bluuebunny/crossref_metadata_2025 huggingface dataset:
Introduction of Local Resonators to a Nonlinear Metamaterial With Topological Features
Authors: LeGrande Joshua , Malla Arun , Bukhari Mohammad , Barry Oumar
Published: February 2024

Recent work in nonlinear topological metamaterials has revealed many useful properties such as amplitude dependent localized vibration modes and nonreciprocal wave propagation. However, thus far, there have not been any studies to include the use of local resonators in these systems. This work seeks to fill that gap through investigating a nonlinear quasi-periodic metamaterial with periodic local resonator attachments. We model a one-dimensional metamaterial lattice as a spring-mass chain with coupled local resonators. Quasi-periodic modulation in the nonlinear connecting springs is utilized to achieve topological features. For comparison, a similar system without local resonators is also modeled. Both analytical and numerical methods are used to study this system. The dispersion relation of the infinite chain of the proposed system is determined analytically through the perturbation method of multiple scales. This analytical solution is compared to the finite chain response, estimated using the method of harmonic balance and solved numerically. The resulting band structures and mode shapes are used to study the effects of quasi-periodic parameters and excitation amplitude on the system behavior both with and without the presence of local resonators. Specifically, the impact of local resonators on topological features such as edge modes is established, demonstrating the appearance of a trivial bandgap and multiple localized edge states for both main cells and local resonators. These results highlight the interplay between local resonance and nonlinearity in a topological metamaterial demonstrating for the first time the presence of an amplitude invariant bandgap alongside amplitude dependent topological bandgaps.
Design of a Simple Valveless Micropump Using Piezoelectric Actuators
Authors: Yu Tai-Ho , Lai Chun-Hung , Chen Yuan-Hsin
Published: February 2024

An open valveless micropump pumped by a disk-shaped piezo-electric actuator was developed, and its working principles were investigated. The electrode of the pump buzzer was divided into two semicircles as piezo-electric actuators, and single-phase or dual-phase AC driving potential was applied. The flowrate of the pump was analyzed when actuated in basic symmetric (W00) and antisymmetric (W01) modes. The finite element package software ANSYS was used to analyze the resonant frequency and mode of the buzzer under fluid loading, and the vibration displacement generated by the single-phase and dual-phase time-harmonic actuation was both simulated by using an additional mass method and experimentally investigated. The experimental results show that the resonant frequency of the disk-shaped actuator decreased due to the fluid loading effect and as the gap distance between the conduit and the actuator decreased. The maximum flow rates of the W00 and W01 mode actuated pumps were 133.13 and 9.63 mL/min, respectively. The driving frequency with the highest pump efficiency was slightly lower than the resonance frequency of the fluid-loaded buzzer. Applying a hydrophobic treatment to the back of the buzzer decreased the resonance frequency under fluid loading. The results show that simulating the structural resonance frequency for various fluid loads by the additional mass method is feasible. The flow direction could be controlled by activating the W01 mode.
Information conveyed by voice quality
Authors: Kreiman Jody
Published: February 2024

The problem of characterizing voice quality has long caused debate and frustration. The richness of the available descriptive vocabulary is overwhelming, but the density and complexity of the information voices convey lead some to conclude that language can never adequately specify what we hear. Others argue that terminology lacks an empirical basis, so that language-based scales are inadequate a priori. Efforts to provide meaningful instrumental characterizations have also had limited success. Such measures may capture sound patterns but cannot at present explain what characteristics, intentions, or identity listeners attribute to the speaker based on those patterns. However, some terms continually reappear across studies. These terms align with acoustic dimensions accounting for variance across speakers and languages and correlate with size and arousal across species. This suggests that labels for quality rest on a bedrock of biology: We have evolved to perceive voices in terms of size/arousal, and these factors structure both voice acoustics and descriptive language. Such linkages could help integrate studies of signals and their meaning, producing a truly interdisciplinary approach to the study of voice.
GCRV-II invades monocytes/macrophages and induces macrophage polarization and apoptosis in tissues to facilitate viral replication and dissemination
Authors: Xia Ning , Zhang Yanqi , Zhu Wentao , Su Jianguo
Published: February 2024

Grass carp reovirus (GCRV), particularly the highly prevalent type II GCRV (GCRV-II), causes huge losses in the aquaculture industry. However, little is known about the mechanisms by which GCRV-II invades grass carp and further disseminates among tissues. In the present study, monocytes/macrophages (Mo/Mφs) were isolated from the peripheral blood of grass carp and infected with GCRV-II. The results of indirect immunofluorescent microscopy, transmission electron microscopy, real-time quantitative RT-PCR (qRT-PCR), western blot (WB), and flow cytometry analysis collectively demonstrated that GCRV-II invaded Mo/Mφs and replicated in them. Additionally, we observed that GCRV-II induced different types (M1 and M2) of polarization of Mo/Mφs in multiple tissues, especially in the brain, head kidney, and intestine. To assess the impact of different types of polarization on GCRV-II replication, we recombinantly expressed and purified the intact cytokines CiIFN-γ2, CiIL-4/13A, and CiIL-4/13B and successfully induced M1 and M2 type polarization of macrophages using these cytokines through
in vitro
experiments. qRT-PCR, WB, and flow cytometry analyses showed that M2 macrophages had higher susceptibility to GCRV-II infection than other types of Mo/Mφs. In addition, we found GCRV-II induced apoptosis of Mo/Mφs to facilitate virus replication and dissemination and also detected the presence of GCRV-II virus in plasma. Collectively, our findings indicated that GCRV-II could invade immune cells Mo/Mφs and induce apoptosis and polarization of Mo/Mφs for efficient infection and dissemination, emphasizing the crucial role of Mo/Mφs as a vector for GCRV-II infection.

