bluuebunny/crossref_metadata_2025 huggingface dataset:
Why put yourself on a pedestal? The pathogenic role of the A/E pedestal
Authors: Miner M. V. , Rauch I.
Published: April 2024

Certain
Escherichia coli
(
E. coli
) strains are attaching and effacing (A/E) lesion pathogens that primarily infect intestinal epithelial cells. They cause actin restructuring and polymerization within the host cell to create an actin-rich protrusion below the site of adherence, termed the pedestal. Although there is clarity on the pathways initiating pedestal formation, the underlying purpose(s) of the pedestal remains ambiguous. The conservation of pedestal-forming activity across multiple pathogens and redundancy in formation pathways indicate a pathogenic advantage. However, few decisive conclusions have been drawn, given that the results vary between model systems. Some research argues that the pedestal increases the colonization capability of the bacterium. These studies utilize A/E pathogens specifically deficient in pedestal formation to evaluate adhesion and intestinal colonization following infection. There have been many proposed mechanisms for the colonization benefit conferred by the pedestal. One suggested benefit is that the pedestal allows for direct cytosolic anchoring through incorporation of the established host cortical actin, causing a stable link between the pathogen and cell structure. The pedestal may confer enhanced motility, as enteropathogenic
E. coli
(EPEC) and enterohemorrhagic
E. coli
(EHEC) are better able to migrate on the surface of host cells and infect neighboring cells in the presence of the pedestal. Additionally, some research suggests that the pedestal improves effector delivery. This review will investigate the purpose of pedestal formation using evidence from recent literature and will critically evaluate the methodology and model systems. Most importantly, we will contextualize the proposed functions to reconcile potential synergistic effects.
Novel mutation N588 residue in the NS1 protein of feline parvovirus greatly augments viral replication
Authors: Li Lisha , Liu Zirui , Liang Rui , Yang Mengfang , Yan Yuanyuan , Jiao Yuzhou , Jiao Zhe , Hu Xiaoshuai , Li Mengxia , Shen Zhou , Peng Guiqing
Published: April 2024

Feline parvovirus (FPV) infection is highly fatal in felines. NS1, which is a key nonstructural protein of FPV, can inhibit host innate immunity and promote viral replication, which is the main reason for the severe pathogenicity of FPV. However, the mechanism by which the NS1 protein disrupts host immunity and regulates viral replication is still unclear. Here, we identified an FPV M1 strain that is regulated by the NS1 protein and has more pronounced suppression of innate immunity, resulting in robust replication. We found that the neutralization titer of the FPV M1 strain was significantly lower than that of the other strains. Moreover, FPV M1 had powerful replication ability, and the FPV M1-NS1 protein had heightened efficacy in repressing interferon-stimulated genes (ISGs) expression. Subsequently, we constructed an FPV reverse genetic system, which confirmed that the N588 residue of FPV M1-NS1 protein is a key amino acid that bolsters viral proliferation. Recombinant virus containing N588 also had stronger ability to inhibit ISGs, and lower ISGs levels promoted viral replication and reduced the neutralization titer of the positive control serum. Finally, we confirmed that the difference in viral replication was abolished in type I IFN receptor knockout cell lines. In conclusion, our results demonstrate that the N588 residue of the NS1 protein is a critical amino acid that promotes viral proliferation by increasing the inhibition of ISGs expression. These insights provide a reference for studying the relationship between parvovirus-mediated inhibition of host innate immunity and viral replication while facilitating improved FPV vaccine production.

IMPORTANCE

FPV infection is a viral infectious disease with the highest mortality rate in felines. A universal feature of parvovirus is its ability to inhibit host innate immunity, and its ability to suppress innate immunity is mainly accomplished by the NS1 protein. In the present study, FPV was used as a viral model to explore the mechanism by which the NS1 protein inhibits innate immunity and regulates viral replication. Studies have shown that the FPV-NS1 protein containing the N588 residue strongly inhibits the expression of host ISGs, thereby increasing the viral proliferation titer. In addition, the presence of the N588 residue can increase the proliferation titer of the strain 5- to 10-fold without affecting its virulence and immunogenicity. In conclusion, our findings provide new insights and guidance for studying the mechanisms by which parvoviruses suppress innate immunity and for developing high-yielding FPV vaccines.
VP2 mediates the release of the feline calicivirus RNA genome by puncturing the endosome membrane of infected cells
Authors: Sun Weiyao , Wang Ming , Shi Zhibin , Wang Pengfei , Wang Jinhui , Du Bingchen , Wang Shida , Sun Zhenzhao , Liu Zaisi , Wei Lili , Yang Decheng , He Xijun , Wang Jingfei
Published: April 2024

Feline calicivirus (FCV) is one of the few members of the
Caliciviridae
family that grows well in cell lines and, therefore, serves as a surrogate to study the biology of other viruses in the family. Conley et al. (
14
) demonstrated that upon the receptor engagement to the capsid, FCV VP2 forms a portal-like assembly, which might provide a channel for RNA release. However, the process of calicivirus RNA release is not yet fully understood. Our findings suggest that the separation of the FCV capsid from its genome RNA (gRNA) occurs rapidly in the early endosomes of infected cells. Using a liposome model decorated with the FCV cell receptor fJAM-A, we demonstrate that FCV releases its gRNA into the liposomes by penetrating membranes under low pH conditions. Furthermore, we found that VP2, which is rich in hydrophobic residues at its N-terminus, functions as the pore-forming protein. When we substituted the VP2 N-terminal hydrophobic residues, the gRNA release efficacy of the FCV mutants decreased. In conclusion, our results suggest that in the acidic environment of early endosomes, FCV VP2 functions as the pore-forming protein to mediate gRNA release into the cytoplasm of infected cells. This provides insight into the mechanism of calicivirus genome release.

