bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro
,
in planta,
and comparative genomic analyses of
Pseudomonas syringae
pv.
syringae
strains of pepper (
Capsicum annuum
var.
annuum
)
Authors: Ranjit Sochina , Deblais Loïc , Poelstra Jelmer W. , Bhandari Menuka , Rotondo Francesca , Scaria Joy , Miller Sally A. , Rajashekara Gireesh
Published: May 2024

Pseudomonas syringae
pv.
syringae
(
Pss
) is an emerging phytopathogen that causes
Pseudomonas
leaf spot (PLS) disease in pepper plants.
Pss
can cause serious economic damage to pepper production, yet very little is known about the virulence factors carried by
Pss
that cause disease in pepper seedlings. In this study,
Pss
strains isolated from pepper plants showing PLS symptoms in Ohio between 2013 and 2021 (
n
= 16) showed varying degrees of virulence (
Pss
populations and disease symptoms on leaves) on 6-week-old pepper seedlings.
In vitro
studies assessing growth in nutrient-limited conditions, biofilm production, and motility also showed varying degrees of virulence, but
in vitro
and
in planta
variation in virulence between
Pss
strains did not correlate. Comparative whole-genome sequencing studies identified notable virulence genes including 30 biofilm genes, 87 motility genes, and 106 secretion system genes. Additionally, a total of 27 antimicrobial resistance genes were found. A multivariate correlation analysis and Scoary analysis based on variation in gene content (
n
= 812 variable genes) and single nucleotide polymorphisms within virulence genes identified no significant correlations with disease severity, likely due to our limited sample size. In summary, our study explored the virulence and antimicrobial gene content of
Pss
in pepper seedlings as a first step toward understanding the virulence and pathogenicity of
Pss
in pepper seedlings. Further studies with additional pepper
Pss
strains will facilitate defining genes in
Pss
that correlate with its virulence in pepper seedlings, which can facilitate the development of effective measures to control
Pss
in pepper and other related
P. syringae
pathovars.

IMPORTANCE

Pseudomonas
leaf spot (PLS) caused by
Pseudomonas syringae
pv.
syringae
(
Pss
) causes significant losses to the pepper industry. Highly virulent
Pss
strains under optimal environmental conditions (cool–moderate temperatures, high moisture) can cause severe necrotic lesions on pepper leaves that consequently can decrease pepper yield if the disease persists. Hence, it is important to understand the virulence mechanisms of
Pss
to be able to effectively control PLS in peppers. In our study,
in vitro
,
in planta
, and whole-genome sequence analyses were conducted to better understand the virulence and pathogenicity characteristics of
Pss
strains in peppers. Our findings fill a knowledge gap regarding potential virulence and pathogenicity characteristics of
Pss
in peppers, including virulence and antimicrobial gene content. Our study helps pave a path to further identify the role of specific virulence genes in causing disease in peppers, which can have implications in developing strategies to effectively control PLS in peppers.
A metagenomics-based workflow for the detection and genomic characterization of GBS in raw freshwater fish
Authors: Sim Kae Hwan , Ho Jiaying , Lim Jia Qi , Chan Sheot Harn , Li Angela , Chng Kern Rei
Published: May 2024

The unexpected foodborne outbreak in Singapore in 2015 has accentuated Group B
Streptococcus
(GBS,
Streptococcus agalactiae
) sequence type 283 as an emerging foodborne pathogen transmitted via the consumption of contaminated raw freshwater fish. Isolation-based workflows utilizing conventional microbiological and whole-genome sequencing methods are commonly used to support biosurveillance efforts critical for the control management of this emerging foodborne pathogen. However, these isolation-based workflows tend to have relatively long turnaround times that hamper a timely response for implementing risk mitigation. To address this gap, we have developed a metagenomics-based workflow for the simultaneous detection and genomic characterization of GBS in raw freshwater fish. Notably, our validation results showed that this metagenomics-based workflow could achieve comparable accuracy and potentially better detection limits while halving the turnaround time (from 2 weeks to 5 days) relative to an isolation-based workflow. The metagenomics-based workflow was also successfully adapted for use on a portable long-read nanopore sequencer, demonstrating its potential applicability for real-time point-of-need testing. Using GBS in freshwater fish as an example, this work represents a proof-of-concept study that supports the feasibility and validity of metagenomics as a rapid and accurate test methodology for the detection and genomic characterization of foodborne pathogens in complex food matrices.