IMPORTANCE

Type II grass carp reovirus (GCRV) is a prevalent viral strain and causes huge losses in aquaculture. However, the related dissemination pathway and mechanism remain largely unclear. Here, our study focused on phagocytic immune cells, monocytes/macrophages (Mo/Mφs) in blood and tissues, and explored whether GCRV-II can invade Mo/Mφs and replicate and disseminate via Mo/Mφs with their differentiated type M1 and M2 macrophages. Our findings demonstrated that GCRV-II infected Mo/Mφs and replicated in them. Furthermore, GCRV-II infection induces an increased number of M1 and M2 macrophages in grass carp tissues and a higher viral load in M2 macrophages. Furthermore, GCRV-II induced Mo/Mφs apoptosis to release viruses, eventually infecting more cells. Our study identified Mo/Mφs as crucial components in the pathway of GCRV-II dissemination and provides a solid foundation for the development of treatment strategies for GCRV-II infection.
Pseudomonas aeruginosa
MipA-MipB envelope proteins act as new sensors of polymyxins
Authors: Janet-Maitre Manon , Job Viviana , Bour Maxime , Robert-Genthon Mylène , Brugière Sabine , Triponney Pauline , Cobessi David , Couté Yohann , Jeannot Katy , Attrée Ina
Published: February 2024

Due to the rising incidence of antibiotic-resistant infections, the last-line antibiotics, polymyxins, have resurged in the clinics in parallel with new bacterial strategies of escape. The Gram-negative opportunistic pathogen
Pseudomonas aeruginosa
develops resistance to colistin/polymyxin B by distinct molecular mechanisms, mostly through modification of the lipid A component of the LPS by proteins encoded within the
arnBCDATEF-ugd
(
arn
) operon. In this work, we characterized a polymyxin-induced operon named
mipBA
, present in
P. aeruginosa
strains devoid of the
arn
operon. We showed that
mipBA
is activated by the ParR/ParS two-component regulatory system in response to polymyxins. Structural modeling revealed that MipA folds as an outer-membrane β-barrel, harboring an internal negatively charged channel, able to host a polymyxin molecule, while the lipoprotein MipB adopts a β-lactamase fold with two additional C-terminal domains. Experimental work confirmed that MipA and MipB localize to the bacterial envelope, and they co-purify
in vitro
. Nano differential scanning fluorimetry showed that polymyxins stabilized MipA in a specific and dose-dependent manner. Mass spectrometry-based quantitative proteomics on
P. aeruginosa
membranes demonstrated that ∆
mipBA
synthesized fourfold less MexXY-OprA proteins in response to polymyxin B compared to the wild-type strain. The decrease was a direct consequence of impaired transcriptional activation of the
mex
operon operated by ParR/ParS. We propose MipA/MipB to act as membrane (co)sensors working in concert to activate ParS histidine kinase and help the bacterium to cope with polymyxin-mediated envelope stress through synthesis of the efflux pump, MexXY-OprA.

IMPORTANCE

Due to the emergence of multidrug-resistant isolates, antibiotic options may be limited to polymyxins to eradicate Gram-negative infections.
Pseudomonas aeruginosa
, a leading opportunistic pathogen, has the ability to develop resistance to these cationic lipopeptides by modifying its lipopolysaccharide through proteins encoded within the
arn
operon. Herein, we describe a sub-group of
P. aeruginosa
strains lacking the
arn
operon yet exhibiting adaptability to polymyxins. Exposition to sub-lethal polymyxin concentrations induced the expression and production of two envelope-associated proteins. Among those, MipA, an outer-membrane barrel, is able to specifically bind polymyxins with an affinity in the 10-µM range. Using membrane proteomics and phenotypic assays, we showed that MipA and MipB participate in the adaptive response to polymyxins via ParR/ParS regulatory signaling. We propose a new model wherein the MipA-MipB module functions as a novel polymyxin sensing mechanism.
Whole genome sequencing of nine
Vibrio parahaemolyticus
strains encoding (
Pir
) toxin-like genes from shrimp cultures in northern Peru using Oxford Nanopore technology
Authors: Tapia-Chirinos Stephanie , Salcedo-Mejia Luis Alberto , Domínguez-Mendoza Luz , Nuñure-Ortega Jeferson , Ramos-Espinoza Fernando , Gómez-Sánchez Muriel , Tataje-Lavanda Luis , Velazco-Peña Rodolfo
Published: February 2024

Nine Peruvian isolates of
Vibrio parahaemolyticus
were characterized through sequencing, revealing the presence of simple sequence repeat, Pir toxin-like genes, and genes associated with antibiotic resistance, toxic components, and transposable elements. These findings expand our understanding of the genetic diversity, disease resistance, and virulence in cultivated shrimp populations in Peru.
Alcohol-induced gut microbiome dysbiosis enhances the colonization of
Klebsiella pneumoniae
on the mouse intestinal tract
Authors: Shen Mengke , Zhao Huajie , Han Meiqing , Su Lin , Cui Xiaojian , Li Duan , Liu Liang , Wang Chuansheng , Yang Fan
Published: February 2024

