bluuebunny/crossref_metadata_2025_split huggingface dataset:
Depressive symptoms and type II diabetes mellitus among midlife women
Authors: Im Eun-Ok , Yi Jee-Seon , Chee Wonshik 
Published: March 2021

Abstract

Objectives:
A decision tree analysis helps determine the complex characteristics of the groups that are closely connected with specific outcomes. Using a decision tree analysis, the purpose of this secondary analysis was to examine the associations of type II diabetes mellitus (DM) to depressive symptoms among midlife women from four major racial/ethnic groups in the US. while identifying the complex characteristics of the women that were closely linked to depressive symptoms.

Methods:
The data from two larger Internet survey studies were used for this analysis. The data from a total of 164 women (62 with type II diabetes and 102 without diabetes) were included. The data were collected using several instruments to measure background characteristics, health and menopausal status, and depressive symptoms (the Depression Index for Midlife Women). The data analysis was conducted using independent t tests, Mann-Whitney U tests, and decision tree analyses.

Results:
The total numbers and total severity scores of depressive symptoms were significantly higher in those with DM compared with those without DM (P < 0.05). There were significant differences in the total numbers and total severity scores of depressive symptoms by menopausal status and race/ethnicity (P < 0.05). DM was a significant factor that influenced the total severity scores of depressive symptoms among midlife women in peri- or postmenopausal stages who were born outside the US and among midlife women in their premenopausal stage (P < 0.05).

Conclusions:
This study indicated several combined characteristics of midlife women at high risk for depressive symptoms that could provide directions for future interventions.

Video Summary:
http://links.lww.com/MENO/A726.
Intraoperative Stromal Vascular Fraction Therapy Improves Histomorphometric and Vascular Outcomes in Irradiated Mandibular Fracture Repair
Authors: Urlaub Kevin M. , Ranganathan Kavitha , Lynn Jeremy V. , Luby Alexandra O. , Patrick Lauren N. , Nelson Noah S. , Donneys Alexis , Buchman Steven R. 
Published: March 2021

Background:
Cell-based treatments have demonstrated the capacity to enhance reconstructive outcomes in recent decades but are hindered in clinical utility by regulatory hurdles surrounding cell culture. This investigation examines the ability of a noncultured stromal vascular fraction derived from lipoaspirate to enhance bone healing during fracture repair to further the development of translatable cell therapies that may improve outcomes in irradiated reconstruction.

Methods:
Isogenic male Lewis rats were divided into three groups: fracture, irradiated fracture, and irradiated fracture with stromal vascular fraction treatment. Irradiated groups received a fractioned dose of 35 Gy before mandibular osteotomy. Stromal vascular fraction was harvested from the inguinal fat of isogenic donors, centrifuged, and placed intraoperatively into the osteotomy site. All mandibles were evaluated for bony union and vascularity using micro–computed tomography before histologic analysis.

Results:
Union rates were significantly improved in the irradiated fracture with stromal vascular fraction treatment group (82 percent) compared to the irradiated fracture group (25 percent) and were not statistically different from the fracture group (100 percent). Stromal vascular fraction therapy significantly improved all metrics of bone vascularization compared to the irradiated fracture group and was not statistically different from fracture. Osteocyte proliferation and mature bone formation were significantly reduced in the irradiated fracture group. Bone cellularity and maturity were restored to nonirradiated levels in the irradiated fracture with stromal vascular fraction treatment group despite preoperative irradiation.

Conclusions:
Vascular and cellular depletion represent principal obstacles in the reconstruction of irradiated bone. This study demonstrates the efficacy of stromal vascular fraction therapy in remediating these damaging effects and provides a promising foundation for future studies aimed at developing noncultured, cell-based therapies for clinical implementation.
Accuracy and precision in super-resolution MRI: Enabling spherical tensor diffusion encoding at ultra-high b-values and high resolution
Authors: Vis Geraline , Nilsson Markus , Westin Carl-Fredrik , Szczepankiewicz Filip 
Published: March 2021

