bluuebunny/crossref_metadata_2025 huggingface dataset:
Metagenomic next-generation sequencing of cerebrospinal fluid for diagnosis of central nervous system infections: 7-year performance of a clinically validated test
Authors: Benoit Patrick , Brazer Noah , Kelly Emily , Servellita Venice , Oseguera Miriam , Nguyen Jenny , Tang Jack , de Lorenzi-Tognon Mikael , Omura Charles , Streithorst Jessica , Hillberg Melissa , Ingebrigtsen Danielle , Zorn Kelsey , Wilson Michael , Blicharz Tim , Wong Amy P. , O’Donovan Brian , Murray Brad , Miller Steve , Chiu Charles Y.
Published: March 2024

Studies have shown that metagenomic next-generation sequencing (mNGS) testing of cerebrospinal fluid (CSF) in central nervous system (CNS) infections can improve diagnostic yields and provide actionable information. We analyzed the results of all CSF mNGS tests (n=4,828) performed at the University of California, San Francisco (UCSF) clinical microbiology laboratory from June 2016 to April 2023. We also assessed clinical metadata from a subset of samples that corresponded to a cohort of UCSF patients (n=1,164) who received CSF mNGS testing, and retrospectively evaluated performance compared to conventional microbiologic testing and adjudicated clinical diagnosis. Overall, 14.4% of CSF mNGS tests were positive for any microorganism. DNA viruses (7% of all samples) were detected most often, followed by RNA viruses (4.3%), bacteria (2.7%), fungi (1.4%), and parasites (0.5%). Using a composite gold standard obtained from clinical adjudication and all microbiological test results, sensitivity, specificity, and accuracy of CSF mNGS in the UCSF cohort who had clinically diagnosed infections were 56.5%, 98.8%, and 90.5%, respectively. The sensitivity of CSF mNGS testing (56.5%) was statistically higher than that from all direct detection testing from CSF (44.8%, p = 0.004), direct detection testing from samples other than CSF (15.2%, p<0.001), and indirect serologic testing (34%, p<0.001). When only considering diagnoses made by direct detection of pathogens on CSF, sensitivity of mNGS was 80.7%. These results justify the incorporation of CSF mNGS testing as part of the routine diagnostic workup in hospitalized patients presenting with potential CNS infection.
Forecasting Acute Kidney Injury and Resource Utilization in ICU patients using longitudinal, multimodal models
Authors: Tan Yukun , Dede Merve , Mohanty Vakul , Dou Jinzhuang , Hill Holly , Bernstam Elmer , Chen Ken
Published: March 2024

Background

Advances in artificial intelligence (AI) have realized the potential of revolutionizing healthcare, such as predicting disease progression via longitudinal inspection of Electronic Health Records (EHRs) and lab tests from patients admitted to Intensive Care Units (ICU). Although substantial literature exists addressing broad subjects, including the prediction of mortality, length-of-stay, and readmission, studies focusing on forecasting Acute Kidney Injury (AKI), specifically dialysis anticipation like Continuous Renal Replacement Therapy (CRRT) are scarce. The technicality of how to implement AI remains elusive.

Objective

This study aims to elucidate the important factors and methods that are required to develop effective predictive models of AKI and CRRT for patients admitted to ICU, using EHRs in the Medical Information Mart for Intensive Care (MIMIC) database.

Methods

We conducted a comprehensive comparative analysis of established predictive models, considering both time-series measurements and clinical notes from MIMIC-IV databases. Subsequently, we proposed a novel multi-modal model which integrates embeddings of top-performing unimodal models, including Long Short-Term Memory (LSTM) and BioMedBERT, and leverages both unstructured clinical notes and structured time series measurements derived from EHRs to enable the early prediction of AKI and CRRT.

Results

Our multimodal model achieved a lead time of at least 12 hours ahead of clinical manifestation, with an Area Under the Receiver Operating Characteristic Curve (AUROC) of 0.888 for AKI and 0.997 for CRRT, as well as an Area Under the Precision Recall Curve (AUPRC) of 0.727 for AKI and 0.840 for CRRT, respectively, which significantly outperformed the baseline models. Additionally, we performed a SHapley Additive exPlanation (SHAP) analysis using the expected gradients algorithm, which highlighted important, previously underappreciated predictive features for AKI and CRRT.

Conclusion

Our study revealed the importance and the technicality of applying longitudinal, multimodal modeling to improve early prediction of AKI and CRRT, offering insights for timely interventions. The performance and interpretability of our model indicate its potential for further assessment towards clinical applications, to ultimately optimize AKI management and enhance patient outcomes.
A signal processing tool for extracting features from arterial blood pressure and photoplethysmography waveforms
Authors: Pal R. , Rudas A. , Kim S. , Chiang J.N. , Cannesson M.
Published: March 2024

