julilili42/papers huggingface dataset:
SARS-CoV-2 Infection Biomarkers Reveal Adaptive Evolutionary Chemistry of Antiviral Nucleoside Metabolism
2023-05-08

We present compelling evidence for the existence of an evolutionary adaptive response to viral agents such as SARS-CoV-2, that results in the human <em>in vivo</em> biosynthesis of a family of compounds with potential antiviral activity. Using nuclear magnetic resonance (NMR) spectroscopy, we detected a characteristic spin-system motif indicative of the presence of an extended panel of urinary and serum metabolites during the acute viral phase. The structure of eight of nucleoside analogues was elucidated (six of which have not previously been reported in human urine), and subsequently confirmed by total-synthesis and matrix spiking. The molecular structures of the nucleoside analogues and their correlation with an array of serum cytokines, including IFN-α2, IFN-γ and IL-10, suggest an association with the viperin enzyme contributing to an endogenous innate immune defense mechanism against viral infection.
Machine learning-based personalized composite score dissects risk and protective factors for cognitive and motor function in elderly
2023-05-08

Abstract Background: Most nations worldwide have aging populations. With age, sensory, cognitive and motor abilities decline and the risk for neurodegenerative disorders increases. These multiple impairments influence the quality of life and increase the need for care, thus putting a high burden on society, the economy, and the healthcare system. Therefore, it is important to identify factors that influence healthy aging, in particular ones that are potentially modifiable by each subject through choice of lifestyle. However, large-scale studies that investigate the influence of multiple multi-modal factors on a global description of healthy aging measured by multiple clinical assessments are sparse. Methods: We propose a Machine Learning model that simultaneously predicts multiple cognitive and motor outcome measurements on a personalized level recorded from one learned composite score. This personalized composite score is derived by the model from a large set of multi-modal components from the TREND cohort including genetic, biofluid, clinical, demographic and lifestyle factors. Results: We found that a model based on a single composite score was able to predict cognitive and motor abilities almost as well as a flexible regression model specifically trained for each single clinical score. In contrast to the flexible regression model, our composite score-based model is able to identify factors that globally influence cognitive and motoric abilities as measured by multiple clinical scores. The model identified several risk and protective factors for healthy aging and recovered physical exercise as a major, modifiable, protective factor. Conclusion: We conclude that our low parametric modeling approach successfully recovered known risk and protective factors of healthy aging on a personalized level while providing an interpretable composite score. The modeling approach is generalizable and could also be applied to other cohorts to investigate the complex interplay of risk and protective factors along with effect sizes from different dimensions such as lifestyle, medical, genetic and biochemical data.
Coherent interface between optical and microwave photons on an integrated superconducting atom chip
2023-05-08

Sub-wavelength arrays of atoms exhibit remarkable optical properties, analogous to those of phased array antennas, such as collimated directional emission or nearly perfect reflection of light near the collective resonance frequency. We propose to use a single-sheet sub-wavelength array of atoms as a switchable mirror to achieve a coherent interface between propagating optical photons and microwave photons in a superconducting coplanar waveguide resonator. In the proposed setup, the atomic array is located near the surface of the integrated superconducting chip containing the microwave cavity and optical waveguide. A driving laser couples the excited atomic state to Rydberg states with strong microwave transition. Then the presence or absence of a microwave photon in the superconducting cavity makes the atomic array transparent or reflective to the incoming optical pulses of proper frequency and finite bandwidth.
SARS-CoV-2 Infection Biomarkers Reveal Adaptive Evolutionary Chemistry of Antiviral Nucleoside Metabolism
2023-05-08

We present compelling evidence for the existence of an evolutionary adaptive response to viral agents such as SARS-CoV-2, that results in the human in vivo biosynthesis of a family of compounds with potential antiviral activity. Using nuclear magnetic resonance (NMR) spectroscopy, we detected a characteristic spin-system motif indicative of the presence of an extended panel of urinary and serum metabolites during the acute viral phase. The structure of eight of nucleoside analogues was elucidated (six of which have not previously been reported in human urine), and subsequently confirmed by total-synthesis and matrix spiking. The molecular structures of the nucleoside analogues and their correlation with an array of serum cytokines, including IFN-&amp;alpha;2, IFN-&amp;gamma; and IL-10, suggest an association with the viperin enzyme contributing to an endogenous innate immune defense mechanism against viral infection.
QCD at the amplitude level: Fock state interference in heavy quark electroproduction
2023-05-08

