bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune response to 2-dose BNT162b2 vaccination and risk of SARS-CoV-2 breakthrough infection: The Shieldvacc-2 study
Authors: Seekircher Lisa , Bánki Zoltán , Kimpel Janine , Rössler Annika , Schäfer Helena , Falkensammer Barbara , Bante David , Forer Lukas , Schönherr Sebastian , Harthaller Teresa , Sacher Magdalena , Ower Cornelia , Tschiderer Lena , Ulmer Hanno , Krammer Florian , Laer Dorothee von , Borena Wegene , Willeit Peter 
Published: May 2022

AbstractIt is uncertain to which extent antibody and T-cell responses after vaccination against SARS-CoV-2 are associated with reduced risk of breakthrough infection and whether their measurement enhances risk prediction. We conducted a phase-4 open-label clinical trial in the pre-omicron era, enrolling 2,760 individuals aged ≥16 years 35±8 days after having received the second dose of BNT162b2 (baseline 15-21 May 2021). Over a median 5.9-month of follow-up, we identified incident SARS-CoV-2 breakthrough infections using weekly antigen tests, a confirmatory PCR test, and/or serological evidence for incident infection. We quantified relative risks adjusted for age, sex, and prior SARS-CoV-2 infection for different immunological parameters and assessed improvements in risk discrimination. In contrast to the T-cell response, higher plasma levels of binding antibodies and antibodies in a surrogate neutralization assay were associated with reduced risk of breakthrough infection. Furthermore, assessment of anti-spike IgG levels enhanced prediction of breakthrough infection and may therefore be a suitable measurable correlate of protection in practice.
SLCO5A1 and synaptic assembly genes contribute to impulsivity in juvenile myoclonic epilepsy
Authors: Panjwani Naim , Shakeshaft Amy , Roshandel Delnaz , Lin Fan , Collingwood Amber , Hall Anna , Keenan Katherine , Deneubourg Celine , Mirabella Filippo , Topp Simon , Zarubova Jana , Thomas Rhys H. , Talvik Inga , Syvertsen Marte , Striano Pasquale , Smith Anna B. , Selmer Kaja K. , Rubboli Guido , Orsini Alessandro , Ng Ching Ching , Møller Rikke S. , Lim Kheng Seang , Hamandi Khalid , Greenberg David A. , Gesche Joanna , Gardella Elena , Fong Choong Yi , Beier Christoph P. , Andrade Danielle M. , Jungbluth Heinz , Richardson Mark P. , Pastore Annalisa , Fanto Manolis , Pal Deb K. , Strug Lisa J. 
Published: May 2022

Introductory ParagraphElevated impulsivity is a key component of attention-deficit hyperactivity disorder (ADHD), bipolar disorder and epilepsy1-5. We performed a genome-wide association, colocalization and pathway analysis of impulsivity in juvenile myoclonic epilepsy (JME). We identify genome-wide associated SNPs at 8q13.3 (p=7.5 × 10−9) and 10p11.21 (p=3.6 × 10−8). The 8q13.3 locus colocalizes with SLCO5A1 expression quantitative trait loci in cerebral cortex (p=9.5 × 10−3). SLCO5A1 codes for a membrane-bound organic anion transporter6 and upregulates synapse assembly/organisation genes7. Pathway analysis also demonstrates 9.3-fold enrichment for synaptic assembly genes (p=0.03) including NRXN1, NLGN1 and PTPRD. RNAi knockdown of Oatp30B, the Drosophila homolog of SLCO5A1, causes both over-reactive startling behaviour (p=8.7 × 10−3) and increased seizure-like events (p=6.8 × 10−7). Polygenic risk score for ADHD correlates with impulsivity scores (p=1.60 × 10−3), demonstrating shared genetic contributions. SLCO5A1 loss-of-function represents a novel impulsivity and seizure mechanism. Synaptic assembly genes may inform the aetiology of impulsivity in health and disease.
Diabetes and neuroaxonal damage in Parkinson’s disease
Authors: Vijiaratnam Nirosen , Lawton Michael , Real Raquel , Heslegrave Amanda J , Guo Tong , Athauda Dilan , Gandhi Sonia , Girges Christine , Ben-Shlomo Yoav , Zetterberg Henrik , Grosset Donald G , Morris Huw R , Foltynie Thomas ,   PRoBaND clinical consortium
Published: May 2022

