Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical prediction rule for SARS-CoV-2 infection from 116 U.S. emergency departments

Objectives: Accurate and reliable criteria to rapidly estimate the probability of infection with the novel coronavirus-2 that causes the severe acute respiratory syndrome (SARS-CoV-2) and associated disease (COVID-19) remain an urgent unmet need, especially in emergency care. The objective was to derive and validate a clinical prediction rule for SARS-CoV-2 infection that uses simple criteria widely available at the point of care. Methods: Data came from the Registry data from the national REgistry of suspected COVID-19 in EmeRgency care (RECOVER network) comprising 116 hospitals from 25 states in the US. Clinical predictors and 30-day outcomes were abstracted from medical records of 19,850 emergency department (ED) patients tested for SARS-CoV-2. The criterion standard for diagnosis of SARS-CoV-2 required a positive molecular test from a swabbed sample or positive antibody testing within 30 days. The prediction rule was derived from a 50% random sample (n=9,925) using unadjusted analysis of 107 candidate variables as a screening step, followed by stepwise forward logistic regression on 72 variables. Results: Multivariable regression yielded a 13-variable score, which was simplified to 13-point rule: +1 point each for age>50 years, measured temperature>37.5 degrees C, oxygen saturation<95%, Black race, Hispanic or Latino ethnicity, household contact with known or suspected COVID-19, patient reported history of dry cough, anosmia/dysgeusia, myalgias or fever; and -1 point each for White race, no direct contact with infected person, or smoking. In the validation sample (n=9,975), the score produced an area under the receiver operating character curve of 0.80 (95% CI: 0.79-0.81), and this level of accuracy was retained across patients enrolled from the early spring to summer of 2020. In the simplified rule, a score of zero produced a sensitivity of 95.6% (94.8-96.3%), specificity of 20.0% (19.0-21.0%), likelihood ratio negative of 0.22 (0.19-0.26). Increasing points on the simplified rule predicted higher probability of infection (e.g., >75% probability with +5 or more points). Conclusion: Criteria that are available at the point of care can accurately predict the probability of SARS-CoV-2 infection. These criteria could assist with decision about isolation and testing at high throughput checkpoints.
International agricultural trade forecasting using machine learning

Abstract Focusing on seven major agricultural commodities with a long history of trade, this study employs data-driven analytics to decipher patterns of trade, namely using supervised machine learning (ML), as well as neural networks. The supervised ML and neural network techniques are trained on data until 2010 and 2014, respectively. Results show the high relevance of ML models to forecasting trade patterns in near- and long-term relative to traditional approaches, which are often subjective assessments or time-series projections. While supervised ML techniques quantified key economic factors underlying agricultural trade flows, neural network approaches provide better fits over the long term.
Impacts of 203/204: RG>KR mutation in the N protein of SARS-CoV-2

We present a structure-based model of phosphorylation-dependent binding and sequestration of SARS-CoV-2 nucleocapsid protein and the impact of two consecutive amino acid changes R203K and G204R. Additionally, we studied how mutant strains affect HLA-specific antigen presentation and correlated these findings with HLA allelic population frequencies. We discovered RG>KR mutated SARS-CoV-2 expands the ability for differential expression of the N protein epitope on Major Histocompatibility Complexes (MHC) of varying Human Leukocyte Antigen (HLA) origin. The N protein LKR region K203, R204 of wild type (SARS-CoVs) and (SARS-CoV-2) observed HLA-A*30:01 and HLA-A*30:21, but mutant SARS-CoV-2 observed HLA-A*31:01 and HLA-A*68:01. Expression of HLA-A genotypes associated with the mutant strain occurred more frequently in all populations studied. Importance The novel coronavirus known as SARS-CoV-2 causes a disease renowned as 2019-nCoV (or COVID-19). HLA allele frequencies worldwide could positively correlate with the severity of coronavirus cases and a high number of deaths.
Environment-Dependent Switch between Two Immune Systems against Ralstonia solanacearum Infections in Pepper

