bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vestibular-autonomic interactions: beyond orthostatic dizziness
Authors: Bogle Jamie M. , Benarroch Eduardo , Sandroni Paola 
Published: November 2021

Purpose of review
This review aims to summarize the current literature describing vestibular-autonomic interactions and to describe their putative role in various disorders’ clinical presentations, including orthostatic dizziness and motion sensitivity.

Recent findings
The vestibular-autonomic reflexes have long been described as they relate to cardiovascular and respiratory function. Although orthostatic dizziness may be in part related to impaired vestibulo-sympathetic reflex (orthostatic hypotension), there are various conditions that may present similarly. A recent clinical classification aims to improve identification of individuals with hemodynamic orthostatic dizziness so that appropriate recommendations and management can be efficiently addressed. Researchers continue to improve understanding of the underlying vestibular-autonomic reflexes with recent studies noting the insular cortex as a cortical site for vestibular sensation and autonomic integration and modulation. Work has further expanded our understanding of the clinical presentation of abnormal vestibular-autonomic interactions that may occur in various conditions, such as aging, peripheral vestibular hypofunction, traumatic brain injury, and motion sensitivity.

Summary
The vestibular-autonomic reflexes affect various sympathetic and parasympathetic functions. Understanding these relationships will provide improved identification of underlying etiology and drive improved patient management.
COVID-19 trends and severity among symptomatic children aged 0-17 years in ten EU countries, 3 August 2020 – 3 October 2021
Authors: Bundle Nick , Dave Nishi , Pharris Anastasia , Spiteri Gianfranco , Deogan Charlotte , Suk Jonathan E. ,   study group members
Published: November 2021

AbstractTo guide evidence-based prevention of COVID-19 in children, we estimated risks of severe outcomes in 820,404 symptomatic paediatric cases reported by 10 EU Member States between August 2020 and October 2021. Case and hospitalisation rates rose as overall transmission increased but severe outcomes were rare: 9,611 (1.2%) were hospitalised, 640 (0.08%) required intensive care and 84 (0.01%) died. Despite increased individual risk (aOR; 95% CI for hospitalisation: 7.3; 3.3 - 16.2, ICU: 8.7; 6.2 - 12.3) in cases with comorbidities such as cancer, diabetes, cardiac or lung disease, most (83.7%) hospitalised children had no reported comorbidity.
The reproduction process of Gram-positive protocells
Authors: Kanaparthi Dheeraj , Lampe Marko , Krohn Jan-Hagen , Zhu Baoli , Hildebrand Falk , Boesen Thomas , Klingl Andreas , Phapale Prasad , Lueders Tillmann 
Published: November 2021

AbstractProkaryotes are hypothesized to have evolved from more primitive protocells. Unlike present-day cells, protocells are thought to have been devoid of complex molecular biological processes. They are believed to have mediated reproduction entirely by biophysical forces under favorable environmental conditions. Despite this proposition, little is known about the actual mechanism of their reproduction. To understand the reproduction process of protocells in their native habitat, here we used a top-down approach to transform bacterial cells into a primitive lipid vesicle-like state. Given that environmental conditions are thought to have played an essential role in mediating protocell reproduction, we then studied these cells under the presumed environmental conditions of Archaean Eon Earth. Even in the absence of functioning biological processes, cells in our study reproduced in a defined sequence of steps, always leading to the formation of viable daughter cells. Their reproduction mechanism can be explained by the interaction between intracellular metabolism, physicochemical properties of cell constituents, and, most importantly, environmental conditions. Given the simplicity of this reproduction mechanism and its suitability to environmental conditions of early Earth, we propose that protocells reproduced by this process. Moreover, this method of reproduction is also in tune with the earlier theoretical propositions on protocells, the results of the top- down approach of building a minimal cell, and the paleontological record of the Achaean Eon. Our study is the first to bridge the gap between non-living systems like lipid vesicles, living cells, and the paleontology of the Archaean Eon.
US women screen at lower rates for both cervical and colorectal cancers than a single cancer
Authors: Harper Diane M , Plegue Melissa , Jimbo Masahito , Sen Ananda , Gorin Sherri Sheinfeld 
Published: November 2021