AbstractDiffusion MRI (dMRI) is a useful probe of tissue microstructure but suffers from low signal-to-noise ratio (SNR) whenever high resolution and/or high diffusion encoding strengths are used. Low SNR leads not only to poor precision but also poor accuracy of the diffusion-weighted signal, as the rectified noise floor gives rise to a positive signal bias. Recently, super-resolution techniques have been proposed for signal acquisition at a low spatial resolution but high SNR, whereafter a higher spatial resolution is recovered by image reconstruction. In this work, we describe a super-resolution reconstruction framework for dMRI and investigate its performance with respect to signal accuracy and precision. Using strictly controlled phantom experiments, we show that the super-resolution approach improves accuracy by facilitating a more beneficial trade-off between spatial resolution and diffusion encoding strength before the noise floor affects the signal. Moreover, precision is shown to have a less straightforward dependency on acquisition, reconstruction, and intrinsic tissue parameters. Indeed, we find that a gain in precision from super-resolution reconstruction (SRR) is substantial only when some spatial resolution is sacrificed. We also demonstrated the value of SRR in the challenging combination of high resolution and spherical b-tensor encoding at ultrahigh b-values—a configuration that produces a unique contrast that emphasizes tissue in which diffusion is restricted in all directions. We conclude that SRR is most valuable in low-SNR conditions, where it can suppress rectified noise floor effects and recover signal with high accuracy. The in vivo application showcases a vastly superior image contrast when using SRR compared to conventional imaging, facilitating investigations of brain tissue that would otherwise have prohibitively low SNR, resolution or required non-conventional MRI hardware.
Antagonistic effects of chemical mixtures on the oxidative stress response are silenced by heat stress and reversed under dietary restriction
Authors: Arulalan Karthik Suresh , Huayta Javier , Stallrich Jonathan W. , San-Miguel Adriana 
Published: March 2021

AbstractChemical agents released into the environment can induce oxidative stress in organisms, which is detrimental for health. Although environmental exposures typically incorporate multiple chemicals, organismal studies on oxidative stress derived from chemical agents commonly study exposures to individual compounds. In this work, we explore how chemical mixtures drive the oxidative stress response under various conditions in the nematodeC. elegans, by quantitatively assessing levels ofgst-4expression. Our results indicate that naphthoquinone mixtures drive responses differently than individual components, and that altering environmental conditions, such as increased heat and reduced food availability, result in dramatically different oxidative stress responses mounted byC. elegans. When exposed to heat, the oxidative stress response is diminished. Notably, when exposed to limited food, the oxidative stress response specific to juglone is significantly heightened, while identified antagonistic interactions between some naphthoquinone components in mixtures are abolished. This implies that organismal responses to xenobiotics is confounded by environment and stressor interactions. Given the high number of variables under study, and their potential combinations, a simplex centroid design was used to capture such non-trivial response over the design space. This makes the case for the adoption of Design of Experiments approaches as they can greatly expand the experimental space probed in noisy biological readouts, and in combinatorial experiments. Our results also reveal gaps in our current knowledge of the organismal oxidative stress response, which can be addressed by employing sophisticated design of experiments approaches to identify significant interactions.
Closed-loop auditory stimulation method to modulate sleep slow waves and motor learning performance in rats
Authors: Moreira Carlos G. , Baumann Christian R. , Scandella Maurizio , Nemirovsky Sergio I. , Leach Sven , Huber Reto , Noain Daniela 
Published: March 2021