IMPORTANCE

Research on the biology and pathogenicity of certain caliciviruses, such as Norovirus and Sapovirus, is hindered by the lack of easy-to-use cell culture system. Feline calicivirus (FCV), which grows effectively in cell lines, is used as a substitute. At present, there is limited understanding of the genome release mechanism in caliciviruses. Our findings suggest that FCV uses VP2 to pierce the endosome membrane for genome release and provide new insights into the calicivirus gRNA release mechanism.
Efficacy of host cell serine protease inhibitor MM3122 against SARS-CoV-2 for treatment and prevention of COVID-19
Authors: Boon Adrianus C. M. , Bricker Traci L. , Fritch Ethan J. , Leist Sarah R. , Gully Kendra , Baric Ralph S. , Graham Rachel L. , Troan Brigid V. , Mahoney Matthew , Janetka James W.
Published: April 2024

We developed a novel class of peptidomimetic inhibitors targeting several host cell human serine proteases, including transmembrane protease serine 2 (TMPRSS2), matriptase, and hepsin. TMPRSS2 is a membrane-associated protease that is highly expressed in the upper and lower respiratory tracts and is utilized by SARS-CoV-2 and other viruses to proteolytically process their glycoproteins, enabling host cell entry, replication, and dissemination of new virus particles. We have previously shown that compound MM3122 exhibited subnanomolar potency against all three proteases and displayed potent antiviral effects against SARS-CoV-2 in a cell viability assay. Herein, we demonstrate that MM3122 potently inhibits viral replication in human lung epithelial cells and is also effective against the EG.5.1 variant of SARS-CoV-2. Furthermore, we evaluated MM3122 in a mouse model of COVID-19 and demonstrated that MM3122 administered intraperitoneally (IP) before (prophylactic) or after (therapeutic) SARS-CoV-2 infection had significant protective effects against weight loss and lung congestion and reduced pathology. Amelioration of COVID-19 disease was associated with a reduction in proinflammatory cytokine and chemokine production after SARS-CoV-2 infection. Prophylactic, but not therapeutic, administration of MM3122 also reduced virus titers in the lungs of SARS-CoV-2-infected mice. Therefore, MM3122 is a promising lead candidate small-molecule drug for the treatment and prevention of infections caused by SARS-CoV-2 and other coronaviruses.

IMPORTANCE

SARS-CoV-2 and other emerging RNA coronaviruses are a present and future threat in causing widespread endemic and pandemic infection and disease. In this paper, we have shown that the novel host cell protease inhibitor, MM3122, blocks SARS-CoV-2 viral replication and is efficacious as both a prophylactic and a therapeutic drug for the treatment of COVID-19 given intraperitoneally in mice. Targeting host proteins and pathways in antiviral therapy is an underexplored area of research, but this approach promises to avoid drug resistance by the virus, which is common in current antiviral treatments.
The virome of the kitome: small circular virus-like genomes in laboratory reagents
Authors: Duan Jiayi , Keeler Emma , McFarland Alexander , Scott Phillip , Collman Ronald G. , Bushman Frederic D.
Published: April 2024

In the course of studying the virome of protozoan parasites, we identified small circular genomes resembling viruses, which turned out to be contaminants from an RNA purification kit. We report their sequences here so others can detect possible contamination in their samples by aligning them to these targets.
Progressive development of stylolites in cryptocrystalline quartz
Authors: Hou Zhaoliang , Qiu Kun-Feng , Rogowitz Anna , Schultz Richard A. , Yu Hao-Cheng , Grasemann Bernhard
Published: April 2024

Stylolites are common dissolution structures in carbonate rocks in the upper crust and document a coupled physical-chemical feedback during pressure solution in rocks. By applying high-resolution electron-based analysis we investigate a rare example of stylolites in cryptocrystalline quartz (novaculite) from western Sichuan Basin, China. The investigated stylolites exhibit an increased amplitude from the tip toward the center, which correlates with the maturity of stylolites and thus provides an excellent opportunity to infer the dynamic processes operating during stylolite formation. Microstructurally, stylolites are characterized by a concentration of biotite and hematite, dissolving irregular quartz grains, and the occurrence of dissolution porosity. By investigating the progressive co-variations between stylolite amplitude and microstructure characteristics from the stylolite tip toward the center, we demonstrate, for the first time, the evidence of stylolite growth through anticracks. It is inferred that stylolites in cryptocrystalline quartz originate from the propagation of mode I micro-cracks around pre-existing biotite, followed by pore-scale dissolution. Both processes, micro-cracking and dissolution, are interacting and co-evolving via a self-organization fashion during shortening. Our study contributes to the ongoing debate about whether stylolites are conduits or barriers for fluid flow.
Supplemental Material: Shallow mantle cycle of subducted sedimentary limestone indicated by carbonate xenoliths
Authors: Xue Shuo , Ling Ming-Xing
Published: April 2024

