Miracle-dz/UniFAR-FTUs huggingface dataset:
Compared Heritability of Chronotype Instruments in a Single Population Sample

It is well established that the oldest chronotype questionnaire, the morningness-eveningness questionnaire (MEQ), has significant heritability, and several associations have been reported between MEQ score and polymorphisms in candidate clock genes, a number of them reproducibly across populations. By contrast, there are no reports of heritability and genetic associations for the Munich chronotype questionnaire (MCTQ). Recent genome-wide association studies (GWAS) from large cohorts have reported multiple associations with chronotype as assessed by a single self-evaluation question. We have taken advantage of the availability of data from all these instruments from a single sample of 597 participants from the Brazilian Baependi Heart Study. The family-based design of the cohort allowed us to calculate the heritability (h2) for these measures. Heritability values for the best-fitted models were 0.37 for MEQ, 0.32 for MCTQ, and 0.28 for single-question chronotype (MEQ Question 19). We also calculated the heritability for the two major factors recently derived from MEQ, “Dissipation of sleep pressure” (0.32) and “Build-up of sleep pressure” (0.28). This first heritability comparison of the major chronotype instruments in current use provides the first quantification of the genetic component of MCTQ score, supporting its future use in genetic analysis. Our findings also suggest that the single chronotype question that has been used for large GWAS analyses captures a larger proportion of the dimensions of chronotype than previously thought.
Cellular 5′-3′ mRNA Exoribonuclease XRN1 Inhibits Interferon Beta Activation and Facilitates Influenza A Virus Replication

A novel mechanistic discovery reveals that the host decay factor XRN1 contributes to influenza A virus replication, which exploits XRN1 activity to inhibit RIG-I-mediated innate immune response. Here, we identified a novel interaction between viral NS1 and host XRN1. ABSTRACT Cellular 5′-3′ exoribonuclease 1 (XRN1) is best known for its role as a decay factor, which by degrading 5′ monophosphate RNA after the decapping of DCP2 in P-bodies (PBs) in Drosophila, yeast, and mammals. XRN1 has been shown to degrade host antiviral mRNAs following the influenza A virus (IAV) PA-X-mediated exonucleolytic cleavage processes. However, the mechanistic details of how XRN1 facilitates influenza A virus replication remain unclear. In this study, we discovered that XRN1 and nonstructural protein 1 (NS1) of IAV are directly associated and colocalize in the PBs. Moreover, XRN1 downregulation impaired viral replication while the viral titers were significantly increased in cells overexpressing XRN1, which suggest that XRN1 is a positive regulator in IAV life cycle. We further demonstrated that the IAV growth curve could be suppressed by adenosine 3′,5′-bisphosphate (pAp) treatment, an inhibitor of XRN1. In virus-infected XRN1 knockout cells, the phosphorylated interferon regulatory factor 3 (p-IRF3) protein, interferon beta (IFN-β) mRNA, and interferon-stimulated genes (ISGs) were significantly increased, resulting in the enhancement of the host innate immune response and suppression of viral protein production. Our data suggest a novel mechanism by which the IAV hijacks the cellular XRN1 to suppress the host innate immune response and to facilitate viral replication. IMPORTANCE A novel mechanistic discovery reveals that the host decay factor XRN1 contributes to influenza A virus replication, which exploits XRN1 activity to inhibit RIG-I-mediated innate immune response. Here, we identified a novel interaction between viral NS1 and host XRN1. Knockdown and knockout of XRN1 expression in human cell lines significantly decreased virus replication while boosting RIG-I-mediated interferon immune response, suggesting that XRN1 facilitates influenza A virus replication. The pAp effect as XRN1 inhibitor was evaluated; we found that pAp was capable of suppressing viral growth. To our knowledge, this study shows for the first time that a negative-strand and nucleus-replicating RNA virus, as influenza A virus, can hijack cellular XRN1 to suppress the host RIG-I-dependent innate immune response. These findings provide new insights suggesting that host XRN1 plays a positive role in influenza A virus replication and that the inhibitor pAp may be used in novel antiviral drug development.
A dual‐channel language decoding from brain activity with progressive transfer training

