bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circadian regulation of breath alcohol concentration
Authors: Rukmini A V , Jos Anna Mini , Yeo Sing-Chen , Lee Noel , Mo Di , Mohapatra Litali , Karamchedu Swathy , Gooley Joshua J 
Published: December 2020

Abstract

Study Objectives
The role of the circadian clock in regulating blood/breath alcohol levels after consuming alcohol is uncertain. Our goal was to evaluate the degree to which the circadian system regulates breath alcohol concentration (BrAC) pharmacokinetic parameters.

Methods
Twenty healthy adults aged 21–30 years took part in a 4-day laboratory study. A 40-h constant routine procedure was used to assess circadian rhythms. Every 4 h, participants were given a fixed oral dose of alcohol with breathalyzer measurements taken every 5 min to construct BrAC curves. Sinusoidal models were used to test for circadian variation of the peak BrAC, the time to reach peak BrAC, the absorption rate, the elimination rate, and the time for BrAC to return to zero after alcohol was ingested.

Results
A significant circadian rhythm was detected for group-averaged peak BrAC values and the time for BrAC to return to zero, but not other BrAC variables. Peak BrAC values were lowest in the evening near the peak of the core body temperature rhythm and nadir of the salivary cortisol rhythm. Peak BrAC values increased during the night and reached their highest levels in the morning and afternoon. The time needed for BrAC to return to zero was also longest in the late morning and afternoon.

Conclusion
The circadian system modulates some BrAC pharmacokinetic parameters. In normally entrained individuals, taking the same oral dose of alcohol at different times of day can result in different BrAC responses. These findings have potential implications for alcohol-related accidents and alcohol toxicity.
Carbon Dioxide Expiration and Performance Fatigability Following Aerobic Exercise Training
Authors: Wooten Liana C. , Neville Brian T. , Guccione Andrew A. , Chin Lisa M.K. , Keyser Randall E. 
Published: December 2020

Purpose:
This study examined the influence of aerobic exercise training (AET) on components of carbon dioxide expiration (VCO2), cardiorespiratory function, and fatigability.

Methods:
Twenty healthy adults completed peak cardiopulmonary exercise (CPX) and submaximal tests before and after a vigorous, 4-week AET regimen. Each test was followed by a 10-minute recovery and endurance test at 70% of peak wattage attained during CPX. Fatigability was assessed using testing durations and power output. Respiratory buffering (excess VCO2) and nonbuffering (metabolic VCO2) were calculated. Data were analyzed for significance (P < .05) using regressions and paired t-tests.

Results:
Significant improvements in all measures of fatigability were observed after AET. A significant increase in excess VCO2 was observed, although not in metabolic VCO2. Excess VCO2 was strongly predictive of fatigability measures.

Conclusion:
Significant decreases in fatigability are often observed in clinical populations such as obstructive or restrictive lung disease or pulmonary hypertension following AET, even when peak cardiorespiratory function does not appear to adapt. Decreases in fatigability seem to predict longevity with no yet identified mechanism. These results suggest that respiratory buffering and metabolic components of VCO2 may adapt independently to AET, introducing foundational plausibility for an influence of respiratory buffering adaptation to AET on fatigability status.
Precision Medicine in Ossiculoplasty
Authors: Mukherjee Payal , Cheng Kai , Chung Johnson , Grieve Stuart M. , Solomon Michael , Wallace Gordon 
Published: December 2020

Introduction:
Long term results of ossiculoplasty surgery are considered poor with displacement and extrusion amongst the common reasons for failure. Application of 3Dimensional (3D) printing may help overcome some of these barriers, however digital methods to attain accurate 3D morphological studies of ossicular anatomy are lacking, exacerbated by the limitation of resolution of clinical imaging.

Methods:
20 human cadaveric temporal bones were assessed using micro computed tomography (CT) imaging to demonstrate the lowest resolution required for accurate 3D reconstruction. The bones were then scanned using conebeam CT (125 μm) and helical CT (0.6 mm). 3D reconstruction using clinical imaging techniques with microCT imaging (40 μm resolution) as a reference was assessed. The incus was chosen as the focus of study. Two different methods of 3D printing techniques were assessed.