AbstractIntroductionUsing screen counts, women 50-64 yo have lower cancer screening rates for cervical and colorectal cancers compared to all other age ranges. The primary aim of this paper is to present cervical cancer and CRC screenings per woman and determine the predictors of being up-to-date for both.MethodsWe used the Behavioral Risk Factor Surveillance System (BRFSS), an annual survey to guide health policy in the US, to explore the up-to-date status of dual cervical and colorectal cancer screening for women 50-64 yo. We categorized women into four mutually exclusive categories: up-to-date for dual screening, each single-screen, or neither screen. Multinomial multivariate regression modeling was used to evaluate the predictors of each category.ResultsAmong women ages 50-64 yo, dual screening was reported for 58.7% (57.6-59.9), cervical cancer screening alone (27.0% (25.9-28.1), CRC screening alone (5.3% (4.8-5.8), and neither screen (9% (8.4-9.6). Age, race, education, income, and chronic health conditions were significantly associated with dual screening compared to neither screen. Hispanic women compared to non-Hispanic White women were more likely to be up-to-date with cervical cancer screening than dual screening (aOR 1.38 (1.08, 1.77). By comparison to younger women, those 60-64 years are significantly more likely to be up-to-date with CRC screening than dual screening (aOR 1.75 (1.30, 2.34)).ConclusionsScreening received by each woman shows a much lower rate of dual screening than prior single cancer screening rates. Addressing dual screening strategies rather than single cancer screening programs for women 50-64 years may increase both cancer screening rates.Graphical AbstractScreening rates differ by calculation approach. A better population metric for cancer prevention is to consider the screens each woman has received. Our data show much lower cervical cancer and CRC screening rates than a single screen calculation.TweetWomen 50-64 years old lack dual cervical and colorectal cancer screening. Women who screen for only one cancer of the two, screen for cervical cancer almost five times more often than colorectal cancer.Lay SummaryRoutine cervical and colorectal cancer (CRC) screenings can detect early, treatable, curable cancers. Using the responses to the 2018 Behavioral Risk Factor Surveillance Survey (BRFSS) we approached prevention by what the woman has received rather than by how many screens were done. We showed that women 50-64 years old were only up-to-date for both cervical and CRC screening 59% of the time, whereas, by traditional screening calculations, our data showed 86% of women were up-to-date for cervical cancer screening and 64% were up to date with CRC screening, irrespective of any other cancer screenings.
Likelihood of infecting or getting infected with COVID-19 as a function of vaccination status, as investigated with a stochastic model for New Zealand (Aotearoa) for Delta and Omicron variants
Authors: Watson Leighton M. 
Published: November 2021

AbstractAimThe New Zealand government has transitioned from the Alert Level framework, which relied on government action and population level controls, to the COVID-19 Protection Framework, which relies on vaccination rates and allows for greater freedoms (for the vaccinated). Under the COVID-19 Protection Framework and current widespread community transmission of Omicron, there is significant interest in understanding the relative risk of spreading COVID-19 posed by unvaccinated, vaccinated, and boosted individuals.MethodsA stochastic branching process model is used to simulate the spread of COVID-19 for outbreaks seeded by unvaccinated, vaccinated, or boosted individuals. The likelihood of infecting or getting infected with COVID-19 is calculated based on vaccination status. The model is applied to both the Delta and Omicron variants.ResultsFor the Delta variant a vaccinated traveler infected with COVID-19 is 9x less likely to seed an outbreak than an unvaccinated traveler infected with COVID-19, however, for the Omicron variant there is little difference between outbreaks seeded by unvaccinated and vaccinated individuals (boosted individuals are slightly less likely to seed large outbreaks). For the Delta variant unvaccinated individuals are responsible for 87% of all infections whereas only 3% of infections are from vaccinated to vaccinated when normalized by population. Therefore, a vaccinated individual is 6.8x more likely to be infected by an unvaccinated individual than by a vaccinated individual. For the Omicron variant unvaccinated individuals are responsible for 45% of all infections compared to 39% for vaccinated (two-doses) and 15% for boosted (three-doses) individuals when normalized by population. Despite the vaccine being less effective at preventing breakthrough transmission for Omicron, only 3% of all infections are from boosted to boosted individuals when normalized by population indicating that three doses of the vaccine provide good protection from infection and breakthrough transmission.ConclusionsThis work demonstrates that most new infections are caused by unvaccinated individuals, especially for the Delta variant. These simulations illustrate the importance of vaccination in stopping individuals from becoming infected with COVID-19 and in preventing onward transmission. For Omicron, individuals vaccinated with two doses are only slightly less likely to spread COVID-19 than those who are unvaccinated. This work suggests that for the current Omicron outbreak the COVID-19 Protection Framework should potentially be updated to distinguish between those who have received two primary doses of the Pfizer-BioNTech vaccine (vaccinated individuals) and those who have received three doses (boosted individuals).
Multi-omics Analyses Provide Insight into the Biosynthesis Pathways of Fucoxanthin in Isochrysis galbana
Authors: Chen Duo , Yuan Xue , Zheng XueHai , Fang Jingping , Lin Gang , Li Rongmao , Chen Jiannan , He Wenjin , Huang Zhen , Fan Wenfang , Liang Limin , Lin Chentao , Zhu Jinmao , Chen Youqiang , Xue Ting 
Published: November 2021