AbstractSlow waves and cognitive output have been modulated in humans by phase-targeted auditory stimulation. However, to advance its technical development and further our understanding, implementation of the method in animal models is indispensable. Here, we report the successful employment of slow waves’ phase-targeted closed-loop auditory stimulation (CLAS) in rats. To validate this new tool both conceptually and functionally, we tested the effects of up- and down-phase CLAS on proportions and spectral characteristics of sleep, and on learning performance in the single pellet-reaching task, respectively. Without affecting 24-h sleep-wake behavior, CLAS specifically altered delta (slow waves) and sigma (sleep spindles) power persistently over chronic periods of stimulation. Down-phase CLAS exerted a detrimental effect on overall engagement and success rate in the behavioral test, and overall CLAS-dependent spectral changes were positively correlated with learning performance. Altogether, our results provide proof-of-principle evidence that phase-targeted CLAS of slow waves in rodents is efficient, safe and stable over chronic experimental periods, enabling the use of this high-specificity tool for basic and preclinical translational sleep research.
Cross-Species Experiments Reveal Widespread Cochlear Neural Damage in Normal Hearing
Authors: Bharadwaj Hari M. , Hustedt-Mai Alexandra R. , Ginsberg Hannah M. , Dougherty Kelsey M. , Muthaiah Vijaya Prakash Krishnan , Hagedorn Anna , Simpson Jennifer M. , Heinz Michael G. 
Published: March 2021

AbstractAnimal models suggest that cochlear afferent nerve endings may be more vulnerable than sensory hair cells to damage from acoustic overexposure and aging, but that such damage cannot be detected in standard clinical audiometry. Co-ordinated experiments in at-risk humans and a chinchilla model using two distinct physiological assays suggest that cochlear neural damage exists even in populations without clinically recognized hearing loss.
RENET2: High-Performance Full-text Gene-Disease Relation Extraction with Iterative Training Data Expansion
Authors: Su Junhao , Wu Ye , Ting Hing-Fung , Lam Tak-Wah , Luo Ruibang 
Published: March 2021

AbstractBackgroundRelation extraction is a fundamental task for extracting gene-disease associations from biomedical text. Existing tools have limited capacity, as they can extract gene-disease associations only from single sentences or abstract texts.ResultsIn this work, we propose RENET2, a deep learning-based relation extraction method, which implements section filtering and ambiguous relations modeling to extract gene-disease associations from full-text articles. We designed a novel iterative training data expansion strategy to build an annotated full-text dataset to resolve the scarcity of labels on full-text articles. In our experiments, RENET2 achieved an F1-score of 72.13% for extracting gene-disease associations from an annotated full-text dataset, which was 27.22%, 30.30% and 29.24% higher than the best existing tools BeFree, DTMiner and BioBERT, respectively. We applied RENET2 to (1) ~1.89M full-text articles from PMC and found ~3.72M gene-disease associations; and (2) the LitCovid articles set and ranked the top 15 proteins associated with COVID-19, supported by recent articles.ConclusionRENET2 is an efficient and accurate method for full-text gene-disease association extraction. The source-code, manually curated abstract/full-text training data, and results of RENET2 are available athttps://github.com/sujunhao/RENET2.
Systematic review ofPlasmodium falciparumandPlasmodium vivaxpolyclonal infections: Impact of prevalence, study population characteristics, and laboratory procedures
Authors: Lopez Luis , Koepfli Cristian 
Published: March 2021

AbstractMultiple infections of genetically distinct clones of the samePlasmodiumspecies are common in many malaria endemic settings. Mean multiplicity of infection (MOI) and the proportion of polyclonal infections are often reported as surrogate marker of transmission intensity, yet the relationship with traditional measures such as parasite prevalence is not well understood. We have searched Pubmed for articles onP. falciparumandP. vivaxmultiplicity, and compared the proportion of polyclonal infections and mean MOI to population prevalence. The impact of the genotyping method, number of genotyping markers, method for diagnosis (microscopy/RDT vs. PCR), presence of clinical symptoms, age, geographic region, and year of sample collection on multiplicity indices were assessed. ForP. falciparum, 153 studies met inclusion criteria, yielding 275 individual data points and 33526 genotyped individuals. The proportion of polyclonal infections ranged from 0-96%, and mean MOI from 1-6.1. ForP. vivax, 54 studies met inclusion criteria, yielding 115 data points and 13325 genotyped individuals. The proportion of polyclonal infections ranged from 0-100%, and mean MOI from 1-3.8. For both species, the proportion of polyclonal infections ranged from very low to close to 100% at low prevalence, while at high prevalence it was always high. Each percentage point increase in prevalence resulted in a 0.34% increase in the proportion of polyclonalP. falciparuminfections (P<0.001), and a 0.78% increase in the proportion of polyclonalP. vivaxinfections (P<0.001). In multivariable analysis, higher prevalence, typing multiple markers, diagnosis of infections by PCR, and sampling in Africa were found to result in a higher proportion ofP. falciparumpolyclonal infections. ForP. vivax, prevalence, year of study, typing multiple markers, and geographic region were significant predictors. In conclusion, polyclonal infections are frequently present in all settings, but the association between multiplicity and prevalence is weak.
Chromatin architecture in addiction circuitry elucidates biological mechanisms underlying cigarette smoking and alcohol use traits
Authors: Sey Nancy Y.A , Hu Benxia , Iskhakova Marina , Sun Huaigu , Shokrian Neda , Hutta Gabriella Ben , Marks Jesse , Quach Bryan C. , Johnson Eric O. , Hancock Dana B. , Akbarian Schahram , Won Hyejung 
Published: March 2021

