bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preserved electrophysiological markers of confidence in schizophrenia spectrum disorder
Authors: Rouy Martin , Roger Matthieu , Goueytes Dorian , Pereira Michael , Roux Paul , Faivre Nathan 
Published: February 2023

AbstractA large number of behavioral studies suggest that confidence judgments are impaired in schizophrenia, motivating the search for neural correlates of an underlying metacognitive impairment. Electrophysiological studies suggest that a specific evoked response potential reflecting performance monitoring, namely the error-related negativity (ERN), is blunted in schizophrenia compared to healthy controls. However, attention has recently been drawn to a potential confound in the study of metacognition, namely that lower task-performance in schizophrenia compared to healthy controls involves a decreased index of metacognitive performance (where metacognitive performance is construed as the ability to calibrate one’s confidence relative to response correctness), independently of metacognitive abilities among patients. Here, we assessed how this confound might also apply to ERN-blunting in schizophrenia. We used an adaptive staircase procedure to titrate task-performance on a motion discrimination task in which participants (N = 14 patients and 19 controls) had to report their confidence after each trial while we recorded high density EEG. Interestingly, not only metaperceptual abilities were preserved among patients at the behavioral level, but contrary to our hypothesis, we also found no electrophysiological evidence for altered EEG markers of performance monitoring. These results bring additional evidence suggesting an unaltered ability to monitor perceptual performance on a trial by trial basis in schizophrenia.
Mycobacterial nucleoid-associated protein Lsr2 is required for productive mycobacteriophage infection
Authors: Dulberger Charles L. , Guerrero-Bustamante Carlos A. , Owen Siân V. , Wilson Sean , Wuo Michael G. , Garlena Rebecca A. , Serpa Lexi A. , Russell Daniel A. , Zhu Junhao , Braunecker Ben J. , Squyres Georgia R. , Baym Michael , Kiessling Laura L. , Garner Ethan C. , Rubin Eric J. , Hatfull Graham F. 
Published: February 2023

AbstractMycobacteriophages are a diverse group of viruses infecting Mycobacterium with substantial therapeutic potential. However, as this potential becomes realized, the molecular details of phage infection and mechanisms of resistance remain ill-defined. Here we use live-cell fluorescence microscopy to visualize the spatiotemporal dynamics of mycobacteriophage infection in single cells and populations, showing that infection is dependent on the host nucleoid-associated Lsr2 protein. Mycobacteriophages preferentially adsorb at Mycobacterium smegmatis sites of new cell wall synthesis and following DNA injection, Lsr2 reorganizes away from host replication foci to establish zones of phage DNA replication (ZOPR). Cells lacking Lsr2 proceed through to cell lysis when infected but fail to generate consecutive phage bursts that trigger epidemic spread of phage particles to neighbouring cells. Many mycobacteriophages code for their own Lsr2-related proteins, and although their roles are unknown, they do not rescue the loss of host Lsr2.
Phase-locked photon–electron interaction without a laser
Authors: Taleb Masoud , Hentschel Mario , Rossnagel Kai , Giessen Harald , Talebi Nahid 
Published: February 2023

AbstractUltrafast photon–electron spectroscopy in electron microscopes commonly requires ultrafast laser setups. Photoemission from an engineered electron source is used to generate pulsed electrons, interacting with a sample excited by the laser pulse at a known time delay. Thus, developing an ultrafast electron microscope demands the exploitation of extrinsic laser excitations and complex synchronization schemes. Here we present an inverse approach to introduce internal radiation sources in an electron microscope based on cathodoluminescence spectroscopy. Our compact method is based on a sequential interaction of the electron beam with an electron-driven photon source and the investigated sample. Such a source in an electron microscope generates phase-locked photons that are mutually coherent with the near-field distribution of the swift electron. We confirm the mutual frequency and momentum-dependent correlation of the electron-driven photon source and sample radiation and determine a degree of mutual coherence of up to 27%. With this level of mutual coherence, we were able to perform spectral interferometry with an electron microscope. Our method has the advantage of being simple, compact and operating with continuous electron beams. It will open the door to local photon–electron correlation spectroscopy of quantum materials, single-photon systems and coherent exciton–polaritonic samples with nanometre resolution.
Bile metabolites as diagnostic biomarkers for perihilar cholangiocarcinoma
Authors: Zhang DengYong , Zhao GuanRu , Sun Wanliang , Wang Dongdong , Zhou Shuo , Liu Zhong , Lu Zheng 
Published: February 2023

