benefits to liposomal bupivacaine in pain severity at individual timepoints up to 72 h, analgesic consumption, time to first analgesic request, opioid-related side effects, patient satisfaction, length of hospital stay, and functional recovery. No liposomal bupivacaine side effects were reported.

Conclusions
Perineural liposomal bupivacaine provided a statistically significant but clinically unimportant improvement in the AUC of postoperative pain scores compared with plain local anesthetic. Furthermore, this benefit was rendered nonsignificant after excluding an industry-sponsored trial, and liposomal bupivacaine was found to be not different from plain local anesthetics for postoperative pain and all other analgesic and functional outcomes. High-quality evidence does not support the use of perineural liposomal bupivacaine over nonliposomal bupivacaine for peripheral nerve blocks.

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Factors Associated with Improved Quality of Life Outcomes in Patients Undergoing Surgery for Adult Spinal Deformity
Authors: Arima Hideyuki , Hasegawa Tomohiko , Yamato Yu , Togawa Daisuke , Yoshida Go , Yasuda Tatsuya , Banno Tomohiro , Oe Shin , Mihara Yuki , Ushirozako Hiroki , Yamada Tomohiro , Watanabe Yuh , Ide Koichiro , Nakai Keiichi , Matsuyama Yukihiro 
Published: December 2020

Study Design.
Retrospective longitudinal cohort study.

Objective.
This study aimed to elucidate factors affecting the likelihood of achieving minimum clinically important difference (MCID) to patient-reported outcomes defined by the Scoliosis Research Society-22r (SRS-22r) among patients with adult spinal deformity (ASD) who underwent extensive corrective fusion surgery from the thoracic spine to the pelvis.

Summary of Background Data.
Achieving MCID for SRS-22r parameters was a measure of surgical efficacy. Patient characteristics and surgical and radiographic factors that affect the likelihood of achieving MCID for SRS-22r parameters are unknown.

Methods.
Data from patients with ASD who underwent extensive corrective fusion surgery from the thoracic spine to the pelvis during 2010 to 2016 were retrospectively reviewed. Data from a total of 167 patients with ≥2 years of follow-up were included. Multivariate analysis was used to investigate factors associated with the likelihood of achieving MCID for each of the SRS-22r domains (Function, Pain, Subtotal) 2 years after surgery. The following MCID values were used: 0.90 for Function, 0.85 for Pain, and 1.05 for the Subtotal.

Results.
MCID achievement rate was 36.5% for Function, 46.1% for Pain, and 44.3% for the Subtotal domain. In multivariate analysis, preoperative SRS-22r Function (odds ratio [OR] = 0.204, 95% confidence interval [CI] 0.105–0.396) increased the likelihood of achieving MCID for SRS-22r Function. Preoperative SRS-22r Subtotal (OR = 0.211, 95% CI, 0.107–0.413), preoperative pelvic tilt (OR = 1.072, 95% CI, 1.012–1.136), preoperative pelvic incidence minus lumbar lordosis (OR = 0.965, 95% CI, 0.934–0.997), and postoperative sagittal vertical axis (OR = 0.985, 95% CI, 0.974–0.995) affected the likelihood of achieving MCID for the SRS-22r Subtotal.

Conclusion.
Patients with poor preoperative health-related quality of life were more likely to achieve improvement in SRS-22r parameters after extensive corrective fusion surgery for ASD. Achieving postoperative sagittal alignment increased the likelihood of achieving MCID for the SRS-22r Subtotal domain.

Level of Evidence: 3
Application of Cooperative Game Theory Principles to Interpret Machine Learning Models of Nonhome Discharge Following Spine Surgery
Authors: Martini Michael L. , Neifert Sean N. , Oermann Eric K. , Gilligan Jeffrey T. , Rothrock Robert J. , Yuk Frank J. , Gal Jonathan S. , Nistal Dominic A. , Caridi John M. 
Published: December 2020

Study Design.
Retrospective analysis of prospectively acquired data.

Objective.
The aim of this study was to identify interaction effects that modulate nonhome discharge (NHD) risk by applying coalitional game theory principles to interpret machine learning models and understand variable interaction effects underlying NHD risk.

Summary of Background Data.
NHD may predispose patients to adverse outcomes during their care. Previous studies identified potential factors implicated in NHD; however, it is unclear how interaction effects between these factors contribute to overall NHD risk.

Methods.
Of the 11,150 reviewed cases involving procedures for degenerative spine conditions, 1764 cases (15.8%) involved NHD. Gradient boosting classifiers were used to construct predictive models for NHD for each patient. Shapley values, which assign a unique distribution of the total NHD risk to each model variable using an optimal cost-sharing rule, quantified feature importance and examined interaction effects between variables.