Table S1: Major- and trace-elemental compositions of the Hannuoba carbonate xenoliths (major elements: wt%, trace elements: ppm). Table S2: Trace-elemental concentrations (ppm) of the calcite and clinopyroxene in Hannuoba carbonate xenoliths. Table S3: Detrital zircon U-Pb isotopic data obtained using LA-ICP-MS. Table S4: C-O isotopic compositions of Hannuoba carbonate xenoliths.
SARS-CoV-2 vaccine uptake and risks of severe COVID-19 disease among people prescribed opioid agonist therapy in Scotland
Authors: Yeung Alan , Wilkinson Max , Bishop Jen , Taylor Bob , Palmateer Norah , Barnsdale Lee , Lang Jaroslaw , Cameron Claire , McCormick Duncan , Clusker Tracey , McAuley Andrew , Hutchinson Sharon
Published: April 2024

Background

There is limited evidence quantifying the risk of severe COVID-19 disease among people with opioid dependence. We examined vaccine uptake and severe disease (admission to critical care or death with COVID-19) among individuals prescribed opioid agonist therapy (OAT).

Method

A case–control design was used to examine vaccine uptake in those prescribed OAT compared with the general population, and the association between severe disease and OAT. In both analyses, 10 controls from the general population were matched (to each OAT recipient and COVID-19 case, respectively) according to socio-demographic factors. Conditional logistic regression was used to estimate rate ratios (RR) for severe disease.

Results

Vaccine uptake was markedly lower in the OAT cohort (dose 1: 67%, dose 2: 53% and dose 3: 31%) compared with matched controls (76%, 72% and 57%, respectively). Those prescribed OAT within the last 5 years, compared with those not prescribed, had increased risk of severe COVID-19 (RR 3.38, 95% CI 2.75 to 4.15), particularly in the fourth wave (RR 6.58, 95% CI 4.20 to 10.32); adjustment for comorbidity and vaccine status attenuated this risk (adjusted RR (aRR) 2.43, 95% CI 1.95 to 3.02; wave 4 aRR 3.78, 95% CI 2.30 to 6.20). Increased risk was also observed for those prescribed OAT previously (>3 months ago) compared with recently (aRR 1.74, 95% CI 1.11 to 2.71).

Conclusions

The widening gap in vaccine coverage for those prescribed OAT, compared with the general population, is likely to have exacerbated the risk of severe COVID-19 in this population over the pandemic. However, continued OAT use may have provided protection from severe COVID-19 among those with opioid dependence.
Shear strength characterization and sustainability assessment of coal bottom ash concrete
Authors: Ankur Nitin , Singh Navdeep
Published: April 2024

The present study investigated the synergistic influence of coal bottom ash (CBA) on the shear strength of concrete. CBA was milled for 2, 6, and 10 h to form grinded CBA (GCBA). “L” shaped specimens were prepared with 10%–30% GCBA and 25%–50% CBA as alternative of Portland cement and natural fine aggregates. Concrete containing 20% GCBA (grinded for 6 h) and 25% CBA reported the highest shear strength owing to pozzolanic reactiveness and filler action. X-ray diffraction, scanning electron microscopy–energy-dispersive spectroscopy and Fourier transform infrared also supported the experimental outcomes. Well fitted mathematical models were derived followed by optimization using desirability function approach recommending 5.71 h of grinding, 26.27% GCBA, and 36.69% CBA as the optimum amount for its successful utilization in concrete. This approach further leads to significant reduction of about 22% in carbon footprints and eco-costs in comparison to conventional concrete.
Chromosomal organization of different repetitive sequences in four wasp species of the genus Trypoxylon Latreille (Hymenoptera: Crabronidae) and insights into the composition of wasp telomeres
Authors: Teixeira Gisele Amaro , Travenzoli Natália Martins , Tavares Mara Garcia
Published: April 2024

This study characterizes the chromosomal organization of DNA repetitive sequences and the karyotypic evolution in four representatives of the solitary wasp genus Trypoxylon using conventional and molecular cytogenetic techniques. Our findings present the first cytogenetic data for Trypoxylon rogenhoferi (2 n = 30) and Trypoxylon albonigrum (2 n = 32), while the karyotypes of Trypoxylon nitidum (2 n = 30) and Trypoxylon lactitarse (2 n = 30) were similar to those previously described. Fluorochrome staining and microsatellite distribution data revealed differences in the constitutive heterochromatin composition among species. Trypoxylon nitidum and T. albonigrum exhibited one major rDNA cluster, potentially representing an ancestral pattern for aculeate Hymenoptera, while T. rogenhoferi and T. lactitarse showed two pericentromeric rRNA gene sites, suggesting amplification events in their ancestral clade. The (TCAGG) n motif hybridized in the terminal regions of the chromosomes in all four Trypoxylon species, which may suggest that this sequence represents DNA telomeric repeat. Notably, the presence of this repetitive sequence in the centromeric regions of certain chromosome pairs in two species supports the hypothesis of chromosomal fusions or inversions in the ancestral karyotype of Trypoxylon. The study expands the chromosomal mapping data of repetitive sequences in wasps and offers insights into the dynamic evolutionary landscape of karyotypes in these insects.
Chloroplast genome of Ecbolium viride (Forssk.) Alston: plastome evolution and phylogenomics of Justiceae (Acanthaceae, Acanthoideae)
Authors: Yaradua Samaila Samaila , Yessoufou Kowiyou
Published: April 2024