AbstractPatient’s with Parkinson’s disease (PD) with coexistent type 2 diabetes (T2DM) can manifest with more severe motor and cognitive phenotypes. The precise reasons for this remain unclear though underlying pathophysiological differences are increasingly implicated. More severe neuroaxonal injury in PD patients with T2DM was recently proposed as a potential mechanism for this. We explored this in the tracking Parkinson’s study and confirmed these findings. Cases with T2DM had higher serum neurofilament light levels and this remained significant after correction for age and vascular risk factor burden. Disentangling the underlying mechanism for more rapid axonal damage will be important in the development of disease modifying therapies for PD.
Reporting of patient involvement: A mixed-methods analysis of current practice in health research publications
Authors: Weschke Sarah , Franzen Delwen Louise , Sierawska Anna Karolina , Bonde Lea-Sophie , Strech Daniel , Schorr Susanne Gabriele 
Published: May 2022

ABSTRACTObjectivesTo evaluate the extent and quality of patient involvement reporting in examples of current practice in health research.DesignMixed-methods study. We used a targeted search strategy across three cohorts to identify health research publications that reported patient involvement: publications published in The BMJ, publications listed in the PCORI database, and publications citing the GRIPP2 reporting checklist for patient involvement or a critical appraisal guideline for user involvement. Publications were coded according to three coding schemes: “Phase of involvement”, the GRIPP2-SF reporting checklist, and the critical appraisal guideline.Outcome measuresThe phase of the study in which patients were actively involved. For the BMJ sample, the proportion of publications that reported patient involvement. The quality of reporting based on the GRIPP2 short form reporting guideline. The quality of patient involvement based on the critical appraisal guideline. Quantitative and qualitative results are reported.ResultsWe included 87 publications that reported patient involvement. Patients were most frequently involved in study design (90% of publications, n=78), followed by study conduct (70%, n=61), and dissemination (40%, n=35). Reporting of patient involvement was often incomplete, e.g., only 39% of publications (n=34) reported the aim of patient involvement. While the methods (56%, n=49) and results (59%, n=51) of involvement were reported more frequently, qualitative analyses showed that reporting was often unspecific and the influence of patients’ input remained vague. Therefore, a systematic assessment of the quality and impact of patient involvement according to the critical appraisal guideline was not feasible across samples.ConclusionsAs patient involvement is increasingly seen as an integral part of the research process and requested by funding bodies, it is essential that researchers receive specific guidance on how to report patient involvement activities. Complete reporting builds the foundation for assessing the quality of patient involvement and its impact on research.PROTOCOLThe protocol was published on the Open Science Framework: https://osf.io/vntgu/STRENGTHS AND LIMITATIONSA targeted search strategy was used to identify examples of patient involvement reporting in a variety of publication types and study designs in health researchA mixed-methods approach allowed for an analysis of both the completeness and quality of patient involvement reportingIn this study, we coded statements reporting on patient involvement in 87 health research publications that may be adapted for further useReporting of patient involvement was insufficiently detailed to allow for a systematic assessment of the quality of patient involvement
Optical coherence tomography assessment of axonal and neuronal damage of the retina in patients with familial and sporadic multiple sclerosis
Authors: Grudziecka Pyrek M , Selmaj K 
Published: May 2022

ABSTRACTObjectiveOptical coherence tomography (OCT) assessment of axonal and neuronal damage of the retina in patients with familial and sporadic multiple sclerosis.Methods45 patients with familial MS (fMS), 58 patients with sporadic MS (sMS) and 35 healthy controls were included in the study. OCT was performed with the spectral domain optical coherence tomography (SD-OCT, Heidelberg Engineering, Germany). The retinal nerve fiber layer (RNFL) thickness and macular volume (MV) were measured.ResultsA significant thinning of the global RNFL thickness was detected in both forms of MS compared to control group, (86,61 (+/- 14,74) µm in sMS, 85,8 (+/- 12,7) µm in fMS, 97,96 (+/- 7,6) µm in control group; p <0,001). There was no significant difference in the global RNFL thickness between sMS and fMS. A significant reduction of the MV was shown in sMS and fMS compared to control group (8,12 (+/- 1,14) mm3 in sMS, 8,1 (+/- 1,12) mm3 in fMS, and 8,81 (+/- 0,31) mm3 in control group; p = 0,003). No difference in MV between sMS and fMS was found. However, in eyes with history of optic neuritis (ON) MV was significantly reduced in sMS versus fMS (8,12 (+/- 2,87) mm3 vs. 8,42 (+/- 0,54) mm3; p=0,05).ConclusionWe confirmed the presence of axonal and neuronal damage of the retina in sMS and fMS. ON induced a significantly greater reduction of MV in sMS compared to fMS, indicating a stronger neuronal damage in ON eyes in sMS than in fMS.KEY MESSAGESThe familial MS accounts for a significant proportion of MS patients and there is still ongoing discussion on the distinction between familial (fMS) and sporadic (sMS) forms of this disease. Using OCT, we confirmed the presence of axonal and neuronal damage in the retina in both forms of MS. We found that optic neuritis (ON) induced a greater retinal neuronal damage in sMS than in fMS. These results support the conclusion that there are some discrete differences in pathological processes occurring in the retina in sMS and fMS.
Accuracy of US CDC COVID-19 Forecasting Models
Authors: Chharia Aviral , Jeevan Govind , Jha Rajat Aayush , Liu Meng , Berman Jonathan M , Glorioso Christin 
Published: May 2022

