julilili42/papers huggingface dataset:
Detection of viral SARS‐CoV‐2 genomes and histopathological changes in endomyocardial biopsies
2020-06-12

Abstract Aims Since December 2019, the novel coronavirus SARS‐CoV‐2 has spread rapidly throughout China and keeps the world in suspense. Cardiovascular complications with myocarditis and embolism due to COVID‐19 have been reported. SARS‐CoV‐2 genome detection in the heart muscle has not been demonstrated so far, and the underlying pathophysiological mechanisms remain to be investigated. Methods and results Endomyocardial biopsies (EMBs) of 104 patients (mean age: 57.90 ± 16.37 years; left ventricular ejection fraction: 33.7 ± 14.6%, sex: n = 79 male/25 female) with suspected myocarditis or unexplained heart failure were analysed. EMB analysis included histology, immunohistochemistry, and detection of SARS‐CoV‐2 genomes by real‐time reverse transcription polymerase chain reaction in the IKDT Berlin, Germany. Among 104 EMBs investigated, five were confirmed with SARS‐CoV‐2 infected by reverse real‐time transcriptase polymerase chain reaction. We describe patients of different history of symptoms and time duration. Additionally, we investigated histopathological changes in myocardial tissue showing that the inflammatory process in EMBs seemed to permeate vascular wall leading to small arterial obliteration and damage. Conclusions This is the first report that established the evidence of SARS‐CoV‐2 genomes detection in EMBs. In these patients, myocardial injury ischaemia may play a role, which could explain the ubiquitous troponin increases. EMB‐based identification of the cause of myocardial injury may contribute to explain the different evolution of complicated SARS‐CoV‐2‐infection and to design future specific and personalized treatment strategies.
Three-dimensional models of core-collapse supernovae from low-mass progenitors with implications for Crab
2020-06-12

ABSTRACT We present 3D full-sphere supernova simulations of non-rotating low-mass (∼9 M⊙) progenitors, covering the entire evolution from core collapse through bounce and shock revival, through shock breakout from the stellar surface, until fallback is completed several days later. We obtain low-energy explosions (∼0.5–1.0 × 1050 erg) of iron-core progenitors at the low-mass end of the core-collapse supernova (LMCCSN) domain and compare to a super-AGB (sAGB) progenitor with an oxygen–neon–magnesium core that collapses and explodes as electron-capture supernova (ECSN). The onset of the explosion in the LMCCSN models is modelled self-consistently using the vertex-prometheus code, whereas the ECSN explosion is modelled using parametric neutrino transport in the prometheus-HOTB code, choosing different explosion energies in the range of previous self-consistent models. The sAGB and LMCCSN progenitors that share structural similarities have almost spherical explosions with little metal mixing into the hydrogen envelope. A LMCCSN with less second dredge-up results in a highly asymmetric explosion. It shows efficient mixing and dramatic shock deceleration in the extended hydrogen envelope. Both properties allow fast nickel plumes to catch up with the shock, leading to extreme shock deformation and aspherical shock breakout. Fallback masses of M⊙ have no significant effects on the neutron star (NS) masses and kicks. The anisotropic fallback carries considerable angular momentum, however, and determines the spin of the newly born NS. The LMCCSN model with less second dredge-up results in a hydrodynamic and neutrino-induced NS kick of &amp;gt;40 km s−1 and a NS spin period of ∼30 ms, both not largely different from those of the Crab pulsar at birth.
Genetic architecture of inherited retinal degeneration in Germany: A large cohort study from a single diagnostic center over a 9‐year period
2020-06-12