When we view a scene, the visual cortex extracts and processes visual information in the scene through various kinds of neural activities. Previous studies have decoded the neural activity into single/multiple semantic category tags which can caption the scene to some extent. However, these tags are isolated words with no grammatical structure, insufficiently conveying what the scene contains. It is well‐known that textual language (sentences/phrases) is superior to single word in disclosing the meaning of images as well as reflecting people's real understanding of the images. Here, based on artificial intelligence technologies, we attempted to build a dual‐channel language decoding model (DC‐LDM) to decode the neural activities evoked by images into language (phrases or short sentences). The DC‐LDM consisted of five modules, namely, Image‐Extractor, Image‐Encoder, Nerve‐Extractor, Nerve‐Encoder, and Language‐Decoder. In addition, we employed a strategy of progressive transfer to train the DC‐LDM for improving the performance of language decoding. The results showed that the texts decoded by DC‐LDM could describe natural image stimuli accurately and vividly. We adopted six indexes to quantitatively evaluate the difference between the decoded texts and the annotated texts of corresponding visual images, and found that Word2vec‐Cosine similarity (WCS) was the best indicator to reflect the similarity between the decoded and the annotated texts. In addition, among different visual cortices, we found that the text decoded by the higher visual cortex was more consistent with the description of the natural image than the lower one. Our decoding model may provide enlightenment in language‐based brain‐computer interface explorations.
Novel Small Molecule Growth Inhibitors of Xanthomonas spp. Causing Bacterial Spot of Tomato.

Bacterial spot (BS) of tomato, caused by Xanthomonas gardneri, X. perforans, X. vesicatoria, and X. euvesicatoria, is difficult to control because of the high prevalence of copper- and streptomycin-resistant strains and the lack of resistance cultivars and effective bactericides. The objective of this study was to identify novel growth inhibitors of BS-causing Xanthomonas (BS-X) species by using small molecules (SM; n = 4,182). Several SMs (X1, X2, X5, X9, X12, and X16) completely inhibited the growth of BS-X isolates (n = 68 X. gardneri, 55 X. perforans, 4 X. vesicatoria, and 32 X. euvesicatoria) at ≥12.5 µM by disrupting Xanthomonas cell integrity through weakening of the cell membrane and formation of pores. These SMs were also effective against biofilm-embedded, copper- and streptomycin-resistant Xanthomonas strains while having minimal impact on other plant pathogenic (n = 20) and beneficial bacteria (n = 12). Furthermore, these SMs displayed equivalent antimicrobial activity against BS-X in seeds and X. gardneri in seedlings compared with conventional control methods (copper sulfate and streptomycin) at similar concentrations while having no detectable toxicity to tomato tissues. SMs X2, X5, and X12 reduced X. gardneri, X. perforans, X. vesicatoria, and X. euvesicatoria populations in artificially infested seeds ≤3.4-log CFU/seed 1 day postinfection (dpi) compared with the infested untreated control (P ≤ 0.05). SMs X1, X2, X5, and X12 reduced disease severity ≤72% and engineered bioluminescent X. gardneri populations ≤3.0-log CFU/plant in infected seedlings at 7 dpi compared with the infected untreated control (P ≤ 0.05). Additional studies are needed to increase the applicability of these SMs for BS management in tomato production.
Magnetic Hyperthermia Properties of Electrosynthesized Cobalt Ferrite Nanoparticles

Using the electrochemical route, cobalt ferrite nanoparticles (NPs) with two different sizes were synthesized and stabilized in water by coating with citric acid. The specific absorption rate (SAR) values of aqueous suspensions of magnetic nanoparticles with crystal sizes of 13 and 28 nm were investigated in the frequency range 32–101 kHz and up to 51 mT. SAR values were higher for the larger NPs and reached 133 W/g. Numerical simulations are used for a quantitative analysis of hyperthermia experiments and seem to indicate that the larger NPs are multidomain. Cytotoxicity analysis was also performed in HeLa tumor cells; a null cytotoxicity of these nanoparticles in cell tissues were obtained.
A model based on clinico‐biochemical characteristics and deep learning features from MR images for assessing necroinflammatory activity in chronic hepatitis B