AbstractIsochrysis galbana is considered an ideal bait for functional foods and nutraceuticals in humans because of its high fucoxanthin (Fx) content. However, multi-omics analysis of the regulation networks for Fx biosynthesis in I. galbana has not been reported. In this study, we report a high-quality genome sequence of I. galbana LG007, which has a 92.73 Mb genome size, with a contig N50 of 6.99 Mb and 14,900 protein-coding genes. Phylogenomic inferences confirmed the monophyly of Haptophyta, with I. galbana sister to Emiliania huxleyi and Chrysochromulina tobinii. Evolutionary analysis revealed an estimated divergence time between I. galbana and E. huxleyi of ~ 133 million years ago (Mya). Gene family analysis indicated that lipid metabolism-related genes exhibited significant expansion, including IgPLMT, IgOAR1 and Δ-4 desaturase. Metabolome analysis showed that the content of carotenoid in I. galbana cultured under green light for 7 days was higher than that of white light, and β-carotene was the main carotenoids, accounting for 79.09% of the total carotenoids. Comprehensive analysis of multi-omics analysis revealed that β-carotene, antheraxanthin, zeaxanthin, and Fx content was increased by green light induction, which was significantly correlated with the expression of IgMYB98, IgZDS, IgPDS, IgLHCX2, IgZEP, IgLCYb, and IgNSY. These findings contribute to understanding Fx biosynthesis and its regulation, providing a valuable reference for food and pharmaceutical applications.
Global analysis of human-to-mouse contact-dependent intercellular mRNA and lncRNA transfer in cell culture
Authors: Dasgupta Sandipan , Dayagi Daniella Y. , Haimovich Gal , Wyler Emanuel , Olender Tsviya , Singer Robert H. , Landthaler Markus , Gerst Jeffrey E. 
Published: November 2021

SummaryFull-length mRNAs can transfer between adjacent mammalian cells via direct cell-to-cell connections called tunneling nanotubes (TNTs). However, the extent of mRNA transfer at the transcriptome-wide level (thetransferome) is unknown. Here, we analyzed whole transcriptome mRNA and lncRNA transfer between heterogeneous human-mouse cell populations inin vitroco-culture using RNA-sequencing. Our data indicate that mRNA transfer is non-selective, prevalent across the human transcriptome, and that the amount of transfer to mouse embryonic fibroblasts (MEFs) strongly correlates with the endogenous level of gene expression in donor human breast cancer cells (MCF7). These results were validated by both quantitative RT-PCR andin situhybridization, and analysis shows that typically <1% of endogenous mRNAs and lncRNAs undergo transfer. Non-selective expression-dependent RNA transfer was further validated using synthetic RNA reporters. Notably, significant differential changes in the native MEF transcriptome were observed in response to co-culture, including the upregulation of multiple cancer and cancer-associated fibroblast-related genes and pathways. Together, these results lead us to suggest that TNT-mediated RNA transfer could be a phenomenon of physiological importance under both normal and pathogenic conditions.
Rethinking protein drug design with highly accurate structure prediction of anti-CRISPR proteins
Authors: Park Ho-min , Park Yunseol , Vankerschaver Joris , Van Messem Arnout , De Neve Wesley , Shim Hyunjin 
Published: November 2021

