bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased pediatric RSV case counts following the emergence of SARS-CoV-2 are attributable to increased testing
Authors: Petros Brittany A. , Milliren Carly E. , Sabeti Pardis C. , Ozonoff Al
Published: February 2024

Background

The incidence of respiratory syncytial virus (RSV) dropped markedly early in the COVID-19 pandemic, followed by a resurgence with heightened case counts. The “immunity debt” hypothesis proposes that the RSV-naive pediatric population increased during the period of low transmission, resulting in a subsequent increased risk of infection. However, the evidence supporting this hypothesis is limited, and no studies have comprehensively evaluated the role of changing respiratory viral testing practices in the perceived surge.

Methods

We conducted a multicenter, retrospective analysis of 342,530 RSV encounters and 980,546 RSV diagnostic tests occurring at 32 United States pediatric hospitals between 2013 and 2023. We used interrupted time series analysis to estimate pandemic-associated changes in RSV patient and testing volume, and to quantify changes in the proportions of patients admitted from the emergency department (ED), admitted to the intensive care unit (ICU), and receiving mechanical ventilation. We quantified the fraction of the observed shifts in case counts and in the age of diagnosed patients attributable to changes in RSV testing practices. Finally, we analyzed 524,404 influenza virus encounters and 1,768,526 influenza diagnostic tests to address the specificity of the findings to RSV.

Findings

RSV patient volume increased 2.4-fold (95% CI: 1.7, 3.5) in 2021-2023 relative to the pre-pandemic phase, and was accompanied by an 18.9-fold increase (95% CI: 15.0, 23.9) in RSV test volume. Over two-thirds of the apparent shifts in patient volume and in patient age were attributable to increased testing, which was concentrated among older pediatric patients. The proportions of patients with RSV requiring hospitalization, intensive care, or mechanical ventilation declined significantly across all patient age groups. These declines were not observed for patients with influenza virus.

Interpretation

A surge in RSV testing, rather than in viral circulation, likely underlies the increased case counts observed in 2021-2023. We identify expected consequences of increased testing, including the diagnosis of less severe cases and a shift in the patient age distribution. These findings warrant a critical assessment of the immunity debt hypothesis, while highlighting the importance of considering the testing denominator when surveillance strategies are dynamic.

Funding

National Institutes of Health & Howard Hughes Medical Institute
Genomic context-dependent histone H3K36 methylation by threeDrosophilamethyltransferases and implications for dedicated chromatin readers
Authors: Jayakrishnan Muhunden , Havlová Magdalena , Veverka Václav , Regnard Catherine , Becker Peter B.
Published: February 2024

Methylation of histone H3 at lysine 36 (H3K36me3) marks active chromatin. The mark is interpreted by epigenetic readers that assist transcription and safeguard the integrity of the chromatin fiber.

The chromodomain protein MSL3 binds H3K36me3 to target X-chromosomal genes in maleDrosophilafor dosage compensation. The PWWP-domain protein JASPer recruits the JIL1 kinase to active chromatin on all chromosomes. Unexpectedly, depletion of K36me3 had variable, locus-specific effects on the interactions of those readers. This observation motivated a systematic and comprehensive study of K36 methylation in a defined cellular model.

Contrasting prevailing models, we found that K36me1, K36me2 and K36me3 each represent independent chromatin states. A gene-centric view of the changing K36 methylation landscape upon depletion of the three methyltransferases Set2, NSD and Ash1 revealed local, context-specific methylation signatures. Set2 catalyzes K36me3 predominantly at transcriptionally active euchromatin. NSD places K36me2/3 at defined loci within pericentric heterochromatin and on weakly transcribed euchromatic genes. Ash1 deposits K36me1 at regions with enhancer signatures.

The genome-wide mapping of MSL3 and JASPer suggested that they bind K36me2 in addition to K36me3, which was confirmed by direct affinity measurement. This dual specificity attracts the readers to a broader range of chromosomal locations and increases the robustness of their actions.
Cellular coordination underpins rapid reversals in gliding filamentous cyanobacteria and its loss results in plectonemes
Authors: Rosko Jerko , Cremin Kelsey , Locatelli Emanuele , Coates Mary , Duxbury Sarah J. N. , Randall Kieran , Croft Katie , Valeriani Chantal , Polin Marco , Soyer Orkun S.
Published: February 2024

Cyanobacteria are key contributors to biogeochemical cycles through photosynthesis and carbon fixation. In filamentous, multicellular cyanobacteria these functions can be influenced through gliding motility, which enables filaments to localise in response to light and also form aggregates. Here, we use the aggregate forming speciesFluctiforma draycotensisto study gliding motility dynamics in detail. We find that filaments move in curved and straight trajectories interspersed with re-orientation or reversal of direction. Most reversals take few seconds but some take substantially longer, resulting in a long-tailed distribution of stoppage times. Mean filament speeds range around a micron per second with a relatively uniform distribution against filament length, implying that all or fixed proportion of cells in a filament contribute to movement. We implement a biophysical model that can recapitulate these findings. Model simulations show that for filaments to reverse quickly, cells in a filament must achieve high coordination of the direction of the forces that they generate. To seek experimental support of this prediction, we track individual cells in a filament. This reveals that cells’ translational movement is fully coupled with their rotation along the long-axis of the filament, and that cellular movement remains coordinated throughout a reversal. For some filaments, especially longer ones, however, we also find that cellular coordination can be lost, and filaments can form buckles that can twist around themselves, resulting in plectonemes. The experimental findings and the biophysical model presented here will inform future studies of individual and collective filament movement.