Arterial blood pressure (ABP) and photoplethysmography (PPG) waveforms contain valuable clinical information and play a crucial role in cardiovascular health monitoring, medical research, and managing medical conditions. The features extracted from PPG waveforms have various clinical applications ranging from blood pressure monitoring to nociception monitoring, while features from ABP waveforms can be used to calculate cardiac output and predict hypertension or hypotension. In recent years, many machine learning models have been proposed to utilize both PPG and ABP waveform features for these healthcare applications. However, the lack of standardized tools for extracting features from these waveforms could potentially affect their clinical effectiveness. In this paper, we propose an automatic signal processing tool for extracting features from ABP and PPG waveforms. Additionally, we generated a PPG feature library from a large perioperative dataset comprising 17,327 patients using the proposed tool. This PPG feature library can be used to explore the potential of these extracted features to develop machine learning models for non-invasive blood pressure estimation.
Dimensional reduction in quantum optics
Authors: Ströhle Jannik , Lopp Richard
Published: March 2024

One-dimensional quantum optical models usually rest on the intuition of large-scale separation or frozen dynamics associated with the different spatial dimensions, for example when studying quasi one-dimensional atomic dynamics, potentially resulting in the violation of (3+1)-dimensional Maxwell's theory. Here, we provide a rigorous foundation for this approximation by means of the light-matter interaction. We show how the quantized electromagnetic field can be decomposed—exactly—into an infinite number of living on a lower-dimensional subspace and containing the entirety of the spectrum when studying axially symmetric setups, such as with an optical fiber, a laser beam, or a waveguide. The approximation then corresponds to a truncation in the number of such subfields that in turn, when considering the interaction with for instance an atom, corresponds to a modification to the atomic spatial profile. We explore under what conditions the standard approach is justified and when corrections are necessary in order to account for the dynamics due to the neglected spatial dimensions. In particular we examine what role vacuum fluctuations and structured laser modes play in the validity of the approximation.

Published by the American Physical Society
2024
Evolutionary adaptation is facilitated by the presence of lethal genotypes
Authors: Blavatska Viktoria , Waclaw Bartlomiej
Published: March 2024

The rate of adaptation in theoretical models of biological evolution generally increases with the mutation rate. However, there is a threshold beyond which mutations into lethal states lead to extinction. It would be logical to assume that eliminating such lethal states could be advantageous for evolution. Here, we demonstrate that lethal mutations actually accelerate adaptation on rugged fitness landscapes with multiple peaks and valleys in the presence of competition for resources. We investigate a modified stochastic version of the quasispecies model, incorporating two types of genotypes—viable and lethal—and show that higher rates of lethal mutations result in shorter evolution times towards the best-fit genotype. This phenomenon can be attributed to an increased frequency of traversing fitness valleys, facilitated by reduced selection pressure against less-fit variants.

Published by the American Physical Society
2024
Nonlinear effects in manybody van der Waals interactions
Authors: Le Dai-Nam , Rodriguez-Lopez Pablo , Woods Lilia M.
Published: March 2024

Van der Waals interactions are ubiquitous and they play an important role for the stability of materials. Current understanding of this type of coupling is based on linear response theory, while optical nonlinearities are rarely considered in this context. Many materials, however, exhibit strong optical nonlinear response, which prompts further evaluation of dispersive forces beyond linear response. Here we present a approach that takes into account linear and nonlinear properties of all dipolar nanoparticles in a given system. This method is based on a Hamiltonian for nonlinear dipoles, which we apply in different systems uncovering a complex interplay of distance, anisotropy, polarizabilities, and hyperpolarizabilities in the vdW energy. This investigation broadens our basic understanding of dispersive interactions, especially in the context of nonlinear materials.

Published by the American Physical Society
2024
Exact analog of the Hatano-Nelson model in one-dimensional continuous nonreciprocal systems
Authors: Maddi A. , Auregan Y. , Penelet G. , Pagneux V. , Achilleos V.
Published: March 2024

Non-Hermitian topology offers a promising avenue toward an enhanced control of waves, and many of the underlying interesting phenomena are studied through the paradigmatic Hatano-Nelson (HN) model, which remains unexplored in continuous wave systems. Herein, we propose a framework to map one-dimensional continuous nonreciprocal systems onto the HN model. Our approach, based on the properties of transfer matrices, is applicable across various physical domains. We experimentally apply our method in audible acoustics using active elements, where we not only observe the predicted skin effect but also access the spectrum topology using stable configurations and observe its subsequent boundary sensitivity. By establishing a connection between continuous wave systems and the discrete HN model, our results significantly broaden the potential application of nonreciprocal topological phenomena.

Published by the American Physical Society
2024
Squeezing Oscillations in a Multimode Bosonic Josephson Junction
Authors: Zhang Tiantian , Maiwöger Mira , Borselli Filippo , Kuriatnikov Yevhenii , Schmiedmayer Jörg , Prüfer Maximilian
Published: March 2024

Quantum simulators built from ultracold atoms promise to study quantum phenomena in interacting many-body systems. However, it remains a challenge to experimentally prepare strongly correlated continuous systems such that the properties are dominated by quantum fluctuations. Here, we show how to enhance the quantum correlations in a one-dimensional multimode bosonic Josephson junction, which is a quantum simulator of the sine-Gordon field theory. Our approach is based on the ability to track the nonequilibrium dynamics of quantum properties. After creating a bosonic Josephson junction at the stable fixed point of the classical phase space, we observe squeezing oscillations in the two conjugate variables. We show that the squeezing oscillation frequency can be tuned by more than one order of magnitude, and we are able to achieve a spin squeezing close to 10 dB by utilizing these oscillatory dynamics. The impact of improved spin squeezing is directly revealed by detecting enhanced spatial phase correlations between decoupled condensates. Our work provides new ways for engineering correlations and entanglement in the external degree of freedom of interacting many-body systems.