ABSTRACTAccurate predictive modeling of pandemics is essential for optimally distributing resources and setting policy. Dozens of case predictions models have been proposed but their accuracy over time and by model type remains unclear. In this study, we analyze all US CDC COVID-19 forecasting models, by first categorizing them and then calculating their mean absolute percent error, both wave-wise and on the complete timeline. We compare their estimates to government-reported case numbers, one another, as well as two baseline models wherein case counts remain static or follow a simple linear trend. The comparison reveals that more than one-third of models fail to outperform a simple static case baseline and two-thirds fail to outperform a simple linear trend forecast. A wave-by-wave comparison of models revealed that no overall modeling approach was superior to others, including ensemble models, and error in modeling has increased over time during the pandemic. This study raises concerns about hosting these models on official public platforms of health organizations including the US-CDC which risks giving them an official imprimatur and further raising concerns if utilized to formulate policy. By offering a universal evaluation method for pandemic forecasting models, we expect this work to serve as the starting point towards the development of more accurate models.
Single-cell mapping of tumor heterogeneity in pediatric rhabdomyosarcoma reveals developmental signatures with therapeutic relevance
Authors: Danielli Sara G , Porpiglia Ermelinda , De Micheli Andrea J , Navarro Natalia , Zellinger Michael J , Bechtold Ingrid , Kisele Samanta , Volken Larissa , Marques Joana G , Kasper Stephanie , Bode Peter K , Henssen Anton G , Gürgen Dennis , Roma Josep , Bühlmann Peter , Blau Helen M , Wachtel Marco , Schäfer Beat W 
Published: May 2022

ABSTRACTRhabdomyosarcoma (RMS) is an aggressive human pediatric cancer. Despite robust expression of myogenic regulatory factors, RMS cells are blocked in a proliferative state and do not terminally differentiate. The extent to which the skeletal muscle lineage is represented in RMS tumors and the mechanisms leading to developmental arrest remain elusive. Here, we combined single-cell RNA sequencing (scRNAseq), mass cytometry (CyTOF) and high-content imaging to resolve RMS heterogeneity. ScRNAseq and CyTOF analysis of a total of 17 patient-derived primary cultures and three cell lines uncovered plastic myogenic subpopulations that delineate a branched trajectory. The less aggressive embryonal RMS (eRMS) harbor primarily muscle stem cell (MuSC)-like cells and exhibit sparse commitment to differentiation. The more aggressive alveolar RMS (aRMS) comprise primarily actively cycling committed progenitors with a paucity of differentiated cells. The oncogenic fusion protein PAX3:FOXO1 sustains aRMS cells in the cycling trajectory loop, which we show can re-wired towards differentiation upon its downregulation or by dual pharmacological RAF and MEK inhibition. Our findings provide insights into the developmental states and trajectories underlying RMS progression and identify the RAS pathway as a promising target of differentiation therapy for human aRMS.STATEMENT OF SIGNIFICANCEWe present the first comprehensive single-cell transcriptomic and proteomic atlas of pediatric rhabdomyosarcoma (RMS), in which we identify impaired myogenic trajectories with prognostic value. We demonstrate that RAS pathway inhibitors disrupt the oncogenic trajectory and induce terminal differentiation, revealing novel therapeutic targets for the aggressive alveolar RMS subtype.
Whole genome sequencing suggests that “non-pathogenicity on banana (NPB)” is the ancestral state of the Ralstonia solanacearum IIB-4 lineage
Authors: Beutler Jonathan , Holden Samuel , Georgoulis Stratton , Williams Darrielle , Norman David J. , Lowe-Power Tiffany M. 
Published: May 2022