Although plant diseases generally cause more severe symptoms under conditions of high temperature and high humidity(HTHH), how plant respond to pathogen attack under this condition remains elusive. As an example, we herein comparatively studied pepper(Capsicum annuum) immunity against Ralstonia solanacearum under HTHH and ambient temperature by approaches of reverse genetics. We found that pepper respond to R.solanacearum infection by activating salicylic-acid- and jasmonic-acid-mediated immunity at ambient temperature. Under HTHH, However, it no longer activates JA-mediated immunity and activates only transient SA signaling at the early stage of R.solanacearum infection, but instead induces cytokinin mediated immunity. These two immune systems are positively regulated by CaWRKY40 via binding the WT-box and a novel W-box like (WL) box, respectively, in an environment-dependent manner: CaWRKY40 is activated upon R. solanacearum infection under HTHH, thereby upregulating ISOPENTENYLTRANSFERASE5(IPT5). The resulting cytokinin then works synergistically with CaWRKY40 in activating a subset of glutathione S-transferase genes via chromatin activation and WL-box binding, but prevent CaWRKY40 from activating ISOCHORISMATE SYNTHASE1 (ICS1) or SA-/JA-dependent pathogenesis-related genes by chromatin inactivation or by blocking WT-box binding. These results highlight the specific pepper immune response to R. solanacearum infection under HTHH and its synergistic activation by CaWRKY40 and cytokinins.
Evaluating extraction methods to study canine urine microbiota

The urinary microbiota is the collection of microbes present in urine that play a role in host health. Studies of urine microbiota have traditionally relied upon culturing methods aimed at identifying pathogens. However, recent culture-free sequencing studies of the urine microbiota have determined that a diverse array of microbes are present in health and disease. To study these microbes and their potential role in diseases like bladder cancer or interstitial cystitis, consistent extraction and detection of microbial DNA from urine is critical. However, urine is a low biomass substrate, requiring sensitive methods to capture DNA and making the risk of contamination high. To address this challenge, we collected urine samples from ten healthy dogs and extracted DNA from each sample using five different commercially available extraction methods. Extraction methods were compared based on total and bacterial DNA concentrations and microbial community composition and diversity assessed through 16S rRNA gene sequencing. Significant differences in the urinary microbiota were observed by dog and sex but not extraction method. The Bacteremia kit yielded the highest total DNA concentrations (Kruskal-Wallis, p = 0.165, not significant) and the highest bacterial DNA concentrations (Kruskal-Wallis, p = 0.044). Bacteremia also extracted bacterial DNA from the greatest number of samples. Taken together, these results suggest that the Bacteremia kit is an effective option for studying the urine microbiota. This work lays the foundation to study the urine microbiome in a wide range of urogenital diseases in dogs and other species. Highlights Canine urine microbiota differed by sex and dog but not extraction method. Qiagen Bacteremia kit yielded the highest bacterial DNA concentrations from urine. The Bacteremia kit extracted bacterial DNA from the greatest number of samples. Absolute abundance of Sphingomonas species increased in female dog urine. Pasteurellaceae bacterium canine oral taxon 272 increased in male dog urine.
Altered temporal sequence of transcriptional regulators in the generation of human cerebellar granule cells

Brain development is regulated by conserved transcriptional programs across species, but little is known about divergent mechanisms that create species-specific characteristics. Among brain regions, the cerebellum is now recognized to contribute to human cognitive evolution having a broad range of non-motor cognitive functions in addition to motor control. Emerging studies highlight the complexity of human cerebellar histogenesis, compared with non-human primates and rodents, making it important to develop methods to generate human cerebellar neurons that closely resemble those in the developing human cerebellum. Here we report a rapid and simple protocol for the directed derivation of the human ATOH1 lineage, the precursor of excitatory cerebellar neurons, from human pluripotent stem cells (hPSC), and strategies to decrease culture variability; a common limitation in hPSC studies. Upon transplantation into juvenile mice, early postmitotic hPSC-derived cerebellar granule cells migrated along glial fibers and integrated into the cerebellar cortex. By Translational Ribosome Affinity Purification (TRAP)-seq, the ATOH1 lineage most closely resembled human cerebellar tissue in the second trimester. Unexpectedly, TRAP-seq identified a heterochronic shift in the expression of RBFOX3 (NeuN) and NEUROD1, which are classically associated with differentiated neurons, within granule cell progenitors (GCPs) in the human external granule layer. This molecular divergence may provide the mechanism by which the GCP pool persists into year two post birth in humans, but only lasts for two weeks in mice. Our approach provides a scalable in vitro model of the human ATOH1 lineage that yields cerebellar granule cells within 48 days as well as a strategy for identifying uniquely human cellular and molecular characteristics.
Morphological Change of Aggregates of Polystyrene-block-poly (2-vinyl pyridine)/HAuCl4 Complexes in Solution

