bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Relationship between Continuity of Care with a Primary Care Provider and Duration of Work Disability in Workers with Low Back Pain: A Retrospective Cohort Study
Authors: Sheehan Luke R , Di Donato Michael , Gray Shannon E , Lane Tyler J , van Vreden Caryn , Collie Alex 
Published: March 2022

AbstractObjectiveTo determine the continuity of care (CoC) provided by general practitioners among workers with low back pain; identify personal, workplace and social factors associated with CoC in this population; and investigate if CoC is associated with working time loss.Data sourcesAn administrative database containing accepted workers’ compensation claim and service level data, for workers with back pain from five Australian jurisdictions, injured between July 2010 and June 2015.Study DesignA retrospective cohort study. Outcomes were CoC with a general practitioner, measured with the Usual Provider Continuity index, and working time loss, measured as the number of weeks for which workers’ compensation income support benefits were paid.Extraction methodsEligible workers had at least four general practitioner services, and greater than two weeks working time loss. Usual Provider Continuity index score was categorised as complete, high, moderate, or low CoC. Ordinal logistic regression models examined factors associated with Usual Provider Continuity category. Quantile regression models examined association between duration of working time loss and Usual Provider Continuity category, in four groups with different volumes of general practitioner services.Principal FindingsComplete CoC was observed in 33.8% of workers, high CoC among 37.7%, moderate CoC in 22.1%, and low CoC in 6.4%. Higher Usual Provider Continuity was associated with fewer general practitioner services, older age, living in urban areas, an occupation as a Community and Personal Service Worker or Clerical and Administrative Worker, and the state of Victoria. In workers with more than two months of time loss, those with complete CoC consistently had shorter durations of time loss.ConclusionsHigher CoC with a general practitioner is associated with less working time loss and this relationship is strongest in the sub-acute phase of low back pain.Callout BoxWhat is known on this topicContinuity of care is a key component of best practice primary careLow back pain is a condition that often requires ongoing management and care from a general practitionerThe relationship between continuity of care and work disability duration, recovery and return to work in workers with low back pain is not knownWhat this study addsWorkers with low back pain who see the same general practitioner for all services (i.e., have a greater continuity of care) generally have shorter durations of working time lossHigher continuity of care was observed in workers who had fewer PCP services, were aged over 45, lived in urban areas, and worked as a Community and Personal Service Worker or Clerical and Administrative WorkerWorkers’ compensation systems should consider policies and guidelines that increase continuity of care in injured workers
Acute temporal effect of ambient air pollution on common congenital cardiovascular defects and cleft palate: a case-crossover study
Authors: Enebish Temuulen , Franklin Meredith , Habre Rima , Breton Carrie , Tuvshindorj Nomindelger , Tumur Gantuya , Munkhuu Bayalag , Warburton David 
Published: March 2022

AbstractThis symmetric bidirectional case-crossover study examined the association between short-term ambient air pollution exposure during weeks 3-8 of pregnancy and certain common congenital anomalies in Ulaanbaatar, Mongolia, between 2014 and 2018. Using predictions from a Random Forest regression model, authors assigned daily ambient air pollution exposure of particulate matter <2.5 um aerodynamic diameter, sulphur dioxide, nitrogen dioxide, and carbon monoxide for each subject based on their administrative area of residence. We used conditional logistic regression with adjustment for corresponding apparent temperature to estimate relative odds of select congenital anomalies per IQR increase in mean concentrations and quartiles of air pollutants. The adjusted relative odds of cardiovascular defects (ICD-10 subchapter: Q20-Q28) was 2.64 (95% confidence interval: 1.02-6.87) per interquartile range increase in mean concentrations of particulate matter <2.5 um aerodynamic diameter for gestational week 7. This association was further strengthened for cardiac septal defects (ICD-10 code: Q21, odds ratio: 7.28, 95% confidence interval: 1.6-33.09) and isolated ventricular septal defects (ICD-10 code: Q21.0, odds ratio: 9.87, 95% confidence interval: 1.6-60.93). We also observed an increasing dose-response trend when comparing the lowest quartile of air pollution exposure with higher quartiles on weeks 6 and 7 for Q20-Q28 and Q21 and week 4 for Q21.0. Other notable associations include increased relative odds of cleft lip and cleft palate subchapter (Q35-Q37) and PM2.5 (OR: 2.25, 95% CI: 0.62-8.1), SO2 (OR: 2.6, 95% CI: 0.61-11.12), and CO (OR: 2.83, 95% CI: 0.92-8.72) in week 4. Our findings contribute to the limited body of evidence regarding the acute effect of ambient air pollution exposure on common adverse birth outcomes.
Organ- and function-specific anatomical organization of the vagus nerve supports fascicular vagus nerve stimulation
Authors: Jayaprakash Naveen , Song Weiguo , Toth Viktor , Vardhan Avantika , Levy Todd , Tomaio Jacquelyn , Qanud Khaled , Mughrabi Ibrahim , Chang Yao-Chuan , Rob Moontahinaz , Daytz Anna , Abbas Adam , Nassrallah Zeinab , Volpe Bruce T. , Tracey Kevin J. , Al-Abed Yousef , Datta-Chaudhuri Timir , Miller Larry , Barbe Mary F. , Lee Sunhee C. , Zanos Theodoros P. , Zanos Stavros 
Published: March 2022