A bstract Quantum chromodynamics (QCD) rigorously predicts the existence of both nonperturbative intrinsic and perturbative extrinsic heavy quark contents of nucleons. In this article we discuss the heavy quark electroproduction on protons induced by the Fock states ∣ uud + g 〉 of three valence quarks in the proton and a nonperturbative gluon, and the <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mo>∣</mml:mo> <mml:mi>uud</mml:mi> <mml:mo>+</mml:mo> <mml:mi>Q</mml:mi> <mml:mover> <mml:mi>Q</mml:mi> <mml:mo> ̄</mml:mo> </mml:mover> <mml:mo>〉</mml:mo> </mml:math> non-perturbative state of three valence quarks and a heavy quark-antiquark pair. The first one gives the perturbative contribution when the gluon produces a heavy quark pair, while the second is the intrinsic part, and they produce amplitude interference. We use nonperturbative light-front wavefunctions for these Fock states, which are computed using the color-confining light-front holographic QCD theory. Due to interference of the amplitudes corresponding to the intrinsic and extrinsic heavy quark contribution to the proton a novel Q vs. <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mover> <mml:mi>Q</mml:mi> <mml:mo> ̄</mml:mo> </mml:mover> </mml:math> asymmetry emerges in the differential cross section of the electroproduction off a proton <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msup> <mml:mi>d</mml:mi> <mml:mn>2</mml:mn> </mml:msup> <mml:msub> <mml:mi>σ</mml:mi> <mml:mrow> <mml:msup> <mml:mi>e</mml:mi> <mml:mo>−</mml:mo> </mml:msup> <mml:mi>p</mml:mi> </mml:mrow> </mml:msub> <mml:mo>/</mml:mo> <mml:mfenced> <mml:mrow> <mml:mi>dxd</mml:mi> <mml:msup> <mml:mi>Q</mml:mi> <mml:mn>2</mml:mn> </mml:msup> </mml:mrow> </mml:mfenced> </mml:math> . Our analysis proposed a novel asymmetry in QCD between intrinsic and extrinsic heavy quark content in nucleon and provides new insights into the physics of heavy quark phenomena in QCD at the amplitude level. This asymmetry is similar to the Brodsky-Gillespie asymmetry discovered before in QED case and confirmed at DESY.
The massless non-adjacent double off-shell scalar box integral — branch cut structure and all-order epsilon expansion
2023-05-08

A bstract We generalize the result of our recent paper on the massless single off-shell scalar box integral to the case of two non-adjacent end points off the light cone. An analytic result in d = 4 − 2 ε dimensions is established in terms of four Gauss hypergeometric 2 F 1 functions respectively their single-valued counterparts. This allows for an explicit splitting of real and imaginary parts, as well as an all-order ε -expansion in terms of single-valued polylogarithms.
Maintained imbalance of triglycerides, apolipoproteins, energy metabolites and cytokines in long-term COVID-19 syndrome patients
2023-05-09

