bluuebunny/crossref_metadata_2025_split huggingface dataset:
A New Methodology for Intraoperative Monitoring of the Functional Integrity of the Phrenic Nerve During Cardiothoracic Surgery
Authors: Lucente Giuseppe , Martinez-Barenys Carlos , Ramos-Fransi Alba , Almendrote-Muñoz Miriam , López de Castro Pedro , Deletis Vedran , Coll-Canti Jaume , Martínez-Piñeiro Alicia 
Published: December 2019

Introduction:The phrenic nerve could be easily injured during cardiothoracic surgeries because of its anatomical relationships. The aim of this study is to describe a new, feasible, and reproducible methodology to achieve a continuous intraoperative neuromonitoring of the phrenic nerve.Methods:Consecutive patients who underwent open-chest surgery were included. The recording active electrode was placed 5 cm superior to the tip of the xiphoid process, and a hook wire inserted at the motor point of the ipsilateral hemidiaphragm was used as the reference electrode.Results:We studied 45 patients (92% men, mean age 67 years). Mean height and weight were 167 ± 6.9 cm and 75.6 ± 12.3 kg, respectively. A reproducible compound motor action potential was recorded in 38 (85%) subjects. The mean latency and amplitude values were 9.68 ± 2.40 ms and 1.36 ± 3.83 mV, respectively. No intraoperative events were recorded.Conclusions:We reported a new methodology which allows the assessment of phrenic nerve functional integrity during surgical procedures.
Can chronic oral inflammation and masticatory dysfunction contribute to cognitive impairment?
Authors: Nangle Matthew R. , Manchery Nithin 
Published: December 2019

Purpose of review
This article provides an overview of current literature focused on oral health and cognitive impairment in older adulthood, focusing in particular on whether oral inflammation, tooth loss and masticatory dysfunction might increase the risk of cognitive impairment in this age group.

Recent findings
There is now general acceptance that cognitive impairment contributes to poor oral health, largely through detrimental changes in behaviours related to maintaining good oral hygiene. There is more limited evidence for the reverse causal direction, but at least some studies now suggest that inflammatory mechanisms, tooth loss and masticatory dysfunction each have the potential to contribute to cognitive decline.

Summary
Poorer oral health significantly correlates with cognitive dysfunction, and at least some studies suggest that there may be a bi-directional causal relationship. Randomized controlled trials assessing cognitive abilities in relation to oral hygiene or oral health interventions, or provision of removable or fixed (implant-supported) dentures, are encouraged.
Going around in circles: deciphering the role of circular RNAs in neurodegenerative disease
Authors: Kondo Mari A. , Mohan Adith , Mather Karen A. 
Published: December 2019

Purpose of review
Circular RNAs are highly expressed in the brain, accumulate with ageing and may play important functional roles. Hence, their role in age-related neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, is under active investigation. This review provides an overview of our current knowledge regarding the roles of circular RNAs in Alzheimer's disease and Parkinson's disease.

Recent findings
More studies have examined Alzheimer's disease than Parkinson's disease. Circular RNA 7 (ciRS-7) has been implicated in both diseases and may play a causative pathological role in at least Alzheimer's disease. The identification of circular RNA interaction networks is a primary focus. However, different analysis pipelines can generate quite disparate results, hence bioinformatically identified candidate circular RNAs require experimental and functional validation.

Summary
Although this field of research is in its infancy, rapid advances holds promise for identifying circular RNAs that are important in neurodegenerative diseases. CiRS-7 is a promising candidate for further examination. More studies are required focussing not only on Alzheimer's disease and Parkinson's disease but also on other neurodegenerative diseases. Whether circular RNAs can be used to inform diagnostic, prognostic and therapeutic strategies for age-related neurodegenerative disease remains unclear.
On the unity and diversity of cilia
Authors: Wan Kirsty Y. , Jékely Gáspár 
Published: December 2019