AbstractVagal fibers travel inside fascicles and form branches to innervate organs and regulate organ functions. Vagus nerve stimulation (VNS) therapies activate fibers non-selectively, often resulting in reduced efficacy and side effects from non-targeted organs. Transverse and longitudinal arrangement of fibers according to functions they mediate and organs they innervate is unknown, however it is crucial for selective VNS. Using microcomputed tomography, we found that, in swine, fascicles are arranged in 2 overlapping axes, with sensory and motor fascicles separated cephalad and merging caudad, and larynx-, heart- and lung-specific fascicles separated caudad and progressively merging cephalad. Using immunohistochemistry, we found that the distribution of single fibers is highly nonuniform: myelinated afferents and efferents occupy separate fascicles, unmyelinated efferents co-localize with myelinated afferents, and small unmyelinated afferents are widely distributed. Using a multi-contact cuff electrode, we delivered fascicular cervical VNS in anesthetized and awake swine. Compound action potentials, from distinct fiber types, and organ responses, including laryngeal muscle, cough, breathing, heart rate and blood pressure responses are elicited in a radially asymmetric manner, with consistent angular separations. These results indicate that vagal fibers are anatomically organized according to functions they mediate and organs they innervate and can be asymmetrically activated by fascicular cervical VNS.
Predicting plant-related and leaf-related parameters of winter wheat using vegetation index: Should phenological correction be applied across growth stages?
Authors: Zhao Yu , Meng Yang , Feng Haikuan , Han Shaoyu , Yang Guijun , Li Zhenhai 
Published: March 2022

AbstractMost existing plant-related and leaf-related parameters models of winter wheat vary across growing seasons, but it is an open question whether a unified statistical model can be developed to predict plant-related and leaf-related parameters using VI across multiple growing seasons, or whether the phenological correction is necessary for each parameter across multiple growing seasons. To explore this question, we measured two plant-related parameters and four leaf-related parameters over five growth stages during the 2017–2021 growing seasons. A hierarchical linear model (HLM) automatically adapts the relationship between VIs and their corresponding parameter across growing seasons and assesses the contribution of phenological variables by applying a sensitivity analysis. The estimates of VI–plant-related parameters [aboveground dry biomass (AGB) and plant nitrogen concentration (PNC)] were scattered over a given growing season, unlike the relationship between VI–leaf-related parameters [leaf dry biomass (LGB), leaf nitrogen concentration (LNC), leaf area index (LAI) and soil and plant analysis development (SPAD)]. In contrast, the AGB, PNC, LGB, LNC, LAI, and SPAD HLM models are stable and can be popularized across growing seasons, with the determination coefficient R2 ranging from 0.84 to 0.86, 0.79 to 0.87, 0.70 to 0.71, 0.68 to 0.86, 0.75 to 0.81, and 0.68 to 0.70, respectively, and the root mean square error ranging from 0.13 to 0.50 t/ha, 0.01 to 0.07%, 0.01 to 0.03 t/ha, 0.02 to 0.03%, 0.02 to 0.07, and 0.47 to 0.69, respectively. The sensitivity index of the phenological information in the AGB and PNC models was 0.56–0.78 and 0.66–0.72, respectively, whereas that in the LGB, LNC, LAI, and SPAD models was 0.01–0.06, 0.01–0.10, 0.02–0.06, and 0.00–0.01, respectively. Although phenological effects have little effect on leaf-related indicators, HLM has a strong potential for application to other crops and regions.
An optimal variant to gene distance window derived from an empirical definition of cis and trans protein QTLs
Authors: Fauman Eric B , Hyde Craig 
Published: March 2022