Abstract We aimed to unravel the molecular genetic basis of inherited retinal degeneration (IRD) in a comprehensive cohort of patients diagnosed in the largest center for IRD in Germany. A cohort of 2,158 affected patients from 1,785 families diagnosed with IRD was analyzed by targeted next‐generation sequencing (NGS). Patients with single‐gene disorders (i.e., choroideremia and retinoschisis) were analyzed by Sanger sequencing and multiplex ligation‐dependent probe amplification. Our study cohort accounts for ∼7% of the estimated 30,000 patients with IRD in Germany, thereby providing representative data for both the prevalence of IRDs and the mutation spectrum of IRD genes for the population in Germany. We achieved a molecular diagnostic rate of 35–95%, depending on the clinical entities, with a high detection rate for achromatopsia, retinoschisis, and choroideremia, and a low detection rate for central areolar choroidal dystrophy and macular dystrophy. A total of 1,161 distinct variants were identified, including 501 novel variants, reaffirming the known vast genetic heterogeneity of IRD in a mainly outbred European population. This study demonstrates the clinical utility of panel‐based NGS in a large and highly heterogeneous cohort from an outbred population and for the first time gives a comprehensive representation of the genetic landscape of IRDs in Germany. The data are valuable and crucial for the scientific community and healthcare providers, but also for the pharmaceutical industry in the progressing field of personalized medicine and gene therapy.
COVID-19 and immunosuppression: a review of current clinical experiences and implications for ophthalmology patients taking immunosuppressive drugs
2020-06-12

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 in Wuhan city, Hubei province, China. This is the third and largest coronavirus outbreak since the new millennium after SARS in 2002 and Middle East respiratory syndrome (MERS) in 2012. Over 3 million people have been infected and the COVID-19 has caused more than 217 000 deaths. A concern exists regarding the vulnerability of patients who have been treated with immunosuppressive drugs prior or during this pandemic. Would they be more susceptible to infection by the SARS-CoV-2 and how would their clinical course be altered by their immunosuppressed state? This is a question the wider medical fraternity—including ophthalmologists, rheumatologists, gastroenterologist and transplant physicians among others—must answer. The evidence from the SARS and MERS outbreak offer some degree of confidence that immunosuppression is largely safe in the current COVID-19 pandemic. Preliminary clinical experiences based on case reports, small series and observational studies show the morbidity and mortality rates in immunosuppressed patients may not differ largely from the general population. Overwhelmingly, current best practice guidelines worldwide recommended the continuation of immunosuppression treatment in patients who require them except for perhaps high-dose corticosteroid therapy and in patients with associated risk factors for severe COVID-19 disease.
Near‐Unity Polarization of Valley‐Dependent Second‐Harmonic Generation in Stacked TMDC Layers and Heterostructures at Room Temperature
2020-06-12

Abstract With unique valley‐dependent optical and optoelectronic properties, 2D transition metal dichalcogenides (2D TMDCs) are promising materials for valleytronics. Second‐harmonic generation (SHG) in 2D TMDCs monolayers has shown valley‐dependent optical selection rules. However, SHG in monolayer TMDCs is generally weak; it is important to obtain materials with both strong SHG signals and a large degree of polarization. In the work, a variety of inversion‐symmetry‐breaking (3R‐like phase) TMDCs (WSe 2 , WS 2 , MoS 2 ) atomic layers, spiral structures, and heterostructures are prepared, and their SHG polarization is studied. Through circular‐polarization‐resolved SHG experiments, it is demonstrated that the SHG intensity is enhanced in thicker samples by breaking inversion symmetry while maintaining the degree of polarization close to unity at room temperature. By studying TMDCs with different twist angles and the spiral structures, it is found that there is no significant effect of multilayer interlayer interaction on valley‐dependent SHG. The realization of strong SHG with high degree of polarization may pave the way toward a new platform for nonlinear optical valleytronics devices based on 2D semiconductors.
Longitudinal isolation of potent near-germline SARS-CoV-2-neutralizing antibodies from COVID-19 patients
2020-06-12

SUMMARY The SARS-CoV-2 pandemic has unprecedented implications for public health, social life, and world economy. Since approved drugs and vaccines are not available, new options for COVID-19 treatment and prevention are highly demanded. To identify SARS-CoV-2 neutralizing antibodies, we analysed the antibody response of 12 COVID-19 patients from 8 to 69 days post diagnosis. By screening 4,313 SARS-CoV-2-reactive B cells, we isolated 255 antibodies from different time points as early as 8 days post diagnosis. Among these, 28 potently neutralized authentic SARS-CoV-2 (IC 100 as low as 0.04 μg/ml), showing a broad spectrum of V genes and low levels of somatic mutations. Interestingly, potential precursors were identified in naïve B cell repertoires from 48 healthy individuals that were sampled before the COVID-19 pandemic. Our results demonstrate that SARS-CoV-2 neutralizing antibodies are readily generated from a diverse pool of precursors, fostering the hope of rapid induction of a protective immune response upon vaccination.
Prognosis of Patients With Stage III Melanoma According to American Joint Committee on Cancer Version 8: A Reassessment on the Basis of 3 Independent Stage III Melanoma Cohorts
2020-06-12