AbstractCigarette smoking and alcohol use are among the most prevalent substances used worldwide and account for a substantial proportion of preventable morbidity and mortality, underscoring the public health significance of understanding their etiology. Genome-wide association studies (GWAS) have successfully identified genetic variants associated with cigarette smoking and alcohol use traits. However, the vast majority of risk variants reside in non-coding regions of the genome, and their target genes and neurobiological mechanisms are unknown. Chromosomal conformation mappings can address this knowledge gap by charting the interaction profiles of risk-associated regulatory variants with target genes. To investigate the functional impact of common variants associated with cigarette smoking and alcohol use traits, we applied Hi-C coupled MAGMA (H-MAGMA) built upon cortical and midbrain dopaminergic neuronal Hi-C datasets to GWAS summary statistics of nicotine dependence, cigarettes per day, problematic alcohol use, and drinks per week. The identified risk genes mapped to key pathways associated with cigarette smoking and alcohol use traits, including drug metabolic processes and neuronal apoptosis. Risk genes were highly expressed in cortical glutamatergic, midbrain dopaminergic, GABAergic, and serotonergic neurons, suggesting them as relevant cell types in understanding the mechanisms by which genetic risk factors influence cigarette smoking and alcohol use. Lastly, we identified pleiotropic genes between cigarette smoking and alcohol use traits under the assumption that they may reveal substance-agnostic, shared neurobiological mechanisms of addiction. The number of pleiotropic genes was ∼26-fold higher in dopaminergic neurons than in cortical neurons, emphasizing the critical role of ascending dopaminergic pathways in mediating general addiction phenotypes. Collectively, brain region- and neuronal subtype-specific 3D genome architecture refines neurobiological hypotheses for smoking, alcohol, and general addiction phenotypes by linking genetic risk factors to their target genes.
No evidence for a special role of language in feature-based categorization
Authors: Benn Yael , Ivanova Anna A. , Clark Oliver , Mineroff Zachary , Seikus Chloe , Silva Jack Santos , Varley Rosemary , Fedorenko Evelina 
Published: March 2021

AbstractThe relationship between language and human thought is the subject of long-standing debate. One specific claim implicates language in feature-based categorization. According to this view, language resources facilitate object categorization based on a certain feature (e.g., color). Specifically, it is hypothesized that verbal labels help maintain focus on a relevant categorization criterion and reduce interference from irrelevant features. As a result, language impairment is expected to affect categorization of items grouped according to a single feature (low-dimensional categories, e.g., ‘Things that are yellow’), where many irrelevant features need to be inhibited, more than categorization of items that share many features (high-dimensional categories, e.g., ‘Animals’), where few irrelevant features need to be inhibited. In two behavioral studies with individuals with aphasia, we failed to find consistent support for the role of language in low-dimensional categorization. We also collected fMRI data from healthy adults and observed little activity in language-responsive brain regions during both low-dimensional and high-dimensional categorization. Combined, these results demonstrate that the language system is not implicated in object categorization. Our work adds to the growing evidence that, although language may assist in accessing task-relevant information (e.g., instructions), many cognitive tasks in adult brains proceed without recruiting the language system.
Optogenetic manipulation of YAP cellular localisation and function
Authors: Toh P. J. Y. , Lai J. K. H. , Hermann A. , Destaing O. , Sheetz M. P. , Sudol M. , Saunders T. E. 
Published: March 2021