AbstractBackgroundA genome-wide association study (GWAS) correlates variation in the genotype with variation in the phenotype across a cohort, but the causal gene mediating that impact is often unclear. When the phenotype is protein abundance, a reasonable hypothesis is that the gene encoding that protein is the causal gene. However, as variants impacting protein levels can occur thousands or even millions of base pairs from the gene encoding the protein, it is unclear at what distance this simple hypothesis breaks down.ResultsBy making the simple assumption that cis-pQTLs should be distance dependent while trans-pQTLs are distance independent, we arrive at a simple and empirical distance cutoff separating cis- and trans-pQTLs. Analyzing a recent large-scale pQTL study (Pietzner, 2021) we arrive at an estimated distance cutoff of 944 kilobasepairs (kbp) (95% confidence interval: 767–1,161) separating the cis and trans regimes.ConclusionsWe demonstrate that this simple model can be applied to other molecular GWAS traits. Since much of biology is built on molecular traits like protein, transcript and metabolite abundance, we posit that the mathematical models for cis and trans distance distributions derived here will also apply to more complex phenotypes and traits.
Learning to Control Complex Rehabilitation Robot Using High-Dimensional Interfaces
Authors: Lee Jongmin M. , Gebrekristos Temesgen , De Santis Dalia , Nejati-Javaremi Mahdieh , Gopinath Deepak , Parikh Biraj , Mussa-Ivaldi Ferdinando A. , Argall Brenna D. 
Published: March 2022

AbstractUpper body function is lost when injuries are sustained to the cervical spinal cord. Assistive machines can support the loss in upper body motor function. To regain functionality at the level of performing activities of daily living (e.g., self-feeding), though, assistive machines need to be able to operate in high dimensions. This means there is a need for interfaces with the capability to match high-dimensional operation. The body-machine interface provides this capability and has shown to be a suitable interface even for individuals with limited mobility. This is because it can take advantage of people’s available residual body movements. Previous studies using this interface have only shown that the interface can control low-dimensional assistive machines. In this pilot study, we demonstrate the interface can scale to high-dimensional robots, can be learned to control a 7-dimensional assistive robotic arm, to perform complex reaching and functional tasks, by an uninjured population. We also share results from various analyses that hint at learning, even when performance is extremely low. Decoupling intrinsic correlations between robot control dimensions seem to be a factor in learning—that is, proficiency in activating each control dimension independently may contribute to learning and skill acquisition of high-dimensional robot control. In addition, we show that learning to control the robot and learning to perform complex movement tasks can occur simultaneously.
Sizing up spotted lanternfly nymphs for instar determination and growth allometry
Authors: Bien Theodore , Alexander Benjamin H. , White Eva , Hsieh S. Tonia , Kane Suzanne Amador 
Published: March 2022

AbstractA major ongoing research effort seeks to understand the behavior, ecology and control of the spotted lanternfly (SLF) (Lycorma delicatula), a highly invasive pest in the U.S. and South Korea. These insects undergo four nymphal stages (instars) before reaching adulthood, and appear to shift host plant preferences, feeding, dispersal and survival patterns, anti-predator behaviors, and response to traps and chemical controls with each stage. However, categorizing SLF life stage is challenging for the first three instars, which have the same coloration and shape, because no comprehensive datasets exist. We present a dataset of body mass and length for SLF nymphs throughout two growing seasons and compare our results with previously-published ranges of instar body lengths. An analysis using two clustering methods revealed that 1st-3rdinstar body mass and length fell into distinct clusters that were consistent between years, supporting using these metrics to stage nymphs during a single growing season. However, the ranges for 2nd-4th instars were not consistent between our results and those from earlier studies for diverse locations. The scaling of SLF nymph body mass with body length varied between isometry (constant shape) and positive allometry (growing faster than predicted by isometry) in the two years studied. Using previously published data, we also found that SLF nymph adhesive footpad area varies in direct proportion to weight, suggesting that footpad adhesion is independent of nymphal stage, while their tarsal claws display positive allometry and hence disproportionately increasing grasp (mechanical adhesion). By contrast, mouthpart dimensions are weakly correlated with body length, consistent with predictions that these features should reflect preferred host plant characteristics rather than body size. We recommend future studies use the body mass vs length growth curve as a fitness benchmark to study how SLF instar development depends on factors such as hatch date, host plant, temperature, and geographic location, to further understanding of life history patterns that help prevent further spread of this invasive insect.
Insertion ofYFPatP5CS1andAFL1shows the potential, and potential complications, of gene tagging for functional analyses of stress-related proteins
Authors: Longkumer Toshisangba , Grillet Louis , Chang Hao-Yi , Lường Tài Chiến , Chen Chih-Yun , Putra Hadi , Schmidt Wolfgang , Verslues Paul E. 
Published: March 2022