PURPOSE Three new therapies have been approved recently for the adjuvant treatment of stage III melanoma, substantially reducing the risk of tumor recurrences. This study evaluates 3 independent data sets to clarify the survival probabilities of patients with stage III melanoma. PATIENTS AND METHODS The Central Malignant Melanoma Registry (CMMR) evaluated 1,553 patients with a primary diagnosis of stage III melanoma from 2000 to 2012. Studies from the European Organisation for Research and Treatment of Cancer (EORTC), of 573 patients in the observation arm of the 18991 study and 445 patients in the placebo arm of the 18071 study, were evaluated as reference cohorts. The survival outcomes were compared with the published American Joint Committee on Cancer version 8 (AJCCv8) stage III survival data. RESULTS For the CMMR stage III cohort versus the AJCCv8 cohort, the melanoma-specific survival (MSS) rates at 5 years were 67% versus 77%, and at 10 years were 56% versus 69%, respectively. For stage IIIA, the MSS rates at 5 years were 80% versus 93%, and at 10 years were 71% versus 88%; for stage IIIB, the MSS rates at 5 years were 75% versus 83%, and at 10 years were 61% versus 77%. The MSS rates of the EORTC studies either overlapped with or were lower than, the CMMR data. CONCLUSION The MSS rates in the CMMR and EORTC cohorts over the entire stage III are less favorable than those published in AJCCv8. This is particularly true for substages IIIA and IIIB.
Features of speech and swallowing dysfunction in pre-ataxic spinocerebellar ataxia type 2
2020-06-12

Speech and swallowing deficits appear sensitive to disease progression in early-stage SCA2, with syllabic rate a viable marker. Findings provide insight into mechanisms of disease progression in early-stage SCA2, signaling an opportunity for stratifying early-stage SCA2 and identifying salient markers of disease onset as well as outcome measures in future early-stage therapeutic studies.
Expanding the Genetic Code for Neuronal Studies
2020-06-12

Abstract Genetic code expansion is one of the most powerful technologies in protein engineering. In addition to the 20 canonical amino acids, the expanded genetic code is supplemented by unnatural amino acids, which have artificial side chains that can be introduced into target proteins in vitro and in vivo. A wide range of chemical groups have been incorporated co‐translationally into proteins in single cells and multicellular organisms by using genetic code expansion. Incorporated unnatural amino acids have been used for novel structure‐function relationship studies, bioorthogonal labelling of proteins in cellulo for microscopy and in vivo for tissue‐specific proteomics, the introduction of post‐translational modifications and optical control of protein function, to name a few examples. In this Minireview, the development of genetic code expansion technology is briefly introduced, then its applications in neurobiology are discussed, with a focus on studies using mammalian cells and mice as model organisms.
Tidying-up the plant nuclear space: domains, functions, and dynamics
2020-06-12

Abstract Understanding how the packaging of chromatin in the nucleus is regulated and organized to guide complex cellular and developmental programmes, as well as responses to environmental cues is a major question in biology. Technological advances have allowed remarkable progress within this field over the last years. However, we still know very little about how the 3D genome organization within the cell nucleus contributes to the regulation of gene expression. The nuclear space is compartmentalized in several domains such as the nucleolus, chromocentres, telomeres, protein bodies, and the nuclear periphery without the presence of a membrane around these domains. The role of these domains and their possible impact on nuclear activities is currently under intense investigation. In this review, we discuss new data from research in plants that clarify functional links between the organization of different nuclear domains and plant genome function with an emphasis on the potential of this organization for gene regulation.
In vivo Downregulation of MHC Class I Molecules by HCMV Occurs During All Phases of Viral Replication but Is Not Always Complete
2020-06-12