Accurate liver necroinflammatory activity diagnosis could guide the clinical decision-making in chronic hepatitis B (CHB) patients.This study aimed to build a non-invasive diagnostic model for liver necroinflammatory activity by incorporating deep learning features and clinico-biochemical characteristics in CHB patients. A total of 239 CHB patients who underwent liver biopsy were recruited and randomly divided into a training cohort (n = 179) and an independent validation cohort (n = 60). Bidirectional stepwise selection identified independent clinico-biochemical characteristics. Multivariate logistic regression analysis was used to establish the final combined model by incorporating clinico-biochemical and deep learning features. Predictive performance was evaluated by discrimination and clinical usefulness. Immunoglobulin M, platelets, laminin, type IV collagen, gamma-glutamyl transferase, alanine aminotransferase, aspartate transaminase, alkaline phosphatase, direct bilirubin, and total bilirubin were identified as independent factors. The combined model exhibited better performance than models based on clinico-biochemical characteristics alone, with an AUC of 0.942 (95% confidence interval [CI], 0.912-0.969) for necroinflammatory activity ≥G2 and 0.885 (95% CI, 0.829-0.934) for ≥G3 in the training cohort, and 0.938 (95% CI, 0.867-0.993) and 0.854 (95% CI, 0.764-0.934) in the validation cohort, respectively. The decision curve confirmed its clinical usefulness. The combined model provided an accurate non-invasive prediction of liver necroinflammatory activity, which might contribute to clinical decision-making in CHB patients.
A C‐terminal BCOR nonsense variant in a male patient expands the phenotypic spectrum of BCOR‐associated syndromic microphthalmia

To the Editor Heterozygous null variants in the X-chromosomal gene BCOR (BCL-6 corepressor) are associated with oculofaciocardiodental syndrome (OFCD; OMIM #300166) in females, whereas hemizygous missense variants cause severe (‘Lenz’) microphthalmia in males with only 10 male affected patients described to date. Males with hemizygous missense variants in BCOR mostly present with bilateral microphthalmia, developmental delay/ intellectual disability (ID) and congenital malformations (CMA). As no affected males with hemizygous null variants in BCOR have been described so far, lethality in males was assumed. We report an 18 year-old male individual presenting with multiple CMA, high myopia and ID, in which a hemizygous nonsense variant in BCOR could be identified by exome sequencing (ES). Prenatally, intrauterine growth restriction and a single umbilical artery were detected.
Association of a Combination of Healthy Lifestyle Behaviors With Reduced Risk of Incident Systemic Lupus Erythematosus

While previous studies have demonstrated an association between individual factors related to lifestyle and the risk of systemic lupus erythematosus (SLE), it is unclear how the combination of these factors might affect the risk of incident SLE. This study was undertaken to prospectively evaluate whether a combination of healthy lifestyle factors is associated with a lower risk of incident SLE and its subtypes (anti–double‐stranded DNA [anti‐dsDNA]–positive and anti‐dsDNA–negative SLE).
Characterization of MW06, a human monoclonal antibody with cross-neutralization activity against both SARS-CoV-2 and SARS-CoV