Significance Statement

Cyanobacteria contribute to global oxygen production and carbon capture. Some cyanobacteria exist as multicellular filaments and display gliding motility that allows them to respond to light and to form aggregates, which influences their biological functions. Here, we study the dynamics of gliding motility. We find that filaments’ movement is interspersed with re-orientation or reversal of direction and that mean filament speed is mostly independent of filament length. We implement a biophysical model that predicts these features to relate to cells in a filament having high coordination of the direction of the forces that they generate. We find experimental support for this predicted cellular coordination, but also discover instances of longer filaments loosing coordination, resulting in buckling and entangling with other filaments.
Multi-GeV wakefield acceleration in a plasma-modulated plasma accelerator
Authors: van de Wetering J. J. , Hooker S. M. , Walczak R.
Published: February 2024

We investigate the accelerator stage of a plasma-modulated plasma accelerator (P-MoPA) [Jakobsson , ] using both the paraxial wave equation and particle-in-cell (PIC) simulations. We show that adjusting the laser and plasma parameters of the modulator stage of a P-MoPA allows the temporal profile of pulses within the pulse train to be controlled, which in turn allows the wake amplitude in the accelerator stage to be as much as 72% larger than that generated by a plasma beat-wave accelerator with the same total drive laser energy. Our analysis shows that Rosenbluth-Liu detuning is unimportant in a P-MoPA if the number of pulses in the train is less than ∼30, and that this detuning is also partially counteracted by increased red-shifting, and hence increased pulse spacing, towards the back of the train. An analysis of transverse mode oscillations of the driving pulse train is found to be in good agreement with 2D (Cartesian) PIC simulations. PIC simulations demonstrating energy gains of ∼1.5GeV (∼2.5GeV) for drive pulse energies of 2.4J (5.0J) are presented. Our results suggest that P-MoPAs driven by few-joule, picosecond pulses, such as those provided by high-repetition-rate thin-disk lasers, could accelerate electron bunches to multi-GeV energies at pulse repetition rates in the kilohertz range.

Published by the American Physical Society
2024
An empirically validated framework for investigating the perception of density
Authors: Patil Madhavi Prashant , Romice Ombretta
Published: February 2024

Purpose

In urban studies, understanding how individuals perceive density is a complex challenge due to the subjective nature of this perception, which is influenced by sociocultural, personal and environmental factors. This study addresses these complexities by proposing a systematic framework for comprehending how people perceive density within urban contexts.

Design/methodology/approach

The methodology for developing the framework involved a systematic review of existing literature on the perception of density and related concepts, followed by integrating insights from empirical investigations. The framework designed through this process overcomes the limitations identified in previous research and provides a comprehensive guide for studying perceived density in urban environments.

Findings

The successful application of the framework on case studies in Glasgow and international settings enabled the identification of 20 critical spatial factors (buildings, public realm and urban massing) influencing density perception. The research provided insights into the subjective nature of density perception and the impact that spatial characters of urban form play, demonstrating the framework's effectiveness in understanding the impact of urban form, which is the realm of design and planning professions, on individual experiences.

Originality/value

The paper's originality lies in its comprehensive synthesis of the existing knowledge on the perception of density, the development of a user-responsive framework adaptable to future research and its application in case studies of different natures to identify recurrent links between urban form and user-specific constructs.
How important is a high-performance work system to improve branch-level performance?
Authors: Riaz Amir , Mahmood Zahid , Qammar Ahmad , Ali Imran
Published: February 2024

Purpose

This study aims to propose and empirically examine the simultaneous complementary mediating role of bank branch collective human capital and justice climate between implemented high-performance work system (HPWS) and bank branch performance in the banking sector.

Design/methodology/approach

Data were collected at three different intervals of time between March 2022 to July 2022 from a final sample of 323 branch managers and 1,369 employees of commercial banks operating in Pakistan. Partial least square structural equation modeling was used to test the theoretical model proposed by this study.

Findings

Study results revealed that collective human capital and justice climate simultaneously mediate the relationship between implemented HPWS and branch performance.

Research limitations/implications

The study contributes to the strategic HRM theory by proposing the complementary mediating roles of human capital and organizational justice to reap the benefits of implementing HPWS for improving branch-level performance. The managers should focus on developing and exploiting the knowledge, skills and experiences (human capital) of branch employees and improve their collective perceptions of justice to reap the benefits of HPWS for enhancing branch-level performance.