Results:
A minimum resolution of 100 μm was needed for adequate 3D reconstruction of the ossicular chain. Conebeam CT gave the most accurate data on 3D analysis, producing the smallest mean variation in surface topography data relative to microCT (mean difference 0.037 mm, p < 0.001). Though the incus varied in shape in between people, paired matches were identical. Thus, the contralateral side can be used for 3D printing source data if the ipsilateral incus is missing. Laser based 3D printing was superior to extrusion based printing to achieve the resolution demands for 3D printed ossicles.

Conclusion:
Resolution of modern imaging allows 3D reconstructions and 3D printing of human ossicles with good accuracy, though it is important to pay attention to thresholding during this process.
Management of Intractable Petrous Bone Cholesteatoma With a Combined Translabyrinthine–Transsphenoidal Approach
Authors: Morino Tsunetaro , Yamamoto Yutaka , Yamamoto Kazuhisa , Komori Manabu , Asaka Daiya , Kojima Hiromi 
Published: December 2020

Objective:
To evaluate whether a combined translabyrinthine–transsphenoidal approach can be used to achieve adequate surgical resection of an extensive petrous bone cholesteatoma and create a debris drainage route for the residual cholesteatoma that is maintained long-term.

Patient:
A 71-year-old man with residual petrous temporal bone cholesteatoma that had spread extensively to the internal carotid artery and posterior cranial fossa.

Intervention:
Surgical resection of the cholesteatoma via a translabyrinthine approach and creation of a debris drainage route into the nasopharynx via a transsphenoidal approach.

Main Outcome Measures:
Control of unresectable petrous temporal bone cholesteatoma and occurrence of cholesteatoma- or surgery-related complications.

Results:
Although complete removal of the cholesteatoma was attempted via a translabyrinthine approach, this was not possible because the epithelium of the cholesteatoma was strongly attached to the internal carotid artery and posterior cranial fossa. A debris drainage route leading to the nasopharynx was created by drilling the clivus on the side of the lesion via a transsphenoidal approach. The patient has had no complications since surgery. The drainage route remains open, and the cholesteatoma has been controlled for 57 months.

Conclusions:
A markedly advanced petrous temporal bone cholesteatoma can be managed safety and reliably by combining a translabyrinthine approach with a transsphenoidal approach. Creation of a debris drainage route into the nasopharynx can prevent isolation of the cholesteatoma and mastoid cavity problems after surgery. This one-stage surgery may be a suitable method for keeping cholesteatoma under control in patients with unresectable petrous bone cholesteatoma.
Posttraumatic Dizziness: Navigating the Maze Towards Accurate Vestibular Diagnosis and Treatment
Authors: Grzesiak Melissa , Carender Wendy , Basura Gregory J. 
Published: December 2020

Objective:
Highlight the importance of establishing a differential diagnosis to identify and treat multiple origins of dizziness in a patient following traumatic brain injury (TBI).

Patient:
73-year-old man with TBI and temporal bone fracture developed posttraumatic bilateral multiple canal benign paroxysmal positional vertigo (BPPV).

Intervention:
Multi-disciplinary diagnostic evaluation and vestibular rehabilitation (VR) treatment focused on canalith repositioning maneuvers (CRMs) and central adaptation.

Main Outcome Measures:
Diagnostic imaging, audiometric testing, clinical evaluation including video recordings of patterns of nystagmus, Dizziness Handicap Inventory (DHI).

Results:
Systematic clinical examination identified multiple semicircular canal BPPV in addition to a suspected underlying unilateral hypofunction. Treatment focused on the appropriate CRMs and adaptation exercises. DHI scores improved significantly and patient returned to work and recreational activities.