AbstractThe bacterial wilt pathogens in the Ralstonia solanacearum species complex (RSSC) have broad but finite host ranges. Population genetic surveys of RSSC pathogens show that many sequevars (subspecies groups) are predominantly recovered from wilting solanaceous plants. In contrast, strains in the IIB-4 sequevar have been isolated from plants in over a dozen families. Certain IIB-4 lineages have been classified as banana-virulent or “not pathogenic to banana (NPB)”. Prior analysis suggested that the NPB lineage has diverged from the banana-virulent IIB-4 strains. To test this model, we analyzed the phenotypes and phylogeny of a diverse collection of 19 IIB-4 isolates. We used Illumina sequencing to assemble draft genomes of 12 new strains. Based on whole genome phylogenetic analysis, these IIB-4 strains clustered into five subclades. We quantified virulence of each strain on tomato, banana, melon, and impatiens plants. Overall, the virulence patterns correlated with phylogeny. Banana virulence was restricted to the 4/4 IIB-4D subclade (N=4/4 strains) and IIB-4E subclade (N=1/2 strains). Subclades IIB-4D and IIB-4E are sister subclades and their closest relative, the IIB-4A-C subclade, lacked virulence on banana. Our data support a revised model in which banana virulence is an innovation within the IIB4D/E subclades.Data SummaryIllumina sequencing and genome assembly data are available as NCBI BioProject PRJNA826884, and Table S1 lists the accession numbers for assemblies in GenBank and raw sequencing data in SRA. To enable future meta-analyses that identify genetic factors that drive host-range, the raw virulence data is included as Table S2.
A Hybrid Method for Ultrasound-Based Tracking of Skeletal Muscle Architecture
Authors: Verheul Jasper , Yeo Sang-Hoon 
Published: May 2022

AbstractTracking skeletal muscle architecture using B-mode ultra-sound is a widely used method in the field of human movement science and biomechanics. Sequential methods based on optical flow algorithms allow for smooth and coherent muscle tracking but are known to drift over time. Non-sequential feature detection methods on the other hand, do not suffer from drift, but are limited to tracking only lower-dimensional features. They are also known to be sensitive to image noise, and therefore often result in highly irregular tracking patterns. Building on the complimentary nature of both approaches, we present a novel fully automated hybrid muscle tracking approach that combines a sequential feature-point tracking method and a non-sequential method based on Hough transform. Tibialis anterior fascicle pennation angle and length, and central aponeurosis displacement, were measured in five healthy individuals during isometric contractions at five different ankle angles. Our hybrid method was demonstrated to significantly (p < 0.001) reduce drift compared to two sequential methods, and curve irregularity was significantly (p < 0.001) decreased compared to a non-sequential method. These findings suggest that the proposed hybrid approach can uniquely mitigate drift and irregularity limitation of individual methods used for tracking skeletal muscle architecture. Fully automated muscle tracking allows for convenient analysis of large datasets, whereas automatic drift correction opens the door for tracking muscle architecture in long ultrasound recordings during common movements, such as walking, running, and jumping without the need for manual intervention.
Chromosome-level genome assembly for the Aldabra giant tortoise enables insights into the genetic health of a threatened population
Authors: Çilingir F.G. , A’Bear L. , Hansen D. , Davis L.R. , Bunbury N. , Ozgul A. , Croll D. , Grossen C. 
Published: May 2022

AbstractThe Aldabra giant tortoise (Aldabrachelys gigantea) is one of only two giant tortoise species left in the world. The species is endemic to Aldabra Atoll in Seychelles and is considered vulnerable due to its limited distribution and threats posed by climate change. Genomic resources forA. giganteaare lacking, hampering conservation efforts focused on both wild and ex-situ populations. A high-quality genome would also open avenues to investigate the genetic basis of the exceptionally long lifespan. Here, we produced the first chromosome-levelde novogenome assembly ofA. giganteausing PacBio High-Fidelity sequencing and high-throughput chromosome conformation capture (Hi-C). We produced a 2.37 Gbp assembly with a scaffold N50 of 148.6 Mbp and a resolution into 26 chromosomes. RNAseq-assisted gene model prediction identified 23,953 protein-coding genes and 1.1 Gbp of repetitive sequences. Synteny analyses among turtle genomes revealed high levels of chromosomal collinearity even among distantly related taxa. We also performed a low-coverage re-sequencing of 30 individuals from wild populations and two zoo individuals. Our genome-wide population structure analyses detected genetic population structure in the wild and identified the most likely origin of the zoo-housed individuals. The high-quality chromosome-level reference genome forA. giganteais one of the most complete turtle genomes available. It is a powerful tool to assess the population structure in the wild population and reveal the geographic origins of ex-situ individuals relevant for genetic diversity management and rewilding efforts.
Macrophages undergo necroptosis during severe influenza A infection and contribute to virus-associated cytokine storm
Authors: Ferreira André C. , Sacramento Carolina Q. , Pereira-Dutra Filipe S. , Fintelman-Rodrigues Natália , Silva Priscila P. , Mattos Mayara , de Freitas Caroline S. , Marttorelli Andressa , de Melo Gabrielle R. , Macedo Mariana C. , Azevedo-Quintanilha Isaclaudia G. , Carlos Aluana S. , Emídio João Vitor , Garcia Cristiana C. , Bozza Patrícia T. , Bozza Fernando A. , Souza Thiago M. L. 
Published: May 2022