AbstractIt is difficult to directly obtain pathological diagnosis of perihilar cholangiocarcinoma (pCCA). Analysis of bile in the pCCA microenvironment, based on metabolomics and statistical methods, can help in clinical diagnosis. Clinical information, bile samples, blood liver function, blood CA199, CEA, and other indicators were collected from 33 patients with pCCA and 16 patients with gallstones. Bile samples were analyzed using untargeted metabolomics methods. A combination of multivariate and univariate analyses were used to screen for potential differential metabolites Through Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and differential metabolite remodeling, we explored changes in the pCCA pathway and potential therapeutic targets. There were significant differences in patient blood TBIL, ALT, AST, TBA, CA19-9, and CEA indices (p < 0.05, |log2(fc)| ≥ 1) between two groups. A significant correlation was found between these different indicators by Spearman's analysis. The clinical parameters were correlated with mass-to-charge ratios of 305 (Positive Ion Mode, POS) and 246 (Negative Ion Mode, NEG) in the metabolic group (|r| ≥ 0.7, P ≤ 10−7). The result of this study indicated that bile untargeted metabolomics combined with statistical analysis techniques may be used for diagnose and treatment of pCCA.
Implicit feedback policies for COVID-19: why “zero-COVID” policies remain elusive
Authors: Jadbabaie Ali , Sarker Arnab , Shah Devavrat 
Published: February 2023

AbstractSuccessful epidemic modeling requires understanding the implicit feedback control strategies used by populations to modulate the spread of contagion. While such strategies can be replicated with intricate modeling assumptions, here we propose a simple model where infection dynamics are described by a three parameter feedback policy. Rather than model individuals as directly controlling the contact rate which governs the spread of disease, we model them as controlling the contact rate’s derivative, resulting in a dynamic rather than kinematic model. The feedback policy used by populations across the United States which best fits observations is proportional-derivative control, where learned parameters strongly correlate with observed interventions (e.g., vaccination rates and mobility restrictions). However, this results in a non-zero “steady-state” of case counts, implying current mitigation strategies cannot eradicate COVID-19. Hence, we suggest making implicit policies a function of cumulative cases, resulting in proportional-integral-derivative control with higher potential to eliminate COVID-19.
Biomechanical consequences of the intervertebral disc centre of rotation kinematics during lateral bending and axial rotation
Authors: Allais Roman , Capart Antoine , Da Silva Anabela , Boiron Olivier 
Published: February 2023

AbstractThe location of the instantaneous centre of rotation (ICR) of a lumbar unit has a considerable clinical importance as a spinal health estimator. Consequently, many studies have been conducted to measure or estimate the ICR during rotations in the three anatomical planes; however the results reported are widely scattered. Even if some inter-subjects variability is to be expected, such inconsistencies are likely explained by the differences in methods and experiments. Therefore, in this paper we seek to model three behaviours of the ICR during lateral bending and axial rotation based on results published in the literature. In order to assess the metabolic and mechanical sensibility to the assumption made on the ICR kinematics, we used a previously validated three dimensional non-linear poroelastic model of a porcine intervertebral disc to simulate physiological lateral and axial rotations. The impact of the geometry was also briefly investigated by considering a 11$$^\circ$$

∘

wedge angle. From our simulations, it appears that the hypothesis made on the ICR location does not significantly affect the critical nutrients concentrations but gives disparate predictions of the intradiscal pressure at the centre of the disc (variation up to 0.7 MPa) and of the displacement fields (variation up to 0.4 mm). On the contrary, the wedge angle does not influence the estimated intradiscal pressure but leads to minimal oxygen concentration decreased up to 33% and increased maximal lactate concentration up to 13%. While we can not settle on which definition of the ICR is more accurate, this work suggests that patient-specific modeling of the ICR is required and brings new insights that can be useful for the development of new tools or the design of surgical material such as total lumbar disc prostheses.
Uncertainty in vulnerability of networks under attack
Authors: Ermagun Alireza , Tajik Nazanin , Mahmassani Hani 
Published: February 2023