AbstractCrispr/CAS9-enabled homologous recombination to insert a tag in frame with an endogenous gene can circumvent difficulties such as context-dependent promoter activity that complicate analysis of gene expression and protein accumulation patterns. However, there have been few reports examining whether such Gene Targeting/Gene Tagging (GT) can alter expression of the target gene. The enzyme encoded by Δ1-pyrroline-5-carboxylate synthetase 1(P5CS1) is key for stress-induced proline synthesis and drought resistance, yet its expression pattern and protein localization have been difficult to assay. We used GT to insertYFPin frame with the 5’ or 3’ ends of the endogenousP5CS1andAt14a-Like 1(AFL1) coding regions. Insertion at the 3’ end of either gene generated homozygous lines with expression of thegene-YFPfusion indistinguishable from the wild type allele. However, forP5CS1this occurred only after selfing and advancement to the T5generation allowed initial homozygous lethality of the insertion to be overcome. Once this was done, the GT-generated P5CS1-YFP plants revealed new information about P5CS1 localization and tissue-specific expression. In contrast, insertion ofYFPat the 5’ end of either gene blocked expression. The results demonstrate that GT can be useful for functional analyses of genes that are problematic to properly express by other means but also show that, in some cases, GT can disrupt expression of the target gene.Summary statementGene tagging ofArabidopsis thaliana P5CS1andAFL1shows the potential of GT for functional analysis of stress-related genes, but also provides examples of how GT can dramatically disrupt expression of the target gene.
Bayesian multi-model-based 13C15N-metabolic flux analysis quantifies carbon-nitrogen metabolism in mycobacteria
Authors: Borah Khushboo , Beyß Martin , Xu Ye , Barber Jim , Costa Catia , Newcombe Jane , Theorell Axel , Bailey Melanie J , Beste Dany JV , McFadden Johnjoe , Nöh Katharina 
Published: March 2022

AbstractMetabolic flux is the final output of cellular regulation and has been extensively studied for carbon but much less is known about nitrogen, which is another important building block for living organisms. For the pathogen Mycobacterium tuberculosis (Mtb), this is particularly important in informing the development of effective drugs targeting Mtb’s metabolism. Here we performed 13C15N dual isotopic labelling of mycobacterial steady state cultures and quantified intracellular carbon-nitrogen (CN) and nitrogen (N) fluxes in addition to carbon (C) fluxes and inferred their reaction bidirectionalities. The combination of 13C15N-MFA with a Bayesian multi-model approach allowed us to resolve C and N fluxes simultaneously which was not possible with classical 13C-MFA. We quantified CN fluxes for amino acid and, for the first time, nucleotide biosynthesis. Our analysis identified glutamate as the central CN and N node in mycobacteria, and improved resolution of the anaplerotic node. Our study describes a powerful platform to measure carbon and nitrogen metabolism in any biological system with statistical rigor.
A CRISPR screen identifies redox vulnerabilities for KEAP1/NRF2 mutant non-small cell lung cancer
Authors: Jiang Chang , Ward Nathan P. , Prieto-Farigua Nicolas , Kang Yun Pyo , Thalakola Anish , Teng Mingxiang , DeNicola Gina M. 
Published: March 2022