AbstractYAP, an effector of the Hippo signalling pathway, promotes organ growth and regeneration. Prolonged YAP activation results in uncontrolled proliferation and cancer. Therefore, exogenous regulation of YAP activity has potential translational applications. We present a versatile optogenetic construct (optoYAP) for manipulating YAP localisation, and consequently its activity and function. We attached a LOV2 domain that photocages a nuclear localisation signal (NLS) to the N-terminus of YAP. In 488 nm light, the LOV2 domain unfolds, exposing the NLS, which shuttles optoYAP into the nucleus. Nuclear import of optoYAP is reversible and tuneable by light intensity. In cell culture, activated optoYAP promotes YAP target gene expression, cell proliferation, and anchorage-independent growth. Similarly, we can utilise optoYAP in zebrafish embryos to modulate target genes. OptoYAP is functional in both cell culture andin vivo, providing a powerful tool to address basic research questions and therapeutic applications in regeneration and disease.
Intraflagellar transport trains can turn around without the ciliary tip complex
Authors: Nievergelt Adrian Pascal , Zykov Ilia , Diener Dennis , Buchholz Tim-Oliver , Delling Markus , Diez Stefan , Jug Florian , S̆tĕpánek Ludĕk , Pigino Gaia 
Published: March 2021

AbstractCilia and flagella are microtubule doublet based organelles found across the eukaryotic tree of life. Their very high aspect ratio and crowded interior are unfavourable to diffusive transport for their assembly and maintenance. Instead, a highly dynamic system of intraflagellar transport (IFT) trains moves rapidly up and down the cilium. However, the mechanism of how these trains turn around upon reaching the ciliary tip has remained elusive. It has been hypothesized that there exists a dedicated calcium-dependent protein-based machinery at the ciliary tip to mediate this conversion. In this work, we use physical and chemical methods to manipulate IFT in the cilia of the unicellular green algaChlamydomonas reinhardtiito show that no such stationary tip-machinery is required for IFT turnaround. Instead, we demonstrate that the conversion from anterograde to retrograde IFT trains is a calcium independent intrinsic ability of the IFT system.
Cell signaling pathways in human mutant PAX6 corneal cells: an in vitro model for aniridia-related keratopathy
Authors: Słoniecka Marta , Vicente André , Byström Berit , Domellöf Fátima Pedrosa 
Published: March 2021

ABSTRACTPURPOSETo establish anin vitromodel of aniridia-related keratopathy (ARK) using CRISPR/Cas9 engineered human keratocytes with mutations in the PAX6 gene, and to study the Notch Homolog 1, Translocation-Associated (Notch1), sonic hedgehog (SHH), mammalian target of rapamycin (mTOR), and Wnt/β-catenin signaling pathways in the PAX6 mutant keratocytes.METHODSPrimary human keratocytes were isolated from healthy corneas. Keratocytes were transduced with Cas9 lentiviral particles in order to create cells stably expressing Cas9 nuclease. Lentiviral particles carrying PAX6 sgRNA were transduced into the Cas9 keratocytes creating mutants. Analysis of signaling pathways was assessed by RT-qPCR for gene expression and western blot for protein expression.RESULTSHuman keratocytes stably expressing Cas9 nuclease were created. Keratocytes carrying PAX6 gene mutation were successfully generated. PAX6 mutant keratocytes showed modified expression patterns of extracellular matrix components such as collagens and fibrotic markers. Analysis of the Notch1, SHH, mTOR, and Wnt/β-catenin signaling pathways in the PAX6 mutant keratocytes revealed altered gene and protein expression of the key players involved in these pathways.CONCLUSIONSA properly functioning PAX6 gene in keratocytes is crucial for the regulation of signaling pathways important for cell fate determination, proliferation, and inflammation. Pax6 mutation in thein vitrosettings leads to changes in these pathways which resemble those found in corneas of patients with ARK.