AbstractThis study builds conceptual explanations and empirical examinations of the vulnerability response of networks under attack. Two quantities of “vulnerability” and “uncertainty in vulnerability” are defined by scrutinizing the performance loss trajectory of networks experiencing attacks. Both vulnerability and uncertainty in vulnerability quantities are a function of the network topology and size. This is tested on 16 distinct topologies appearing in infrastructure, social, and biological networks with 8 to 26 nodes under two percolation scenarios exemplifying benign and malicious attacks. The findings imply (i) crossing path, tree, and diverging tail are the most vulnerable topologies, (ii) complete and matching pairs are the least vulnerable topologies, (iii) complete grid and complete topologies show the most uncertainty for vulnerability, and (iv) hub-and-spoke and double u exhibit the least uncertainty in vulnerability. The findings also imply that both vulnerability and uncertainty in vulnerability increase with an increase in the size of the network. It is argued that in networks with no undirected cycle and one undirected cycle, the uncertainty in vulnerability is maximal earlier in the percolation process. With an increase in the number of cycles, the uncertainty in vulnerability is accumulated at the end of the percolation process. This emphasizes the role of tailoring preparedness, response, and recovery phases for networks with different topologies when they might experience disruption.
Osteoprotegerin deficiency aggravates methionine–choline-deficient diet-induced nonalcoholic steatohepatitis in mice
Authors: Wu Shaobo , Wu Yao , Lin Lan , Ruan Changshun , Li Fang , Chen Rong , Du Hongxin , Zhang Xianxiang , Luo Xiaohe 
Published: February 2023

AbstractClinical studies have shown that osteoprotegerin (OPG) is reduced in patients with nonalcoholic steatohepatitis (NASH), but the underlying mechanisms are unclear. The current study focuses on the role of OPG in the NASH pathogenesis. OPG knockout mice and wild-type control mice fed a methionine choline-deficient diet (MCD) for 4 weeks resulted in an animal model of NASH. Measurement of triglycerides (TG) in serum and liver to assess steatosis. Hematoxylin eosin (HE), Sirius Red and Masson staining were used to assess the liver damage. Transcriptome sequencing analysis, qPCR and western blot were to analyze changes in lipid metabolism and inflammation-related indicators in the liver. In vivo knockout of OPG resulted in a reduction of TG levels in the liver and a significant increase in serum ALT and AST. The expression of inflammatory factors and fibrosis genes was significantly upregulated in the livers of OPG knockout mice. Transcriptome sequencing analysis showed that OPG knockout significantly enhanced MCD diet-induced activation of the mitogen-activated protein kinase (MAPK) signaling pathway. Mechanistically, OPG may inhibit MAPK signaling pathway activity by upregulating the expression of dual specificity phosphatase 14 (DUSP14), thereby reducing inflammatory injury. OPG could regulate the activity of the MAPK signaling pathway via DUSP14, thus regulating the expression of some inflammatory factors in NASH, it may be a promising target for the treatment of NASH.
Numerical solution of neutral delay differential equations using orthogonal neural network
Authors: Vinodbhai Chavda Divyesh , Dubey Shruti 
Published: February 2023

AbstractIn this paper, an efficient orthogonal neural network (ONN) approach is introduced to solve the higher-order neutral delay differential equations (NDDEs) with variable coefficients and multiple delays. The method is implemented by replacing the hidden layer of the feed-forward neural network with the orthogonal polynomial-based functional expansion block, and the corresponding weights of the network are obtained using an extreme learning machine(ELM) approach. Starting with simple delay differential equations (DDEs), an interest has been shown in solving NDDEs and system of NDDEs. Interest is given to consistency and convergence analysis, and it is seen that the method can produce a uniform closed-form solution with an error of order$$2^{-n}$$2-n, wherenis the number of neurons. The developed neural network method is validated over various types of example problems(DDEs, NDDEs, and system of NDDEs) with four different types of special orthogonal polynomials.
A constant domain mutation in a patient-derived antibody light chain reveals principles of AL amyloidosis
Authors: Rottenaicher Georg J. , Absmeier Ramona M. , Meier Laura , Zacharias Martin , Buchner Johannes 
Published: February 2023