Originality/value

Drawing upon the resource-based view of the firm and organizational justice theory, this novel study examines the simultaneous and complementary mediating effects of collective human capital and justice climate between implemented HPWS and branch performance relationships at the branch-level analysis.
Flying responsibly: effects of perceived corporate social responsibility on attitudes and behaviors of employees in the European aviation industry
Authors: Athanasiadou Chrisalena , Theriou Georgios , Chatzoudes Dimitrios
Published: February 2024

Purpose

This study aims to examine how corporate social responsibility (CSR) affected the attitudes and behaviors of employees in the European aviation industry amidst the COVID-19 pandemic and to explore any moderating effect of empathetic leadership.

Design/methodology/approach

Based on the social identity and social exchange theories, a research model was developed and tested against empirical data collected from employees of the European aviation industry, in 2021. Structural equation modeling and regression analyses were used for testing the hypothesized causal relationships.

Findings

Perceived CSR is directly related to work engagement and indirectly associated with work engagement and job insecurity via organizational pride. The presence of an empathetic leader does not intensify the effects of perceptions of CSR on organizational pride. Work engagement, in turn, impacts organizational citizenship behavior, while no such effect of job insecurity is supported.

Originality/value

This study provides insight into the underlying mechanisms via which CSR affects employees during a crisis. It, also, has significant implications on human resources management within the industries severely affected by the pandemic.
Restorative justice in safeguarding adults with hate crime and discriminatory abuse: exploring the evidence
Authors: Mason Karl , Dray Rosslyn , Healy Jane C. , Wells Joanna
Published: February 2024

Purpose

The purpose of this paper is to consider what safeguarding responses to discriminatory abuse and hate crime might learn from existing research on restorative justice and to drive practice development based on available evidence.

Design/methodology/approach

This paper is based on a scoping review of literature using four academic databases and reference harvesting. This comprised a critical appraisal of 30 articles, which were thematically analysed to appreciate the benefits and challenges of restorative justice responses to hate crime and how this might inform safeguarding responses to discriminatory abuse and hate crime.

Findings

The analysis identifies four domains where learning can be drawn. These relate to theory on restorative justice; restorative justice practices; perspectives from lived experience of restorative justice and hate crime; and an appraisal of critiques about restorative justice.

Originality/value

This paper connects the emerging evidence on restorative criminal justice responses to hate crime to the “turn” towards strengths-based practices in adult safeguarding. Although this provides a fertile environment for embedding restorative practices, the authors argue certain precautions are required based on evidence from existing research on hate crime and restorative justice.
The impact of the US stock market on the BRICS and G7: a GVAR approach
Authors: Attílio Luccas Assis , Faria Joao Ricardo , Prado Mauricio
Published: February 2024

Purpose

The authors investigate the impact of the US stock market on the economies of the BRICS and major industrialized economies (G7).

Design/methodology/approach

The authors construct the world economy and the vulnerability between economies using three economic integration variables: bilateral trade, bilateral direct investment and bilateral equity positions. Global vector autoregressive (GVAR) empirical studies usually adopt trade integration to estimate models. The authors complement these studies by using bilateral financial flows.

Findings

The authors summarize the results in four points: (1) financial integration variables increase the effect of the US stock market on the BRICS and G7, (2) the US shock produces similar responses in these groups regarding industrial production, stock markets and confidence but different responses regarding domestic currencies: in the BRICS, the authors detect appreciation of the currencies, while in the G7, the authors find depreciation, (3) G7 stock markets and policy rates are more sensitive to the US shock than the BRICS and (4) the estimates point out to heterogeneities such as the importance of industrial production to the transmission shock in Japan and China, the exchange rate to India, Japan and the UK, the interest rates to the Eurozone and the UK and confidence to Brazil, South Africa and Canada.

Research limitations/implications

The results reinforce the importance of taking into account different levels of economic development.

Originality/value

The authors construct the world economy and the vulnerability between economies using three economic integration variables: bilateral trade, bilateral direct investment and bilateral equity positions. GVAR empirical studies usually adopt trade integration to estimate models. The authors complement these studies by using bilateral financial flows.
Impact of non thermal techniques on millets
Authors: Kaur Chinkle , Kaur Jasleen
Published: February 2024

Purpose

Millets are ancient grains, following wheat, that have been a fundamental source of human sustenance. These are nutrient-rich small-seeded grains that have gained prominence and admiration globally due to their super resilience in diverse climates and significant nutritional benefits. As millets are renowned for their nutritional richness, the demand for millet-based products increases. Hence, this paper aims in identifying the growing need for innovative processing techniques that not only preserve their nutritional content but also extend their shelf life.

Design/methodology/approach

In traditional times, heat was the only means of cooking and processing of the foods, but the amount of damage they used to cause to the sensorial and nutritional properties was huge. Millets’ sensitivity toward heat poses a challenge, as their composition is susceptible to disruption during various heat treatments and manufacturing processes. To cater to this drawback while ensuring the prolonged shelf life and nutrient preservation, various innovative approaches such as cold plasma, infrared technology and high hydrostatic pressure (HPP) processing are being widely used. These new methodologies aim on inactivating the microorganisms that have been developed within the food, providing the unprocessed, raw and natural form of nutrients in food products.