AbstractInfluenza A virus (IAV) causes a major public health concern, because it is one of the leading causes of respiratory tract infections and hospitalization. Severe influenza has been associated with the cytokine storm, and IAV productive infection cell death in airway epithelial cells may contribute to the exacerbation of this proinflammatory event. On the other hand, IAV replication in macrophages is non-permissive and whether this immune cell may contribute to severe influenza physiopathology requires more details. Here, we investigated IAV-induced macrophage death, along with potential therapeutic intervention. We found that IAV or simply its surface glycoprotein hemagglutinin (HA) triggers necroptosis in human and murine macrophages in a Toll-like receptor-4 (TLR4) and TNF-dependent manner. Anti-TNF treatment, with the clinically approved drug etanercept, prevented the engagement of the necroptotic loop and mice mortality. impaired IAV-induced pro-inflammatory cytokine storm and lung injury. Our results implicate macrophage necroptosis with severe influenza in experimental models and potentially repurpose a clinically available therapy.Author SummaryVarious fates of cell death have an integral role in the influenza A virus (IAV) pathogenesis and lung/respiratory dysfunction. IAV physiopathology is not restricted to airway epithelial cells, where this virus actively replicated. Macrophages should support both viral clearance and priming of adaptative immune response in patients that adequately control influenza. However, during severe IAV infection, macrophages – which are unable to support a permissive viral replication - undergo disruptive cell death and contribute to the exacerbated production of proinflammatory cytokines/chemokines. We characterized this process by showing that IAV or just its surface glycoprotein hemagglutinin (HA) trigger necroptosis, a disruptive and TNF-dependent cells death. Since TNF is a hallmark of pro-inflammatory cell death, we blocked this mediator with a repurposed biomedicine etanercept, which prevented the severe IAV infection in the experimental model. The present work improves the knowledge of influenza pathophysiology by highlighting the importance of macrophage cell death during severe infection.
Uncovering the structural flexibility of SARS-CoV-2 glycoprotein spike variants
Authors: Arruda Hiam R. S. , Lima Tulio M. , Alvim Renata G. F. , Victorio Fernanda B. A. , Abreu Daniel P. B. , Marsili Federico F. , Cruz Karen D. , Sosa-Acosta Patricia , Quinones-Vega Mauricio , Guedes Jéssica de S. , Nogueira Fábio C. S. , Silva Jerson L. , Castilho Leda R. , de Oliveira Guilherme A. P. 
Published: May 2022

AbstractThe severe acute respiratory syndrome CoV-2 rapidly spread worldwide, causing a pandemic. After a period of evolutionary stasis, a set of SARS-CoV-2 mutations has arisen in the spike, the leading glycoprotein at the viral envelope and the primary antigenic candidate for vaccines against the 2019 CoV disease (COVID-19). Here, we present comparative biochemical data of the glycosylated full-length ancestral and D614G spike together with three other highly transmissible strains classified by the World Health Organization as variants of concern (VOC): beta, gamma, and delta. By showing that only D614G early variant has less hydrophobic surface exposure and trimer persistence at mid-temperatures, we place D614G with features that support a model of temporary fitness advantage for virus spillover worldwide. Further, during the SARS-CoV-2 adaptation, the spike accumulates alterations leading to less structural rigidity. The decreased trimer stability observed for the ancestral and the gamma strain and the presence of D614G uncoupled conformations mean higher ACE-2 affinities when compared to the beta and delta strains. Mapping the energetic landscape and flexibility of spike variants is necessary to improve vaccine development.