Justicieae is the most taxonomically complex tribe in Acanthaceae. Here, we sequenced the plastome of Ecbolium viride, a medicinally important species. The genome was analyzed with previously reported plastome of Justiceae. The plastome of E. viride has quadripartite structure with a length of 151 185 bp. The comparative genomic analyses revealed no structural inversion in Justiceae and some regions ( rpoC2, ycf2, ycf1, ndhH rps16-trnQ-UGG, and trnL-CAA-ycf15) exhibiting a significant level of nucleotide divergence. The positive selection analyses revealed that some species in the tribe have undergone adaptive evolution. The visualization of the boundaries between the single copy and inverted repeat regions revealed that Justiceae chloroplast genome experienced some levels of variation, which give an insight into the evolution of the species. The longest genome was in the earliest diverged taxa of the tribe Pseuderanthemum haikangense and from this genome, a series of contraction and expansion occurred contributing to the evolution of other lineages. The plastome-based phylogeny revealed and confirmed the monophyly of Justiceae, polyphyly of Justicia and supported the tribal classification Graptophyllinae, Tetrameriinae, and Isoglossinae. We proposed that Declipterinae should be treated as subtribe and the status of Justiciinae can only be confirmed after the resolution of the polyphyletic Justicia.
Nonlinear Dynamic Bifurcation and Chaos Characteristics of Piezoelectric Composite Lattice Sandwich Plates
Authors: Ma Ting , Zhang Wei , Zhang Yufei , Amer A. , Lim C. W.
Published: April 2024

This paper investigates the nonlinear bifurcation and chaos characteristics of piezoelectric composite lattice sandwich plates at 1:3 internal resonance. The nonlinear vibration partial differential equation is first discretized to become an ordinary differential equation by applying the Galerkin method. The main resonance modulation equations and the parametric resonance for the external excitation frequency that is close to the system’s second-order modal frequency are then obtained by using the multiscale method. The Newton–Raphson method is subsequently applied to obtain the bifurcation diagram of the steady-state equilibrium of modulation equation with varying system parameters. The equilibrium stability is finally analyzed. We confirm the existence of static bifurcation such as saddle-node bifurcation, pitchfork bifurcation, and Hopf dynamic bifurcation. A detailed analysis is also conducted on the complex nonlinear jump phenomenon caused by the presence of multiple nonlinear steady-state solution regions. In the dynamic Hopf bifurcation interval, the fourth-order Runge–Kutta method is used to continue to track the dynamic periodic solution of the modulation equation in Cartesian coordinates. It is found that there are multiple boundary crises and attractor merging crises in the vibration system for piezoelectric composite lattice sandwich plates.
Multiobjective Optimization of Chaotic Image Encryption Based on ABC Algorithm and DNA Coding
Authors: Yu Jinwei , Xie Wei , Zhang Langwen
Published: April 2024

As digital communication and storage continue to expand, the protection of image privacy information becomes increasingly critical. To safeguard sensitive visual information from unauthorized access, this paper proposes a novel image encryption scheme that integrates multiobjective Artificial Bee Colony (ABC) optimization algorithm and DNA coding. Multiple evaluation metrics including correlation relationship, Number of Pixel Change Rate (NPCR), Unified Average Changing Intensity (UACI), and information entropy are collaboratively optimized by the ABC algorithm. The proposed method begins with the application of the SHA-256 algorithm to generate keys and random sequences using chaotic systems. These sequences are then employed for shuffling, DNA coding, decoding, and diffusion, generating initial encrypted images. Subsequently, the encrypted images serve as individuals within the ABC algorithm to determine optimal parameters of the chaotic systems and the best ciphertext image. Simulation experiments demonstrate that the ciphertext images achieved excellent results in information entropy, pixel correlation coefficient, NPCR, and UACI. The integration of the multiobjective ABC optimization algorithm with DNA coding in our proposed image encryption scheme results in heightened security, as evidenced by superior performance in various metrics.
INVESTIGATING THE RELATIONSHIP BETWEEN PORE CHARACTERISTICS, FRACTAL DIMENSION, AND PERMEABILITY OF LIMESTONE USING HIGH-PRESSURE MERCURY INTRUSION, SEM ANALYSIS, AND BP NEURAL NETWORK
Authors: WU JINSUI , XIE DONGYU , JOUINI MOHAMED SOUFIANE , YIN SHANGXIAN , JI PING , BOUCHAALA FATEH , SUN HUAFENG , YI SIHAI , LIAN HUIQING
Published: April 2024

In this study, limestone samples from a coal mine in the North China region were selected for analysis. High Pressure Mercury Intrusion (HPMI) and Scanning Electron Microscopy (SEM) experiments were conducted to explore the impact of pore characteristics and fractal dimension of limestone on permeability. Additionally, regression analysis and a Backpropagation Neural Network (BPNN) were employed to predict permeability. The results of this study reveal that the pore-throat distribution of the limestone samples is non-uniform, indicating significant heterogeneity. The difference of pressure curve morphology affects the permeability. Utilizing multivariate regression analysis, a relationship was established between permeability and parameters such as mean radius, porosity, and fractal dimension. Furthermore, the BP neural network was effectively employed to predict permeability values, with small discrepancies between predicted and measured values. This study establishes a link between microstructural attributes and macroscopic permeability providing a robust theoretical foundation for permeability assessment and engineering applications pertaining to limestone.
RELATIVE PERMEABILITY MODEL OF TWO-PHASE FLOW IN ROUGH CAPILLARY ROCK MEDIA BASED ON FRACTAL THEORY
Authors: YANG SHANSHAN , CHEN SHUAIYIN , YUAN XIANBAO , ZOU MINGQING , ZHENG QIAN
Published: April 2024