Based on cell culture data, MHC class I downregulation by HCMV on infected cells has been suggested as a means of immune evasion by this virus. In order to address this issue in vivo, an immunohistochemical analysis of tissue sections from biopsy and autopsy materials of HCMV infected organs was performed. HCMV antigens from the immediate early, early, and late phase of viral replication, and cellular MHC class I molecules were detected simultaneously or in serial sections by immuno-peroxidase and immuno-alkaline phosphatase techniques. Investigated organs included lung, gastrointestinal tract, and placenta. Colocalization of MHC molecules with sites of viral replication as well as MHC expression in individual infected cells were analyzed. To detect immune effector cells at sites of viral replication, leukocytes, CD8+ lymphocytes, and HCMV antigens were stained in serial sections. While strong MHC class I expression was detected in the cells surrounding infected cells, it appeared downregulated in the majority of infected cells themselves, particularly in the late replication phase. Despite significantly reduced MHC class I signals on infected cells, sites of infection were infiltrated by inflammatory cells that consisted predominantly of CD8+ lymphocytes. The extent of inflammatory infiltrates was negatively correlated with the extent of HCMV infected cells. Taken together, our findings indicate that HCMV can downmodulate MHC class I expression in vivo, whereas cytokines originating from infiltrating immune effector cells probably up regulates MHC class I expression in noninfected bystander cells. The presence of cytotoxic lymphocytes in close contact to infected cells may reflect control of viral spread by these cells despite MHC class I downmodulation.
Reproducible, portable, and efficient ancient genome reconstruction with nf-core/eager
2020-06-12

Abstract The broadening utilisation of ancient DNA to address archaeological, palaeontological, and biological questions is resulting in a rising diversity in the size of laboratories and scale of analyses being performed. In the context of this heterogeneous landscape, we present nf-core/eager, an advanced and entirely redesigned and extended version of the EAGER pipeline for the analysis of ancient genomic data. This Nextflow pipeline aims to address three main themes: accessibility and adaptability to different computing configurations, reproducibility to ensure robust analytical standards, and updating the pipeline to the latest routine ancient genomic practises. This new version of EAGER has been developed within the nf-core initiative to ensure high-quality software development and maintenance support; contributing to a long-term lifecycle for the pipeline. nf-core/eager will assist in ensuring that ancient DNA sequencing data can be used by a diverse range of research groups and fields.
Estimating the Impact of Control Measures to Prevent Outbreaks of COVID-19 Associated with Air Travel into a COVID-19-free country: A Simulation Modelling Study
2020-06-12

Abstract Aims We aimed to estimate the risk of COVID-19 outbreaks associated with air travel from a country with a very low prevalence of COVID-19 infection (Australia) to a COVID-19-free country (New Zealand; [NZ]), along with the likely impact of various control measures for passengers and cabin crew. Methods A stochastic version of the SEIR model CovidSIM v1.1, designed specifically for COVID-19 was utilized. It was populated with data for both countries and parameters for SARS-CoV-2 transmission and control measures. We assumed one Australia to NZ flight per day. Results When no interventions were in place, an outbreak of COVID-19 in NZ was estimated to occur after an average time of 1.7 years (95% uncertainty interval [UI]: 0.04-6.09). However, the combined use of exit and entry screening (symptom questionnaire and thermal camera), masks on aircraft and two PCR tests (on days 3 and 12 in NZ), combined with self-reporting of symptoms and contact tracing and mask use until the second PCR test, reduced this risk to one outbreak every 29.8 years (0.8 to 110). If no PCR testing was performed, but mask use was used by passengers up to day 15 in NZ, the risk was one outbreak every 14.1 years. However, 14 days quarantine (NZ practice in May 2020), was the most effective strategy at one outbreak every 34.1 years (0.06 to 125); albeit combined with exit screening and mask use on flights. Conclusions Policy-makers can require multi-layered interventions to markedly reduce the risk of importing the pandemic virus into a COVID-19-free nation via air travel. There is potential to replace 14-day quarantine with PCR testing or interventions involving mask use by passengers in NZ. However, all approaches require continuous careful management and evaluation.
Genetic Characterization of an Endangered Chilean Endemic Species, Prosopis burkartii Muñoz, Reveals its Hybrids Parentage
2020-06-12