Findings

Among these approaches, nonthermal technology has emerged as a key player that prioritizes brief treatment periods and avoids the use of high temperatures. Nonthermal techniques (cold plasma, infrared radiation, HPP processing, ultra-sonication and pulsed electric field) facilitate the conservation of millet’s nutritional integrity by minimizing the degradation of heat-sensitive nutrients like vitamins and antioxidants. Acknowledging the potential applications and processing efficiency of nonthermal techniques, the food industry has embarked on substantial investments in this technology. The present study provides an in-depth exploration of the array of nonthermal technologies used in the food industry and their effects on the physical and chemical composition of diverse millet varieties.

Originality/value

Nonthermal techniques, compared to conventional thermal methods, are environmentally sound processes that contribute to energy conservation. However, these conveniences are accompanied by challenges, and this review not only elucidates these challenges but also focuses on the future implications of nonthermal techniques.
How grumpy cat helped students learn management concepts
Authors: Julien Mark , Stratton Micheal , Schmidt Gordon B. , Clayton Russell
Published: February 2024

Purpose

Management educators often seek out innovative ways to introduce theories and concepts in such a way that students are more engaged and connected with the course material. A meme is an image juxtaposed with short text that elicits emotional responses from its readers and is now a staple in social media. Examples include: grumpy cat, success kid and distracted boyfriend. The authors have successfully used memes both online and in-person as a teaching tool. This paper aims to describe how the authors have used memes and some of the best practices and lessons learned from this experience.

Design/methodology/approach

Students in a training and development undergraduate course and an organizational behavior MBA course were tasked with creating and presenting memes that reflected the subject matter in their respective courses.

Findings

Their fellow students were successful in identifying the course theory or concept when these student presenters presented their memes in class. This suggests that this type of activity is helpful for students to apply a key course concept or theory in a way that was fun and interactive. Follow-up feedback from the students indicated that they enjoyed this type of activity and felt that it aided in their retention of course material.

Originality/value

While memes are quite popular in social media, there is a paucity of academic articles on the application of memes for teaching management concepts. This article guides instructors on how the authors have used memes in the classroom and offers some suggestions for doing a debrief afterward.
Perspectives on gender diversity in the Australian valuation industry: experiences and insights from management and senior leadership
Authors: Callanan Judith , Leshinsky Rebecca , Halvitigala Dulani , Amponsah Effah
Published: February 2024

Purpose

This paper examines gender diversity in the Australian valuation industry from the perspective of valuers in senior management and leadership roles and discusses gender diversity policies and practices in their organisations. Then, it explores the initiatives that can be implemented to improve gender diversity in the Australian valuation industry.

Design/methodology/approach

A focus group discussion was conducted with valuers in senior management and leadership roles from selected large valuation firms and government valuation agencies in Melbourne, Australia. Data collected through the focus group discussion was combined with secondary data sourced from journals, online articles and archival materials.

Findings

The findings reveal that whilst gender diversity in the Australian valuation industry has improved over the years, females remain underrepresented. Nonetheless, whilst some valuation companies have recognised the need to address the underrepresentation of women and introduced specific gender-focussed human resource policies and practices, these initiatives are not streamlined and implemented across the industry.

Research limitations/implications

The study highlights the need for closer collaboration between key stakeholders such as universities, professional associations, valuation companies and government agencies in devising strategies to attract female talents into the valuation industry.

Originality/value

The paper is the first empirical study to assess gender diversity in the Australian valuation industry from the perspective of valuers in management and leadership roles. The proposed policies can inform future initiatives to improve gender diversity in the valuation industry.
Creating a Framework for Virtual Reality Learning Environment (VRLE) for Studio-Based Learning
Authors: Mike Choong Wai Keng , Mohamad Yatim Maizatul Hayati , Saad Noorhayati
Published: February 2024

Higher education academics are lacking the knowledge on how to implement Design Thinking (DT) for transdisciplinary design studies that would produce Fourth Industrial Revolution Workforce Skills (4IRSkills), due to the sparsity in literature and implementation guidelines. This article discusses on the creation process of a Teaching and Learning Framework (TLF) for transdisciplinary design studies with a desktop-based Virtual Reality Learning Environment (VRLE) simulation of studio-based learning. The framework was created using a Selander’s Learning Design Sequence (LDS) with DT approach. The LDS helped the researcher to understand the processes of teaching and learning, especially on the affordances of various modes. The DT approach was used to facilitate the process of solving problems through the practice of empathy, reframing, prototyping, experimentation, testing, and redesign. A sequential explanatory mixed method was used, and the data were analyzed through inferential statistical analysis, thematic analysis and convergent coding matrix triangulation protocol. The findings indicated that the TLF with VRLE showed a positive and significant relationship with students' achievement of 4IRSkills. The TLF Design Process and Collaborative Design variables were positively correlated with students' 4IRSkills, while there was no correlation for the VRLE Representational Fidelity and Learner Interaction variables. In conclusion, the TLF with VRLE proves to be an effective and suitable method for guiding the implementation of pedagogies that teaches 4IRSkills at the tertiary level in fully online learning environments.
Research on Automotive Seat Heating Strategy Based on Objective Thermal Comfort Evaluation
Authors: Wang Shuang , Ren Siyuan
Published: February 2024