IMPORTANCE

The need for a rapid and accurate food microbiological testing method is apparent for a timely and effective foodborne outbreak response. This is particularly relevant for emerging foodborne pathogens such as Group B
Streptococcus
(GBS) whose associated food safety risk might be undercharacterized. By using GBS in raw freshwater fish as a case example, this study describes the development of a metagenomics-based workflow for rapid food microbiological safety testing and surveillance. This study can inform as a working model for various foodborne pathogens in other complex food matrices, paving the way for future methodological development of metagenomics for food microbiological safety testing.
Utility of a multiplex pathogen detection system directly from respiratory specimens for treatment and diagnostic stewardship
Authors: Srivastava Smriti , Sharad Neha , Kiro Vandana Vijayeta , Ningombam Aparna , Shrivastava Sharad , Farooque Kamran , Mathur Purva
Published: May 2024

The availability of syndrome-based panels for various ailments has widened the scope of diagnostics in many clinical settings. These panels can detect a multitude of pathogens responsible for a particular condition, which can lead to a timely diagnosis and better treatment outcomes. In contrast to traditional identification methods based on pathogen growth on culture, syndrome-based panels offer a quicker diagnosis, which can be especially beneficial in situations requiring urgent care, such as intensive care units. One such panel is the Biofire Filmarray Pneumonia plus Panel (BFP), which we have compared against microbiological culture and identification. The lower respiratory samples from patients were tested with BFP, culture, and identification with culture considered the gold standard. The phenotypic antibiotic susceptibility results (Vitek 2) were compared with the antimicrobial resistance (AMR) genes detected in BFP. Statistical analysis was carried out using GraphPad 7.0 and MS Excel (Microsoft Inc.). The results showed a positive percent agreement of 100% and a negative percent agreement of 47.8% with an overall agreement of 76.72% compared to culture. BFP was better at identifying fastidious bacteria, and the agreement with culture was higher for high bacterial identification numbers (10
7
and 10
6
). There was also a correlation between the number of pathogens detected and growth in culture. Carbapenemase genes were detected in around 80% of phenotypically resistant samples and correlated with in-house PCR 60% of the time. Hence, BFP results need to be interpreted with caution especially when multiple pathogens are detected. Similarly, the presence or absence of AMR genes should be used to guide the therapy while being watchful of unusual resistance or susceptibility. The cost constraints and low throughput call for patient selection criteria and prioritization in emergency or resource-limited conditions.

IMPORTANCE

Application of syndrome-based panels in clinical microbiology is of huge support in infectious conditions requiring urgent interventions, such as pneumonia. Interpreting the results requires caution; hence, we have compared the results obtained from Biofire Filmarray Pneumonia plus Panel with standard microbiological methods.
A pyocin-like T6SS effector mediates bacterial competition in
Yersinia pseudotuberculosis
Authors: Yang Leilei , Jia Shuangkai , Sun Sihuai , Wang Lei , Zhao Bobo , Zhang Mengsi , Yin Yanling , Yang Mingming , Fulano Alex M. , Shen Xihui , Pan Junfeng , Wang Yao
Published: May 2024

Within the realm of Gram-negative bacteria, bacteriocins are secreted almost everywhere, and the most representative are colicin and pyocin, which are secreted by
Escherichia coli
and
Pseudomonas aeruginosa
, respectively. Signal peptides at the amino terminus of bacteriocins or ABC transporters can secrete bacteriocins, which then enter bacteria through cell membrane receptors and exert toxicity. In general, the bactericidal spectrum is usually narrow, killing only the kin or closely related species. Our previous research indicates that YPK_0952 is an effector of the third Type VI secretion system (T6SS-3) in
Yersinia pseudotuberculosis
. Next, we sought to determine its identity and characterize its toxicity. We found that YPK_0952 (a pyocin-like effector) can achieve intra-species and inter-species competitive advantages through both contact-dependent and contact-independent mechanisms mediated by the T6SS-3 while enhancing the intestinal colonization capacity of
Y. pseudotuberculosis
. We further identified YPK_0952 as a DNase dependent on Mg
2+
, Ni
2+
, Mn
2+
, and Co
2+
bivalent metal ions, and the homologous immune protein YPK_0953 can inhibit its activity. In summary, YPK_0952 exerts toxicity by degrading nucleic acids from competing cells, and YPK_0953 prevents self-attack in
Y. pseudotuberculosis
.

IMPORTANCE

Bacteriocins secreted by Gram-negative bacteria generally enter cells through specific interactions on the cell surface, resulting in a narrow bactericidal spectrum. First, we identified a new pyocin-like effector protein, YPK_0952, in the third Type VI secretion system (T6SS-3) of
Yersinia pseudotuberculosis
. YPK_0952 is secreted by T6SS-3 and can exert DNase activity through contact-dependent and contact-independent entry into nearby cells of the same and other species (e.g.,
Escherichia coli
) to help
Y. pseudotuberculosis
to exert a competitive advantage and promote intestinal colonization. This discovery lays the foundation for an in-depth study of the different effector protein types within the T6SS and their complexity in competing interactions. At the same time, this study provides a new development for the toolbox of toxin/immune pairs for studying Gram-negative bacteriocin translocation.
Supplemental Material: Structural and metamorphic architecture of the Zanskar Himalaya, Suru Valley region, NW India: Implications for the evolution of the Himalayan metamorphic core
Authors: Cawood I.P. , et al.
Published: May 2024