The self-assembly of polystyrene-b-poly(2-vinylpyridine) (PS-b-P2VP)/HAuCl4 complexes in solutions is described. A morphological change from spheres to aggregated spheres, and then to vesicles, all of which contain Au precursor within the micellar corona or vesicle shell, can be prepared from an identical diblock copolymer by controlling the solvent selectivity. The possible mechanisms leading to the morphological transitions are also discussed. This may be a simple, facile route for preparation of a desired gold-containing aggregate.
Ultrasound-mediated blood-brain barrier disruption improves anti-pyroglutamate3 Aβ antibody efficacy and enhances phagocyte infiltration into brain in aged Alzheimer’s disease-like mice

Pyroglutamate-3 amyloid-β (pGlu3 Aβ) is an N-terminally modified, toxic form of amyloid-β that is present in cerebral amyloid plaques and vascular deposits. Using the Fc-competent murine anti-pGlu3 Aβ monoclonal antibody (mAb), 07/2a, we present here a nonpharmacological approach using focused ultrasound (FUS) with intravenous (i.v.) injection of microbubbles (MB) to facilitate i.v. delivery of the 07/2a mAb across the blood brain barrier (BBB) in order to improve Aβ removal and restore memory in aged APP/PS1 mice, an Alzheimer’s disease (AD)-like model of amyloidogenesis. Compared to sham-treated controls, aged APP/PS1 mice treated with 07/2a immediately prior to FUS-mediated BBB disruption (mAb + FUS-BBBD combination treatment) showed significantly better spatial learning and memory in the Water T Maze. FUS-BBBD treatment alone improved contextual fear learning and memory in aged WT and APP/PS1 mice, respectively. APP/PS1 mice given the combination treatment had reduced Aβ42 and pGlu3 Aβ hippocampal plaque burden compared to PBS-treated APP/PS1 mice. Hippocampal synaptic puncta density and synaptosomal synaptic protein levels were also higher in APP/PS1 mice treated with 07/2a just prior to BBB disruption. Increased Iba-1+ microglia were observed in the hippocampi of AD mice treated with 07/2a with and without FUS-BBBD, and APP/PS1 mice that received hippocampal BBB disruption and 07/2a showed increased Ly6G+ monocytes in hippocampal CA3. FUS-induced BBB disruption did not increase the incidence of microhemorrhage in mice with or without 07/2a mAb treatment. Our findings suggest that FUS is useful tool that may enhance delivery of an anti-pGlu3 Aβ mAb for immunotherapy. FUS-mediated BBB disruption in combination with the 07/2a mAb also appears to facilitate monocyte infiltration in this AD model. Overall, these effects resulted in greater sparing of synapses and improved cognitive function without causing overt damage, suggesting the possibility of FUS as a noninvasive method to increase the therapeutic efficacy in AD patients.
Hydrophobic residues advance the onset of simple coacervation in intrinsically disordered proteins at low densities: Insights from field theoretical simulations studies