In this paper, the gas-water two-phase flow characteristics of rock media are studied based on fractal theory and the relative roughness model, and the analytical model of gas-water relative permeability of rock pores with relative roughness is derived. Through numerical simulation, it is found that the maximum flow velocity in the rough microchannel is greater than the maximum flow velocity in the smooth microchannel, but the average flow velocity in the rough microchannel is less than the average flow velocity in the smooth microchannel. The theoretical model results show that the dimensionless permeability of gas-water two-phase flow is inversely proportional to the fractal dimension of relative roughness and tortuosity, and the relative permeability of gas-water two-phase flow is inversely proportional to the relative roughness. The correctness of the model is verified by comparing it with the relevant experimental data.
Maximum Principle for Mean Field Type Control Problems with General Volatility Functions
Authors: Bensoussan Alain , Huang Ziyu , Yam Sheung Chi Phillip
Published: April 2024

In this paper, we study the maximum principle of mean field type control problems when the volatility function depends on the state and its measure and also the control, by using our recently developed method in [Bensoussan, A., Huang, Z. and Yam, S. C. P. [2023] Control theory on Wasserstein space: A new approach to optimality conditions, Ann. Math. Sci. Appl.; Bensoussan, A., Tai, H. M. and Yam, S. C. P. [2023] Mean field type control problems, some Hilbert-space-valued FBSDEs, and related equations, preprint (2023), arXiv:2305.04019; Bensoussan, A. and Yam, S. C. P. [2019] Control problem on space of random variables and master equation, ESAIM Control Optim. Calc. Var. 25, 10]. Our method is to embed the mean field type control problem into a Hilbert space to bypass the evolution in the Wasserstein space. We here give a necessary condition and a sufficient condition for these control problems in Hilbert spaces, and we also derive a system of forward–backward stochastic differential equations.
Nonperturbative thermodynamic extrinsic curvature of the anyon gas
Authors: Kachi Mahnaz Tavakoli , Mirza Behrouz , Hashemi Fatemeh Sadat
Published: April 2024

Thermodynamic extrinsic curvature is a new mathematical tool in thermodynamic geometry. By using the thermodynamic extrinsic curvature, one may obtain a more complete geometric representation of the critical phenomena and thermodynamics. We introduce nonperturbative thermodynamic extrinsic curvature of an ideal two-dimensional gas of anyons. Using extrinsic curvature, we find new fixed points in nonperturbative thermodynamics of the anyon gas that particles behave as semions. Here, we investigate the critical behavior of thermodynamic extrinsic curvature of two-dimensional Kagome Ising model near the critical point [Formula: see text] in a constant magnetic field and show that it behaves as [Formula: see text] with [Formula: see text], where [Formula: see text] denotes the critical exponent of the specific heat. Then, we consider the three-dimensional spherical model and show that the scaling behavior is [Formula: see text], where [Formula: see text]. Finally, using a general argument, we show that extrinsic curvature [Formula: see text] has two different scaling behaviors for positive and negative [Formula: see text]. For [Formula: see text], our results indicate that [Formula: see text]. However, for [Formula: see text], we found a different scaling behavior, where [Formula: see text].
Neuromorphic Perception and Navigation for Mobile Robots: A Review
Authors: Novo Alvaro , Lobon Francisco , Garcia de Marina Hector , Romero Samuel , Barranco Francisco
Published: April 2024

With the fast and unstoppable evolution of robotics and artificial intelligence, effective autonomous navigation in real-world scenarios has become one of the most pressing challenges in the literature. However, demanding requirements, such as real-time operation, energy and computational efficiency, robustness, and reliability, make most current solutions unsuitable for real-world challenges. Thus, researchers are fostered to seek innovative approaches, such as bio-inspired solutions. Indeed, animals have the intrinsic ability to efficiently perceive, understand, and navigate their unstructured surroundings. To do so, they exploit self-motion cues, proprioception, and visual flow in a cognitive process to map their environment and locate themselves within it. Computational neuroscientists aim to answer “how” and “why” such cognitive processes occur in the brain, to design novel neuromorphic sensors and methods that imitate biological processing. This survey aims to comprehensively review the application of brain-inspired strategies to autonomous navigation. The paper delves into areas such as neuromorphic perception, asynchronous event processing, energy-efficient and adaptive learning, and the emulation of brain regions vital for navigation, such as the hippocampus and entorhinal cortex.
Foundations & Trends in Multimodal Machine Learning: Principles, Challenges, and Open Questions
Authors: Liang Paul Pu , Zadeh Amir , Morency Louis-Philippe
Published: April 2024