ABSTRACT The global pandemic of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in widespread social and economic disruption. Effective interventions are urgently needed for the prevention and treatment of COVID-19. Neutralizing monoclonal antibodies (mAbs) have demonstrated their prophylactic and therapeutic efficacy against SARS-CoV-2, and several have been granted authorization for emergency use. Here, we discover and characterize a fully human cross-reactive mAb, MW06, which binds to both SARS-CoV-2 and SARS-CoV spike receptor-binding domain (RBD) and disrupts their interaction with angiotensin-converting enzyme 2 (ACE2) receptors. Potential neutralization activity of MW06 was observed against both SARS-CoV-2 and SARS-CoV in different assays. The complex structure determination and epitope alignment of SARS-CoV-2 RBD/MW06 revealed that the epitope recognized by MW06 is highly conserved among SARS-related coronavirus strains, indicating the potential broad neutralization activity of MW06. In in vitro assays, no antibody-dependent enhancement (ADE) of SARS-CoV-2 infection was observed for MW06. In addition, MW06 recognizes a different epitope from MW05, which shows high neutralization activity and has been in a Phase 2 clinical trial, supporting the development of the cocktail of MW05 and MW06 to prevent against future escaping variants. MW06 alone and the cocktail show good effects in preventing escape mutations, including a series of variants of concern, B.1. 1.7, P.1, B.1. 351, and B.1. 617.1. These findings suggest that MW06 recognizes a conserved epitope on SARS-CoV-2, which provides insights for the development of a universal antibody-based therapy against SARS-related coronavirus and emerging variant strains, and may be an effective anti-SARS-CoV-2 agent.
Interactive Graph Stream Analytics in Arkouda

Data from emerging applications, such as cybersecurity and social networking, can be abstracted as graphs whose edges are updated sequentially in the form of a stream. The challenging problem of interactive graph stream analytics is the quick response of the queries on terabyte and beyond graph stream data from end users. In this paper, a succinct and efficient double index data structure is designed to build the sketch of a graph stream to meet general queries. A single pass stream model, which includes general sketch building, distributed sketch based analysis algorithms and regression based approximation solution generation, is developed, and a typical graph algorithm—triangle counting—is implemented to evaluate the proposed method. Experimental results on power law and normal distribution graph streams show that our method can generate accurate results (mean relative error less than 4%) with a high performance. All our methods and code have been implemented in an open source framework, Arkouda, and are available from our GitHub repository, Bader-Research. This work provides the large and rapidly growing Python community with a powerful way to handle terabyte and beyond graph stream data using their laptops.
Construction of Co–Mn Prussian Blue Analog Hollow Spheres for Efficient Aqueous Zn‐ion Batteries

Abstract Prussian blue analogs (PBAs) are considered as reliable and promising cathode materials for aqueous Zn‐ion batteries (AZIBs), but they suffer from low capacity and poor cycling stability due to insufficient active sites and structural damage caused by the ion insertion/extraction processes. Herein, a template‐engaged ion exchange approach has been developed for the synthesis of Co‐substituted Mn‐rich PBA hollow spheres (CoMn‐PBA HSs) as cathode materials for AZIBs. Benefiting from the multiple advantageous features including hollow structure, abundant active sites, fast Zn2+ ion diffusion, and partial Co substitution, the CoMn‐PBA HSs electrode shows efficient zinc ion storage properties in terms of high capacity, decent rate capability and prolonged cycle life.
Sequential modeling, monitoring, and forecasting of streaming web traffic data

In this paper we introduce strategies for modeling, monitoring, and forecasting sequential web trafﬁc data using ﬂows from the Fox News website. In our analysis we consider a family of Poisson-gamma state space (PGSS) models that can accurately quantify the uncertainty exhibited by web trafﬁc data, can provide fast sequential monitoring and prediction mechanisms for high frequency time intervals, and are computationally feasible when structural breaks are present. As such, we extend the family of PGSS models to include the state augmented (sa-)PGSS model whose state evolution structure is ﬂexible and responsive to sudden changes. Such adaptability is achieved by augmenting the state vector of the PGSS model with an additional state variable for a time-varying discount factor. We develop an efﬁcient particle-based estimation procedure that is suitable for sequential analysis, allowing us to estimate dynamic state variables and static parameters via closed-form conditional sufﬁcient statistics. We compare the performance of the PGSS family of models against viable alternatives from the literature and argue that, especially in the presence of structural breaks, our proposed approach yields superior sequential model ﬁt and predictive performance while preserving computational feasibility. We provide additional insights by designing a simulation study that mimics potential web trafﬁc data patterns.
Response to: “I just stand around and look friendly” – comparing medical students’ and physicians’ ward round scripts