Seat heating is an essential means to improve cabin occupant thermal comfort. How to set a reasonable seat heating strategy is very important to improve occupant thermal comfort and reduce vehicle energy consumption. Based on objective thermal comfort evaluation criteria, this paper analyzes three strategies: fixed heating power, fixed seat surface temperature, and intermittent seat heating. It explores the occupant thermal comfort characteristics under different strategies. It is found that the optimum heating power or optimum seat surface temperature to maintain occupant thermal comfort varies with the initial seat temperature. Compared with the two strategies of fixed heating power and fixed seat surface temperature, the intermittent seat heating proposed in this paper can make the human body reach the optimal state of comfort in a shorter period, and the power consumption is less as the seat heating is opened for a longer time. This intermittent seat heating strategy not only adapts to different low-temperature environments outside but also provides sufficient safety guarantees while improving human thermal comfort. It can provide some references for the design of car seat heating and research on passenger cabin thermal comfort.
Design of Self-Organizing Systems Using Multi-Agent Reinforcement Learning and the Compromise Decision Support Problem Construct
Authors: Jiang Mingfei , Ming Zhenjun , Li Chuanhao , Allen Janet K. , Mistree Farrokh
Published: February 2024

In this paper, we address the following question: How can multi-robot self-organizing systems be designed so that they show the desired behavior and are able to perform tasks specified by the designers? Multi-robot self-organizing systems, e.g., swarm robots, have great potential for adapting when performing complex tasks in a changing environment. However, such systems are difficult to design due to the stochasticity of system performance and the non-linearity between the local actions/interaction and the desired global behavior. In order to address this, in this paper, we propose a framework for designing self-organizing systems using Multi-Agent Reinforcement Learning (MARL) and the compromise Decision-Support Problem (cDSP) construct. The proposed framework consists of two stages, namely, preliminary design followed by design improvement. In the preliminary design stage, MARL is used to help designers train the robots so that they show stable group behavior for performing the task. In the design improvement stage, the cDSP construct is used to explore the design space and identify satisfactory solutions considering several performance indicators. Surrogate models are used to map the relationship between local parameters and global performance indicators utilizing the data generated in the preliminary design. These surrogate models represent the goals of the cDSP. Our focus in this paper is to describe the framework. A multi-robot box-pushing problem is used as an example to test the framework’s efficacy. This framework is general and can be extended to design other multi-robot self-organizing systems.
Tracking Flying Targets and Measurements of Their Surface Temperature using High Speed Infrared Imaging.
Authors: Tombet Stephane Boubanga , Marcotte Frederick , Morton Vince
Published: February 2024

Measurements of the flying target’s dynamic parameters is of growing interest for space scientists and army researchers. As flying target velocities increase, the study of heat exchange dynamics between the projectile and its environment is one of the indexes for assessing the performances of materials for the fabrication of bombs and cannons, as well as thermal protection systems used by planetary-entry and Earth-return missions. One of the challenges in ballistic heat transfer studies is the measurements of projectile surface temperature. Temperature is one of the critical parameters used in the design of projectile materials and shapes. While there are a significant number of numerical codes which predict projectile surface temperatures for a variety of conditions, relatively little experimental data has been produced for the purpose of verifying these numerical predictions. In this work, a Telops infrared camera mounted to a trajectory tracker was used to track a space re-entry probe at supersonic velocities and measure its in-flight heat transfer with the surrounding atmosphere. Physical phenomena such as shock waves were successfully captured by the IR camera and the interaction between the probe and the shock waves was studied. The unique features of Telops IR cameras make them well-suited investigation tools to bring ballistic tracking and research to the next level.
Articulating Hypervelocity Linear Accelerator Structure (Atlas) for Planetary Impact Science
Authors: Morton Joseph , Barnouin Olivier , Cooper Scott , Lamberson Leslie , Daly R. Terik
Published: February 2024

Hypervelocity impact cratering by asteroids and comets is one of the most common geological processes in the solar system. Investigations of the cratering process can be used to characterize the physical attributes of planetary surfaces and interiors, and to understand solar system evolution. Fundamental parameters including density, mass, and macro-porosity can dramatically affect a surface’s response to impact, consequently affecting the understanding of its evolution and history. Further, most natural impact events are oblique and can occur at a wide range of velocities, ranging from m/s for re-impacting crater ejecta, to 10s of km/s for asteroids and comets on terrestrial planets. As a result, laboratory experiments are a critical tool for investigating planetary impact cratering. Impact experiments can readily use rubble-pile and granular-media targets, which are difficult to model numerically, span a range of impact angles, and access hypervelocities. A new alternative design has been developed for conducting hypervelocity impact experiments for planetary impact science, using an Articulating hypervelociTy Linear Accelerator Structure (ATLAS). This design provides a concise solution for the investigation of a broader range of parameters on planetary bodies in hypervelocity impact research. Impact experiments require a relatively environment-free target chamber with little to no interference from combustion contaminants or sub-system gases associated with the accelerator. To address these needs, we present a combustionfree, two-stage light-gas-gun facility and articulating substructure that will be retrofitted to an existing linear singlestage accelerator housed at the Planetary Impact Laboratory at the Johns Hopkins University Applied Physics Laboratory [1].
Powder diet exacerbates oropharyngeal candidiasis in a mouse model
Authors: Vazquez-Munoz Roberto , Thompson Angela , Sobue Takanori , Dongari-Bagtzoglou Anna
Published: February 2024