Chronic alcohol consumption, an important risk factor for diseases and deaths, can cause intestinal microbiota dysbiosis and increase the infection of some opportunistic pathogens. However, the current studies on the effects of alcohol-induced intestinal microbiota dysbiosis on gut colonization of
Klebsiella pneumoniae
are still scarce. In the present study, we established a binge-on-chronic alcohol model in mice to identify the characteristics of alcohol-induced intestinal microbiome and metabolite dysbiosis using multi-omics and explored the effects and potential mechanisms of these dysbioses on the intestinal colonization of
K. pneumoniae
. The results show that chronic alcohol consumption alters the diversity and composition of gut microbiota (including bacteria and fungi), decreases the complexity of the interaction between intestinal bacteria and fungi, disturbs the gut metabolites, and promotes the colonization of
K. pneumoniae
on the gut of mice. The relevance analyses find that alcohol-induced gut microbiome dysbiosis has a strong correlation with the alteration of secondary bile acids.
In vitro
results suggest that the high concentration of lithocholic acid, a secondary bile acid, could significantly inhibit the proliferation of
K. pneumoniae
, and the adhesion of
K. pneumoniae
to Caco-2 cells. Our results indicate that alcohol-induced microbiome dysbiosis contributes to decreased levels of secondary bile acids, which was one of the main reasons affecting the colonization of
K. pneumoniae
in mice’s intestines. Some secondary bile acids (e.g., lithocholic acid) might be a potential drug to prevent the colonization and spread of
K. pneumoniae
.

IMPORTANCE

Alcohol is one of the most commonly misused substances in our lives. However, long-term heavy drinking will increase the colonization of some opportunistic pathogens (e.g.,
Klebsiella pneumoniae
) in the body. Here, we revealed that binge-on-chronic alcohol consumption disrupted the balance between gut bacteria and fungi, induced the gut microbiome and metabolites dysbiosis, and promoted the colonization of
K. pneumoniae
in the intestine of mice. In particular, alcohol-taking disrupted intestinal bile acid metabolism and reduced the lithocholic acid concentration. However, a high concentration of lithocholic acid can protect against intestinal colonization of
K. pneumoniae
by inhabiting the bacterial growth and adhesion to the host cell. Hence, regulating the balance of gut microbiota and intestinal bile acid metabolism may be a potential strategy for reducing the risk of
K. pneumoniae
infection and spread.
Supplemental Material: Tracking cycles of Phanerozoic opening and closing of ocean basins using detrital rutile and zircon geochronology and geochemistry
Authors: Odlum Margaret , al. et
Published: February 2024

Detailed methods and U-Pb and TREE data tables.  
High-Fidelity and Robust Stimulated Raman Transition with Parameter-Modulated Optimal Control
Authors: Wu X.-X. , Li S. , Zhou J. , Xue Z.-Y.
Published: February 2024

High-fidelity and robust quantum control is essential for large-scale quantum information processing. The stimulated Raman transition that utilizes second-order coupling effect is a valuable and conventional technique for manipulating states in multi-level quantum systems, but its accuracy is limited by the driving-induced Stark shift. Here, we propose a new parameter-modulated method to effectively compensate the Stark-shift effect, so that we are able to realize high-fidelity and robust stimulated Raman transition with optimal control. Additionally, its robustness against different systematic errors can be further improved via optimization its average fidelity under these specific errors. Besides, our method has potential applications for high-fidelity and robust quantum control in high-order coupling scenarios.
Superconducting Order Parameter Structure in the Nematic Phase of Iron-based Materials
Authors: Korshunov M. M. , Togushova Yu. N.
Published: February 2024

We consider the effect of the nematic order on the formation of the superconducting state in iron pnictides and chalcogenides. Nematic order with the $${{B}_{{2g}}}$$ symmetry is modelled as the d-type Pomeranchuk instability and treated within the mean-field approach. Calculated nematic order parameter depends on the nematic interaction coefficient and abruptly changes with the coefficient’s increase. The superconducting solution is obtained within the spin-fluctuation pairing theory. We show that the leading solution in the nematic phase has a $${{s}_{{\pi \pm }}}$$ structure. From the critical temperature $${{T}_{c}}$$ estimations, we conclude that the nematic superconducting state of the $${{s}_{{\pi \pm }}}$$ type is more favorable than the usual $${{s}_{ \pm }}$$ and $${{d}_{{{{x}^{2}} - {{y}^{2}}}}}$$ type states appearing in the absence of the nematicity.
Comparison of definitive approaches for conotruncal defects following bidirectional Glenn procedure
Authors: Liu Yuze , He Qiyu , Dou Zheng , Ma Kai , Lin Xinjie , Li Shoujun
Published: February 2024

Background

Staged repair is common for complex conotruncal defects, often involving bidirectional Glenn (BDG) procedure. Following the cavopulmonary shunt, both Fontan completion and biventricular conversion (BiVC) serve as definitive approaches. The optimal strategy remains controversial.

Methods

The baseline, perioperative and follow-up data were obtained for all paediatric patients with conotruncal defects who underwent BDG procedure as palliation in Fuwai Hospital from 2013 to 2022. Patients with single ventricle were excluded. The primary outcome was mortality. The secondary outcome was reintervention, including any cardiovascular surgeries and non-diagnostic catheterisations.

Results

A total of 232 patients were included in the cohort, with 142 underwent Fontan (61.2%) and 90 underwent BiVC (38.8%). The median interstage period from BDG to the definitive procedure was 3.83 years (IQR: 2.72–5.42) in the overall cohort, 3.62 years (IQR: 2.57–5.15) in the Fontan group and 4.15 years (IQR: 3.05–6.13) in the BiVC group (p=0.03). The in-hospital outcomes favoured the Fontan group, including duration of cardiopulmonary bypass, aortic cross-clamp, mechanical ventilation and intensive care unit stay. Postoperative mortality was generally low and comparable, as was the reintervention rate (HR=1.42, 95% CI: 0.708 to 2.85, p=0.32). The left ventricular size was smaller at baseline and within the normal range at follow-up for both Fontan and BiVC groups; however, it was significantly larger with BiVC at follow-up.

