bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rehabilitation needs and mortality associated with the Covid-19 pandemic: a population-based study of all hospitalised and home-healthcare individuals in a Swedish healthcare region
Authors: Divanoglou Anestis , Samuelsson Kersti , Sjödahl Emer. Rune , Andersson Christer , Levi Richard 
Published: May 2021

AbstractBackgroundThis first report of the Linköping Covid-19 Study (LinCoS) aimed at determination of Covid-19-associated mortality, impairments, activity and participation limitations denoting rehabilitation needs four months after discharge from hospital.MethodsAn ambidirectional population-based cohort study including all confirmed Covid-19 cases admitted to hospital during 1/03-31/05 and those living in home healthcare settings identified through a regional registry and evaluated through medical records, including WHO Clinical Progression Scale (CPS). All patients discharged from hospital were followed-up by structured telephone interview at 4 months post-discharge. Respondents indicated any new or aggravated persisting problems in any of 25 body functions and 12 activity/participation items and rated them for impact on daily life.FindingsOut of 734 hospitalised patients, 149 were excluded, 125 died, and 460 were alive at 4-month follow-up of whom 433 (94.1%) were interviewed. In total, 40% reported impairments and activity/participation limitations affecting daily life and warranted further multi-professional rehabilitation assessment, predominantly those with severe disease and a considerable proportion of those with moderate disease. Cognitive and affective impairments were equally common in all groups and were reported by 20-40% of cases. Limb weakness was reported by 31%, with CPS 7-9 being four times more likely to report this problem as compared to CPS 4-5. 26% of those working or studying reported difficulties returning to these activities, this being 3.5 times more likely in CPS 7-9 as compared to CPS 4-5. 25% reported problems walking >1 km, with CPS 7-9 over three times more likely to report this as compared to the other two sub-groups. 90-day mortality rate of Covid-19 associated deaths was 15.1%.InterpretationMost rehabilitation needs after Covid-19 involved higher cerebral dysfunction both in patients with moderate and severe disease. This should be considered when designing services aiming at minimizing long-term disability.FundingALF grant and Region Östergötland.
Characterization of the skin microbiota in bullous pemphigoid patients and controls reveals novel microbial indicators of disease
Authors: Belheouane Meriem , Hermes Britt M. , Van Beek Nina , Benoit Sandrine , Bernard Philippe , Drenovska Kossara , Gerdes Sascha , Gläser Regine , Goebeler Matthias , Günther Claudia , von Georg Anabelle , Hammers Christoph M. , Holtsche Maike M. , Homey Bernhard , Horváth Orsolya N. , Hübner Franziska , Linnemann Beke , Joly Pascal , Márton Dalma , Patsatsi Aikaterini , Pföhler Claudia , Sárdy Miklós , Huilaja Laura , Vassileva Snejina , Zillikens Detlef , Ibrahim Saleh , Sadik Christian D. , Schmidt Enno , Baines John F. 
Published: May 2021

ABSTRACTIntroductionBullous pemphigoid (BP) is the most common autoimmune blistering disease. It predominately afflicts the elderly and is significantly associated with increased mortality. The observation of age-dependent changes in the skin microbiota as well as its involvement in other inflammatory skin disorders suggests that skin microbiota may play a role in the emergence of BP blistering. We hypothesize that changes in microbial diversity associated with BP might occur before the emergence of disease lesions, and thus could represent an early indicator of blistering risk.ObjectivesThe present study aims to investigate potential relationships between skin microbiota and BP and elaborate on important changes in microbial diversity associated with blistering in BP.MethodsThe study consisted of an extensive sampling effort of the skin microbiota in patients with BP and age- and sex-matched controls to analyze whether intra-individual, body site, and/or geographical variation correlate with changes in skin microbial composition in BP and/or blistering status.ResultsWe find significant differences in the skin microbiota of patients with BP compared to that of controls, and moreover that disease status rather than skin biogeography (body site) governs skin microbiota composition in patients with BP. Our data reveal a discernible transition between normal skin and the skin surrounding BP lesions, which is characterized by a loss of protective microbiota and an increase in sequences matching Staphylococcus aureus, a known inflammation-promoting species. Notably, S. aureus is ubiquitously associated with BP disease status, regardless of the presence of blisters.ConclusionThe present study suggests S. aureus may be a key taxon associated with BP disease status. Importantly, differences in a few key indicator taxa reliably discriminate between patients with BP and matched controls. This may serve as valuable information for assessing blistering risk and treatment outcomes in a clinical setting.
Haplotype Associated RNA Expression (HARE) Improves Prediction of Complex Traits in Maize
Authors: Giri Anju , Khaipho-Burch Merritt , Buckler Edward S. , Ramstein Guillaume P. 
Published: May 2021