Published by the American Physical Society
2024
A workflow for single-particle structure determination via iterative phasing of rotational invariants in fluctuation X-ray scattering
Authors: Berberich Tim B. , Molodtsov Serguei L. , Kurta Ruslan P.
Published: March 2024

Fluctuation X-ray scattering (FXS) offers a complementary approach for nano- and bioparticle imaging with an X-ray free-electron laser (XFEL), by extracting structural information from correlations in scattered XFEL pulses. Here a workflow is presented for single-particle structure determination using FXS. The workflow includes procedures for extracting the rotational invariants from FXS patterns, performing structure reconstructions via iterative phasing of the invariants, and aligning and averaging multiple reconstructions. The reconstruction pipeline is implemented in the open-source software xFrame and its functionality is demonstrated on several simulated structures.
Millisecond X-ray reflectometry and neural network analysis: unveiling fast processes in spin coating
Authors: Schumi-Mareček David , Bertram Florian , Mikulík Petr , Varshney Devanshu , Novák Jiří , Kowarik Stefan
Published: March 2024

X-ray reflectometry (XRR) is a powerful tool for probing the structural characteristics of nanoscale films and layered structures, which is an important field of nanotechnology and is often used in semiconductor and optics manufacturing. This study introduces a novel approach for conducting quantitative high-resolution millisecond monochromatic XRR measurements. This is an order of magnitude faster than in previously published work. Quick XRR (qXRR) enables real time and in situ monitoring of nanoscale processes such as thin film formation during spin coating. A record qXRR acquisition time of 1.4 ms is demonstrated for a static gold thin film on a silicon sample. As a second example of this novel approach, dynamic in situ measurements are performed during PMMA spin coating onto silicon wafers and fast fitting of XRR curves using machine learning is demonstrated. This investigation primarily focuses on the evolution of film structure and surface morphology, resolving for the first time with qXRR the initial film thinning via mass transport and also shedding light on later thinning via solvent evaporation. This innovative millisecond qXRR technique is of significance for in situ studies of thin film deposition. It addresses the challenge of following intrinsically fast processes, such as thin film growth of high deposition rate or spin coating. Beyond thin film growth processes, millisecond XRR has implications for resolving fast structural changes such as photostriction or diffusion processes.
Research on mechanism of servant leadership on employees' customer-oriented deviance: the mediating role of psychological security and the moderating role of error management climate
Authors: Zhang Yi , Zhao Jingyi , Qin Jian
Published: March 2024

Purpose

In the era of the service economy, the personalized needs of customers are increasing rapidly. It often occurs that front-line employees bend organizational rules to help customers. The study sought to explore the influence mechanism of servant leadership on specific dimensions of customer-oriented deviance from the manager’s perspective, examine the mediating role of psychological security, and the moderating role of error management climate in the process.

Design/methodology/approach

We conducted an online survey study in China from April 10 to 29, 2023. We use online survey questionnaire technique and random sampling method for data collection. The authors collected 385 questionnaires from China and tested the model by SPSS 26.0 and AMOS 24.0.

Findings

The results show that servant leadership significantly promotes employees' deviant customer-oriented behaviors, psychological security plays a mediating role between servant leadership and deviant customer-oriented behaviors, and error management climate has a positive moderating effect between servant leadership and deviant customer-oriented behaviors.

Originality/value

This study explores the influence mechanism of servant leadership on deviant customer-oriented behaviors. The results of this study not only enrich the theoretical research on the formation mechanism of deviant customer-oriented behaviors but also provide a reference for leaders to correctly view and effectively manage employees' deviant customer-oriented behaviors.
Construction hazard-recognition training for generation Z students: a comparison study based on eye-movement data
Authors: Liu Ding , Li Chenglin
Published: March 2024

Purpose

Safety training can effectively facilitate workers’ safety awareness and prevent injuries and fatalities on construction sites. Traditional training methods are time-consuming, low participation, and less interaction, which is not suitable for students who are born in Generation Z (Gen Z) and expect to be positively engaged in the learning process. With the characteristic of immersive, interaction, and imagination, virtual reality (VR) has become a promising training method. The purpose of this study is to explore Gen Z students’ learning differences under VR and traditional conditions and determine whether VR technology is more suitable for Gen Z students.

Design/methodology/approach

This paper designed a comparison experiment that includes three training conditions: VR-based, classroom lecturing, and on-site practice. 32 sophomore students were divided into four groups and received different training methods. The eye movement data and hazard-identification index (HII) scores from four groups were collected to measure their hazard-identification ability. The differences between the participants before and after the test were tested by paired sample t-test, and the differences between the groups after the test were analyzed by one-way Welch’s analysis of variance (ANOVA) test.