Conclusion

In paediatric patients with conotruncal heart defects who underwent BDG procedure, BiVC is a feasible option, especially for patients with certain Fontan risk factors, and are not ideal candidates for successful Fontan completion.
Going Beyond XAI: A Systematic Survey for Explanation-Guided Learning
Authors: Gao Yuyang , Gu Siyi , Jiang Junji , Hong Sungsoo Ray , Yu Dazhou , Zhao Liang
Published: February 2024

As the societal impact of Deep Neural Networks (DNNs) grows, the goals for advancing DNNs become more complex and diverse, ranging from improving a conventional model accuracy metric to infusing advanced human virtues such as fairness, accountability, transparency, and unbiasedness. Recently, techniques in Explainable Artificial Intelligence (XAI) have been attracting considerable attention and have tremendously helped Machine Learning (ML) engineers in understand AI models. However, at the same time, we started to witness the emerging need beyond XAI among AI communities; based on the insights learned from XAI, how can we better empower ML engineers in steering their DNNs so that the model’s reasonableness and performance can be improved as intended? This article provides a timely and extensive literature overview of the field Explanation-Guided Learning (EGL), a domain of techniques that steer the DNNs’ reasoning process by adding regularization, supervision, or intervention on model explanations. In doing so, we first provide a formal definition of EGL and its general learning paradigm. Second, an overview of the key factors for EGL evaluation, as well as summarization and categorization of existing evaluation procedures and metrics for EGL are provided. Finally, the current and potential future application areas and directions of EGL are discussed, and an extensive experimental study is presented aiming at providing comprehensive comparative studies among existing EGL models in various popular application domains, such as Computer Vision and Natural Language Processing domains. Additional resources related to event prediction are included in the article website:
https://kugaoyang.github.io/EGL/
Mobile Health Interventions for Substance Use Disorders
Authors: Businelle Michael S. , Perski Olga , Hébert Emily T. , Kendzor Darla E.
Published: February 2024

Substance use disorders (SUDs) have an enormous negative impact on individuals, families, and society as a whole. Most individuals with SUDs do not receive treatment because of the limited availability of treatment providers, costs, inflexible work schedules, required treatment-related time commitments, and other hurdles. A paradigm shift in the provision of SUD treatments is currently underway. Indeed, with rapid technological advances, novel mobile health (mHealth) interventions can now be downloaded and accessed by those that need them anytime and anywhere. Nevertheless, the development and evaluation process for mHealth interventions for SUDs is still in its infancy. This review provides a critical appraisal of the significant literature in the field of mHealth interventions for SUDs with a particular emphasis on interventions for understudied and underserved populations. We also discuss the mHealth intervention development process, intervention optimization, and important remaining questions.
Impact of Acute Alcohol Consumption on Sexuality: A Look at Psychological Mechanisms
Authors: George William H. , Blayney Jessica A. , Davis Kelly Cue
Published: February 2024

Alcohol's link with sexuality is long-standing and prominent. While research continues to document robust associations between drinking and sexual behavior, scientific attention now centers primarily on evaluating mechanisms and attendant theoretical frameworks to advance our understanding of how alcohol exerts a causal impact. We describe four domains with reliable evidence of alcohol effects: sexualized social perceptions, sexual arousal, sexual risk taking, and sexual assault. We consider three contextual frames: distal factors associated with encountering opportunities for alcohol-involved sex, proximal factors associated with alcohol's acute effects, and distal–proximal interactions. We then examine the empirical support for mechanisms embedded within four theoretical frameworks: alcohol disinhibition, alcohol expectancy, alcohol myopia, and emotion regulation. Support for disinhibition mechanisms is evident with sexual arousal only. Expectancy and myopia mechanisms enjoy support across domains and make up bases for integrative expectancy–myopia causal explanations. Emotion regulation mechanisms evidence preliminary support in risk taking and sexual assault. Implications and future directions are considered.
Protective Al2O3 Thin Film Coating by ALD to Enhance the Anodic Stability of Metallic Current Collectors in Ethereal Mg Electrolyte Solutions
Authors: Maddegalla Ananya , Kumar Yogendra , Akella Sri Harsha , Taragin Sarah , Bravo-Zhivotovskii Dmitry , Sadhanala Hari Krishna , Aurbach Doron , Noked Malachi
Published: February 2024