Oropharyngeal candidiasis (OPC) is a multifactorial disease and a significant health concern. We found that the physical form of the diet plays a critical role in the severity and progression of OPC. We developed a modified cortisone OPC murine model that facilitates studies investigating pathogenesis and recovery processes.
Serovar-level identification of bacterial foodborne pathogens from full-length 16S rRNA gene sequencing
Authors: Grinevich Dmitry , Harden Lyndy , Thakur Siddhartha , Callahan Benjamin
Published: February 2024

The resolution of variation within species is critical for interpreting and acting on many microbial measurements. In the key foodborne pathogens
Salmonella
and
Escherichia coli
, the primary subspecies classification scheme used is serotyping: differentiating variants within these species by surface antigen profiles. Serotype prediction from whole-genome sequencing (WGS) of isolates is now seen as comparable or preferable to traditional laboratory methods where WGS is available. However, laboratory and WGS methods depend on an isolation step that is time-consuming and incompletely represents the sample when multiple strains are present. Community sequencing approaches that skip the isolation step are, therefore, of interest for pathogen surveillance. Here, we evaluated the viability of amplicon sequencing of the full-length 16S rRNA gene for serotyping
Salmonella enterica
and
E. coli
. We developed a novel algorithm for serotype prediction, implemented as an R package (Seroplacer), which takes as input full-length 16S rRNA gene sequences and outputs serovar predictions after phylogenetic placement into a reference phylogeny. We achieved over 89% accuracy in predicting
Salmonella
serotypes on
in silico
test data and identified key pathogenic serovars of
Salmonella
and
E. coli
in isolate and environmental test samples. Although serotype prediction from 16S rRNA gene sequences is not as accurate as serotype prediction from WGS of isolates, the potential to identify dangerous serovars directly from amplicon sequencing of environmental samples is intriguing for pathogen surveillance. The capabilities developed here are also broadly relevant to other applications where intraspecies variation and direct sequencing from environmental samples could be valuable.

IMPORTANCE

In order to prevent and stop outbreaks of foodborne pathogens, it is important that we can detect when pathogenic bacteria are present in a food or food-associated site and identify connections between specific pathogenic bacteria present in different samples. In this work, we develop a new computational technology that allows the important foodborne pathogens
Escherichia coli
and
Salmonella enterica
to be serotyped (a subspecies level classification) from sequencing of a single-marker gene, and the 16S rRNA gene often used to surveil bacterial communities. Our results suggest current limitations to serotyping from 16S rRNA gene sequencing alone but set the stage for further progress that we consider likely given the rapid advance in the long-read sequencing technologies and genomic databases our work leverages. If this research direction succeeds, it could enable better detection of foodborne pathogens before they reach the public and speed the resolution of foodborne pathogen outbreaks.
Increased antibody titers but induced T cell AICD and apoptosis response in COVID-19 convalescents by inactivated vaccine booster
Authors: Zhao Jingmin , Zhang Han , Jiang Lina , Cheng Fang , Li Wei , Wang Zihao , Liu Hongyang , Li Shaohua , Jiang Yiyun , Li Meiling , Li Yan , Liu Shuhong , Fang Min , Zhou Xuyu , Ye Xin , Zhao Shousong , Zheng Yuxuan , Meng Songdong
Published: February 2024

It is urgently needed to evaluate the necessity and benefits of booster vaccination against the coronavirus 2 of the severe acute respiratory syndrome (SARS-CoV-2) Omicron to facilitate clinical decision-making for 2019 coronavirus disease (COVID-19) convalescents. We conducted a multicenter, prospective clinical trial (registration number: ChiCTR2100045810) in the first patients with COVID-19 from 28 January 2020 to 20 February 2020 to assess the long-term durability of neutralizing antibodies against live Omicron BA.5 and further assess the efficiency and safety of CoronaVac in the convalescent group. A total of 96 COVID-19 convalescents were enrolled in this study. Neutralizing antibody titers in convalescents were significantly reduced in 9–10 months. A dose-refreshing vaccination in 28 convalescents with an antibody titer below 96 significantly induced neutralizing antibodies against live Omicron by 4.84-fold. Meanwhile, the abundance of naive T cells increased dramatically, and T
EMRA
and T
EM
cells gradually decreased after vaccination. Activation-induced cell death and apoptosis-related genes were significantly elevated after vaccination in all T-cell subtypes. One-dose booster vaccination was effective in inducing a robust antibody response against SARS-CoV-2 Omicron in COVID-19 convalescents with low antibody titers. However, vaccine-mediated T-cell consumption and regeneration patterns may be detrimental to the antiviral response.