Cilia are specialized cellular organelles that are united in structure and implicated in diverse key life processes across eukaryotes. In both unicellular and multicellular organisms, variations on the same ancestral form mediate sensing, locomotion and the production of physiological flows. As we usher in a new, more interdisciplinary era, the way we study cilia is changing. This special theme issue brings together biologists, biophysicists and mathematicians to highlight the remarkable range of systems in which motile cilia fulfil vital functions, and to inspire and define novel strategies for future research.
This article is part of the Theo Murphy meeting issue ‘Unity and diversity of cilia in locomotion and transport’.
Asymmetries in the cilia ofChlamydomonas
Authors: Dutcher Susan K. 
Published: December 2019

The generation of ciliary waveforms requires the spatial and temporal regulation of dyneins. This review catalogues many of the asymmetric structures and proteins in the cilia ofChlamydomonas, a unicellular alga with two cilia that are used for motility in liquid medium. These asymmetries, which have been identified through mutant analysis, cryo-EM tomography and proteomics, provide a wealth of information to use for modelling how waveforms are generated and propagated.This article is part of the Theo Murphy meeting issue ‘Unity and diversity of cilia in locomotion and transport’.
Cilia-driven flows in the brain third ventricle
Authors: Eichele Gregor , Bodenschatz Eberhard , Ditte Zuzana , Günther Ann-Kathrin , Kapoor Shoba , Wang Yong , Westendorf Christian 
Published: December 2019

The brain ventricles are interconnected, elaborate cavities that traverse the brain. They are filled with cerebrospinal fluid (CSF) that is, to a large part, produced by the choroid plexus, a secretory epithelium that reaches into the ventricles. CSF is rich in cytokines, growth factors and extracellular vesicles that glide along the walls of ventricles, powered by bundles of motile cilia that coat the ventricular wall. We review the cellular and biochemical properties of the ventral part of the third ventricle that is surrounded by the hypothalamus. In particular, we consider the recently discovered intricate network of cilia-driven flows that characterize this ventricle and discuss the potential physiological significance of this flow for the directional transport of CSF signals to cellular targets located either within the third ventricle or in the adjacent hypothalamic brain parenchyma. Cilia-driven streams of signalling molecules offer an exciting perspective on how fluid-borne signals are dynamically transmitted in the brain.
This article is part of the Theo Murphy meeting issue ‘Unity and diversity of cilia in locomotion and transport’.
Cilia oscillations
Authors: Man Yi , Ling Feng , Kanso Eva 
Published: December 2019

Cilia, or eukaryotic flagella, are microscopic active filaments expressed on the surface of many eukaryotic cells, from single-celled protozoa to mammalian epithelial surfaces. Cilia are characterized by a highly conserved and intricate internal structure in which molecular motors exert forces on microtubule doublets causing cilia oscillations. The spatial and temporal regulations of this molecular machinery are not well understood. Several theories suggest that geometric feedback control from cilium deformations to molecular activity is needed. Here, we implement a recent sliding control model, where the unbinding of molecular motors is dictated by the sliding motion between microtubule doublets. We investigate the waveforms exhibited by the model cilium, as well as the associated molecular motor dynamics, for hinged and clamped boundary conditions. Hinged filaments exhibit base-to-tip oscillations while clamped filaments exhibit both base-to-tip and tip-to-base oscillations. We report the change in oscillation frequencies and amplitudes as a function of motor activity and sperm number, and we discuss the validity of these results in the context of experimental observations of cilia behaviour.This article is part of the Theo Murphy meeting issue ‘Unity and diversity of cilia in locomotion and transport’.
Testing the role of intraflagellar transport in flagellar length control using length-altering mutants ofChlamydomonas
Authors: Wemmer Kimberly , Ludington William , Marshall Wallace F. 
Published: December 2019