Findings

The statistical findings showed that participants under VR technology condition spent less time finding and arriving at the Areas of Interest (AOIs). Both the eye movement data and HII scores indicated that VR-based safety training is an alternative approach for Gen Z students to traditional safety training methods.

Originality/value

These findings contribute to the theoretical implications by proving the applicability of VR technology to Gen Z students and empirical implications by guiding colleges and universities to design attractive safety training lessons.
Translating team-member exchange relationships to school outcomes: the mediating role of leader-member exchange
Authors: Birani-Nasraldin Dalia , Bogler Ronit , Somech Anit
Published: March 2024

Purpose

Relying on the principles of the social exchange theory, the current study is aimed at investigating the impact of team-member exchange relationships (TMX) among school management team (SMT) members on school outcomes (organizational citizenship behavior [OCB], job satisfaction and innovation) via the mediating role of leader-member exchange (LMX) relationships between principals and SMTs.

Design/methodology/approach

Data were collected from multiple sources in 86 elementary and junior high schools to avoid one-source bias: 86 principals, 357 SMT members and 683 schoolteachers who were not members of the management teams.

Findings

The results revealed a positive relationship between TMX and teachers' job satisfaction and OCB, but no significant link between TMX and innovation. LMX partially mediated the relationship between TMX and OCB and between TMX and teachers' job satisfaction. Full mediation was found in TMX-innovation relationship.

Practical implications

The findings carry a message for school principals and policymakers regarding the importance of developing and maintaining high-quality horizontal and vertical exchange relationships among the SMT members for their positive influence on school outcomes.

Originality/value

To the best of the authors' knowledge, this is the first study to examine the link between TMX and LMX as a team phenomenon, and specifically in the educational setting. The finding that there is a positive link between the two constructs may imply that SMTs contribute to school success not only directly by exhibiting high-quality TMX but also indirectly through the high-quality LMX.
The parental role in intergenerational educational persistence: an empirical investigation with cross-country panel data
Authors: Salomone Marino Francesco , Berrittella Maria
Published: March 2024

Purpose

The main aim of this study is to investigate the role of fathers and mothers in the intergenerational educational persistence for sons and daughters under two dimensions that characterize the clusters of countries: redistributive policy and governance.

Design/methodology/approach

Data from the Global Database of Intergenerational Mobility (GDIM), hierarchical cluster analysis on principal components and panel regression are used in this study to estimate intergenerational educational correlation and to investigate its determinants related to the parents’ and descendants’ education variables in 93 countries grouped in four clusters. The empirical analysis is differentiated by gender combinations of parents and descendants.

Findings

In the clusters of countries characterized by high inequalities and poor governance, our findings show that the role of the fathers is stronger than that of the mothers in educational transmission; fathers and mothers are more influential for the daughters rather than for the sons; parental educational privilege is the main driver of intergenerational educational persistence; there is an inverse U-curve in the association between educational inequality of the parents and educational correlation for the sons. Differently, in the countries characterized by high income, low redistributive conflict and better governance, the role of the mothers is stronger and education mobility for the daughters is higher than that for the sons.

Social implications

The authors’ results remark on the importance of social welfare policies aimed to expand a meritocratic public education system including schooling transfers for lower social class students and narrowing the gender gap in educational mobility between daughters and sons. Social welfare policies should also be oriented to spread high quality child care systems that help to foster greater women equality in the labor market, because the strength of educational persistence depends on the position of the mother in the economic hierarchy.

Originality/value

The distinctiveness of the paper can be found in the fact that this study investigates the parental role differentiating by gender and coupling hierarchical cluster analysis on principal components with panel regression models. This allows us to have a sample of 93 countries aggregated in four groups defined in two dimensions: redistributive policy and governance. Amongst the determinants of educational transmission, we consider not only education’s years of the parents but also other determinants, such as educational inequality and privilege of the parents. We also identify the effects of investment in human capital and educational inequalities for the descendants on education mobility.
Learning English for specific purposes (ESPs) through social media platforms (SMPs): a systematic review
Authors: Alshaye Rasha Abdullah , Wannas Amr Selim , Bakr Mohamed Saeed
Published: March 2024

Purpose

The search for new techniques to teach English nowadays has been more than ever. These techniques have to be interesting and enjoyable in order to lower the anxiety levels of students when learning English (Bakhsh, 2016). That is why many scholars and teachers look forward to integrating technology into language teaching. Social media platforms (SMPs) are among these techniques since millions of people around the world utilize them for daily interaction. Yet, teaching English for specific purposes (ESPs) relies on learners’ needs and employs an eclectic approach in delivering its course content. For this reason, the current study reviewed articles that tackled the topic of teaching or learning ESP from SMPs so as to uncover their effect and the attitude or motivation of learners.

Design/methodology/approach

The researchers used the PRISMA flowchart model in order to identify, screen and include articles in the study.

Findings

The results revealed that SMPs are effective in teaching and learning ESP writing, speaking and vocabulary. Yet, the included studies showed that learners’ attitude toward SMPs is positive as they believe that they are motivating and interesting.

Research limitations/implications

Some aspects of social media have turned out to be beneficial in the learning process and they need further investigation from ESP practitioners and scholars.