Conclusion:
This Clinical Capsule Report highlights the importance of a comprehensive clinical evaluation of the TBI patient with dizziness when making an accurate diagnosis and treatment plan. Due to the complexity of differentiating between multiple canal BPPV in addition to other central and vestibular disorders, it is imperative for the clinician to have a clear understanding of nystagmus patterns for multicanal BPPV as well as other vestibular pathology.
Social and racial inequalities in COVID-19 risk of hospitalisation and death across São Paulo state, Brazil
Authors: Li Sabrina L , Pereira Rafael H M , Prete Carlos A , Zarebski Alexander E , Emanuel Lucas , Alves Pedro JH , Peixoto Pedro S , Braga Carlos KV , de Souza Santos Andreza A , de Souza William M , Barbosa Rogerio J , Buss Lewis F , Mendrone Alfredo , de Almeida-Neto Cesar , Ferreira Suzete C , Salles Nanci A , Marcilio Izabel , Wu Chieh-Hsi , Gouveia Nelson , Nascimento Vitor H , Sabino Ester C , Faria Nuno R , Messina Jane P 
Published: December 2020

SummaryBackgroundLittle evidence exists on the differential health effects of COVID-19 on disadvantaged population groups. Here we characterise the differential risk of hospitalisation and death in São Paulo state, Brazil and show how vulnerability to COVID-19 is shaped by socioeconomic inequalities.MethodsWe conducted a cross-sectional study using hospitalised severe acute respiratory infections (SARI) notified from March to August 2020, in theSistema de Monitoramento Inteligente de São Paulo(SIMI-SP) database. We examined the risk of hospitalisation and death by race and socioeconomic status using multiple datasets for individual-level and spatio-temporal analyses. We explained these inequalities according to differences in daily mobility from mobile phone data, teleworking behaviour, and comorbidities.FindingsThroughout the study period, patients living in the 40% poorest areas were more likely to die when compared to patients living in the 5% wealthiest areas (OR: 1·60, 95% CI: 1·48 – 1·74) and were more likely to be hospitalised between April and July, 2020 (OR: 1·08, 95% CI: 1·04 – 1·12). Black andPardoindividuals were more likely to be hospitalised when compared to White individuals (OR: 1·37, 95% CI: 1·32 – 1·41; OR: 1·23, 95% CI: 1·21 – 1·25, respectively), and were more likely to die (OR: 1·14, 95% CI: 1·07 – 1·21; 1·09, 95% CI: 1·05 – 1·13, respectively).InterpretationLow-income and Black andPardocommunities are more likely to die with COVID-19. This is associated with differential access to healthcare, adherence to social distancing, and the higher prevalence of comorbidities.FundingThis project was supported by a Medical Research Council-São Paulo Research Foundation (FAPESP) CADDE partnership award (MR/S0195/1 and FAPESP 18/14389-0) (http://caddecentre.org/). This work received funding from the U.K. Medical Research Council under a concordat with the U.K. Department for International Development.
Increased prefrontal top-down control in older adults predicts motor performance and age-group association
Authors: Loehrer Philipp Alexander , Nettersheim Felix Sebastian , Oehrn Carina , Homberg Fabienne , Tittgemeyer Marc , Timmermann Lars , Weber Immo 
Published: December 2020

AbstractBimanual motor control declines during ageing, affecting the ability of older adults to maintain independence. An important underlying factor is cortical atrophy, particularly affecting frontal and parietal areas in older adults. As these regions and their interplay are highly involved in bimanual motor preparation, we investigated age-related connectivity changes between prefrontal and premotor areas of young and older adults during the preparatory phase of complex bimanual movements using high-density electroencephalography. Generative modelling showed that excitatory interhemispheric prefrontal to premotor coupling in older adults predicted age-group affiliation and was associated with poor motor-performance. In contrast, excitatory intrahemispheric prefrontal to premotor coupling enabled older adults to maintain motor-performance at the cost of lower movement speed. Our results disentangle the complex interplay in the prefrontal-premotor network during movement preparation underlying reduced bimanual control and the well-known speed-accuracy trade-off seen in older adults.
A comparative study of deconvolution methods for RNA-seq data under a dynamic testing landscape
Authors: Jin Haijing , Liu Zhandong 
Published: December 2020