IMPORTANCE

The globally dominant coronavirus 2 of the severe acute respiratory syndrome (SARS-CoV-2) Omicron variant raises the possibility of repeat infections among 2019 coronavirus disease (COVID-19) convalescents with low neutralizing antibody titers. The importance of this multicenter study lies in its evaluation of the long-term durability of neutralizing antibodies in COVID-19 convalescents and the efficacy of a booster vaccination against the live Omicron. The findings suggest that a one-dose booster vaccination is effective in inducing a robust antibody response against SARS-CoV-2 Omicron in convalescents with low antibody titers. However, the study also highlights the potential detrimental effects on the antiviral response due to vaccine-mediated T-cell consumption and regeneration patterns. These results are crucial for facilitating clinical decision-making for COVID-19 convalescents and informing public health policies regarding booster vaccinations.
The potential of
Rhodobacter sphaeroides
extract as an alternative supplement for cell culture systems
Authors: Lee Subin , Kim Yang-Hoon , Min Jiho
Published: February 2024

It is essential to identify suitable supplements that enhance cell growth, viability, and functional development in cell culture systems. The use of fetal bovine serum (FBS) has been common, but it has limitations, such as batch-to-batch variability, ethical concerns, and risks of environmental contamination. In this study, we explore the potential of
Rhodobacter sphaeroides
extract, derived from a probiotic photosynthetic bacterium, as an alternative supplement. Our results demonstrate that the extract from
R. sphaeroides
significantly improves various aspects of cell behavior compared to serum-free conditions. It enhances cell growth and viability to a greater extent than FBS supplementation. Additionally, the extract alleviates oxidative stress by reducing intracellular levels of reactive oxygen species and stimulates lysosomal activity, contributing to cellular processes. The presence of abundant amino acids, glycine and arginine, in the extract may play a role in promoting cell growth. These findings emphasize the potential of
R. sphaeroides
extract as a valuable supplement for cell culture, offering advantages over the use of FBS.

IMPORTANCE

The choice of supplements for cell culture is crucial in biomedical research, but the widely used fetal bovine serum (FBS) has limitations in terms of variability, ethics, and environmental risks. This study explores the potential of an extract from
Rhodobacter sphaeroides
, a probiotic bacterium, as an alternative supplement. The findings reveal that the
R. sphaeroides
extract surpasses FBS in enhancing cell growth, viability, and functionality. It also mitigates oxidative stress and stimulates lysosomal activity, critical for cellular health. The extract’s abundance of glycine and arginine, amino acids with known growth-promoting effects, further highlights its potential. By providing a viable substitute for FBS, the
R. sphaeroides
extract addresses the need for consistent, ethical, and environmentally friendly cell culture supplements. This research paves the way for sustainable and reliable cell culture systems, revolutionizing biomedical research and applications in drug development and regenerative medicine.
Coordination of prophage and global regulator leads to high enterotoxin production in staphylococcal food poisoning-associated lineage
Authors: Sato'o Yusuke , Hisatsune Junzo , Aziz Fatkhanuddin , Tatsukawa Nobuyuki , Shibata-Nakagawa Mari , Ono Hisaya K. , Naito Ikunori , Omoe Katsuhiko , Sugai Motoyuki
Published: February 2024

Staphylococcus
species in food produce Staphylococcal enterotoxins (SEs) that cause Staphylococcal food poisoning (SFP). More than 20 SE types have been reported, among which Staphylococcal enterotoxin A (SEA) has been recognized as one of the most important SEs associated with SFP. However, the regulatory mechanisms underlying its production remain unclear. Previously, we identified a major SFP clone in Japan, CC81 subtype-1, which exhibits high SEA production. In this study, we attempted to identify the factors contributing to this phenomenon. Thus, we demonstrated that the attenuation of the activity of endogenous regulator, Staphylococcal accessory regulator S (SarS), and the lysogenization of a high SEA-producing phage contributed to this phenomenon in CC81 subtype-1. Furthermore, our results indicated that SarS could directly bind to the promoter upstream of the
sea
gene and suppress SEA expression; this low SarS repression activity was identified as one of the reasons for the high SEA production observed. Therefore, we revealed that both exogenous and endogenous factors may probably contribute to the high SEA production. Our results confirmed that SE production is a fundamental and critical factor in SFP and clarified the associated production mechanism while enhancing our understanding as to why a specific clone frequently causes SFP.