Results.
Models constructed from features identified by Shapley values were highly predictive of patient-level NHD risk (mean C-statistic = 0.91). Supervised clustering identified distinct patient subgroups with variable NHD risk and their shared characteristics. Focused interaction analysis of surgical invasiveness, age, and comorbidity burden suggested age as a worse risk factor than comorbidity burden due to stronger positive interaction effects. Additionally, negative interaction effects were found between age and low blood loss, indicating that intraoperative hemostasis may be critical for reducing NHD risk in the elderly.

Conclusion.
This strategy provides novel insights into feature interactions that contribute to NHD risk after spine surgery. Patients with positively interacting risk factors may require special attention during their hospitalization to control NHD risk.

Level of Evidence: 3
OPTIC DISK PIT ASSOCIATED WITH AN UNUSUAL OUTER RETINAL HOLE AND NASAL PERIPHERAL RETINOSCHISIS
Authors: Corvi Federico , Nguyen Tieu Vy , Juhn Alexander , Corradetti Giulia , Al-Sheikh Mayss , Zweifel Sandrine A. , Sadda SriniVas R. 
Published: December 2020

Purpose:
To document a peculiar case of optic disk pit-associated maculopathy with extensive nasal retinoschisis with lamellar outer retinal hole.

Methods:
A 41-year-old woman presented to the eye clinic complaining of new photopsias and enlargement of the blind spot in the left eye. Uncorrected visual acuity was 20/20 in both eyes. Fundus examination of the left eye revealed an anomalous appearing optic nerve with a gray oval depression at the temporal margin of the disk consistent with an optic disk pit.

Results:
Optical coherence tomography confirmed the presence of the pit and demonstrated outer plexiform layer schisis superonasal to the fovea and extensive inner and outer retinal schisis nasal to the nerve extending to the equator. A large lamellar outer retinal hole was noted nasal to the disk without associated retinal detachment. The vitreous appeared to be attached over the nasal retina.

Conclusion:
Multimodal imaging revealed an unusual optic disk pit-associated retinopathy with dramatically more extensive retinoschisis and a lamellar outer retinal hole nasal to the nerve despite the temporal location of the pit. Although the precise pathophysiologic mechanisms are not fully understood, forces associated with the vitreo-retinal adhesion may have contributed to the distribution of the schisis in this case.
FOCAL RETINAL ISCHEMIA REVEALED BY MULTIMODAL IMAGING AFTER TRAUMATIC PARTIAL OPTIC NERVE AVULSION
Authors: Van Brummen Alexandra , Mustafi Debarshi , Chee Yewlin E. 
Published: December 2020

Purpose:
Traumatic optic neuropathy can have varying presentations. Blunt focal trauma can lead to optic nerve avulsion with underlying retinal findings. A case of partial optic nerve avulsion after finger poke injury leading to focal retinal ischemia is reported.

Methods:
Visual acuity, fundus photography with fluorescein angiography, and spectral-domain optical coherence tomography were performed to document the findings in a 16-year-old man who presented after a finger poke injury to the left orbit during a water polo match.

Results:
On initial presentation, examination revealed decreased visual acuity with a fixed left pupil and afferent pupillary defect by reverse. On slit-lamp examination of the left eye, a hyphema was present. Dilated fundus examination revealed layering vitreous hemorrhage over the posterior pole and an avulsed vitreous base. On follow-up, a gap temporal to the optic nerve head consistent with a partial optic nerve avulsion was noted once the vitreous hemorrhage cleared. Multimodal imaging revealed retinal ischemia temporal to the disc on fluorescein angiography with corresponding changes in the inner retinal layers and retinal nerve fiber layer using spectral-domain optical coherence tomography.

Conclusion:
Clinicians should have a high suspicion for optic nerve avulsion if a patient presents with new vitreous hemorrhage and afferent pupillary defect after a finger-poke injury. Optic nerve avulsion injury can cause retinal ischemia, likely because of interruption of retinal blood flow as a result of nerve shearing injury. Multimodal imaging can reveal focal retinal injury and aid in proper diagnosis and follow-up.
Automated control of fraction of inspired oxygen: is it time for widespread adoption?
Authors: Mitra Souvik , McMillan Douglas 
Published: December 2020

Purpose of review
Over the past two decades, numerous algorithms for automated control of the fraction of inspired oxygen (FiO2) have been developed and incorporated into contemporary neonatal ventilators and high-flow devices in an attempt to optimize supplemental oxygen therapy in preterm infants. This review explores whether current evidence is sufficient to recommend widespread adoption of automated oxygen control in neonatal care.