Multimodal machine learning is a vibrant multi-disciplinary research field that aims to design computer agents with intelligent capabilities such as understanding, reasoning, and learning through integrating multiple communicative modalities, including linguistic, acoustic, visual, tactile, and physiological messages. With the recent interest in video understanding, embodied autonomous agents, text-to-image generation, and multisensor fusion in application domains such as healthcare and robotics, multimodal machine learning has brought unique computational and theoretical challenges to the machine learning community given the heterogeneity of data sources and the interconnections often found between modalities. However, the breadth of progress in multimodal research has made it difficult to identify the common themes and open questions in the field. By synthesizing a broad range of application domains and theoretical frameworks from both historical and recent perspectives, this article is designed to provide an overview of the computational and theoretical foundations of multimodal machine learning. We start by defining three key principles of modality
heterogeneity
,
connections
, and
interactions
that have driven subsequent innovations, and propose a taxonomy of six core technical challenges:
representation
,
alignment
,
reasoning
,
generation
,
transference
, and
quantification
covering historical and recent trends. Recent technical achievements will be presented through the lens of this taxonomy, allowing researchers to understand the similarities and differences across new approaches. We end by motivating several open problems for future research as identified by our taxonomy.
Identification of Potential Clusters of Signs and Symptoms to Prioritize Patients’ Eligibility for AADCd Screening by 3‐OMD Testing: An Italian Delphi Consensus
Authors: Spagnoli Carlotta , Battini Roberta , Manti Filippo , Cordelli Duccio Maria , Pession Andrea , Bellini Melissa , Bordugo Andrea , Cantalupo Gaetano , Riva Antonella , Striano Pasquale , Spada Marco , Porta Francesco , Fusco Carlo
Published: April 2024

Introduction. AADCd is an ultrarare, underdiagnosed neurometabolic disorder for which a screening test (3‐OMD dosing on dried blood spot (DBS)) and targeted gene therapy (authorized in the EU and the UK) are available. Therefore, it is mandatory to raise awareness of presenting symptoms and signs among practitioners. Delivering scientifically sound information to promote screening of patients with the correct cluster of symptoms and signs would be critical. Materials and Methods. In light of the lack of sound evidence on this issue, expert opinion level of evidence was elicited with the Delphi method. Fourteen steering committee members invited a panel of 29 Italian experts to express their opinions on a series of crucial but controversial topics related to using 3‐OMD DBS as a screening method in AADCd. Clusters of symptoms and signs were divided into typical or atypical, depending on age groups. Inclusion in newborn screening programs and the usefulness of a clinical score were investigated. A five‐point Likert scale was used to rate the level of priority attributed to each statement. Results. The following statements reached the highest priority: testing pediatric patients with hypotonia, developmental delay, movement disorders, and oculogyric crises; inclusion of 3‐OMD dosing on DBS in neonatal screening programs; development of a clinical score to support patients’ selection for 3‐OMD screening; among atypical phenotypes based on clinical characteristics of Italian patients: testing patients with intellectual disability and parkinsonism‐dystonia. Discussion. Clusters of symptoms and signs can be used to prioritize testing with 3‐OMD DBS. A clinical score was rated as highly relevant for the patient’s selection. The inclusion of 3‐OMD dosing in newborn screening programs was advocated with high clinical priority.
Global Flow of Foreign Aid and Change in Recipients’ Local Labor Institutions
Authors: Niu Shuzhen , Gao Xiang , Gu Zhenhua , Zhang Yingchao , Wei Qian
Published: April 2024

How does foreign aid affect recipient countries’ labor institutions? Extant empirical evidence is sparse due to ambiguous theoretical predictions and potential endogeneity issues. This study uses data detailing aid flow and institutional functions to mitigate such inconclusiveness and displays originality by constructing a concise theoretical framework in which foreign aid contributes to the improvement of the labor institutions in recipient countries through two mechanisms—economic growth purpose and expected aid attraction. The findings indicate that only aid to enhance local economic growth provides incentives to change domestic labor markets. Such effects have a more crucial influence on labor institutions of minimum wage, collective bargaining rights, and working hours than those related to hiring and firing regulations, mandated costs for worker dismissal, and conscription. For comparison with the actual aid level, we construct forecasted proxies to capture exogenous fluctuations in aid, determining that domestic labor markets can also change via a novel mechanism, as the recipient voluntarily mimics the funder’s labor policies in anticipation of receiving future aid, with exact amounts derived from the noninstitutional characteristics of pairs of bilateral recipient and giver economies. Therefore, we provide policy implications for the aid giver on how to secure a continued and increased aid flow and for the aid receivers on which aspects of reforming measures are most effective in enhancing the labor market regulations.
Application of CNN‐LSTM Model for Vehicle Acceleration Prediction Using Car‐following Behavior Data
Authors: Tang Shuning , Zou Yajie , Zhang Hao , Zhang Yue , Kong Xiaoqiang
Published: April 2024

Accurate vehicle acceleration prediction is useful for developing reliable Advanced Driving Assistance Systems (ADAS) and improving road safety. The existence of driver heterogeneity magnifies the variations in acceleration data, leading to consequential impacts on the precision of vehicle acceleration prediction. However, few studies have fully considered the driver heterogeneity when predicting vehicle acceleration. To model the characteristics of individual drivers, this study first identifies the driving behavior semantics which is defined as the underlying patterns of driving behaviors. The analysis results from the coupled hidden Markov model (CHMM) are used to evaluate the driving behavior differences between different drivers by Wasserstein distance. Then the convolutional neural network (CNN) and long short‐term memory (LSTM) network are applied to predict vehicle acceleration. To validate the accuracy of the proposed prediction framework, vehicle acceleration data in car‐following conditions is extracted from the safety pilot model deployment (SPMD) dataset. The segmentation results indicate that the CHMM possesses a robust capacity for modeling driving behavior. The prediction results demonstrate that the proposed framework, which incorporates driver clustering before prediction, significantly improves the accuracy of predictions. And the CNN‐LSTM outperforms the LSTM in predicting vehicle acceleration during car‐following scenarios. The findings from this study can enhance the development of personalized functionalities within ADAS to promote its deployment, thereby improving its acceptance and safety.
Influences of Nursing Professionalism, Empathy, and Clinical Decision-Making Ability on Shared Decision-Making Awareness among Hemodialysis Nurses
Authors: Yun Junghwa , Seong Mihyeon , Cho Youngmi , Sok Sohyune
Published: April 2024