Originality/value

According to the study, it is crystal clear that the various social networks and platforms are beneficial and helpful for improving ESP productive skills.
Japanese consumers’ interpretation of food origin information and their preferences for domestic foods
Authors: Sameshima Nana , Akamatsu Rie
Published: March 2024

Purpose

This study aims to determine the extent to which consumers perceive food-related information to be tied to the intrinsic characteristics of food, particularly safety.

Design/methodology/approach

The authors examined Japanese consumers’ preferences regarding domestic or foreign perishables, as well as how they interpret origin information, focusing on their perceptions of safety using descriptive analysis and binary logistic regression analysis.

Findings

The results indicated that a high proportion of Japanese consumers considered domestic foods to be safer; in particular, people affected by food safety information obtained through personal communication, books and magazines tended to choose domestically produced perishables rather than imported ones.

Originality/value

The belief that domestic foods are safer than imported ones was highly universal among Japanese consumers, although this belief is not necessarily grounded in scientific evidence. When considering strategies to improve consumers’ information literacy, factors that have fostered this belief must be discussed. For consumers to make logical food choices, both food businesses and consumers require scientific and informational literacy and policy support.
Influences of hygrothermal conditions and structure parameters on moisture diffusion behavior in a system‐in‐package module by moisture-thermal-mechanical-coupled finite element modeling
Authors: Liu Li , Zhang Chunhua , Hu Ping , Liu Sheng , Chen Zhiwen
Published: March 2024

Purpose

This paper aims to investigate the moisture diffusion behavior in a system-in-package module systematically by moisture-thermalmechanical-coupled finite element modeling with different structure parameters under increasingly harsh environment.

Design/methodology/approach

A finite element model for a system-in-package module was built with moisture-thermal-mechanical-coupled effects to study the subsequences of hygrothermal conditions.

Findings

It was found in this paper that the moisture diffusion path was mainly dominated by hygrothermal conditions, though structure parameters can affect the moisture distribution. At lower temperatures (30°C~85°C), the direction of moisture diffusion was from the periphery to the center of the module, which was commonly found in simulations and literatures. However, at relatively higher temperatures (125°C~220°C), the diffusion was from printed circuit board (PCB) to EMC due to the concentration gradient from PCB to EMC across the EMC/PCB interface. It was also found that there exists a critical thickness for EMC and PCB during the moisture diffusion. When the thickness of EMC or PCB increased to a certain value, the diffusion of moisture reached a stable state, and the concentration on the die surface in the packaging module hardly changed. A quantified correlation between the moisture diffusion coefficient and the critical thickness was then proposed for structure parameter optimization in the design of system-in-package module.

Originality/value

The different moisture diffusion behaviors at low and high temperatures have seldom been reported before. This work can facilitate the understanding of moisture diffusion within a package and offer some methods about minimizing its effect by design optimization.
Options on temporary water allocation rights and their pricing
Authors: Lee Geoff , Dong Wenfeng , Zhu Zili
Published: March 2024

This paper presents a methodology for defining the spot price of temporary water allocation rights for trading zones within the water market in the southern Murray–Darling Basin situated in Australia. The historical spot price is then used to calibrate a stochastic process depicting the dynamics of the water price, allowing the computation of prices of options on the underlying water price with the aim of producing reference prices to catalyse an options trading market. The most suitable stochastic model representing the water price dynamics is selected through comparing the option prices generated from four different models. Using the selected stochastic model, the most liquid trading zone in the Murray–Darling Basin water market (Zone 7) is used to demonstrate how the methodologies developed in the paper are used to calibrate the log‐mean stochastic model representing the stochastic spot price dynamics and compute prices for call and put options on the underlying water spot prices. Sensitivities of the water options prices to market input data can be calculated from the formulae provided in the paper. The results presented in this work can serve as a reference tool by industry practitioners and the farming community in using options for effective risk management of water resources.
Identification and functional characterization of chemosensory genes in olfactory and taste organs of Spodoptera litura (Lepidoptera: Noctuidae)
Authors: Yang Jun , Mo Bao‐Tong , Li Guo‐Cheng , Huang Ling‐Qiao , Guo Hao , Wang Chen‐Zhu
Published: March 2024

The tobacco cutworm Spodoptera litura is one of the most destructive polyphagous crop pests. Olfaction and taste play a crucial role in its host plant selection and sexual communication, but the expression profile of chemosensory genes remains unclear. In this study, we identified 185 chemosensory genes from 7 organs in S. litura by transcriptome sequencing, of which 72 genes were published for the first time, including 27 odorant receptors (ORs), 26 gustatory receptors (GRs), 1 ionotropic receptor (IR), 16 odorant‐binding proteins (OBPs), and 2 chemosensory proteins (CSPs). Phylogenetic analyses revealed that ORs, IRs, OBPs, and sensory neuron membrane proteins (SNMPs) were mainly expressed in antennae and sequence‐conserved among Noctuidae species. The most differentially expressed genes (DEGs) between sexes were ORs and OBPs, and no DEGs were found in GRs. GR transcripts were enriched in proboscis, and the expression of sugar receptors was the highest. Carbon dioxide receptors, sugar receptor‐SliuGR6, and bitter GRs‐SlituGR43 and SlituGR66 had higher sequence identities between Noctuidae species. CSPs were broadly expressed in various organs, and SlituCSP13 was a DEG in adult antennae. The functional analysis in the Drosophila OR67d expression system found that SlituOR50, a receptor highly expressed in female antennae, is selectively tuned to farnesyl acetate. The results provide a solid foundation for understanding the molecular mechanisms by which chemosensory genes operate to elicit behavioral responses in polyphagous insects.
Association between oral microbiome and breast cancer in the east Asian population: A Mendelian randomization and case–control study
Authors: Feng Kexin , Ren Fei , Shang Qingyao , Wang Xin , Wang Xiang
Published: March 2024