AbstractProtein therapeutics play an important role in controlling the functions and activities of disease-causing proteins in modern medicine. Despite protein therapeutics having several advantages over traditional small-molecule therapeutics, further development has been hindered by drug complexity and delivery issues. However, recent progress in deep learning-based protein structure prediction approaches such as AlphaFold opens new opportunities to exploit the complexity of these macro-biomolecules for highly-specialised design to inhibit, regulate or even manipulate specific disease-causing proteins. Anti-CRISPR proteins are small proteins from bacteriophages that counter-defend against the prokaryotic adaptive immunity of CRISPR-Cas systems. They are unique examples of natural protein therapeutics that have been optimized by the host-parasite evolutionary arms race to inhibit a wide variety of host proteins. Here, we show that these Anti-CRISPR proteins display diverse inhibition mechanisms through accurate structural prediction and functional analysis. We find that these phage-derived proteins are extremely distinct in structure, some of which have no homologues in the current protein structure domain. Furthermore, we find a novel family of Anti-CRISPR proteins which are structurally homologous to the recently-discovered mechanism of manipulating host proteins through enzymatic activity, rather than through direct inference. Using highly accurate structure prediction, we present a wide variety of protein-manipulating strategies of anti-CRISPR proteins for future protein drug design.
Functionalizing lipid sponge droplets with DNA
Authors: Cho Christy , Niederholtmeyer Henrike , Seo Hyeonglim , Bhattacharya Ahanjit , Devaraj Neal K. 
Published: November 2021

AbstractNucleic acids are among the most versatile molecules for the construction of biomimetic systems because they can serve as information carriers and programmable construction materials. How nucleic acids interact with membranous coacervate compartments such as lipid sponge droplets is not known. Here we systematically characterize the potential of DNA to functionalize lipid sponge droplets and demonstrate a strong size dependence for sequestration into the sponge phase. Double stranded DNA molecules of more than 300 bp are excluded and form a corona on the surface of droplets they are targeted to. Shorter DNA molecules partition efficiently into the lipid sponge phase and can direct DNA-templated reactions to droplets. We demonstrate repeated capture and release of labeled DNA strands by dynamic hybridization and strand displacement reactions that occur inside droplets. Our system opens new opportunities for DNA-encoded functions in lipid sponge droplets such as cargo control and signaling.
Oncogenic RAS commandeers amino acid sensing machinery to aberrantly activate mTORC1 in multiple myeloma
Authors: Yang Yandan , Oellerich Thomas , Chen Ping , Bolomsky Arnold , Ceribelli Michele , Häupl Björn , Wright George W. , Phelan James D. , Huang Da Wei , Lord James W. , Van Winkle Callie K. , Yu Xin , Wisnieski Jan , Wang James Q. , Tosto Frances A. , Beck Erin , Wilson Kelli , McKnight Crystal , Travers Jameson , Klumpp-Thomas Carleen , Smith Grace A. , Pittaluga Stefania , Maric Irina , Kazandjian Dickran , Thomas Craig J. , Young Ryan M. 
Published: November 2021

AbstractOncogenic mutations within the RAS pathway are common in multiple myeloma (MM), an incurable malignancy of plasma cells. However, the mechanisms of pathogenic RAS signaling in this disease remain enigmatic and difficult to inhibit therapeutically. We employed an unbiased proteogenomic approach to dissect RAS signaling in MM by combining genome-wide CRISPR-Cas9 screening with quantitative mass spectrometry focused on RAS biology. We discovered that mutant isoforms of RAS organized a signaling complex with the amino acid transporter, SLC3A2, and MTOR on endolysosomes, which directly activated mTORC1 by co-opting amino acid sensing pathways. MM tumors with high expression of mTORC1-dependent genes were more aggressive and enriched in RAS mutations, and we detected interactions between RAS and MTOR in MM patient tumors harboring mutant RAS isoforms. Inhibition of RAS-dependent mTORC1 activity synergized with MEK and ERK inhibitors to quench pathogenic RAS signaling in MM cells. This study redefines the RAS pathway in MM and provides a mechanistic and rational basis to target this novel mode of RAS signaling.
Optimizing multiplexed imaging experimental design through tissue spatial segregation estimation
Authors: Bost Pierre , Schulz Daniel , Engler Stefanie , Wasserfall Clive , Bodenmiller Bernd 
Published: November 2021