Aim. To examine the relationships among nursing professionalism, empathy, and clinical decision-making ability and the factors influencing shared decision-making awareness in hemodialysis nurses. Background. Self-management and treatment for hemodialysis patients are essential for maintaining health and life in daily life. In this process, shared decision-making in which patients, nurses, and medical teams participate and make decisions together has a greater impact on the health recovery and improvement of quality of life for hemodialysis patients than for any other chronic disease patients. Methods. A cross-sectional descriptive design was employed. Participants were 145 nurses working in the hemodialysis centers at hospitals in Seoul and Gyeonggi-do. Measures included the general characteristics of study participants, nursing professionalism, empathy, clinical decision-making ability, and shared decision-making awareness. Data were collected from May to July, 2022, and multiple linear regression analysis was used to examine the predictive factors of shared decision-making awareness. Results. The strongest predictor was empathy, followed by clinical decision-making ability and the level of education. The explanatory power of the final regression model was 23%. Conclusions. Empathy towards hemodialysis patients was an important factor influencing the shared decision-making awareness in hemodialysis nurses. Implications for Nursing Management. In nursing management, nursing managers or nurses should pay attention to influencing factors to improve the shared decision-making awareness of hemodialysis nurses. Empathy towards hemodialysis patients need to be reinforced to improve the shared decision-making awareness of hemodialysis nurses.
Home-Based Titration with Duodenal Infusion of Levodopa-Carbidopa Intestinal Gel in People with Parkinson’s Disease: An Observational Feasibility Study
Authors: Thomsen Trine Hørmann , Nielsen Nick Schou , Isenberg Asher Lou , Møller Michael Hougaard , Clausen Jesper Bøje , Schack Frederiksen Inge Mona , Olsen Louise , Javidi Mahsa , Vilhelmsen Jeanet , Olsen Marc Klee , Biering-Sørensen Bo
Published: April 2024

Background. Testing and titration of the right levodopa equivalent dose are usually performed during a hospital admission. However, optimal dose titration in people with Parkinson’s disease (PwPs) may depend on home environment, emotional stress, and physical activity of everyday life. Objective. Firstly, to evaluate the feasibility and safety of a home-based LCIG titration program and patients’/caregivers’ satisfaction. Secondly, to identify barriers and facilitators for home-based titration. Method. This study assesses the feasibility and safety of home-based titration of levodopa duodenal infusions with the use of self-reported evaluation questionnaires with open-ended questions included, registration of total time used, and number of contacts/visits. A telemedicine solution was used to remotely monitor the patients, adjust treatment, and provide support and guidance to patients and caregivers. Results. Ten of 12 PwPs (5 females and 7 males) completed the total titration program. Eight of the 12 PwPs were dependent on help. These 8 PwPs also had a high burden of nonmotor symptoms (NMS). Cognitive impairments varied in severity (range 16–30). Time spent with home visits was on average 93.4 minutes (ranging from 35 to 180 minutes), and the length of the total titration (LCIG initiation to termination of titration) was on average 3.4 days with 2–5 (mean 3.2) contacts/visits with PD team members. The average score on the satisfaction evaluation questionnaires was lower in the caregiver group (mean 31.8) than the PwP outcome (mean 36.2). Conclusions. Telehealth-assisted home-based titration programs are feasible due to the length of the titration period, number of contacts, and time spent in PwPs’ private homes, are rated satisfactory and safe by PwPs and caregivers, and may be a substitute for in-hospital treatment. Clinical recommendations including facilitators and barriers from a patient/caregiver perspective are displayed. This trial is registered with NCT4196647.
Validation of Machine Learning-Based Assessment of Major Depressive Disorder from Paralinguistic Speech Characteristics in Routine Care
Authors: Bauer Jonathan F. , Gerczuk Maurice , Schindler-Gmelch Lena , Amiriparian Shahin , Ebert David Daniel , Krajewski Jarek , Schuller Björn , Berking Matthias
Published: April 2024

New developments in machine learning-based analysis of speech can be hypothesized to facilitate the long-term monitoring of major depressive disorder (MDD) during and after treatment. To test this hypothesis, we collected 550 speech samples from telephone-based clinical interviews with 267 individuals in routine care. With this data, we trained and evaluated a machine learning system to identify the absence/presence of a MDD diagnosis (as assessed with the Structured Clinical Interview for DSM-IV) from paralinguistic speech characteristics. Our system classified diagnostic status of MDD with an accuracy of 66% (sensitivity: 70%, specificity: 62%). Permutation tests indicated that the machine learning system classified MDD significantly better than chance. However, deriving diagnoses from cut-off scores of common depression scales was superior to the machine learning system with an accuracy of 73% for the Hamilton Rating Scale for Depression (HRSD), 74% for the Quick Inventory of Depressive Symptomatology–Clinician version (QIDS-C), and 73% for the depression module of the Patient Health Questionnaire (PHQ-9). Moreover, training a machine learning system that incorporated both speech analysis and depression scales resulted in accuracies between 73 and 76%. Thus, while findings of the present study demonstrate that automated speech analysis shows the potential of identifying patterns of depressed speech, it does not substantially improve the validity of classifications from common depression scales. In conclusion, speech analysis may not yet be able to replace common depression scales in clinical practice, since it cannot yet provide the necessary accuracy in depression detection. This trial is registered with DRKS00023670.
FIGURE 1 from Inhibition of NEK2 Promotes Chemosensitivity and Reduces KSHV-positive Primary Effusion Lymphoma Burden
Authors: White Maria C. , Wong Jason P. , Damania Blossom
Published: April 2024