Cilia and flagella are ideal model organelles in which to study the general question of organelle size control. Flagellar microtubules are steady-state structures whose size is set by the balance of assembly and disassembly. Assembly requires intraflagellar transport (IFT), and measurements of IFT have shown that the rate of entry of IFT particles into the flagellum is a decreasing function of length. It has been proposed that this length dependence of IFT may be the basis for flagellar length control. Here, we test this idea by showing that three different long-flagella mutations inChlamydomonasall cause increased IFT injection, thus confirming that IFT can influence length control. However, quantitative comparisons with mathematical models suggest that the increase in injection is not sufficient to explain the full increase in length seen in these mutants; hence, some other mechanism may be at work. One alternative mechanism that has been proposed is length-regulated binding of tubulin to the IFT particles. However, we find that the apparent length dependence of tubulin loading that has previously been reported may actually reflect length-dependent organization of IFT trains.This article is part of the Theo Murphy meeting issue ‘Unity and diversity of cilia in locomotion and transport’.
An antibody drug conjugate targeting a GSTA glycosite-signature epitope of mucin1 expressed by non-small cell lung cancer
Authors: Pan Deng , Tang Yubo , Tong Jiao , Xie Chengmei , Chen Jiaxi , Feng Chunchao , Hwu Patrick , Huang Wei , Zhou Dapeng 
Published: December 2019

AbstractBackgroundAntibodies targeting abnormally glycosylated proteins have been ineffective in treating cancer. Antibody-drug conjugates are emerging as an efficient option, which allow specific delivery of drugs into tumors. We and others have dissected the abnormally glycosylated tandem repeat region of MUC1 glycoprotein as three site-specific glycosylated neoantigen peptide motifs (PDTR, GSTA, GVTS) for monoclonal antibody binding.MethodsInternalization of monoclonal antibodies was studied by immunofluorescence staining and colocalization with lysosomal markers in live cells. Antibody positivity in tumor and peritumoral tissue samples were studied by immunohistochemistry. The efficacy of anti-MUC1 ADCs were evaluated with various cancer cell lines and mouse tumor xenograft model.ResultsWe describe an anti-MUC1 ADC by conjugating GSTA neoantigen-specific 16A with monomethyl auristatin E (MMAE). 16A-MMAE showed potent antitumoral efficacy with IC50ranging from 0.2 to 49.4 nM toward multiple types of cancer cells.In vivo, 16A-MMAE showed dose-dependent inhibition of tumor growth in mouse xenograft of NCI-H838 NSCLC cell line, with minimum effective dose at 1 mg/kg. At the dose of 3 mg/kg, 16A-MMAE did not cause significant toxicity in a transgenic mouse expressing human MUC1.ConclusionsThe high antitumoral efficacy of 16A-MMAE suggest that aberrant glycosylated MUC1 neoantigen is a target with high positivity in multiple cancer types for ADC development. Personalized therapy may be achieved by development of glycosite-specific antibody-drug conjugates.
Combining molecular dynamics simulations with small-angle X-ray and neutron scattering data to study multi-domain proteins in solution
Authors: Larsen Andreas Haahr , Wang Yong , Bottaro Sandro , Grudinin Sergei , Arleth Lise , Lindorff-Larsen Kresten 
Published: December 2019

AbstractMany proteins contain multiple folded domains separated by flexible linkers, and the ability to describe the structure and conformational heterogeneity of such flexible systems pushes the limits of structural biology. Using the three-domain protein TIA-1 as an example, we here combine coarse-grained molecular dynamics simulations with previously measured small-angle scattering data to study the conformation of TIA-1 in solution. We show that while the coarse-grained potential (Martini) in itself leads to too compact conformations, increasing the strength of protein-water interactions results in ensembles that are in very good agreement with experiments. We show how these ensembles can be refined further using a Bayesian/Maximum Entropy approach, and examine the robustness to errors in the energy function. In particular we find that as long as the initial simulation is relatively good, reweighting against experiments is very robust. We also study the relative information in X-ray and neutron scattering experiments and find that refining against the SAXS experiments leads to improvement in the SANS data. Our results suggest a general strategy for studying the conformation of multi-domain proteins in solution that combines coarse-grained simulations with small-angle X-ray scattering data that are generally most easy to obtain. These results may in turn be used to design further small-angle neutron scattering experiments that exploit contrast variation through1H/2H isotope substitutions.
Radiomics Features of 18F-fluorodeoxyglucose Positron-Emission Tomography as a Novel Prognostic Signature in Colorectal Cancer
Authors: Kang Jeonghyun , Lee Jae-Hoon , Lee Hye Sun , Cho Eun-Suk , Park Eun Jung , Baik Seung Hyuk , Lee Kang Young , Park Chihyun , Yeu Yunku , Clemenceau Jean R. , Park Sunho , Xu Hongming , Hong Changjin , Hwang Tae Hyun 
Published: December 2019