Recent findings
To date, 15 studies have compared automated versus manual control of FiO2 in preterm infants on respiratory support. This includes four new randomized cross-over trials published in the last 2 years. Available evidence consistently demonstrates a significant improvement in time spent within the target saturation range with automated FiO2 control. There are fewer episodes of severe hypoxemia and fewer manual FiO2 adjustments with automated oxygen control. Nursing workload may be reduced. However, no currently completed studies report on clinical outcomes, such as chronic lung disease or retinopathy of prematurity.

Summary
Automated oxygen control appears to be a reasonable option for FiO2 titration in preterm infants on respiratory support, if resources are available, and might substantially reduce nursing workload. Further randomized clinical trials to explore its effects on clinical outcomes are required.
When should we use corticosteroids in severe community-acquired pneumonia?
Authors: Póvoa Pedro , Coelho Luís , Salluh Jorge 
Published: December 2020

Purpose of review
This review aims to evaluate the evidence and recommendations for the prescription of corticosteroids as adjunctive therapy in patients with severe community-acquired pneumonia.

Recent findings
Corticosteroids have been prescribed with the objective to attenuate the marked and persistent activation of the immune system. However, some causes of community-acquired pneumonia, namely viral, are associated with unexpected low levels of cytokines and depressed cellular immunity. As a result, several recent randomized controlled trials and large prospective observational studies repeatedly showed that corticosteroids had no impact on survival, and in some types of pneumonia like influenza, its use was associated with potential harmful effects like invasive aspergillosis. Apart from this, adverse effects, namely hyperglycemia, superinfections and increased length-of-stay, were frequent findings in the corticosteroid-treated patients.

Summary
According to the current evidence, corticosteroids are recommended in Pneumocystis jiroveci pneumonia in HIV-infected patients and recommendations are against its use in influenza. In all other forms of severe community-acquired pneumonia, with the exclusion of SARS-CoV-2 pneumonia, the strength of the evidence does not support the safe and widespread use of corticosteroids as adjunctive therapy. Further studies are needed to identify subgroups of severe community-acquired pneumonia that can benefit or not from corticosteroids.
Reversing Transcriptome-Wide Association Studies to improve expression Quantitative Trait Loci associations
Authors: Yuan Jie , Lai Ben , Pe’er Itsik 
Published: December 2020

1AbstractTranscriptome-Wide Association Studies discover SNP effects mediated by gene expression through a two-stage process: a typically small reference panel is used to infer SNP-expression effects, and then these are applied to discover associations between imputed expression and phenotypes. We investigate whether the accuracy of SNP-expression and expression-phenotype associations can be increased by performing inference on both the reference panel and independent GWAS cohorts simultaneously. We develop EMBER (Estimation of Mediated Binary Effects in Regression) to re-estimate these effects using a liability threshold model with an adjustment to variance components accounting for imputed expression from GWAS data. In simulated data with only gene-mediated effects, EMBER more than doubles the performance of SNP-expression linear regression, increasing meanr2from 0.3 to 0.65 with a gene-mediated variance explained of 0.01. EMBER also improves estimation accuracy when the fraction of cis-SNP variance mediated by genes is as low as 30%. We apply EMBER to genotype and gene expression data in schizophrenia by combining 512 samples from the CommonMind Consortium and 56,081 samples from the Psychiatric Genomic Consortium. We evaluate performance of EMBER in 36 genes suggested by TWAS by concordance of inferred effects with effects reported independently for frontal cortex expression. Applying the EMBER framework to a baseline linear regression model increases performance in 26 out of 36 genes (sign test p-value .0020) with an increase in meanr2from 0.200 to 0.235.
Evaluation of exosome-encapsulated miR-23a/b in the diagnosis of human coronary heart diseases
Authors: Xu Changzhi , Xiao Hui , Yi Yanhua , Zhu Donglin , Yue Xiaojing , Xi Yun 
Published: December 2020