Intrinsically disordered proteins (IDPs) have engendered a definitive change in the way we think about the classical “sequence-structure-function” dogma. Their conformational pliability and rich molecular recognition features endow them with the ability to bind to diverse partners and predispose them to an elaborate functional armory. And of late, with studies on IDP-based liquid-liquid phase separation (LLPS) leading to formation of functional subcellular coacervates - best described as “membrane-less organelles (MLOs)”, IDPs are also bringing about paradigmatic changes in the way we think about biomolecular assemblies and subcellular organization. Though it is well recognized that the phase behavior of a given IDP is tightly coupled to its amino-acid sequences, there are only a few theories to model polyampholyte coacervation for IDPs. Recently, Joan-Emma Shea and co-workers used field theoretical simulations (FTS) to elucidate the complete phase diagram for LLPS of IDPs by considering different permutations of 50-residues chain representing 25 Lysine and 25 Glutamic acid [1]. Our work is an extension of that FTS framework where we develop and solve an augmented Hamiltonian that also accounts for hydrophobic interactions in the chain. We show that incorporation of hydrophobic interactions result in an advanced onset of coacervation at low densities. The patterning of hydrophobic, positive and negative residues plays important role in determining relative differences in the onset of phase separation. Though still very coarse-grained, once additional chemical specificities are incorporated, these high throughput analytical theory methods can be used as a starting point for designing sequences that drive LLPS.
The landscape of transcriptional and translational changes over 22 years of bacterial adaptation

Organisms can adapt to an environment by taking multiple mutational paths. This redundancy at the genetic level, where many mutations have similar phenotypic and fitness effects, can make untangling the molecular mechanisms of complex adaptations difficult. Here, we use the Escherichia coli long-term evolution experiment (LTEE) as a model to address this challenge. To understand how different genomic changes could lead to parallel fitness gains, we characterize the landscape of transcriptional and translational changes across 12 replicate populations evolving in parallel for 50,000 generations. By quantifying absolute changes in mRNA abundances, we show that not only do all evolved lines have more mRNAs but that this increase in mRNA abundance scales with cell size. We also find that despite few shared mutations at the genetic level, clones from replicate populations in the LTEE are remarkably similar in their gene expression patterns at both the transcriptional and translational levels. Furthermore, we show that the majority of the expression changes are due to changes at the transcriptional level with very few translational changes. Finally, we show how mutations in transcriptional regulators lead to consistent and parallel changes in the expression levels of downstream genes. These results deepen our understanding of the molecular mechanisms underlying complex adaptations and provide insights into the repeatability of evolution.
High rates of evolution preceded shifts to sex-biased gene expression in Leucadendron, the most sexually dimorphic angiosperms

The males and females of many dioecious plants differ in morphological (Dawson and Geber 1999; Barrett and Hough 2013; Tonnabel et al. 2017), physiological (Juvany and Munné-Bosch 2015), life-history (Delph 1999), and defence traits (Cornelissen and Stiling 2005). Ultimately, such sexual dimorphism must largely be due to differential gene expression between the sexes (Ellegren and Parsch 2007), but little is known about how sex-biased genes are recruited and how their expression evolves over time. We measured gene expression in leaves of males and females of ten species sampled across the South African Cape genus Leucadendron, which shows repeated changes in sexual dimorphism and includes the most extreme differences between males and females in flowering plants (Midgley 2010; Barrett and Hough 2013; Tonnabel et al. 2014). Even in the most dimorphic species in our sample, fewer than 2% of genes showed sex-biased gene expression (SBGE) in vegetative tissue, with surprisingly little correspondence between SBGE and vegetative dimorphism across species. The identity of sex-biased genes in Leucadendron was highly species-specific, with a rapid turnover among species. In animals, sex-biased genes often evolve more quickly than unbiased genes in their sequences and expression levels (Ranz et al. 2003; Khaitovich et al. 2005; Ellegren and Parsch 2007; Voolstra et al. 2007; Harrison et al. 2015; Naqvi et al. 2019), consistent with hypotheses invoking rapid evolution due to sexual selection. Our phylogenetic analysis in Leucadendron, however, clearly indicates that sex-biased genes are recruited from a class of genes with ancestrally rapid rates of expression evolution, perhaps due to low evolutionary or pleiotropic constraints. Nevertheless, we also find evidence for adaptive evolution of expression levels once sex bias evolves. Thus, although the expression of sex-biased genes is ultimately responsive to selection, high rates of expression evolution might usually predate the evolution of sex bias.
Selective metal extraction by biologically produced siderophores during bioleaching from low-grade primary and secondary mineral resources