Background

The causal relationship between breast cancer (BC) and the oral microbiome remains unclear. In this case–control study, using two‐sample Mendelian randomization (MR), we thoroughly explored the relationship between the oral microbiome and BC in the East Asian population.

Methods

Genetic summary data related to oral microbiota and BC were collected from genome‐wide association studies involving participants of East Asian descent. MR estimates were generated by conducting various analyses. Sequencing data from a case–control study were used to verify the validity of these findings.

Results

MR analysis revealed that 30 tongue and 37 salivary bacterial species were significantly associated with BC. Interestingly, in both tongue and salivary microbiomes, we observed the causal effect of six genera, namely, Aggregatibacter, Streptococcus, Prevotella, Haemophilus, Lachnospiraceae, Oribacterium, and Solobacterium, on BC. Our case–control study findings suggest differences in specific bacteria between patients with BC and healthy controls. Moreover, sequencing data confirmed the MR analysis results, demonstrating that compared with the healthy control group, the BC group had a higher relative abundance of Pasteurellaceae and Streptococcaceae but a lower relative abundance of Bacteroidaceae.

Conclusions

Our MR analysis suggests that the oral microbiome exerts a causative effect on BC risk, supported by the sequencing data of a case–control study. In the future, studies should be undertaken to comprehensively understand the complex interaction mechanisms between the oral microbiota and BC.
Infection risk and antimicrobial prophylaxis in bendamustine‐treated patients with indolent non‐Hodgkin lymphoma: An Australasian Lymphoma Alliance study
Authors: Manos Kate , Churilov Leonid , Grigg Andrew , Di Ciaccio Pietro , Wong Jonathan , Chandra Sekaran Usha , Wight Joel , Goh Zhong , Jina Hayden , Butler Llewyn , Yannakou Costas K. , Hamad Nada , Gregory Gareth P. , Gangatharan Shane , Cochrane Tara , Hawkes Eliza A. , Lasica Masa
Published: March 2024

Infection and lymphopenia are established bendamustine‐related complications. The relationship between lymphopenia severity and infection risk, and the role of antimicrobial prophylaxis, is not well described. This multicentre retrospective study analysed infection characteristics and antimicrobial prophylaxis in 302 bendamustine‐treated indolent non‐Hodgkin lymphoma patients. Lymphopenia (<1 × 109/L) was near universal and time to lymphocyte recovery correlated with cumulative bendamustine dose. No association between lymphopenia severity and duration with infection was observed. Infections occurred in 44% of patients (50% bacterial) with 27% hospitalised; 32% of infections occurred ≥3 months post bendamustine completion. Infection was associated with obinutuzumab and/or maintenance anti‐CD20 therapy, prior therapy and advanced stage. Twenty‐four opportunistic infections occurred in 21 patients: ten varicella zoster virus (VZV), seven herpes simplex virus (HSV), one cytomegalovirus, one progressive multifocal leucoencephalopathy, one nocardiosis, one Pneumocystis jiroveci pneumonia (PJP) and three other fungal infections. VZV/HSV and PJP prophylaxis were prescribed to 42% and 54% respectively. Fewer VZV/HSV infections occurred in patients receiving prophylaxis (HR 0.14, p = 0.061) while PJP prophylaxis was associated with reduced risk of bacterial infection (HR 0.48, p = 0.004). Our study demonstrates a significant infection risk regardless of lymphopenia severity and supports prophylaxis to mitigate the risk of early and delayed infections.
Preclinical and translational pharmacology of afucosylated anti‐CCR8 antibody for depletion of tumour‐infiltrating regulatory T cells
Authors: Gampa Gautham , Spinosa Phillip , Getz Jennifer , Zhong Yu , Halpern Wendy , Esen Emel , Davies John , Chou Cassie , Kwong Mandy , Wang Yingyun , Arenzana Teresita L. , Shivva Vittal , Huseni Mahrukh , Hsieh Robert , Schartner Jill , Koerber James T. , Rutz Sascha , Hosseini Iraj
Published: March 2024

Background and Purpose

RO7502175 is an afucosylated antibody designed to eliminate C–C motif chemokine receptor 8 (CCR8)+ Treg cells in the tumour microenvironment through enhanced antibody‐dependent cellular cytotoxicity (ADCC).

Experimental Approach

We report findings from preclinical studies characterizing pharmacology, pharmacokinetics (PK)/pharmacodynamics (PD) and safety profile of RO7502175 and discuss the translational PK/PD approach used to inform first‐in‐human (FiH) dosing strategy and clinical development in solid tumour indications.