AbstractPurposeThe aim of this study was to investigate the prognostic value of radiomics signatures derived from 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography (PET) in patients with colorectal cancer (CRC).MethodsFrom April 2008 to Jan 2014, we identified CRC patients who underwent 18F-FDG-PET before starting any neoadjuvant treatments and surgery. Radiomics features were extracted from the primary lesions identified on 18F-FDG-PET. Patients were divided into a training and a validation set by random sampling. A least absolute shrinkage and selection operator (LASSO) Cox regression model was applied for prognostic signature building with progression-free survival (PFS) using the training set. Using the calculated radiomics score, a nomogram was developed, and the clinical utility of this nomogram was assessed in the validation set.ResultsThree-hundred-and-eight-one patients with surgically resected CRC patients (training set 228 vs. validation set 153) were included. In the training set, a radiomics signature called a rad_score was generated using two PET-derived features such as Gray Level Run Length Matrix_Long-Run Emphasis (GLRLM_LRE) and Grey-Level Zone Length Matrix_Short-Zone Low Gray-level Emphasis (GLZLM_SZLGE). Patients with a high-rad_score in the training and validation set had shorter PFS. Multivariable analysis revealed that the rad_score was an independent prognostic factor in both training and validation sets. A radiomics nomogram, developed using rad_score, nodal stage, and lymphovascular invasion, showed good performance in the calibration curve and comparable predictive power with the staging system in the validation set.ConclusionTextural features derived from 18F-FDG-PET images may enable more detailed stratification of prognosis in patients with CRC.
Empirical decomposition of the explained variation in the variance components form of the mixed model
Authors: Schreck Nicholas 
Published: December 2019

AbstractThe coefficient of determination is a standard characteristic in linear models. It is widely used to assess the proportion of variation explained, to determine the goodness-of-fit and to compare models with different covariates. However, there has not been an agreement on a similar quantity for the class of linear mixed models yet. We introduce a natural extension of the well-known adjusted coefficient of determination in linear models to the variance components form of the linear mixed model. We propose a novel coefficient of determination which is dimensionless, has an intuitive and simple definition in terms of variance explained, is additive for several random effects and reduces to the adjusted coefficient of determination in the linear model. To this end, we prove a full decomposition of the sum of squares of the independent variable into the explained and residual variance. Based on the restricted maximum likelihood equations, we introduce a novel measure for the explained variation which we allocate specifically to the contribution of the fixed and the random covariates of the model. We illustrate on two genomic datasets that the novel coefficient of determination can be applied as an improved estimator of the heritability of complex traits. Exemplarily, we allocate the explained variation to the five chromosomes of the model plantArabidopsis thalianaand determine the contribution of each chromosome as well as cross-correlations between the chromosomes to the trait heritability.
Organelle specific protein profiling with light mediated proximal labeling in living cells
Authors: Li Zefan 
Published: December 2019