AbstractGenomic prediction typically relies on associations between single-site polymorphisms and traits of interest. This representation of genomic variability has been successful for prediction within populations. However, it usually cannot capture the complex effects due to combination of alleles in haplotypes. Therefore, accuracy across populations has usually been low. Here we present a novel and cost-effective method for imputingcishaplotype associated RNA expression (HARE, RNA expression of genes by haplotype), studied their transferability across tissues, and evaluated genomic prediction models within and across populations. HARE focuses on tightly linkedcisacting causal variants in the immediate vicinity of the gene, while excludingtranseffects from diffusion and metabolism, so it would be more transferrable across different tissues and populations. We showed that HARE estimates captured one-third of the variation in gene expression and were more transferable across diverse tissues than the measured transcript expression. HARE estimates were used in genomic prediction models evaluated within and across two diverse maize panels – a diverse association panel (Goodman Association panel) and a large half-sib panel (Nested Association Mapping panel) – for predicting 26 complex traits. HARE resulted in up to 15% higher prediction accuracy than control approaches that preserved haplotype structure, suggesting that HARE carried functional information in addition to information about haplotype structure. The largest increase was observed when the model was trained in the Nested Association Mapping panel and tested in the Goodman Association panel. Additionally, HARE yielded higher within-population prediction accuracy as compared to measured expression values. The accuracy achieved by measured expression was variable across tissues whereas accuracy using HARE was more stable across tissues. Therefore, imputing RNA expression of genes by haplotype is stable, cost-effective, and transferable across populations.Author summaryThe increasing availability of genomic data has been widely used in the prediction of many traits. However, genome wide prediction has been mostly carried out within populations and without explicit modeling of RNA or protein expression. In this study, we explored the prediction of field traits within and across populations using estimated RNA expression attributable to only the DNA sequence around a gene. We showed that the estimated RNA expression was more transferable than overall measured RNA expression. We improved prediction of field traits up to 15% using estimated gene expression as compared to observed expression or gene sequence alone. Overall, these findings indicate that structural and functional information in the gene sequence are highly transferable.
Treatment with sodium butyrate induces autophagy resulting in therapeutic benefits for spinocerebellar ataxia type 3
Authors: Watchon Maxinne , Robinson Katherine J. , Luu Luan , An Yousun , Yuan Kristy C. , Plenderleith Stuart K. , Cheng Flora , Don Emily K. , Nicholson Garth A. , Lee Albert , Laird Angela S. 
Published: May 2021

AbstractSpinocerebellar ataxia type 3 (SCA3, also known as Machado Joseph disease) is a fatal neurodegenerative disease caused by expansion of the trinucleotide repeat region within theATXN3/MJDgene. Mutation ofATXN3causes formation of ataxin-3 protein aggregates, neurodegeneration and motor deficits. Here we investigated the therapeutic potential and mechanistic activity of sodium butyrate (SB), the sodium salt of butyric acid, a metabolite naturally produced by gut microbiota, on cultured SH-SY5Y cells and transgenic zebrafish expressing human ataxin-3 containing 84 glutamine (Q) residues to model SCA3. SCA3 SH-SY5Y cells were found to contain high molecular weight ataxin-3 species and detergent insoluble protein aggregates. Treatment with SB increased activity of the autophagy protein quality control pathway in the SCA3 cells, decreased presence of ataxin-3 aggregates and presence of high molecular weight ataxin-3 in an autophagy-dependent manner. Treatment with SB was also beneficialin vivo,improving swimming performance, increasing activity of the autophagy pathway and decreasing presence of insoluble ataxin-3 protein species in the transgenic SCA3 zebrafish. Co-treating the SCA3 zebrafish with SB and chloroquine, an autophagy inhibitor, prevented the beneficial effects of SB on zebrafish swimming, indicating that the improved swimming performance was autophagy-dependent. To understand the mechanism by which SB induces autophagy we performed proteomic analysis of protein lysates from the SB treated and untreated SCA3 SH-SY5Y cells. We found that SB treatment had increased activity of Protein Kinase A and AMPK signalling, with immunoblot analysis confirming that SB treatment had increased levels of AMPK protein and its substrates. Together our findings indicate that treatment with SB can increase activity of the autophagy pathway through a PKA/AMPK-dependent process and that this has beneficial effectsin vitroandin vivo. We propose that treatment with sodium butyrate warrants further investigation as a potential treatment for neurodegenerative diseases underpinned by mechanisms relating to protein aggregation including SCA3.
Pathway centered analysis to guide clinical decision-making in precision medicine
Authors: Carvalho Luís B. , Capelo J. L. , Lodeiro Carlos , Dhir Rajiv , Pinheiro Luis Campos , Medeiros Mariana , Santos Hugo M. 
Published: May 2021