AbstractDeconvolution analyses have been widely used to track compositional alternations of cell-types in gene expression data. Even though numerous novel methods have been developed in recent years, researchers are still having difficulty selecting optimal deconvolution methods due to the lack of comprehensive benchmarks relative to the newly developed methods. To systematically reveal the pitfalls and challenges of deconvolution analyses, we studied the impact of several technical and biological factors such as simulation model, quantification unit, component number, weight matrix, and unknown content by constructing three benchmarking frameworks that cover comparative analysis of 11 popular deconvolution methods under 1,766 conditions. We hope this study can provide new insights to researchers for future application, standardization, and development of deconvolution tools on RNA-seq data.
IGI-LuNER: single-well multiplexed RT-qPCR test for SARS-CoV-2
Authors: Stahl Elizabeth C. , Tsuchida Connor A. , Hamilton Jennifer R. , Lin-Shiao Enrique , McDevitt Shana L. , Moehle Erica A. , Witkowsky Lea B. , Tsui C. Kimberly , Pestal Kathleen , Gildea Holly K. , McElroy Matthew , Keller Amanda , Sylvain Iman , Williams Clara , Hirsh Ariana , Ciling Alison , Ehrenberg Alexander J. ,   IGI SARS-CoV-2 consortium, Urnov Fyodor D. , Ringeisen Bradley R. , Giannikopoulos Petros , Doudna Jennifer A. 
Published: December 2020

AbstractCommonly used RT-qPCR-based SARS-CoV-2 diagnostics require 2-3 separate reactions or rely on detection of a single viral target, adding time and cost or risk of false-negative results. Currently, no test combines detection of widely used SARS-CoV-2 E- and N-gene targets and a sample control in a single, multiplexed reaction. We developed the IGI-LuNER RT-qPCR assay using the Luna Probe Universal One-Step RT-qPCR master mix with publicly available primers and probes to detect SARS-CoV-2 N gene, E gene, and human RNase P (NER). This combined, cost-effective test can be performed in 384-well plates with detection sensitivity suitable for clinical reporting, and will aid in future sample pooling efforts, thus improving throughput of SARS-CoV-2 detection.Graphical Abstract
The first dinosaur egg remains a mystery
Authors: Legendre Lucas J. , Rubilar-Rogers David , Vargas Alexander O. , Clarke Julia A. 
Published: December 2020

AbstractA recent study by Norell et al. (2020) described new egg specimens for two dinosaur species, identified as the first soft-shelled dinosaur eggs. The authors used phylogenetic comparative methods to reconstruct eggshell type in a sample of reptiles, and identified the eggs of dinosaurs and archosaurs as ancestrally soft-shelled, with three independent acquisitions of a hard eggshell among dinosaurs. This result contradicts previous hypotheses of hard-shelled eggs as ancestral to archosaurs and dinosaurs. Here we estimate the ancestral condition for dinosaur and archosaur eggs by reanalyzing the original data from Norell et al. and that from a recent study on reptile eggshells (Legendre et al., 2020) with the addition of these new dinosaur specimens. We show that the recovery of dinosaur eggs as ancestrally soft-shelled is conditioned by the discretization of a continuous character (eggshell thickness), the exclusion of turtle outgroups from the original sample, and a lack of branch length information. When using a larger sample, calibrated trees, and a definition of hard-shelled eggs referencing their unique prismatic structure, we recover dinosaur and archosaur eggs as either hard-shelled or uncertain (i.e. equal probability for hard- and soft-shelled). This remaining ambiguity is due to uncertainty in the assessment of eggshell type in two dinosaur species, i.e. ∼1% of the total sample. We conclude that more reptile egg specimens and a strict comparative framework are necessary to decipher the evolution of dinosaur eggs in a phylogenetic context.
The function of SIRT3 explored through the substrate interaction network
Authors: Nahálková Jarmila 
Published: December 2020