AbstractOrganelle specific protein identification is essential for understanding how cell functions on a subcellular level. Here, we report a light mediated proximal labeling (LIMPLA) strategy for organelle specific protein profiling in living cells. In this strategy, various commercial mitochondria-localized fluorescent trackers, such as Mitoview 405 and Rhodamine 123, can activate 2-Propynylamine (PA) to label proximal proteins in mitochondria under illumination. PA tagged proteins are subsequently derivatized via click chemistry with azido fluorescent dye for imaging or with azido biotin for further enrichment and mass-spec identification. This strategy can be generalized to other organelles specific protein labeling. For example, proteins in nucleus are labeled by utilizing the commercial nucleus tracker DRAQ5. As compared with other chemical strategies for subcellular protein labeling, there are several advantages for this LIMPLA strategy. First, this approach allows minimal interference to the cell’s status by avoiding exogenous gene tansduction and some special treatment such as hydrogen peroxide or serum starvation. Second, all reagents used in this strategy are commercially available without additional synthesis work. Further, this strategy holds the potential for analyzing proximal proteins of specific macromolecules that can be tagged with fluorescent dye by metabolic labeling strategy.
Graded recruitment of pupil-linked neuromodulation by parametric stimulation of the vagus nerve
Authors: Mridha Z. , de Gee J. W. , Shi Y. , Alkashgari R. , Williams J. , Suminski A. , Ward M. P. , Zhang W. , McGinley M. J. 
Published: December 2019

AbstractVagus nerve stimulation (VNS) is thought to affect neural activity by recruiting brain-wide release of neuromodulators. VNS is used in treatment-resistant epilepsy, and is increasingly being explored for other disorders, such as depression, and as a cognitive enhancer. However, the promise of VNS is only partially fulfilled due to a lack of mechanistic understanding of the transfer function between stimulation parameters and neuromodulatory response, together with a lack of biosensors for assaying stimulation efficacy in real time. We here develop an approach to VNS in head-fixed mice on a treadmill and show that pupil dilation is a reliable and convenient biosensor for VNS-evoked cortical neuromodulation. In an ‘optimal’ zone of stimulation parameters, current leakage and off-target effects are minimized and the extent of pupil dilation tracks VNS-evoked basal-forebrain cholinergic axon activity in neocortex. Thus, pupil dilation is a sensitive readout of the moment-by-moment, titratable effects of VNS on brain state.
Conglomeration of highly antigenic nucleoproteins to inaugurate a heterosubtypic next generation vaccine candidate against Arenaviridae family
Authors: Azim Kazi Faizul , Lasker Tahera , Akter Rahima , Hia Mantasha Mahmud , Bhuiyan Omar Faruk , Hasan Mahmudul , Hossain Md. Nazmul 
Published: December 2019

AbstractArenaviral infections often resulting in lethal Hemorrhagic Fevers (HF) affect primarily African and South American regions. To date, there is no FDA-approved licensed vaccine against arenaviruses and treatments have been limited to supportive therapies. Hence, the study was employed to design a highly immunogenic heterosubtypic vaccine candidate against Arenaviridae family. The whole proteomes of Lassa virus (LASV), Lymphocytic Chorio Meningitis Virus (LCMV), Lujo virus and Guanarito virus were retrieved from NCBI database and assessed to determine the most antigenic viral proteins. Only the conserved sequences were used for T cell and B cell epitope prediction to ensure protective response against a wide range of viral strains. For each virus, nucleoproteins were identified as most antigenic which generated a plethora of antigenic epitopes. The proposed epitopes were highly conserved (up to 100%) and showed high cumulative population coverage. Moreover, results revealed that among the top epitopes, T cell epitope GWPYIGSRS were conserved in Argentine mammarenavirus (Junin virus) and Brazilian mammarenavirus (Sabia virus), while B cell epitope NLLYKICLSG were conserved in Bolivian mammarenavirus (Machupo virus) and Brazilian mammarenavirus (Sabia virus), indicating the possibility of final vaccine constructs to confer broad range immunity in the host. A total 3 constructs were designed by the combination of top epitopes from each protein along with suitable adjuvant and linkers. Different physicochemical properties revealed the superiority of construct V1 in terms of safety and efficacy. Docking analysis of the refined vaccine structure with different MHC molecules and human immune receptors were also biologically significant. The vaccine receptor complex (V1-TLR3) showed minimal deformability at molecular level. Moreover, construct V1 was compatible for insertion into pET28a(+) vector and heterologous cloning inE. colisrain K12. However, the results were based on different sequence analysis and various immune databases. Further wet lab based studies using model animals are highly recommended for the experimental validation of the designed vaccine candidates.