ObjectiveCoronary heart disease (CHD) is currently one of the major causes of death with high morbidity. Due to the increasing heterogeneity and complexity in the CHDs progression, biomarkers for specific diagnosis and monitoring of disease progression need to be developed. The study was aimed to investigate the roles of serum exosomal miR-23a and miR-23b in diagnosis of CHDs.Methods16 healthy individuals and 56 patients with CHDs were enrolled in this study, including the CHDs of stable angina, unstable angina, non-ST elevation myocardial infarction (NSTEMI), ST elevation myocardial infarction (STEMI) and acute myocardial infarction (AMI). Serum exosomal miR-23a and miR-23b were quantified by Q-PCR. The associations of miR-23a/b with multiple clinical parameters were analyzed.ResultsSerum exosomal miR-23a was downregulated in the 56 CHD patients. In the specific prediction of stable angina and AMI, miR-23a achieved the area under the receiver operating characteristic (AUC-ROC) of 0.809 and 0.783, respectively. The levels of serum creatinine (CREA) and miR-23a were associated, which was consistent with risk of kidney injury in CHDs patients. Exosomal miR-23b levels showed no difference among CHD groups.ConclusionsmiR-23a may serve as a non-invasive marker in predicting stable angina and AMI. The level of miR-23a was implicated in CREA-dependent CHD-renal damage.
Coupling between ribotypic and phenotypic traits of protists across life-cycle stages and temperatures
Authors: Zou Songbao , Fu Rao , Deng Huiwen , Zhang Qianqian , Gentekaki Eleni , Gong Jun 
Published: December 2020

AbstractRelationships between ribotypic and phenotypic traits of protists across life-cycle stages remain largely unknown. Herein, we used single cells of two soil and two marine ciliate species to examine phenotypic and ribotypic traits and their relationships across lag, log, plateau, cystic stages and temperatures. We found thatColpoda inflataandC. steiniidemonstrated allometric relationships between 18S rDNA copy number per cell (CNPC), cell volume (CV), and macronuclear volume across all life-cycle stages. Integrating previously reported data ofEuplotes vannusandStrombidium sulcatumindicated taxon-dependent rDNA CNPC–CV functions. Ciliate and prokaryote data analysis revealed that the rRNA CNPC followed a unified power-law function, only if the rRNA-deficient resting cysts were not considered. Hence, a theoretical framework was proposed to estimate the relative quantity of resting cysts in the protistan populations with total cellular rDNA and rRNA copy numbers. Using rDNA CNPC was a better predictor of growth rate at a given temperature than rRNA CNPC and CV, suggesting replication of redundant rDNA operons as a key factor that slows cell division. Single-cell high throughput sequencing and analysis after correcting sequencing errors revealed multiple rDNA and rRNA variants per cell. Both encystment and temperature affected the number of rDNA and rRNA variants in several cases. The divergence of rDNA and rRNA sequence in a single cell ranged from 1% to 10%, depending on species. These findings have important implications for inferring cell-based biological traits (e.g., species richness, abundance and biomass, activity, and community structure) of protists using molecular approaches.ImportanceBased on phenotypic traits, traditional surveys usually characterize organismal richness, abundance, biomass, and growth potential to describe diversity, organization and function of protistan populations and communities. The ribosomal RNA gene (rDNA) and its transcripts have been widely used as molecular markers in ecological studies of protists. Nevertheless, the manner in which these molecules relate to cellular (organismal) and physiological traits remains poorly understood, which could lead to misinterpretations of protistan diversity and ecology. The current research highlights the dynamic nature of cellular rDNA and rRNA contents, which tightly couple with multiple phenotypic traits in ciliated protists. We demonstrate that quantity of resting cysts and maximum growth rate of a population can be theoretically estimated using ribotypic trait-based models. The intra-individual sequence polymorphisms of rDNA and rRNA can be influenced by encystment and temperature, which should be considered when interpreting species-level diversity and community structure of microbial eukaryotes.
Design Principles of the ESCRT-III Vps24-Vps2 Module
Authors: Banjade Sudeep , Shah Yousuf H. , Tang Shaogeng , Emr Scott D. 
Published: December 2020

AbstractESCRT-III polymerization is required for all ESCRT-dependent events in the cell. However, the relative contributions of the eight ESCRT-III subunits differ between each process. The minimal features of ESCRT-III proteins necessary for function, and the role for the multiple ESCRT-III subunits remain unclear. To identify essential features of ESCRT-III subunits, we previously studied the polymerization mechanisms of two ESCRT-III subunits Snf7 and Vps24, identifying the association of the helix-4 region of Snf7 with the helix-1 region of Vps24 (Banjade et al., 2019). Here, we find that mutations in the helix-1 region of another ESCRT-III subunit Vps2 can functionally replace Vps24 inS. cerevisiae. Engineering and genetic selections revealed the required features of both subunits. Our data allow us to propose three minimal features required for ESCRT-III function – spiral formation, lateral association of the spirals through heteropolymerization, and binding to the AAA+ ATPase Vps4 for dynamic remodeling.