Background Deep metabolomic, proteomic and immunologic phenotyping of patients suffering from an infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have matched a wide diversity of clinical symptoms with potential biomarkers for coronavirus disease 2019 (COVID-19). Several studies have described the role of small as well as complex molecules such as metabolites, cytokines, chemokines and lipoproteins during infection and in recovered patients. In fact, after an acute SARS-CoV-2 viral infection almost 10-20% of patients experience persistent symptoms post 12 weeks of recovery defined as long-term COVID-19 syndrome (LTCS) or long post-acute COVID-19 syndrome (PACS). Emerging evidence revealed that a dysregulated immune system and persisting inflammation could be one of the key drivers of LTCS. However, how these biomolecules altogether govern pathophysiology is largely underexplored. Thus, a clear understanding of how these parameters within an integrated fashion could predict the disease course would help to stratify LTCS patients from acute COVID-19 or recovered patients. This could even allow to elucidation of a potential mechanistic role of these biomolecules during the disease course. Methods This study comprised subjects with acute COVID-19 (n=7; longitudinal), LTCS (n=33), Recov (n=12), and no history of positive testing (n=73). 1 H-NMR-based metabolomics with IVDr standard operating procedures verified and phenotyped all blood samples by quantifying 38 metabolites and 112 lipoprotein properties. Univariate and multivariate statistics identified NMR-based and cytokine changes. Results Here, we report on an integrated analysis of serum/plasma by NMR spectroscopy and flow cytometry-based cytokines/chemokines quantification in LTCS patients. We identified that in LTCS patients lactate and pyruvate were significantly different from either healthy controls (HC) or acute COVID-19 patients. Subsequently, correlation analysis in LTCS group only among cytokines and amino acids revealed that histidine and glutamine were uniquely attributed mainly with pro-inflammatory cytokines. Of note, triglycerides and several lipoproteins (apolipoproteins Apo-A1 and A2) in LTCS patients demonstrate COVID-19-like alterations compared with HC. Interestingly, LTCS and acute COVID-19 samples were distinguished mostly by their phenylalanine, 3-hydroxybutyrate (3-HB) and glucose concentrations, illustrating an imbalanced energy metabolism. Most of the cytokines and chemokines were present at low levels in LTCS patients compared with HC except for IL-18 chemokine, which tended to be higher in LTCS patients. Conclusion The identification of these persisting plasma metabolites, lipoprotein and inflammation alterations will help to better stratify LTCS patients from other diseases and could help to predict ongoing severity of LTCS patients.
Modeling land susceptibility to wind erosion hazards using LASSO regression and graph convolutional networks
2023-05-09

Predicting land susceptibility to wind erosion is necessary to mitigate the negative impacts of erosion on soil fertility, ecosystems, and human health. This study is the first attempt to model wind erosion hazards through the application of a novel approach, the graph convolutional networks (GCNs), as deep learning models with Monte Carlo dropout. This approach is applied to Semnan Province in arid central Iran, an area vulnerable to dust storms and climate change. We mapped 15 potential factors controlling wind erosion, including climatic variables, soil characteristics, lithology, vegetation cover, land use, and a digital elevation model (DEM), and then applied the least absolute shrinkage and selection operator (LASSO) regression to discriminate the most important factors. We constructed a predictive model by randomly selecting 70% and 30% of the pixels, as training and validation datasets, respectively, focusing on locations with severe wind erosion on the inventory map. The current LASSO regression identified eight out of the 15 features (four soil property categories, vegetation cover, land use, wind speed, and evaporation) as the most important factors controlling wind erosion in Semnan Province. These factors were adopted into the GCN model, which estimated that 15.5%, 19.8%, 33.2%, and 31.4% of the total area is characterized by low, moderate, high, and very high susceptibility to wind erosion, respectively. The area under curve (AUC) and SHapley Additive exPlanations (SHAP) of game theory were applied to assess the performance and interpretability of GCN output, respectively. The AUC values for training and validation datasets were estimated at 97.2% and 97.25%, respectively, indicating excellent model prediction. SHAP values ranged between −0.3 and 0.4, while SHAP analyses revealed that the coarse clastic component, vegetation cover, and land use were the most effective features of the GCN output. Our results suggest that this novel suite of methods is highly recommended for future spatial prediction of wind erosion hazards in other arid environments around the globe.
Prehistoric Hunter-Gatherers in the Philippines—Subsistence strategies, adaptation, and behaviour in maritime environments
2023-05-09

Archaeological research in the Philippines has produced a timeline of currently over 700,000 years of human occupation. However, while an initial presence of early hominins has been securely established through several radiometric dates between 700 ka to 1 ma from Luzon Island, there is currently little evidence for the presence of hominins after those episodes until c. 67 to 50 ka for Luzon or any of the other Philippine islands. At approximately 40 ka, anatomically modern humans had arrived in the Philippines. Early sites with fossil and/or artifactual evidence are Tabon Cave in Palawan and Bubog 1 in Occidental Mindoro, the latter situated in the Wallacean part of the archipelago. This paper presents an overview of the archaeological research on the prehistory of the Philippines from the Pleistocene until the Late Holocene and the arrival of the first farmers, presumably from Austronesian language groups approximately 4,000 years ago. Research on this topic has significantly intensified over the past 20 years and is providing a variety of evidence for the successful adaptation of those first islanders to maritime environments, the diversity of technological and subsistence strategies, and increasingly complex interrelationships across Island Southeast Asia.
Uncovering transcriptomic landscape alterations of CAN-2409 in in vitro and in vivo glioma models
2023-05-09