IMPORTANCE

The importance of this study lies in its unveiling of a molecular regulatory mechanism associated with the most important food poisoning toxin and the evolution of Staphylococcal food poisoning (SFP)-associated clone. SFP is primarily caused by
Staphylococcus aureus
, with Staphylococcal enterotoxin A (SEA) being commonly involved in many cases. Thus, SEA has been recognized as a major toxin type. However, despite almost a century since its discovery, the complete mechanism of SEA production is as yet unknown. In this study, we analyzed an SEA-producing SFP clone isolated in East Asia and discovered that this strain, besides acquiring the high SEA-producing phage, exhibits remarkably high SEA production due to the low activity of SarS, an intrinsic regulatory factor. This is the first report documenting the evolution of the SFP clone through the coordinated action of exogenous mobile genetic factors and endogenous regulators on this notorious toxin.
Regulation of Onecut2 by miR-9-5p in Japanese encephalitis virus infected neural stem/progenitor cells
Authors: Sharma Shivangi , Majumdar Atreye , Basu Anirban
Published: February 2024

Japanese encephalitis virus (JEV) is one of the major neurotropic viral infections that is known to dysregulate the homeostasis of neural stem/progenitor cells (NSPCs) and depletes the stem cell pool. NSPCs are multipotent stem cell population of the central nervous system (CNS) which are known to play an important role in the repair of the CNS during insults/injury caused by several factors such as ischemia, neurological disorders, CNS infections, and so on. Viruses have evolved to utilize host factors for their own benefit and during JEV infection, host factors, including the non-coding RNAs such as miRNAs, are reported to be affected, thereby cellular processes regulated by the miRNAs exhibit perturbed functionality. Previous studies from our laboratory have demonstrated the role of JEV infection in dysregulating the function of neural stem cells (NSCs) by altering the cell fate and depleting the stem cell pool leading to a decline in stem cell function in CNS repair mechanism post-infection. JEV-induced alteration in miRNA expression in the NSCs is one of the major interest to us. In prior studies, we have observed an altered expression pattern of certain miRNAs following JEV infection. In this study, we have validated the role of JEV infection in NSCs in altering the expression of miR-9-5p, which is a known regulator of neurogenesis in NSCs. Furthermore, we have validated the interaction of this miRNA with its target, Onecut2 (OC2), in primary NSCs utilizing miRNA mimic and inhibitor transfection experiments. Our findings indicate a possible role of JEV mediated dysregulated interaction between miR-9-5p and its putative target OC2 in NSPCs.

IMPORTANCE

MicroRNAs have emerged as key disease pathogenic markers and potential therapeutic targets. In this study, we solidify this concept by studying a key miRNA, miR-9-5p, in Japanese encephalitis virus infection of neural stem/progenitor cells. miRNA target Onecut2 has a possible role in stem cell pool biology. Here, we show a possible mechanistic axis worth investing in neurotropic viral biology.
A photocontrolled one-pot isothermal amplification and CRISPR-Cas12a assay for rapid detection of SARS-CoV-2 Omicron variants
Authors: Sun Qian , Lin Hongqing , Li Yuan , Yuan Liping , Li Baisheng , Ma Yunan , Wang Haiying , Deng Xiaoling , Chen Hongliang , Tang Shixing
Published: February 2024

CRISPR-Cas technology has widely been applied to detect single-nucleotide mutation and is considered as the next generation of molecular diagnostics. We previously reported the combination of nucleic acid amplification (NAA) and CRISPR-Cas12a system to distinguish major severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. However, the mixture of NAA and CRISPR-Cas12a reagents in one tube could interfere with the efficiency of NAA and CRISPR-Cas12a cleavage, which in turn affects the detection sensitivity. In the current study, we employed a novel photoactivated CRISPR-Cas12a strategy integrated with recombinase polymerase amplification (RPA) to develop one-pot RPA/CRISPR-Cas12a genotyping assay for detecting SARS-CoV-2 Omicron sub-lineages. The new system overcomes the potential inhibition of RPA due to early CRISPR-Cas12a activation and cleavage of the target template in traditional one-pot assay using photocleavable p-RNA, a complementary single-stranded RNA to specifically bind crRNA and precisely block Cas12a activation. The detection can be finished in one tube at 39℃ within 1 h and exhibits a low limit of detection of 30 copies per reaction. Our results demonstrated that the photocontrolled one-pot RPA/CRISPR-Cas12a assay could effectively identify three signature mutations in the spike gene of SARS-CoV-2 Omicron variant, namely, R346T, F486V, and 49X, and distinguish Omicron BA.1, BA.5.2, and BF.7 sub-lineages. Furthermore, the assay achieved a sensitivity of 97.3% and a specificity of 100.0% and showed a concordance of 98.3% with Sanger sequencing results.

IMPORTANCE

We successfully developed one-pot recombinase polymerase amplification/CRISPR-Cas12a genotyping assay by adapting photocontrolled CRISPR-Cas technology to optimize the conditions of nucleic acid amplification and CRISPR-Cas12a-mediated detection. This innovative approach was able to quickly distinguish severe acute respiratory syndrome coronavirus 2 Omicron variants and can be readily modified for detecting any nucleic acid mutations. The assay system demonstrates excellent clinical performance, including rapid detection, user-friendly operations, and minimized risk of contamination, which highlights its promising potential as a point-of-care testing for wide applications in resource-limiting settings.