AbstractChanges in the human proteome caused by disease before, during and after medical care is phenotype-dependent, so the proteome of each individual at any time point is a snapshot of the body’s response to disease and to disease treatment. Here, we introduce a new concept named differential Personal Pathway index (dPPi). This tool extracts and summates comprehensive disease-specific information contained within an individual’s proteome as a holistic way to follow the response to disease and medical care over time. We demonstrate the principle of the dPPi algorithm on proteins found in urine from patients suffering from neoplasia of the bladder. The relevance of the dPPi results to the individual clinical cases is described. The dPPi concept can be extended to other malignant and non-malignant diseases, and to other types of biopsies, such as plasma, serum or saliva. We envision the dPPi as a tool for clinical decision-making in precision medicine.
Structure of the hexameric fungal plasma membrane proton pump in its auto-inhibited state
Authors: Heit Sabine , Geurts Maxwell M.G. , Murphy Bonnie J. , Corey Robin A. , Mills Deryck J. , Kühlbrandt Werner , Bublitz Maike 
Published: May 2021

AbstractThe fungal plasma membrane H+-ATPase Pma1 is a vital enzyme, generating a proton-motive force that drives the import of essential nutrients. Auto-inhibited Pma1 hexamers in starving fungi are activated by glucose signalling resulting in phosphorylation of the auto-inhibitory domain. As related P-type ATPases are not known to oligomerise, the physiological relevance of Pma1 hexamers remains unknown. We have determined the structure of hexameric Pma1 from Neurospora crassa by cryo-EM at 3.3 Å resolution, elucidating the molecular basis for hexamer formation and auto-inhibition, and providing a basis for structure-based drug development. Coarse-grained molecular dynamics simulations in a lipid bilayer suggest lipid-mediated contacts between monomers and a substantial protein-induced membrane deformation that could act as a proton-attracting funnel.
Unfolding and Translocation of Knotted Proteins by Clp Biological Nanomachines: Synergistic Contribution of Primary Sequence and Topology Revealed by Molecular Dynamics Simulations
Authors: Fonseka Hewafonsekage Yasan Y. , Javidi Alex , Oliveira Luiz F. L. , Micheletti Cristian , Stan George 
Published: May 2021

AbstractWe use Langevin dynamics simulations to model, at atomistic resolution, how various natively–knotted proteins are unfolded in repeated allosteric translocating cycles of the ClpY ATPase. We consider proteins representative of different topologies, from the simplest knot (trefoil 31), to the three–twist 52knot, to the most complex stevedore, 61, knot. We harness the atomistic detail of the simulations to address aspects that have so far remained largely unexplored, such as sequence–dependent effects on the ruggedness of the landscape traversed during knot sliding. Our simulations reveal the combined effect on translocation of the knotted protein structure, i.e. backbone topology and geometry, and primary sequence, i.e. side chain size and interactions, and show that the latter can even dominate translocation hindrance. In addition, we observe that, due to the interplay between the knotted topology and intramolecular contacts, the transmission of tension along the peptide chain occurs very differently from homopolymers. Finally, by considering native and non–native interactions, we examine how the disruption or formation of such contacts can affect the translocation processivity and concomitantly create multiple unfolding pathways with very different activation barriers.
Modular development enables rapid design of media for alternative hosts
Authors: Biedermann Andrew M. , Gengaro Isabella R. , Rodriguez-Aponte Sergio A. , Love Kerry R. , Love J. Christopher 
Published: May 2021