AbstractLight chain (AL) amyloidosis is a debilitating disease in which mutant antibody light chains (LC), secreted by aberrant plasma cell clones, misfold and form insoluble fibrils, which can be deposited in various organs. In the majority of cases, the fibrillar deposits consist of LC variable domains (VL) containing destabilizing mutations compared to their germline counterparts. This is also true for the patient LC FOR005. However, this pathogenic LC sequence contains an additional mutation in the constant domain (CL). The mechanistic impact of CL mutations is not yet understood in the context of AL amyloidosis. Our analysis reveals that the FOR005 CL mutation influences the amyloid pathway in specific ways: (1) folding and stability of the patient CL domain are strongly impaired; (2) the mutation disrupts the LC dimer interface and weakens dimerization; (3) the CL mutation promotes proteolytic cleavage of the LC monomers resulting in an isolated, amyloidogenic VL domain while dimeric LCs are not cleaved. The enhanced proteolysis rates and the inability of full-length LCs to form amyloid fibrils even in the presence of a destabilized CL domain support a model for AL amyloidosis in which the CL domain plays a protective role and in which proteolytic cleavage precedes amyloid formation.
Assessment of the drugability of initial malaria infection through miniaturized sporozoite assays and high-throughput screening
Authors: Miglianico Marie , Bolscher Judith M. , Vos Martijn W. , Koolen Karin J. M. , de Bruijni Marloes , Rajagopal Deeya S. , Chen Emily , Kiczun Michael , Gray David , Campo Brice , Sauerwein Robert W. , Dechering Koen J. 
Published: February 2023

AbstractThe sporozoite stages of malaria parasites are the primary cause of infection of the vertebrate host and are targeted by (experimental) vaccines. Yet, little is known about their susceptibility to chemical intervention. Phenotypic high-throughput screens have not been feasible due to a lack of in vitro systems. Here we tested 78 marketed and experimental antimalarial compounds in miniaturized assays addressing sporozoite viability, gliding motility, hepatocyte traversal, and intrahepatocytic schizogony. None potently interfered with sporozoite viability or motility but ten compounds acted at the level of schizogony with IC50s < 100 nM. To identify compounds directly targeting sporozoites, we screened 81,000 compounds from the Global Health Diversity and reFRAME libraries in a sporozoite viability assay using a parasite expressing a luciferase reporter driven by the circumsporozoite promoter. The ionophore gramicidin emerged as the single hit from this screening campaign. Its effect on sporozoite viability translated into reduced gliding motility and an inability of sporozoites to invade human primary hepatocytes and develop into hepatic schizonts. While providing proof of concept for a small molecule sporontocidal mode of action, our combined data indicate that liver schizogony is more accessible to chemical intervention by (candidate) antimalarials.
A recyclable stereoauxiliary aminocatalyzed strategy for one-pot synthesis of indolizine-2-carbaldehydes
Authors: Zeng Kui , Mei Ruhuai , Dechert Sebastian , Ackermann Lutz , Zhang Kai 
Published: February 2023

AbstractIndolizine-carbaldehydes with the easily modifiable carbaldehyde group are important synthetic targets as versatile precursors for distinct indolizines. However, the efficient one-pot construction of trisubstituted indolizine-2-carbaldehydes represents a long-standing challenge. Herein, we report an unprecedented recyclable stereoauxiliary aminocatalytic approachviaaminosugars derived from biomass, which enable the efficient one-pot synthesis of desired trisubstituted indolizine-2-carbaldehydesvia[3+2] annulations of acyl pyridines andα,β-unsaturated aldehyde. Compared to the steric shielding effect fromα-anomer, a stereoauxiliary effect favored byβ-anomer of D-glucosamine is supported by control experiments. Furthermore, polymeric chitosan containing predominantlyβ-D-anhydroglucosamine units also shows excellent catalytic performance in aqueous solutions for the conversion of various substrates, large-scale synthesis and catalytic cycling experiments. Thus, our approach advances the existing methodologies by providing a rich library of indolizine-2-aldehydes. In addition, it delivers an efficient protocol for a set of late-stage diversification and targeted modifications of bioactive molecules or drugs, as showcased with 1,2,3-trisubstituted indolizine-2-carbaldehydes.
Shifts in flood generation processes exacerbate regional flood anomalies in Europe
Authors: Tarasova Larisa , Lun David , Merz Ralf , Blöschl Günter , Basso Stefano , Bertola Miriam , Miniussi Arianna , Rakovec Oldrich , Samaniego Luis , Thober Stephan , Kumar Rohini 
Published: February 2023