Rationale CAN-2409 is a locally delivered oncolytic therapy, which results in vaccination against the injected tumor. CAN-2409 consists of a non-replicating adenovirus armed with the Herpes virus thymidine kinase, which metabolizes ganciclovir into a phosphorylated nucleotide that is incorporated into the tumor cell’s genome, thereby inflicting immunogenic cancer cell death. While CAN-2409’s immunological impact has been well characterized, its effects on the tumor cells transcriptome remains unknown. We compared the transcriptomic landscape after treatment of glioblastoma models with CAN-2409 in vitro and in vivo to assess how the interplay with the tumor microenvironment influences CAN-2409-mediated transcriptome alterations. Methods We performed RNA-Seq with CAN-2409 treated patient-derived glioma stem-like cells and tumors of C57/BL6 mice and compared KEGG pathway usage and differential gene expression focusing on immune cell and cytokine profiles. T -cell -killing assays were performed to assess candidate effectors. Results PCA analysis showed distinct clustering of control and CAN-2409 samples under both conditions. KEGG pathway analysis revealed significant enrichment for p53 signaling and cell cycle pathway, with similar dynamics for key regulators of both pathways in vitro and in vivo , including MYC, CCNB1, PLK1 and CDC20 . Selected alterations (PLK1 and CCNB1) were validated at the protein level. Cytokine expression analysis revealed upregulation of pro-inflammatory IL12a under both conditions; immune cell gene profiling showed reduction of myeloid associated genes. T -cell-killing assays showed increased killing in the presence of IL-12. Conclusion CAN-2409 significantly alters the transcriptome both in vitro and in vivo . Comparison of pathway enrichment revealed mutual and differential utilization of pathways under both conditions, suggesting a modulating influence on the cell cycle in tumor cells, and of the tumor microenvironment on the transcriptome in vivo . IL-12 synthesis likely depends on interactions with the tumor microenvironment, and it facilitates CAN-2409 cell killing. This dataset provides potential to understand resistance mechanisms and identify potential biomarkers for future studies.
Thoracic lymphatic anomalies in patients with univentricular hearts: correlation of morphologic findings in isotropic T2-weighted MRI with the outcome after fontan palliation
2023-05-09

Objectives In this study we examined the correlation between the extent of thoracic lymphatic anomalies in patients after surgical palliation by total cavopulmonary connection (TCPC) and their outcome in terms of clinical and laboratory parameters. Materials and methods We prospectively examined 33 patients after TCPC with an isotropic heavily T2-weighted MRI sequence on a 3.0 T scanner. Examinations were performed after a solid meal, slice thickness of 0.6 mm, TR of 2400 ms, TE of 692 ms, FoV of 460 mm, covering thoracic and abdominal regions. Findings of the lymphatic system were correlated with clinical and laboratory parameters obtained at the annual routine check-up. Results Eight patients (group 1) showed type 4 lymphatic abnormalities. Twentyfive patients (group 2) presented less severe anomalies (type 1–3). In the treadmill CPET, group 2 reached step 7.0;6.0/8.0 vs. 6.0;3.5/6.8 in group 1 ( p = 0.006*) and a distance of 775;638/854 m vs. 513;315/661 m ( p = 0.006*). In the laboratory examinations, group 2 showed significantly lower levels of AST, ALT and stool calprotectin as compared to group 1. There were no significant differences in NT-pro-BNP, total protein, IgG, lymphocytes or platelets, but trends. A history of ascites showed 5/8 patients in group 1 vs. 4/25 patients in group 2 ( p = 0.02*), PLE occurred in 4/8 patient in group 1 vs. 1/25 patients in group 2 ( p = 0.008*). Conclusion In the long-term follow-up after TCPC, patients with severe thoracic and cervical lymphatic abnormalities showed restrictions in exercise capacity, higher liver enzymes and an increased rate of symptoms of imminent Fontan-failure such as ascites and PLE.
Alpha-180 spin-echo based line-scanning method for high resolution laminar-specific fMRI
2023-05-09