Siderophores are a class of biogenic macromolecules that have high affinities for metals in the environment, thus could be exploited for alternate sustainable metal recovery technologies. Here, we assess the role of siderophores in the extraction and complexation of metals from an iron oxide-rich metallurgical processing residue and a low-grade primary Ni ore. Evaluation of the biological siderophore bioproduction by three pseudomonads, P. fluorescens, P. azotoformans and P. putida identified that P. putida could generate the highest siderophore yield, which was characterized as a hydroxamate and catecholate mixed-type pyoverdine PyoPpC-3B. Key physiochemical parameters involved in raw siderophore mediated metal extraction were identified using a fractional factorial design of experiments (DOE) and subsequently employed in purified PyoPpC-3B leaching experiments. Further targeted experiments with hydroxamate and catecholate functional analogues of PyoPpC-3B confirmed their marked ability to competitively or selectively leach and chelate hard metal ions, including Al(OH)4-, Mn2+ and Zn2+. Interestingly, complexation of Mn and Zn ions exceeded the natural affinity of pyoverdine for Fe3+, thus despite the low metal recoveries from the materials tested in this study, this work provides important new insights in siderophore-metal interactions.
Molecular dynamic simulation reveals E484K mutation enhances spike RBD-ACE2 affinity and the combination of E484K, K417N and N501Y mutations (501Y.V2 variant) induces conformational change greater than N501Y mutant alone, potentially resulting in an escape mutant

Rapidly spreading SARS-CoV-2 variants present not only an increased threat to human health due to the confirmed greater transmissibility of several of these new strains but, due to conformational changes induced by the mutations, may render first-wave SARS-CoV-2 convalescent sera, vaccine-induced antibodies, or recombinant neutralizing antibodies (nAbs) ineffective. To be able to assess the risk of viral escape from neutralization by first-wave antibodies, we leveraged our capability for Molecular Dynamic (MD) simulation of the spike receptor binding domain (S RBD) and its binding to human angiotensin-converting enzyme 2 (hACE2) to predict alterations in molecular interactions resulting from the presence of the E484K, K417N, and N501Y variants found in the South African 501Y.V2 strain – alone and in combination. We report here the combination of E484K, K417N and N501Y results in the highest degree of conformational alterations of S RBD when bound to hACE2, compared to either E484K or N501Y alone. Both E484K and N501Y increase affinity of S RBD for hACE2 and E484K in particular switches the charge on the flexible loop region of RBD which leads to the formation of novel favorable contacts. Enhanced affinity of S RBD for hACE2 very likely underpins the greater transmissibility conferred by the presence of either E484K or N501Y; while the induction of conformational changes may provide an explanation for evidence that the 501Y.V2 variant, distinguished from the B.1. 1.7 UK variant by the presence of E484K, is able to escape neutralization by existing first-wave anti-SARS-CoV-2 antibodies and re-infect COVID-19 convalescent individuals.
Eye movements elevate crowding in congenital idiopathic nystagmus

Congenital idiopathic nystagmus (sometimes known as infantile nystagmus) is a disorder characterised by involuntary eye movements, which leads to decreased acuity and visual function. One such function is visual crowding, a process whereby objects that are easily recognised in isolation become impaired by nearby flankers. Crowding typically occurs in the peripheral visual field, though elevations in foveal vision have been reported in congenital nystagmus, similar to those found with amblyopia (another developmental visual disorder). Here we examine whether the elevated foveal crowding with nystagmus is driven by similar mechanisms to those documented in amblyopia – long-term neural changes associated with a sensory deficit – or by the momentary displacement of the stimulus through nystagmus eye movements. We used a Landolt-C orientation identification task to measure threshold gap sizes with and without flanker Landolt-Cs that were either horizontally or vertically placed. Because nystagmus is predominantly horizontal, crowding should be stronger with horizontal flankers if eye movements cause the interference, whereas a sensory deficit should be equivalent for the two dimensions. Consistent with an origin in eye movements, we observe elevations in nystagmic crowding that are above that of typical vision, and stronger with horizontal than vertical flankers. This horizontal elongation was not found in either amblyopic or typical vision. We further demonstrate that the same pattern of performance can be obtained in typical vision with stimulus movement that simulates nystagmus. We consequently propose that the origin of nystagmic crowding lies in the eye movements, either through relocation of the stimulus into peripheral retina or image smear of the target and flanker elements. waveforms.