a bleep, meaning they didn’t have to rely on busy staff to alert them to a trauma. Furthermore, we surveyed our colleagues’ experiences of the role. Over two-thirds of those who had acted as trauma scribe described themselves as feeling confident in the role. We received lots of positive feedback describing it as a valuable experience that engaged students and integrated them within the trauma team. The students reported being well supported by the surrounding healthcare professionals, never feeling as though they were acting outside their capabilities. Overall, we feel that the role of trauma scribe is an effective way to deploy students appropriately within the trauma team, and thus aids learning within an otherwise potentially intimidating situation.
Vitamin D modulates hepatic microRNAs and mitigates tamoxifen‐induced steatohepatitis in female rats

Tamoxifen (TAM) is a life‐saving and cost‐effective drug widely used in the prevention and treatment of breast cancer. However, the adverse effects of tamoxifen can lead to non‐adherence and poor patient outcomes. Therefore, exploring novel strategies to improve TAM safety profile is crucial. Given the key role that vitamin D (VD) plays in modulating lipid metabolism and inflammation, in addition to its benefits in reducing risk and progression of breast cancer, we evaluated the protective potential of VD against TAM‐induced hepatotoxicity focusing on lipid metabolism and microRNAs (miRNAs) regulation. Female rats were pretreated with VD as cholecalciferol (500 IU/kg/day, po) for 4 weeks before receiving TAM (40 mg/kg/day, po) concurrently with VD during the fifth and sixth weeks. Liver histology, lipid profile and expression of genes, proteins, and miRNAs involved in lipid metabolism and inflammation were examined. TAM‐induced steatohepatitis was evidenced by elevated liver triglycerides and cholesterol contents, increased serum miRNA‐122 level, and ALT activity, in parallel with accumulation of lipid droplets, focal necrosis, and inflammatory cells infiltration in hepatocytes. Prophylactic use of VD mitigated TAM‐induced steatohepatitis by modulating key transcription factors in the liver: PPAR‐α, Srebf1, and NF‐κB and their downstream genes/proteins Fas, CPT‐1A, and TNF‐α resulting in reduced hepatic lipids and suppressed pro‐inflammatory signaling. Notably, VD pretreatment mitigated TAM‐induced alterations in the expression of serum miRNA‐122, hepatic miRNA‐21, and miRNA‐33. The combination therapy of VD and TAM has complementary benefits in terms of safety and not only efficacy and should be further investigated clinically.
Determination of Ligand Binding Modes in Hydrated Viral Ion Channels to Foster Drug Design and Repositioning

Target-based design and repositioning are mainstream strategies of drug discovery. Numerous drug design and repositioning projects have been launched to fight the ongoing COVID-19 pandemic. The resulting drug candidates have often failed due to the misprediction of their target-bound structures. The determination of water positions of such structures is particularly challenging due to the large number of possible drugs and the diversity of their hydration patterns. To answer this challenge and help correct predictions, we introduce a new protocol HydroDock, which can build hydrated drug–target complexes from scratch. HydroDock requires only the dry target and drug structures and produces their complexes with appropriately positioned water molecules. As a test application of the protocol, we built the structures of amantadine derivatives in complex with the influenza M2 transmembrane ion channel. The repositioning of amantadine derivatives from this influenza target to the SARS-CoV-2 envelope protein was also investigated. Excellent agreement was observed between experiments and the structures determined by HydroDock. The atomic resolution complex structures showed that water plays a similar role in the binding of amphipathic amantadine derivatives to transmembrane ion channels of both influenza A and SARS-CoV-2. While the hydrophobic regions of the channels capture the bulky hydrocarbon group of the ligand, the surrounding waters direct its orientation parallel with the axes of the channels via bridging interactions with the ionic ligand head. As HydroDock supplied otherwise undetermined structural details, it can be recommended to improve the reliability of future design and repositioning of antiviral drug candidates and many other ligands with an influence of water structure on their mechanism of action.