Key Results

RO7502175 demonstrated selective ADCC against human CCR8+ Treg cells from dissociated tumours in vitro. In cynomolgus monkeys, RO7502175 exhibited a biphasic concentration–time profile consistent with immunoglobulin G1 (IgG1) antibodies, reduced CCR8+ Treg cells in the blood, induced minimal and transient cytokine secretion, and was well tolerated with a no‐observed‐adverse‐effect level (NOAEL) of 100 mg·kg−1. Moreover, RO7502175 caused minimal cytokine release from peripheral blood mononuclear cells (PBMCs) in vitro. A quantitative model was developed to capture surrogate anti‐murine CCR8 antibody PK/PD and tumour dynamics in mice and RO7502175 PK/PD in cynomolgus monkeys. Subsequently, the model was used to project RO7502175 human PK and receptor occupancy (RO) in patients. Because traditional approaches resulted in a low FiH dose for this molecule, even with its superior preclinical safety profile, an integrated approach based on the totality of preclinical data and modelling insights was used for starting dose selection.

Conclusion and Implications

This work demonstrates a translational research strategy for collecting and utilizing relevant nonclinical data, developing a mechanistic PK/PD model and using a comprehensive approach to inform clinical study design for RO7502175.
Characterizing enteric neurons in dopamine transporter (DAT)‐Cre reporter mice reveals dopaminergic subtypes with dual‐transmitter content
Authors: Recinto Sherilyn Junelle , Premachandran Shobina , Mukherjee Sriparna , Allot Alexis , MacDonald Adam , Yaqubi Moein , Gruenheid Samantha , Trudeau Louis‐Eric , Stratton Jo Anne
Published: March 2024

The enteric nervous system (ENS) comprises a complex network of neurons whereby a subset appears to be dopaminergic although the characteristics, roles, and implications in disease are less understood. Most investigations relating to enteric dopamine (DA) neurons rely on immunoreactivity to tyrosine hydroxylase (TH)—the rate‐limiting enzyme in the production of DA. However, TH immunoreactivity is likely to provide an incomplete picture. This study herein provides a comprehensive characterization of DA neurons in the gut using a reporter mouse line, expressing a fluorescent protein (tdTomato) under control of the DA transporter (DAT) promoter. Our findings confirm a unique localization of DA neurons in the gut and unveil the discrete subtypes of DA neurons in this organ, which we characterized using both immunofluorescence and single‐cell transcriptomics, as well as validated using in situ hybridization. We observed distinct subtypes of DAT‐tdTomato neurons expressing co‐transmitters and modulators across both plexuses; some of them likely co‐releasing acetylcholine, while others were positive for a slew of canonical DAergic markers (TH, VMAT2 and GIRK2). Interestingly, we uncovered a seemingly novel population of DA neurons unique to the ENS which was ChAT/DAT‐tdTomato‐immunoreactive and expressed Grp, Calcb, and Sst. Given the clear heterogeneity of DAergic gut neurons, further investigation is warranted to define their functional signatures and decipher their implication in disease.
GW9508 ameliorates cognitive dysfunction via autophagy pathway in streptozotocin‐induced mouse model of Alzheimer's disease
Authors: Wang Yanan , Chen Jingjing , Wang Chen , Chen Tong , He Ling
Published: March 2024

Background

G protein‐coupled receptor 40 (GPR40) is a potential drug target for Alzheimer's disease (AD), and its agonist GW9508 ameliorates cognitive impairment by intravenous administration.

Objectives

The present study was conducted to investigate the efficacy of GW9508 administered peripherally on cognitive dysfunction in streptozotocin (STZ)‐induced AD mice.

Methods

Seventy male ICR mice were randomly divided into seven groups: vehicle sham group, model, Donepezil, GW9508‐L, GW9508‐M, GW9508‐H, and GW1100 + GW9508‐H groups, and administered either vehicle (artificial cerebrospinal fluid [aCSF]) or STZ (3 mg/kg in the vehicle) once a day (9:00 a.m.) by intracerebroventricular injection bilaterally on day 1 and day 3, respectively. After 2 weeks of recovery, all mice were given drug treatment. Behavioral experiments were applied to test the recognition and spatial memory of mice, while molecular biology experiments such as Western blot, ELISA, and Nissl staining were used to detect the corresponding changes of signaling pathways.

Results

Intraperitoneal administration of GW9508 prevented STZ‐induced cognitive impairment as well as decreased the level of p‐tau and Aβ1–42 in plasma and brain. GW9508 upregulated the expression of gut‐brain peptides like PYY, CCK, IGF‐1, and GLP‐1 both in blood circulation and brain and downregulated the expression level of autophagy‐related proteins through activating Akt/mTOR signaling pathway. Meanwhile, the treatment effect of GW9508 was reversed by GPR40 antagonist GW1100 significantly.