AbstractRecent advances in multiplexed imaging methods allow simultaneous detection of dozens of proteins and hundreds of RNAs enabling deep spatial characterization of both healthy and diseased tissues. Parameters for design of optimal sequencing-based experiments have been established, but such parameters, especially those estimating how much area has to be imaged to capture all cell phenotype clusters, are lacking for multiplex imaging studies. Here, using a spatial transcriptomic atlas of healthy and tumor human tissues, we developed a new statistical framework that determines the number and area of fields of view necessary to accurately identify all cell types that are part of a tissue. Using this strategy on imaging mass cytometry data, we identified a measurement of tissue spatial segregation that enables optimal experimental design. This strategy will enable significantly improved design of multiplexed imaging studies.
Joint Learning of Full-structure Noise in Hierarchical Bayesian Regression Models
Authors: Hashemi Ali , Cai Chang , Gao Yijing , Ghosh Sanjay , Müller Klaus-Robert , Nagarajan Srikantan S. , Haufe Stefan 
Published: November 2021

AbstractWe consider the reconstruction of brain activity from electroencephalography (EEG). This inverse problem can be formulated as a linear regression with independent Gaussian scale mixture priors for both the source and noise components. Crucial factors influencing the accuracy of the source estimation are not only the noise level but also its correlation structure, but existing approaches have not addressed the estimation of noise covariance matrices with full structure. To address this shortcoming, we develop hierarchical Bayesian (type-II maximum likelihood) models for observations with latent variables for source and noise, which are estimated jointly from data. As an extension to classical sparse Bayesian learning (SBL), where across-sensor observations are assumed to be independent and identically distributed, we consider Gaussian noise with full covariance structure. Using the majorization-maximization framework and Riemannian geometry, we derive an efficient algorithm for updating the noise covariance along the manifold of positive definite matrices. We demonstrate that our algorithm has guaranteed and fast convergence and validate it in simulations and with real MEG data. Our results demonstrate that the novel framework significantly improves upon state-of-the-art techniques in the real-world scenario where the noise is indeed non-diagonal and full-structured. Our method has applications in many domains beyond biomagnetic inverse problems.
Processing of oxidatively damaged DNA dirty ends by APE1
Authors: Whitaker Amy M. , Stark Wesley J. , Freudenthal Bret D. 
Published: November 2021

ABSTRACTReactive oxygen species attack the structure of DNA, thus altering its base-pairing properties. Consequently, oxidative stress-associated DNA lesions are a major source of the mutation load that gives rise to cancer and other diseases. Base excision repair (BER) is the pathway primarily tasked with repairing DNA base damage, with apurinic/apyrimidinic endonuclease (APE1) having both AP-endonuclease and 3’ to 5’ exonuclease (exo) DNA cleavage functions. The lesion 8-oxo-7,8-dihydroguanine (8-oxoG) can enter the genome as either a product of direct damage to the DNA, or through polymerase insertion at the 3’-end of a DNA strand during replication or repair. Importantly, 3’-8-oxoG impairs the ligation step of BER and therefore must be removed by the exo activity of a surrogate enzyme to prevent double stranded breaks and cell death. In the present study, we characterize the exo activity of APE1 on 3’-8-oxoG substrates. These structures demonstrate that APE1 uses a unified mechanism for its exo activities that differs from its more canonical AP-endonuclease activity. In addition, through complementation of the structural data with enzyme kinetics and binding studies employing both wild-type and rationally designed APE1 mutants, we were able to identify and characterize unique protein:DNA contacts that specifically mediate 8-oxoG removal by APE1.