ABSTRACTThe redox regulator NRF2 is hyperactivated in a large percentage of non-small cell lung cancer (NSCLC) cases, which is associated with chemotherapy and radiation resistance. To identify redox vulnerabilities for KEAP1/NRF2 mutant NSCLC, we conducted a CRISPR-Cas9-based negative selection screen for antioxidant enzyme genes whose loss sensitized cells to sub-lethal concentrations of the superoxide (O2•−)-generating drug β-Lapachone. While our screen identified expected hits in the pentose phosphate pathway, the thioredoxin-dependent antioxidant system, and glutathione reductase, we also identified the mitochondrial superoxide dismutase 2 (SOD2) as one of the top hits. Surprisingly, β-Lapachone did not generate mitochondrial O2•−but rather SOD2 loss enhanced the efficacy of β-Lapachone due to loss of iron-sulfur protein function, loss of mitochondrial ATP maintenance and deficient NADPH production. Importantly, inhibition of mitochondrial electron transport activity sensitized to β-Lapachone, demonstrating these effects may be translated to increase ROS sensitivity therapeutically.
A Non-conventional Archaeal Fluorinase Identified by In Silico Mining Catalyzes the Fastest Natural Nucleophilic Fluorination
Authors: Pardo Isabel , Bednar David , Calero Patricia , Volke Daniel C. , Damborský Jiří , Nikel Pablo I. 
Published: March 2022

ABSTRACTFluorinases, the only enzymes known to catalyze the transfer of fluorine to an organic molecule, are essential biocatalysts for the sustainable synthesis of valuable organofluorines. However, the few fluorinases identified so far have low turnover rates that hamper biotechnological applications. Here, we isolated and characterized putative fluorinases retrieved from systematic in silico mining and identified a non-conventional archaeal enzyme from Methanosaeta sp. that mediates the highest fluorination rate reported to date. Furthermore, we demonstrate enhanced production of fluoronucleotides in vivo in a bacterial host engineered with this archaeal fluorinase, paving the way towards synthetic metabolism for efficient biohalogenations.Fastest biological SN2 fluorination
Inter- and intra-Subunit interactions driving the MukBEF ATPase
Authors: Bahng Soon , Kumar Rupesh , Marians Kenneth J. 
Published: March 2022

AbstractMukBEF, an SMC-like protein complex, is the bacterial condensin. It is likely that it compacts DNA via an ATP hydrolysis-dependent, DNA loop-extrusion reaction as has been demonstrated for the yeast SMC proteins condensin and cohesin. MukB also interacts with the ParC subunit of the cellular chromosomal decatenase topoisomerase IV, an interaction that is required for proper chromosome condensation and segregation in E. coli, although it suppresses the MukB ATPase activity. We have investigated the MukBEF ATPase activity, identifying inter- and intra-subunit interactions by protein-protein crosslinking and site-specific mutagenesis. We show that interactions between the hinge of MukB and its neck region are essential for the ATPase activity, that the ParC subunit of Topo IV inhibits the MukB ATPase by preventing this interaction, that MukE interaction with DNA is likely essential for viability, and that interactions between MukF and the MukB neck region are necessary for ATPase activity and viability.
PtdIns(3,4)P2, Lamellipodin, and VASP coordinate cytoskeletal remodeling during phagocytic cup formation in macrophages
Authors: Montaño-Rendón Fernando , Walpole Glenn F. W. , Krause Matthias , Hammond Gerald R.V. , Grinstein Sergio , Fairn Gregory D. 
Published: March 2022

AbstractPhosphoinositides are pivotal regulators of vesicular traffic and signaling during phagocytosis. Phagosome formation, the initial step of the process, is characterized by local membrane remodelling and reorganization of the actin cytoskeleton that leads to formation of the pseudopods that drive particle engulfment. Using genetically-encoded fluorescent probes we found that upon particle engagement a localized pool of PtdIns(3,4)P2 is generated by the sequential activities of class I phosphoinositide 3-kinases and phosphoinositide 5-phosphatases. Depletion of the enzymes responsible for this locally generated pool of PtdIns(3,4)P2 blocks pseudopod progression and ultimately phagocytosis. We show that the PtdIns(3,4)P2 effector Lamellipodin (Lpd) is recruited to nascent phagosomes by PtdIns(3,4)P2. Furthermore, we show that silencing of Lpd inhibits phagocytosis and produces aberrant pseudopodia with disorganized actin filaments. Lastly, vasodilator-stimulated phosphoprotein (VASP) was identified as a key actin-regulatory protein mediating phagosome formation downstream of Lpd. Mechanistically, our findings imply that a pathway involving PtdIns(3,4)P2, Lpd and VASP mediates phagocytosis at the stage of particle engulfment.