AbstractAnomalies in the frequency of river floods, i.e., flood-rich or -poor periods, cause biases in flood risk estimates and thus make climate adaptation measures less efficient. While observations have recently confirmed the presence of flood anomalies in Europe, their exact causes are not clear. Here we analyse streamflow and climate observations during 1960-2010 to show that shifts in flood generation processes contribute more to the occurrence of regional flood anomalies than changes in extreme rainfall. A shift from rain on dry soil to rain on wet soil events by 5% increased the frequency of flood-rich periods in the Atlantic region, and an opposite shift in the Mediterranean region increased the frequency of flood-poor periods, but will likely make singular extreme floods occur more often. Flood anomalies driven by changing flood generation processes in Europe may further intensify in a warming climate and should be considered in flood estimation and management.
Importance of mobile genetic element immunity in numerically abundant Trichodesmium clades
Authors: Webb Eric A , Held Noelle A , Zhao Yiming , Graham Elaina D , Conover Asa E , Semones Jake , Lee Michael D , Feng Yuanyuan , Fu Fei-xue , Saito Mak A , Hutchins David A 
Published: February 2023

Abstract
The colony-forming cyanobacteria Trichodesmium spp. are considered one of the most important nitrogen-fixing genera in the warm, low nutrient ocean. Despite this central biogeochemical role, many questions about their evolution, physiology, and trophic interactions remain unanswered. To address these questions, we describe Trichodesmium pangenomic potential via significantly improved genomic assemblies from two isolates and 15 new &gt;50% complete Trichodesmium metagenome-assembled genomes from hand-picked, Trichodesmium colonies spanning the Atlantic Ocean. Phylogenomics identified ~four N2 fixing clades of Trichodesmium across the transect, with T. thiebautii dominating the colony-specific reads. Pangenomic analyses showed that all T. thiebautii MAGs are enriched in COG defense mechanisms and encode a vertically inherited Type III-B Clustered Regularly Interspaced Short Palindromic Repeats and associated protein-based immunity system (CRISPR-Cas). Surprisingly, this CRISPR-Cas system was absent in all T. erythraeum genomes, vertically inherited by T. thiebautii, and correlated with increased signatures of horizontal gene transfer. Additionally, the system was expressed in metaproteomic and transcriptomic datasets and CRISPR spacer sequences with 100% identical hits to field-assembled, putative phage genome fragments were identified. While the currently CO2-limited T. erythraeum is expected to be a ‘winner’ of anthropogenic climate change, their genomic dearth of known phage resistance mechanisms, compared to T. thiebautii, could put this outcome in question. Thus, the clear demarcation of T. thiebautii maintaining CRISPR-Cas systems, while T. erythraeum does not, identifies Trichodesmium as an ecologically important CRISPR-Cas model system, and highlights the need for more research on phage-Trichodesmium interactions.
Pairing of single-cell RNA analysis and T cell antigen receptor profiling indicates breakdown of T cell tolerance checkpoints in atherosclerosis
Authors: Wang Zhihua , Zhang Xi , Lu Shu , Zhang Chuankai , Ma Zhe , Su Rui , Li Yuanfang , Sun Ting , Li Yutao , Hong Mingyang , Deng Xinyi , Rafiee Monjezi Mohammad , Hristov Michael , Steffens Sabine , Santovito Donato , Dornmair Klaus , Ley Klaus , Weber Christian , Mohanta Sarajo K. , Habenicht Andreas J. R. , Yin Changjun 
Published: February 2023

AbstractAtherosclerotic plaques form in the inner layer of arteries triggering heart attacks and strokes. Although T cells have been detected in atherosclerosis, tolerance dysfunction as a disease driver remains unexplored. Here we examine tolerance checkpoints in atherosclerotic plaques, artery tertiary lymphoid organs and lymph nodes in mice burdened by advanced atherosclerosis, via single-cell RNA sequencing paired with T cell antigen receptor sequencing. Complex patterns of deteriorating peripheral T cell tolerance were observed being most pronounced in plaques followed by artery tertiary lymphoid organs, lymph nodes and blood. Affected checkpoints included clonal expansion of CD4+, CD8+ and regulatory T cells; aberrant tolerance-regulating transcripts of clonally expanded T cells; T cell exhaustion; Treg–TH17 T cell conversion; and dysfunctional antigen presentation. Moreover, single-cell RNA-sequencing profiles of human plaques revealed that the CD8+ T cell tolerance dysfunction observed in mouse plaques was shared in human coronary and carotid artery plaques. Thus, our data support the concept of atherosclerosis as a bona fide T cell autoimmune disease targeting the arterial wall.