ABSTRACT Laminar-specific functional magnetic resonance imaging (fMRI) has been widely used to study circuit-specific neuronal activity by mapping spatiotemporal fMRI response patterns across cortical layers. Hemodynamic responses reflect indirect neuronal activity given limit of spatial and temporal resolution. Previous gradient-echo based line-scanning fMRI (GELINE) method was proposed with high temporal (50 ms) and spatial (50 μm) resolution to better characterize the fMRI onset time across cortical layers by employing 2 saturation RF pulses. However, the imperfect RF saturation performance led to poor boundary definition of the reduced region of interest (ROI) and aliasing problems outside of the ROI. Here, we propose α (alpha)-180 spin-echo-based line-scanning fMRI (SELINE) method to resolve this issue by employing a refocusing 180° RF pulse perpendicular to the excitation slice. In contrast to GELINE signals peaked at the superficial layer, we detected varied peaks of laminar-specific BOLD signals across deeper cortical layers with the SELINE method, indicating the well-defined exclusion of the large drain-vein effect with the spin-echo sequence. Furthermore, we applied the SELINE method with 200 ms TR to sample the fast hemodynamic changes across cortical layers with a less draining vein effect. In summary, this SELINE method provides a novel acquisition scheme to identify microvascular-sensitive laminar-specific BOLD responses across cortical depth.
Recombination between heterologous human acrocentric chromosomes
2023-05-10

Abstract The short arms of the human acrocentric chromosomes 13, 14, 15, 21 and 22 (SAACs) share large homologous regions, including ribosomal DNA repeats and extended segmental duplications 1,2 . Although the resolution of these regions in the first complete assembly of a human genome—the Telomere-to-Telomere Consortium’s CHM13 assembly (T2T-CHM13)—provided a model of their homology 3 , it remained unclear whether these patterns were ancestral or maintained by ongoing recombination exchange. Here we show that acrocentric chromosomes contain pseudo-homologous regions (PHRs) indicative of recombination between non-homologous sequences. Utilizing an all-to-all comparison of the human pangenome from the Human Pangenome Reference Consortium 4 (HPRC), we find that contigs from all of the SAACs form a community. A variation graph 5 constructed from centromere-spanning acrocentric contigs indicates the presence of regions in which most contigs appear nearly identical between heterologous acrocentric chromosomes in T2T-CHM13. Except on chromosome 15, we observe faster decay of linkage disequilibrium in the pseudo-homologous regions than in the corresponding short and long arms, indicating higher rates of recombination 6,7 . The pseudo-homologous regions include sequences that have previously been shown to lie at the breakpoint of Robertsonian translocations 8 , and their arrangement is compatible with crossover in inverted duplications on chromosomes 13, 14 and 21. The ubiquity of signals of recombination between heterologous acrocentric chromosomes seen in the HPRC draft pangenome suggests that these shared sequences form the basis for recurrent Robertsonian translocations, providing sequence and population-based confirmation of hypotheses first developed from cytogenetic studies 50 years ago 9 .
Increased mutation and gene conversion within human segmental duplications
2023-05-10

Abstract Single-nucleotide variants (SNVs) in segmental duplications (SDs) have not been systematically assessed because of the limitations of mapping short-read sequencing data 1,2 . Here we constructed 1:1 unambiguous alignments spanning high-identity SDs across 102 human haplotypes and compared the pattern of SNVs between unique and duplicated regions 3,4 . We find that human SNVs are elevated 60% in SDs compared to unique regions and estimate that at least 23% of this increase is due to interlocus gene conversion (IGC) with up to 4.3 megabase pairs of SD sequence converted on average per human haplotype. We develop a genome-wide map of IGC donors and acceptors, including 498 acceptor and 454 donor hotspots affecting the exons of about 800 protein-coding genes. These include 171 genes that have ‘relocated’ on average 1.61 megabase pairs in a subset of human haplotypes. Using a coalescent framework, we show that SD regions are slightly evolutionarily older when compared to unique sequences, probably owing to IGC. SNVs in SDs, however, show a distinct mutational spectrum: a 27.1% increase in transversions that convert cytosine to guanine or the reverse across all triplet contexts and a 7.6% reduction in the frequency of CpG-associated mutations when compared to unique DNA. We reason that these distinct mutational properties help to maintain an overall higher GC content of SD DNA compared to that of unique DNA, probably driven by GC-biased conversion between paralogous sequences 5,6 .