The hybridization of Prosopis burkartii, a critically endangered endemic species, and the identification of its paternal species has not been genetically studied before. In this study we aimed to genetically confirm the origin of this species. To resolve the parental status of P. burkartii, inter-simple sequence repeat (ISSR), simple sequence repeats (SSR) and intron trnL molecular markers were used, and compared with Chilean species from the Algarobia and Strombocarpa sections. Out of seven ISSRs, a total of 70 polymorphic bands were produced in four species of the Strombocarpa section. An Multi-dimensional scaling (MDS) and Bayasian (STRUCTURE) analysis showed signs of introgression of genetic material in P. burkartii. Unweighted pair group method with arithmetic average (UPGMA) cluster analysis showed three clusters, and placed the P. burkartii cluster nested within the P. tamarugo group. Sequencing of the trnL intron showed a fragment of 535 bp and 529 bp in the species of the Algarobia and Strombocarpa sections, respectively. Using maximum parsimony (MP) and maximum likelihood (ML) trees with the trnL intron, revealed four clusters. A species-specific diagnostic method was performed, using the trnL intron Single Nucleotide Polymorphism (SNP). This method identified if individuals of P. burkartii inherited their maternal DNA from P. tamarugo or from P. strombulifera. We deduced that P. tamarugo and P. strombulifera are involved in the formation of P. burkartii.
VLT/SPHERE survey for exoplanets around young early-type stars, including systems with multi-belt architectures
2020-06-12

Context. Dusty debris disks around pre- and main-sequence stars are potential signposts for the existence of planetesimals and exoplanets. Giant planet formation is therefore expected to play a key role in the evolution of the disk. This is indirectly confirmed by extant submillimeter near-infrared images of young protoplanetary and cool dusty debris disks around main-sequence stars that usually show substantial spatial structures. With two decades of direct imaging of exoplanets already studied, it is striking to note that a majority of recent discoveries of imaged giant planets have been obtained around young early-type stars hosting a circumstellar disk. Aims. Our aim was to create a direct imaging program designed to maximize our chances of giant planet discovery and target 22 young early-type stars. About half of them show indications of multi-belt architectures. Methods. Using the IRDIS dual-band imager and the IFS integral field spectrograph of SPHERE to acquire high-constrast coronagraphic differential near-infrared images, we conducted a systematic search in the close environment of these young, dusty, and early-type stars. We used a combination of angular and spectral differential imaging to reach the best detection performances down to the planetary mass regime. Results. We confirm that companions detected around HIP 34276, HIP 101800, and HIP 117452 are stationary background sources and binary companions. The companion candidates around HIP 8832, HIP 16095, and HIP 95619 are determined as background contaminations. Regarding the stars for which we infer the presence of debris belts, a theoretical minimum mass for planets required to clear the debris gaps can be calculated. The dynamical mass limit is at least 0.1 M J and can exceed 1 M J . Direct imaging data is typically sensitive to planets down to ~3.6 M J at 1′′, and 1.7 M J in the best case. These two limits tightly constrain the possible planetary systems present around each target. These systems will be probably detectable with the next generation of planet imagers.
Verbal Communication using Intracortical Signals in a Completely Locked In-Patient
2020-06-12

Abstract Patients with amyotrophic lateral sclerosis (ALS) can lose all muscle-based routes of communication as motor neuron degeneration progresses, and ultimately, they may be left without any means of communication. While others have evaluated communication in people with remaining muscle control, to the best of our knowledge, it is not known whether neural-based communication remains possible in a completely locked-in state (CLIS). With consent and approval of the participant, family, and legal authority for this study, two 64 microelectrode arrays were implanted in the supplementary and primary motor cortex of a CLIS patient with ALS. The patient modulated neural firing rates based on auditory feedback, and he used this strategy to select letters one at a time to form words and phrases to communicate his needs and experiences. This case study provides novel evidence that brain-based volitional communication is possible even in a completely locked-in state.