Rechargeable magnesium batteries (RMBs) have the potential to contribute towards alternative energy storage due to their low cost, high abundance, dendrites free deposition of Mg and high volumetric energy density. Organometallic complex-based electrolytes in ethereal solutions have been extensively studied in the context of RMBs due to their ability to facilitate highly reversible magnesium deposition in rechargeable magnesium batteries, while demonstrating wide enough electrochemical stability windows. However, these solutions containing unique mixture of organo-halo aluminate complexes have detrimental effect on the anodic stability of metallic current collectors for cathodes, like Ni and Al foils. In this work, we were able to synthesize and isolate Mg2Cl3(THF)6Ph2AlCl2/THF electrolyte as the sole electroactive species using simple precursors: Ph2AlCl and MgCl2 in THF, via atom efficient mono-chloro abstraction Schlenk technique. We characterized the anodic stability of Ni, Ni@C, Al, and Al@C current collectors by monitoring their electrochemical behavior. In addition, we investigated the anodic stability enhancement of various current collectors by Al2O3 thin films coating using Atomic Layer Deposition (ALD). Linear sweep voltametric studies showed that coating current collectors enhanced the oxidative stability of Al and Ni foils by 0.1–0.3 V vs Mg/Mg2+ compared to the uncoated foils. In particular, Al2O3 coated Al@C showed an improved oxidative stability of 2.8 V vs Mg/Mg2+. Our findings show that current collectors protection by ALD coating can help in long-term stability and improving RMBs’ energy density by using high voltage cathode materials, a crucial step in developing practical rechargeable Mg batteries.
Efficacy of Hot Tea Infusion vs. Ethanolic Extract of Moringa oleifera for the Simultaneous Treatment of Nonalcoholic Fatty Liver, Hyperlipidemia, and Hyperglycemia in a Murine Model Fed with a High-Fat Diet
Authors: Cortes-Alvarez Salma I. , Delgado-Enciso Ivan , Rodriguez-Hernandez Alejandrina , Hernandez-Fuentes Gustavo A. , Aurelien-Cabezas Nomely S. , Moy-Lopez Norma A. , Cortes-Alvarez Nadia Y. , Guzman-Muñiz Jorge , Guzman-Esquivel Jose , Rodriguez-Sanchez Iram P. , Martinez-Fierro Margarita L. , Mokay-Ramirez Karen A. , Barajas-Saucedo Carlos E. , Sanchez-Ramirez Carmen A.
Published: February 2024

Moringa oleifera (MO) is a native tree of Asia and is cultivated in some areas of Mexico as part of traditional horticulture. The aim of the present study was to compare the efficacy of MO infusion vs. MO ethanolic extract for the simultaneous treatment of nonalcoholic fatty liver (NAFLD), hyperlipidemia, and hyperglycemia in a murine model fed with a high-fat diet (HFD). BALB/c mice were fed a balanced diet (healthy control) or an HFD for 6 months. With this, the NAFLD model was established before starting a therapeutic intervention with MO for two months. The phytochemical analysis by nuclear magnetic resonance in 1H and 13C experiments showed signals for pyrrole alkaloids and triterpenes as the main constituents of the extract and infusion preparation. A significant reduction of SGPT, SGOT, lipids, urea, and glucose in blood among NAFLD groups treated with MO (infusion or extract) was found, when compared to the NAFLD-placebo group. Steatosis and liver inflammation were found to be decreased in the MO groups, as infusion or ethanolic extract. Infusion produced a better therapeutic effect than the extract in all parameters, except glycemic control, where the extract was better. As an additional finding, it is noteworthy that treatment with MO, particularly through infusion, resulted in improved motor activity. Moreover, a reduction in anxiety-like behavior was observed exclusively with the administration of infusion. These observations provide valuable insights into the potential broader effects of Moringa oleifera beyond the primary aim of the study.
Global Stability with Lyapunov Function and Dynamics of SEIR-Modified Lassa Fever Model in Sight Power Law Kernel
Authors: Farman Muhammad , Alfiniyah Cicik , Saqib Muhammad
Published: February 2024

Lassa fever is an acute viral hemorrhagic disease that affects humans and is endemic in various West African nations. In this study, a fractional-order model is constructed using the Caputo operator for SEIR-type Lassa fever transmission, including the control strategy. The proposed model examines the dynamics of Lassa fever transmission from rodents to humans and from person to person and in territories with infection in society. The model is analyzed both qualitatively and quantitatively. We examine the positively invariant area and demonstrate positive, bounded solutions to the model. We also show the equilibrium states for the occurrence and extinction of infection. The proposed nonlinear system is verified to be present, and a unique solution is shown to exist using fixed point theorems. Using the Volterra-type Lyapunov function, we investigate the global stability of the suggested system with a fractional Caputo derivative. To study the impact of the fractional operator through computational simulations, results are generated employing a two-step Lagrange polynomial in the generalized version of the power law kernel. A graphical evaluation is provided to show the simplicity and dependability of the model, and all rodents that could be source viruses are important in ecological research. The findings with a value equal to 1 are stronger, according to the comparison of outcomes with different fractional orders. The adverse effect of Lassa fever increases when all modes of transmission are taken into account, according to the study, with fractional-order findings indicating less detrimental effects on specific transmission routes.
The Navigation of Home Service Robot Based on Deep Learning and Machine Learning
Authors: Yan Yupei , Ma Weimin , Wong Sengfat , Yin Xuemei , Pan Qiang , Liao Zhiwen , Lin Xiaoxin
Published: February 2024

This paper discusses how to improve the accuracy of navigation for home service robot based on the deep learning and machine learning. First, the crawling programing is applied to collect enough images of fridge and washing machine on the web; a deep learning framework is proposed that can distinguish fridge and washing machine more accurately. Following, the data come from the robot operating system topics are collected and cleaned, the linear regression, decision tree, and linear SVR algorithms are applied and compared to predict the power consumption of the robot, and a conclusion is obtained that liner movement will consume more power, which provides a reference for the path planning of the robot. Lastly, the conclusions are proposed that a novel methodology is applied to distinguish different home appliances, which is useful for the accurate navigation of the robot; the liner movement will consume more power compared to turning left or right, which supplies a reference for the optimized path planning for the robot.
Upper Airway Epithelial Tissue Transcriptome Analysis Reveals Immune Signatures Associated with COVID‐19 Severity in Ghanaians
Authors: Sandi John Demby , Levy Joshua I. , Tapela Kesego , Zeller Mark , Yeboah Joshua Afari , Saka Daniel Frimpong , Grant Donald S. , Awandare Gordon A. , Quashie Peter K. , Andersen Kristian G. , Paemka Lily
Published: February 2024