AbstractDeveloping media to sustain cell growth and production is an essential and ongoing activity in bioprocess development. Modifications to media can often address host or product-specific challenges, such as low productivity or poor product quality. For other applications, systematic design of new media can facilitate the adoption of new industrially relevant alternative hosts. Despite manifold existing methods, common approaches for optimization often remain time and labor intensive. We present here a novel approach to conventional media blending that leverages stable, simple, concentrated stock solutions to enable rapid improvement of measurable phenotypes of interest. We applied this modular methodology to generate high-performing media for two phenotypes of interest: biomass accumulation and heterologous protein production, using high-throughput, milliliter-scale batch fermentations ofPichia pastorisas a model system. In addition to these examples, we also created a flexible open-source package for modular blending automation on a low-cost liquid handling system to facilitate wide use of this method. Our modular blending method enables rapid, flexible media development, requiring minimal labor investment and prior knowledge of the host organism, and should enable developing improved media for other hosts and phenotypes of interest.
ImprovedApis melliferareference genome based on the alternative long-read-based assemblies
Authors: Kaskinova Milyausha , Yunusbayev Bayazit , Altinbaev Radick , Raffiudin Rika , Carpenter Madeline H. , Nikolenko Alexey , Harpur Brock A. , Yunusbaev Ural 
Published: May 2021

ABSTRACTApis melliferaL., the western honey bee is a major crop pollinator that plays a key role in beekeeping and serves as an important model organism in social behavior studies. Recent efforts have improved on the quality of the honey bee reference genome and developed a chromosome-level assembly of sixteen chromosomes, two of which are gapless. However, the rest suffer from 51 gaps, 160 unplaced/unlocalized scaffolds, and the lack of 2 distal telomeres. The gaps are located at the hard-to-assemble extended highly repetitive chromosomal regions that may contain functional genomic elements. Here, we usede-novore-assemblies from the most recent reference genome Amel_HAv_3.1 raw reads and other long-read-based assemblies (INRA_AMelMel_1.0, ASM1384120v1, and ASM1384124v1) of the honey bee genome to resolve 13 gaps, five unplaced/unlocalized scaffolds and, the lacking telomeres of the Amel_HAv_3.1. The total length of the resolved gaps is 848,747 bp. The accuracy of the corrected assembly was validated by mapping PacBio reads and performing gene annotation assessment. Comparative analysis suggests that the PacBio-reads-based assemblies of the honey bee genomes failed in the same highly repetitive extended regions of the chromosomes, especially on chromosome 10. To fully resolve these extended repetitive regions, further work using ultra-long Nanopore sequencing would be needed. Our updated assembly facilitates more accurate reference-guided scaffolding and marker/sequence mapping in honey bee genomics studies.
Use of U.S. Blood Donors for National Serosurveillance of SARS-CoV-2 Antibodies: Basis for an Expanded National Donor Serosurveillance Program
Authors: Stone Mars , Germanio Clara Di , Wright David J. , Sulaeman Hasan , Dave Honey , Fink Rebecca V. , Notari Edward P. , Green Valerie , Strauss Donna , Kessler Debra , Destree Mark , Saa Paula , Williamson Phillip C. , Simmons Graham , Stramer Susan L. , Opsomer Jean , Jones Jefferson M. , Kleinman Steven , Busch Michael P. ,   for the NHLBI Recipient Epidemiology and Donor Evaluation Study-IV-Pediatric (REDS-IV-P)
Published: May 2021