Conclusion

Peripheral administration of GW9508 exhibits neuroprotective effects, and it could be a promising therapy for AD. The neuroprotective mechanism of GW9508 was based on promoting gut‐brain peptide secretion, activating Akt/mTOR signal pathway, and regulating neuronal autophagy.
TPACK expression patterns in preservice teachers' design of innovative physics teaching and learning materials
Authors: Kim Hyojoon , Song Jinwoong , Ha Sangwoo
Published: March 2024

Background

TPACK is a widely used framework for assessing teachers' competence in integrating technology in education. However, previous studies have shown varying interpretations of the relationship between TPACK elements. Qualitative studies that assess the manifestations of TPACK by examining the practices of pre‐service teachers are rare.

Objectives

This study investigates technology integration in innovative physics teaching and learning materials designed by pre‐service teachers and the manifestation of technological pedagogical content knowledge (TPACK) in empirical cases.

Methods

We qualitatively extracted the components of PCK, TPK, and TCK from the innovative physics teaching and learning materials developed by 22 pre‐service teachers in their fourth year at a teachers' college in South Korea. We scored them based on the new evaluation criteria established in this study.

Results and Conclusions

Based on the materials, we identified three types of technology integration: Learning Materials Providing, Learning Activity Providing, and Virtual Experiments Creating. This study identifies teachers' level of TK and integrates it with TPACK expression. Results confirm the connection between TK and TCK and show that a strong PCK can serve as a basis for TPK. The TPACK expression pattern can help achieve balanced development of TPACK in teacher education.
Comparing methods for determining the metabolic capacity of lumpfish (Cyclopterus lumpus Linnaeus 1758)
Authors: Eisenberg Rachel M. , Sandrelli Rebeccah M. , Gamperl Anthony Kurt
Published: March 2024

Lumpfish (Cyclopterus lumpus) mortalities have been reported during the summer at some North Atlantic salmon cage‐sites where they serve as “cleaner fish.” To better understand this species' physiology and whether limitations in their metabolic capacity and thermal tolerance can explain this phenomenon, we compared the aerobic scope (AS) of 6°C‐acclimated lumpfish (~50 g and 8.8 cm in length at the beginning of experiments) when all individuals (N = 12) were given a chase to exhaustion, a critical swim speed (Ucrit) test, and a critical thermal maximum (CTMax) test (rate of warming 2°C h−1). The Ucrit and CTMax of the lumpfish were 2.36 ± 0.08 body lengths per second and 20.6 ± 0.3°C. The AS of lumpfish was higher during the Ucrit test (206.4 ± 8.5 mg O2 kg−1 h−1) versus that measured in either the CTMax test or after the chase to exhaustion (141.0 ± 15.0 and 124.7 ± 15.5 mg O2 kg−1 h−1, respectively). Maximum metabolic rate (MMR), AS, and “realistic” AS (ASR) measured using the three different protocols were not significantly correlated, indicating that measurements of metabolic capacity using one of these methods cannot be used to estimate values that would be obtained using another method. Additional findings include that (1) the lumpfish's metabolic capacity is comparable to that of Atlantic cod, suggesting that they are not as “sluggish” as previously suggested in the literature, and (2) their CTMax (20.6°C when acclimated to 6°C), in combination with their recently determined ITMax (20.6°C when acclimated to 10°C), indicates that high sea‐cage temperatures are unlikely to be the primary cause of lumpfish mortalities at salmon sea‐cages during the summer.
Longitudinal effects of ambivalent and guilt feelings on dementia family caregivers' depressive symptoms
Authors: Losada‐Baltar Andrés , Mausbach Brent T. , Romero‐Moreno Rosa , Jiménez‐Gonzalo Lucía , Huertas‐Domingo Cristina , Fernandes‐Pires José A. , Barrera‐Caballero Samara , Gallego‐Alberto Laura , Martín‐María Natalia , Olazarán Javier , Márquez‐González María
Published: March 2024

Background

The world prevalence of people with dementia is increasing. Most of the care received by people with dementia is provided by family caregivers, and this prolonged activity has a significant impact on caregivers' levels of depression. Stressors and frequency of leisure are known predictors of caregivers' depressive levels. The longitudinal impact of caregivers' ambivalent and guilt feelings is unknown.

Methods

Participants were 177 family caregivers of relatives with dementia who were assessed three times during a 2‐year period. In addition to demographic variables, psychological symptoms of the dementias, and frequency of leisure activities, caregivers' ambivalent feelings, guilt, and depressive symptoms were measured. The longitudinal association of changes in these variables with changes in caregivers' depressive symptoms over time was assessed using mixed linear models.

Results

Changes over time in the assessed variables predicted 48.05% of variance of changes over time in depressive symptoms. Even when variables strongly associated with increased depressive symptoms were controlled (lower caregivers' age and educational level, higher reaction to BPSD, and lower leisure activities), increases in ambivalence and guilt contributed to an increase of 9.22% of the variance of changes depressive symptoms over a 2‐year period. The effects of ambivalent feelings on depression are indirect, mediated by guilt feelings. Cessation of caregiving do not seem to alter these findings.

Conclusions

Caregivers' ambivalent and guilt feelings are significant predictors of caregivers' mental health. Caregivers may significantly benefit from early detection of ambivalent and guilt feelings and preventive strategies targeting triggers associated with ambivalent and guilt symptoms.