The immunological signatures driving the severity of coronavirus disease 19 (COVID‐19) in Ghanaians remain poorly understood. We performed bulk transcriptome sequencing of nasopharyngeal samples from severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2)‐infected Ghanaians with mild and severe COVID‐19, as well as healthy controls to characterize immune signatures at the primary SARS‐CoV‐2 infection site and identify drivers of disease severity. Generally, a heightened antiviral response was observed in SARS‐CoV‐2‐infected Ghanaians compared with uninfected controls. COVID‐19 severity was associated with immune suppression, overexpression of proinflammatory cytokines, including CRNN, IL1A, S100A7, and IL23A, and activation of pathways involved in keratinocyte proliferation. SAMD9L was among the differentially regulated interferon‐stimulated genes in our mild and severe disease cohorts, suggesting that it may play a critical role in SARS‐CoV‐2 pathogenesis. By comparing our data with a publicly available dataset from a non‐African (Indians) (GSE166530), an elevated expression of antiviral response‐related genes was noted in COVID‐19‐infected Ghanaians. Overall, the study describes immune signatures driving COVID‐19 severity in Ghanaians and identifies immune drivers that could serve as potential prognostic markers for future outbreaks or pandemics. It further provides important preliminary evidence suggesting differences in antiviral response at the upper respiratory interface in sub‐Saharan Africans (Ghanaians) and non‐Africans, which could be contributing to the differences in disease outcomes. Further studies using larger datasets from different populations will expand on these findings.
A Brief Review on Engaging and Interactive Learning for Children: Exploring the Potential of Metaverse‐Based Oral Health Promotion
Authors: Mehta Vini , Mathur Ankita , Chaurasia Himanshu , Obulareddy Vishnu Teju , D’Amico Cesare , Fiorillo Luca
Published: February 2024

The importance of oral health for overall health makes it critical to establish proper oral hygiene practices in children early on. The traditional approaches to teaching children about dental health may not be successful since they may not be able to keep their interest. Metaverse technology offers a promising alternative, allowing for the design of engaging and immersive worlds that can effectively educate children about oral health. Despite the growing interest in the use of metaverse technology in healthcare, there is a lack of comprehensive reviews on its potential for oral health promotion in children. This review aims to fill this gap by providing an overview of the current state of metaverse‐based oral health promotion for children, discussing its benefits and challenges, and highlighting its potential for improving children’s oral health. By conducting this review, the authors hope to provide new information on the potential of metaverse‐based oral health promotion for children and to contribute to the ongoing discussion on the use of metaverse technology in healthcare. This review may also provide valuable insights for dental organizations and practitioners interested in using metaverse technology to promote oral health and healthy living among children.
Two Main Cancer Biomarkers as Molecular Targets of Binase Antitumor Activity
Authors: Dudkina Elena , Ulyanova Vera , Asmandiyarova Violetta , Vershinina Valentina , Ilinskaya Olga
Published: February 2024

Cancer is frequently coupled with the disturbance of key signaling pathways. Aberrant activation of the mitogen-activated protein kinase (MAPK) signaling cascade, occurring in over 85% of cancers, is mainly caused by the genetic alterations of its main components—oncogenes EGFR and RAS, and plays a crucial role in cell fate. The importance of EGFR and RAS proteins in a variety of tumors suggests that they would be good therapeutic targets, but at present, no effective targeted therapy against these two oncogenes has been proven. Here, we show that ribonuclease from Bacillus pumilus (binase) inhibits MAPK signaling through direct interaction with EGFR and RAS proteins. This effect contributes to the antitumor potential of binase along with its enzymatic activity. Multitargeticity of binase prevents the development of drug resistance, which is considered a major obstacle to effective anticancer treatment.
Validation of the Prognostic Performance of Breast Cancer Index in Hormone Receptor–Positive Postmenopausal Breast Cancer Patients in the TEAM Trial
Authors: Bartlett John M.S. , Xu Keying , Wong Jenna , Pond Gregory , Zhang Yi , Spears Melanie , Salunga Ranelle , Mallon Elizabeth , Taylor Karen J. , Hasenburg Annette , Markopoulos Christos , Dirix Luc , van de Velde Cornelis J.H. , Rea Daniel , Schnabel Catherine A. , Treuner Kai , Bayani Jane
Published: February 2024

Purpose:

Patients with early-stage hormone receptor–positive (HR+) breast cancer face a prolonged risk of recurrence even after adjuvant endocrine therapy. The Breast Cancer Index (BCI) is significantly prognostic for overall (0–10 years) and late (5–10 years) distant recurrence (DR) risk in N0 and N1 patients. Here, BCI prognostic performance was evaluated in HR+ postmenopausal women from the Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial.

Experimental Design:

3,544 patients were included in the analysis (N = 1,519 N0, N = 2,025 N+). BCI risk groups were calculated using pre-specified cutoff points. Kaplan–Meier analyses and log-rank tests were used to assess the prognostic significance of BCI risk groups based on DR. Hazard ratios (HR) and confidence intervals (CI) were calculated using Cox models with and without clinical covariates.