AbstractIntroductionThe REDS-IV-P Epidemiology, Surveillance and Preparedness of the Novel SARS-CoV-2 Epidemic (RESPONSE) seroprevalence study conducted monthly cross-sectional testing for SARS-CoV-2 antibodies on blood donors in six U.S. metropolitan regions to estimate the extent of SARS-COV-2 infections over time.Study Design/MethodsDuring March-August 2020, approximately ≥1,000 serum specimens were collected monthly from each region and tested for SARS-CoV-2 antibodies using a well-validated algorithm. Regional seroprevalence estimates were weighted based on demographic differences with the general population. Seroprevalence was compared with reported COVID-19 case rates over time.Results/FindingsFor all regions, seroprevalence was <1.0% in March 2020. New York experienced the biggest increase (peak seroprevalence, 15.8 % in May). All other regions experienced modest increases in seroprevalence(1-2% in May-June to 2-4% in July-August). Seroprevalence was higher in younger, non-Hispanic Black, and Hispanic donors. Temporal increases in donor seroprevalence correlated with reported case rates in each region. In August, 1.3-5.6 estimated cumulative infections (based on seroprevalence data) per COVID-19 case reported to CDC.ConclusionIncreases in seroprevalence were found in all regions, with the largest increase in New York. Seroprevalence was higher in non-Hispanic Black and Hispanic blood donors than in non-Hispanic White blood donors. SARS-CoV-2 antibody testing of blood donor samples can be used to estimate the seroprevalence in the general population by region and demographic group. The methods derived from the RESPONSE seroprevalence study served as the basis for expanding SARS-CoV-2 seroprevalence surveillance to all 50 states and Puerto Rico.SummarySARS-CoV-2 serosurveillance data from blood donors in 6 US regions were used to estimate population weighted seroprevalence. Seroprevelance rates were higher in case rates. The study was expanded to a national donor serosurveillance program.DisclaimerThe content is solely the responsibility of the authors and does not represent the policy of the National Institutes of Health or the Department of Health and Human Services. Any specific brandnames included in this manuscript are for identification purposes only and are not intended to represent an endorsement by CDC. The findings and conclusions in this report are those of the authorsand do not necessarily represent the official position of the Centers of Disease Control and Prevention.
THE EFFECT OF A BOARDING RESTRICTION PROTOCOL ON EMERGENCY DEPARTMENT CROWDING
Authors: Lee Ji Hwan , Kim Ji Hoon , Park Incheol , Lee Hyun Sim , Park Joon Min , Chung Sung Phil , Kim Hyeon Chang , Kim Min Joung 
Published: May 2021

ABSTRACTBackgroundAccess block due to a lack of hospital beds causes emergency department (ED) crowding. We initiated the “boarding restriction protocol” that limits ED length of stay (LOS) for patients awaiting hospitalization to 24 hours from arrival. This study aimed to determine the effect of the protocol on ED crowding.MethodThis was a pre-post comparative study to compare ED crowding before and after protocol implementation. The primary outcome was the red stage fraction with more than 71 occupying patients in the ED (severe crowding level). LOS in the ED, treatment time and boarding time were compared. Additionally, the pattern of boarding patients staying in the ED according to the day of the week was confirmed.ResultsAnalysis of the number of occupying patients in the ED, measured at 10-minute intervals, indicated a decrease from 65.0 (51.0–79.0) to 55.0 (43.0–65.0) in the pre- and post-periods, respectively (p<0.0001). The red stage fraction decreased from 38.9% to 15.1% of the pre- and post-periods, respectively (p<0.0001). The proportion beyond the goal of this protocol of 24 hours decreased from 7.6% to 4.0% (p<0.0001). The ED LOS of all patients was similar: 238.2 (134.0–465.2) and 238.3 (136.9–451.2) minutes in the pre- and post-periods, respectively. In admitted patients, ED LOS decreased from 770.7 (421.4–1587.1) to 630.2 (398.0–1156.8) minutes (p<0.0001); treatment time increased from 319.6 (198.5–482.8) to 344.7 (213.4–519.5) minutes (p<0.0001); and boarding time decreased from 298.9 (109.5–1149.0) to 204.1 (98.7–545.7) minutes (p<0.0001). In the pre-period, boarding patients accumulated in the ED on weekdays, with the accumulation resolved on Fridays; this pattern was alleviated in the post-period.ConclusionsThe protocol effectively resolved excessive ED crowding by alleviating the accumulation of boarding patients in the ED on weekdays. Additional studies should be conducted on changes this protocol brings to patient flow hospital-wide.