AbstractSIRT3 is the mitochondrial protein lysine deacetylase with a prominent role in the maintenance of mitochondrial integrity vulnerable in the range of diseases. The present study examines the SIRT3 substrate interaction network for the identification of its biological functions in the cellular anti-aging mechanisms. The pathway enrichment, the protein function prediction, and the protein node prioritization analysis were performed based on 407 SIRT3 substrates, which were collected by the data mining. The substrates are interlinked by 1230 direct protein-protein interactions included in the GeneMania database. The analysis of the SIRT3 substrate interaction network highlighted Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and non-alcoholic fatty liver disease (NAFLD) as the most associated with SIRT3 lysine deacetylase activity. The most important biological functions of SIRT3 substrates are within the respiratory electron transport chain, tricarboxylic acid cycle and fatty acid, triacylglycerol, and ketone body metabolism. In brown adipose tissue, SIRT3 activity contributes to the adaptive thermogenesis by the increase of energy production of the organisms. SIRT3 exhibits several modes of neuroprotective actions in the brain and liver including prevention of the mitochondrial damages due to the respiratory electron transfer chain failure, the quenching of ROS, the inhibition of the mitochondrial membrane potential loss, and the regulation of mitophagy. Related to its role in Alzheimer’s disease, SIRT3 activation performs as a repressor of BACE1 through SIRT3-LKB1-AMPK-CREB-PGC-1α-PPARG-BACE1 (SIRT3-BACE1) pathway, which was created based on the literature mining and by employing Wikipathways application. The pathway enrichment analysis of the extended interaction network of the SIRT3-BACE1 pathway nodes displayed the functional relation to the circadian clock, which also deteriorates during the progress of AD and it is the causative of AD, PD, and HD. The use of SIRT3 activators in combination with the stimulating effect of regular exercise is further discussed as an attractive option for the improvement of cognitive decline during aging and the progressive stages of neurodegeneration.
Distinct cortical correlation structures of fractal and oscillatory neuronal activity
Authors: Chaoul Andrea Ibarra , Siegel Markus 
Published: December 2020

AbstractElectrophysiological population signals contain oscillatory and fractal (1/frequency) components. So far research has largely focused on oscillatory activity and only recently interest in fractal population activity has gained momentum. Accordingly, while the cortical correlation structure of oscillatory population activity has been characterized, little is known about the correlation of fractal neuronal activity. To address this, we investigated fractal neuronal population activity in the human brain using resting-state magnetoencephalography (MEG). We combined source-analysis, signal orthogonalization and irregular-resampling auto-spectral analysis (IRASA) to systematically characterize the cortical distribution and correlation of fractal neuronal activity. We found that fractal population activity is robustly correlated across the cortex and that this correlation is spatially well structured. Furthermore, we found that the cortical correlation structure of fractal activity is similar but distinct from the correlation structure of oscillatory neuronal activity. Anterior cortical regions showed the strongest differences between oscillatory and fractal correlation patterns. Our results suggest that correlations of fractal population activity serve as robust markers of cortical network interactions. Furthermore, our results show that fractal and oscillatory signal components provide non-redundant information about large-scale neuronal correlations. This may reflect at least partly distinct neuronal mechanisms underlying and reflected by oscillatory and fractal neuronal population activity.
TrancriptomeReconstructoR: data-driven annotation of complex transcriptomes
Authors: Ivanov Maxim , Sandelin Albin , Marquardt Sebastian 
Published: December 2020

AbstractBackgroundThe quality of gene annotation determines the interpretation of results obtained in transcriptomic studies. The growing number of genome sequence information calls for experimental and computational pipelines forde novotranscriptome annotation. Ideally, gene and transcript models should be called from a limited set of key experimental data.ResultsWe developed TranscriptomeReconstructoR, an R package which implements a pipeline for automated transcriptome annotation. It relies on integrating features from independent and complementary datasets: i) full-length RNA-seq for detection of splicing patterns and ii) high-throughput 5’ and 3’ tag sequencing data for accurate definition of gene borders. The pipeline can also take a nascent RNA-seq dataset to supplement the called gene model with transient transcripts.We reconstructedde novothe transcriptional landscape of wild typeArabidopsis thalianaseedlings as a proof-of-principle. A comparison to the existing transcriptome annotations revealed that our gene model is more accurate and comprehensive than the two most commonly used community gene models, TAIR10 and Araport11. In particular, we identify thousands of transient transcripts missing from the existing annotations. Our new annotation promises to improve the quality ofA.thalianagenome research.ConclusionsOur proof-of-concept data suggest a cost-efficient strategy for rapid and accurate annotation of complex eukaryotic transcriptomes. We combine the choice of library preparation methods and sequencing platforms with the dedicated computational pipeline implemented in the TranscriptomeReconstructoR package. The pipeline only requires prior knowledge on the reference genomic DNA sequence, but not the transcriptome. The package seamlessly integrates with Bioconductor packages for downstream analysis.