Results:

For overall 10-year DR, BCI was significantly prognostic in Ni0 (N = 1,196) and N1 (N = 1,234) patients who did not receive prior chemotherapy (P < 0.001). In patients who were DR-free for 5 years, 10-year late DR rates for low- and high-risk groups were 5.4% and 9.3% (N0 cohort, N = 1,285) and 4.8% and 12.2% (N1 cohort, N = 1,625) with multivariate HRs of 2.25 (95% CI, 1.30–3.88; P = 0.004) and 2.67 (95% CI, 1.53–4.63; P < 0.001), respectively. Late DR performance was substantially improved using previously optimized cutoff points, identifying BCI low-risk groups with even lower 10-year late DR rates of 3.8% and 2.7% in N0 and N1 patients, respectively.

Conclusions:

The TEAM trial represents the largest prognostic validation study for BCI to date and provides a more representative assessment of late DR risk to guide individualized treatment decision-making for HR+ patients with early-stage breast cancer.
RAS/RAF Comutation and ERBB2 Copy Number Modulates HER2 Heterogeneity and Responsiveness to HER2-directed Therapy in Colorectal Cancer
Authors: Singh Harshabad , Sahgal Pranshu , Kapner Kevin , Corsello Steven M. , Gupta Hersh , Gujrathi Rahul , Li Yvonne Y. , Cherniack Andrew D. , El Alam Raquelle , Kerfoot Joseph , Andrews Elizabeth , Lee Annette , Nambiar Chetan , Hannigan Alison M. , Remland Joshua , Brais Lauren , Leahy Meghan E. , Rubinson Douglas A. , Schlechter Benjamin L. , Meyerson Matthew , Kuang Yanan , Paweletz Cloud P. , Lee Jessica K. , Quintanilha Julia C.F. , Aguirre Andrew J. , Perez Kimberly J. , Huffman Brandon M. , Rossi Humberto , Abrams Thomas A. , Kabraji Sheheryar , Trusolino Livio , Bertotti Andrea , Sicinska Ewa T. , Parikh Aparna R. , Wolpin Brian M. , Schrock Alexa B. , Giannakis Marios , Ng Kimmie , Meyerhardt Jeffrey A. , Hornick Jason L. , Sethi Nilay S. , Cleary James M.
Published: February 2024

Purpose:

ERBB2-amplified colorectal cancer is a distinct molecular subtype with expanding treatments. Implications of concurrent oncogenic RAS/RAF alterations are not known.

Experimental Design:

Dana-Farber and Foundation Medicine Inc. Colorectal cancer cohorts with genomic profiling were used to identify ERBB2-amplified cases [Dana-Farber, n = 47/2,729 (1.7%); FMI, n = 1857/49,839 (3.7%)]. Outcomes of patients receiving HER2-directed therapies are reported (Dana-Farber, n = 9; Flatiron Health-Foundation Medicine clinicogenomic database, FH-FMI CGDB, n = 38). Multisite HER2 IHC and genomic profiling were performed to understand HER2 intratumoral and interlesional heterogeneity. The impact of concurrent RAS comutations on the effectiveness of HER2-directed therapies were studied in isogenic colorectal cancer cell lines and xenografts.

Results:

ERBB2 amplifications are enriched in left-sided colorectal cancer. Twenty percent of ERBB2-amplified colorectal cancers have co-occurring oncogenic RAS/RAF alterations. While RAS/RAF WT colorectal cancers typically have clonal ERBB2 amplification, colorectal cancers with co-occurring RAS/RAF alterations have lower level ERRB2 amplification, higher intratumoral heterogeneity, and interlesional ERBB2 discordance. These distinct genomic patterns lead to differential responsiveness and patterns of resistance to HER2-directed therapy. ERBB2-amplified colorectal cancer with RAS/RAF alterations are resistant to trastuzumab-based combinations, such as trastuzumab/tucatinib, but retain sensitivity to trastuzumab deruxtecan in in vitro and murine models. Trastuzumab deruxtecan shows clinical efficacy in cases with high-level ERBB2-amplified RAS/RAF coaltered colorectal cancer.

Conclusions:

Co-occurring RAS/RAF alterations define a unique subtype of ERBB2-amplified colorectal cancer that has increased intratumoral heterogeneity, interlesional discordance, and resistance to trastuzumab-based combinations. Further examination of trastuzumab deruxtecan in this previously understudied cohort of ERBB2-amplified colorectal cancer is warranted.
TABLE 2 from Phase I Study of mTORC1/2 Inhibitor Sapanisertib (CB-228/TAK-228) in Combination with Metformin in Patients with mTOR/AKT/PI3K Pathway Alterations and Advanced Solid Malignancies
Authors: Subbiah Vivek , Coleman Niamh , Piha-Paul Sarina A. , Tsimberidou Apostolia M. , Janku Filip , Rodon Jordi , Pant Shubham , Dumbrava Ecaterina E. Ileana , Fu Siqing , Hong David S. , Zhang Shizhen , Sun Ming , Jiang Yunfang , Roszik Jason , Song Juhee , Yuan Ying , Meric-Bernstam Funda , Naing Aung
Published: February 2024

Tumor response according to RECIST v1.1 (investigator assessment) in response-evaluable patients
Table S6 from Single-cell Multiomics Analysis of Myelodysplastic Syndromes and Clinical Response to Hypomethylating Therapy
Authors: Campillo-Marcos Ignacio , Casado-Pelaez Marta , Davalos Veronica , Ferrer Gerardo , Mata Caterina , Mereu Elisabetta , Roué Gael , Valcárcel David , Molero Antonieta , Zamora Lurdes , Xicoy Blanca , Palomo Laura , Acha Pamela , Manzanares Ana , Tobiasson Magnus , Hellström-Lindberg Eva , Solé Francesc , Esteller Manel
Published: February 2024