NEK2 depletion decreases PEL survival. A, Western blot analysis for NEK2 expression in PEL cells. B, Western blot analysis for NEK2 expression in normal PBMCs alongside PEL cells. C–D, Western blots for shRNA-mediated knockdown of NEK2 expression in PEL cells and subsequent cell viability assays measuring PEL survival over time after treatment with two different NEK2 shRNAs (dotted lines) or nontemplate control (NTC, solid black line). Data are representative of three independent biological replicates, each performed in triplicate. Viability data were normalized to 0-hour luminescence values for each treatment, fitted using nonlinear regression, and analyzed using two-way ANOVA with Dunnett multiple comparisons. ****, P < 0.0001. C, ***P = 0.0001; **, P < 0.0005. D, ***, P < 0.0005; *, P = 0.0009, E, ***, P = 0.0003. The BCBL1 loading control blot in C is the same as in Fig. 3E.
Inhibition of NEK2 Promotes Chemosensitivity and Reduces KSHV-positive Primary Effusion Lymphoma Burden
Authors: White Maria C. , Wong Jason P. , Damania Blossom
Published: April 2024

Non–Hodgkin lymphoma (NHL) is a common cancer in both men and women and represents a significant cancer burden worldwide. Primary effusion lymphoma (PEL) is a subtype of NHL infected with Kaposi sarcoma–associated herpesvirus (KSHV). PEL is an aggressive and lethal cancer with no current standard of care, owing largely to its propensity to develop resistance to current chemotherapeutic regimens. Here, we report a reliance of KSHV-positive PEL on the mitotic kinase, NEK2, for survival. Inhibition of NEK2 with the inhibitor, JH295, resulted in caspase 3–mediated apoptotic cell death of PEL. Furthermore, NEK2 inhibition significantly prolonged survival and reduced tumor burden in a PEL mouse model. We also demonstrate that the ABC transporter proteins, MDR1 and MRP, are most active in PEL and that inhibition of NEK2 in PEL reduced the expression and activity of these ABC transporter proteins, which are known to mediate drug resistance in cancer. Finally, we report that JH295 treatment sensitized lymphomas to other chemotherapeutic agents such as rapamycin, resulting in enhanced cancer cell death. Overall, these data offer important insight into the mechanisms underlying PEL survival and drug resistance, and suggest that NEK2 is a viable therapeutic target for PEL.

Significance:

The mitotic kinase, NEK2, is important for the survival of KSHV-positive PEL. NEK2 inhibition resulted in PEL apoptosis and reduced tumor burden in a mouse model. NEK2 inhibition also reduced drug resistance.
Brain-Thymus connections in Chagas Disease
Authors: González Florencia Belén , Savino Wilson , Pérez Ana Rosa
Published: April 2024

Background: The brain and the immune systems represent the two primary adaptive systems within the body. Both are involved in a dynamic process of communication, vital for the preservation of mammalian homeostasis. This interplay involves two major pathways: the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS). Summary: The establishment of infection can affect immunoneuroendocrine interactions, with functional consequences for immune organs, particularly the thymus. Interestingly, the physiology of this primary organ is not only under the control of the central nervous system (CNS), but also exhibits autocrine/paracrine regulatory circuitries mediated by hormones and neuropeptides that can be altered in situations of infectious stress or chronic inflammation. In particular, Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, impacts upon immunoneuroendocrine circuits disrupting thymus physiology. Here, we discuss the most relevant findings reported in relation to brain-thymic connections during T. cruzi infection, as well as their possible implications for the immunopathology of human Chagas disease.
Key Messages: During Trypanosoma cruzi infection, the CNS influences thymus physiology through an intricate network involving hormones, neuropeptides, and pro-inflammatory cytokines. Despite some uncertainties in the mechanisms and the fact that the link between these abnormalities and CCC is still unknown, it is evident that the precise control exerted by the brain over the thymus is markedly disrupted throughout the course of Trypanosoma cruzi infection.
Antígona na Catalunha: Notas Sobre a Antígona de Espriu
Authors: Duarte Adriane da Silva
Published: April 2024

Escrita sob o impacto da queda de Barcelona diante das tropas de Franco, a Antígona (1939-1969), de Salvador Espriu (1913-1985), revisita o mito dos labdácidas a partir dos acontecimentos traumáticos que marcam a história da Espanha no século XX. Composta em catalão, quando a língua já estava proscrita, a peça só foi encenada ao fim da Segunda Grande Guerra, quando o grande sucesso das peças homônimas de Anouilh e Brecht conferem-lhe novo significado. Este artigo visa lançar luz sobre essa singular recepção da tragédia grega na Catalunha.