Karyotype and mutations (bulk NGS and single-cell DNAseq) at diagnosis for the studied MDS cases
Table S5 from Single-cell Multiomics Analysis of Myelodysplastic Syndromes and Clinical Response to Hypomethylating Therapy
Authors: Campillo-Marcos Ignacio , Casado-Pelaez Marta , Davalos Veronica , Ferrer Gerardo , Mata Caterina , Mereu Elisabetta , Roué Gael , Valcárcel David , Molero Antonieta , Zamora Lurdes , Xicoy Blanca , Palomo Laura , Acha Pamela , Manzanares Ana , Tobiasson Magnus , Hellström-Lindberg Eva , Solé Francesc , Esteller Manel
Published: February 2024

Fisher exact test for each mutated gene, comparing responders vs. non-responders at diagnosis
Figure S5 from Single-cell Multiomics Analysis of Myelodysplastic Syndromes and Clinical Response to Hypomethylating Therapy
Authors: Campillo-Marcos Ignacio , Casado-Pelaez Marta , Davalos Veronica , Ferrer Gerardo , Mata Caterina , Mereu Elisabetta , Roué Gael , Valcárcel David , Molero Antonieta , Zamora Lurdes , Xicoy Blanca , Palomo Laura , Acha Pamela , Manzanares Ana , Tobiasson Magnus , Hellström-Lindberg Eva , Solé Francesc , Esteller Manel
Published: February 2024

Impact of AZA treatment on cell populations according to response status
Data from Single-cell Multiomics Analysis of Myelodysplastic Syndromes and Clinical Response to Hypomethylating Therapy
Authors: Campillo-Marcos Ignacio , Casado-Pelaez Marta , Davalos Veronica , Ferrer Gerardo , Mata Caterina , Mereu Elisabetta , Roué Gael , Valcárcel David , Molero Antonieta , Zamora Lurdes , Xicoy Blanca , Palomo Laura , Acha Pamela , Manzanares Ana , Tobiasson Magnus , Hellström-Lindberg Eva , Solé Francesc , Esteller Manel
Published: February 2024

Abstract
Alterations in epigenetic marks, such as DNA methylation, represent a hallmark of cancer that has been successfully exploited for therapy in myeloid malignancies. Hypomethylating agents (HMA), such as azacitidine, have become standard-of-care therapy to treat myelodysplastic syndromes (MDS), myeloid neoplasms that can evolve into acute myeloid leukemia. However, our capacity to identify who will respond to HMAs, and the duration of response, remains limited. To shed light on this question, we have leveraged the unprecedented analytic power of single-cell technologies to simultaneously map the genome and immunoproteome of MDS samples throughout clinical evolution. We were able to chart the architecture and evolution of molecular clones in precious paired bone marrow MDS samples at diagnosis and posttreatment to show that a combined imbalance of specific cell lineages with diverse mutational profiles is associated with the clinical response of patients with MDS to hypomethylating therapy.
Significance:
MDS are myeloid clonal hemopathies with a low 5-year survival rate, and approximately half of the cases do not respond to standard HMA therapy. Our innovative single-cell multiomics approach offers valuable biological insights and potential biomarkers associated with the demethylating agent efficacy. It also identifies vulnerabilities that can be targeted using personalized combinations of small drugs and antibodies.
Low-dose Paclitaxel with Pembrolizumab Enhances Clinical and Immunologic Responses in Platinum-refractory Urothelial Carcinoma
Authors: Bitting Rhonda L. , Tooze Janet A. , Goodman Michael , Vile Donald C. , Brown Jessica M. , Thomas Christopher Y. , Neve Morgan , Kooshki Mitra , Addo Safoa , Triozzi Pierre L. , Dubey Purnima
Published: February 2024

Purpose:

Single-agent checkpoint inhibition is effective in a minority of patients with platinum-refractory urothelial carcinoma; therefore, the efficacy of combining low-dose paclitaxel with pembrolizumab was tested.

Materials and Methods:

This was a prospective, single-arm phase II trial with key inclusion criteria of imaging progression within 12 months of platinum therapy and Eastern Cooperative Oncology Group ≤1. Treatment was pembrolizumab 200 mg day 1 and paclitaxel 80 mg/m2 days 1 and 8 of a 21-day cycle for up to eight cycles unless progression or unacceptable adverse events (AE). The primary endpoint was overall response rate (ORR) with overall survival (OS), 6-month progression-free survival (PFS), and safety as key secondary endpoints. Change in circulating immune cell populations, plasma, and urinary miRs were evaluated.

Results:

Twenty-seven patients were treated between April 2016 and June 2020, with median follow-up of 12.4 months. Baseline median age was 68 years, with 81% men and 78% non-Hispanic White. ORR was 33% by intention to treat and 36% in imaging-evaluable patients with three complete responses. Six-month PFS rate was 48.1% [95% confidence interval (CI): 28.7–65.2] and median OS 12.4 months (95% CI: 8.7 months to not reached). Common ≥ grade 2 possibly-related AEs were anemia, lymphopenia, hyperglycemia, and fatigue; grade 3/4 AEs occurred in 56%, including two immune-mediated AEs (pneumonitis and nephritis). Responding patients had a higher percentage of circulating CD4+IFNγ+ T cells. Levels of some miRs, including plasma miR 181 and miR 223, varied in responders compared with nonresponders.

Conclusions:

The addition of low-dose paclitaxel to pembrolizumab is active and safe in platinum-refractory urothelial carcinoma.

Significance:

We found that combining pembrolizumab with low-dose paclitaxel may be effective in patients with urothelial carcinoma progressing on platinum chemotherapy, with favorable safety profiles.