Supplemental Text S1 consists of methods, detailed descriptions of lithostratigraphic units, observations of fabric-defining metamorphic mineral assemblages, and further mineral growth-deformation fabric relationships. Figures S1–S7 consist of collated pressure-temperature and geochronological datasets from previous studies across NW India, simplified geological maps highlighting different sets of structural data, and additional field and petrographic photographs that illustrate the relationship between mineral growth and the development of deformation fabrics.
Do movement behaviours influence the association between early menarche and depression symptoms among Brazilian adolescents?
Authors: Silva Diego Augusto Santos , Duncan Markus Joseph , Kuzik Nicholas , Tremblay Mark S.
Published: May 2024

Early menarche has been associated with adverse health outcomes, such as depressive symptoms. Discovering effect modifiers across these conditions in the pediatric population is a constant challenge. We tested whether movement behaviours modified the effect of the association between early menarche and depression symptoms among adolescents. This cross-sectional study included 2031 females aged 15–19 years across all Brazilian geographic regions. Data were collected using a self-administered questionnaire; 30.5% ( n = 620) reported having experienced menarche before age 12 years (i.e., early menarche). We used the Patient Health Questionnaire (PHQ-9) to evaluate depressive symptoms. Accruing any moderate–vigorous physical activity during leisure time, limited recreational screen time, and having good sleep quality were the exposures investigated. Adolescents who experienced early menarche and met one ( B: –4.45, 95% CI: (–5.38, –3.51)), two ( B: –6.07 (–7.02, –5.12)), or three ( B: –6.49 (–7.76, –5.21)), and adolescents who experienced not early menarche and met one ( B: –5.33 (–6.20; –4.46)), two ( B: –6.12 (–6.99; –5.24)), or three ( B: –6.27 (–7.30; –5.24)) of the movement behaviour targets had lower PHQ-9 scores for depression symptoms than adolescents who experienced early menarche and did not meet any of the movement behaviours. The disparities in depressive symptoms among the adolescents (early menarche vs. not early menarche) who adhered to all three target behaviours were not statistically significant ( B: 0.41 (–0.19; 1.01)). Adherence to movement behaviours modified the effect of the association between early menarche and depression symptoms.
Quantum homomorphic aggregation signature scheme based on GHZ states
Authors: Wei Xingjia , Li Zhihui , Duan Haozhe , Hu Kexin
Published: May 2024

A quantum homomorphic aggregation signature scheme is proposed based on GHZ states, combined with homomorphic aggregation techniques. The scheme has the following features: Firstly, by changing the existing quantum homomorphic signature scheme which generally uses Bell state as the signature particle, and choosing GHZ state as the signature particle, it can realize the signature of the multi-bit messages by preparing fewer quantum resources; Secondly, the idea of classical aggregated signature is introduced, where multiple message signatures are aggregated into a single signature by quantum entanglement swapping technique, and the verifier can determine the validity of all signatures by only one verification; At the same time, the verification of individual signatures by the aggregator is realized, and dishonest behaviors among the signature members can be detected in time; Finally, the whole signature process satisfies the basic homomorphic property. Compared with the existing quantum homomorphic signature scheme, this scheme can effectively reduce the consumption of quantum resources, improving the efficiency of signature verification and enhancing the reliability of the signature. The security analysis shows that the scheme has the verifiability, unforgeability and non-repudiation.
Improved-equivalent-input-disturbance-based preview repetitive control for Takagi–Sugeno fuzzy system with state delay
Authors: Luo Zhao , Lan Yonghong , Zheng Litao , Ding Lei
Published: May 2024

This paper designs a preview repetitive control (PRC) policy for a class of Takagi–Sugeno (T–S) fuzzy systems with time-varying delay and external disturbances. First, the T–S fuzzy model is employed to represent a nonlinear plant, once the nonlinear plant is represented by a T–S fuzzy model, a fuzzy improved-equivalent-input-disturbance (IEID)-based PRC law can be designed to achieve better tracking performance and disturbance rejection. Next, based on a new equality constraint, we derive a continuous-discrete two-dimensional (2D) system that paves the way to solve the design problem of the IEID-based PRC law using linear matrix inequality (LMI) approach. Then, by solving LMIs, the gains of the controller and state observer can be obtained. Finally, a numerical example is included to show the effectiveness of the proposed method.
Realization of Robust Formation for Multi-UAV Systems Using Control Barrier Functions
Authors: Zhang Zhaoming , Wu Yiming , Jiang Jie , Zheng Ning , Meng Wei
Published: May 2024

Network robustness is a necessary prerequisite for the effective execution of resilient control in distributed multiple unmanned aerial vehicles (UAVs). However, it remains a challenging task to construct a communication graph that satisfies specific network robustness properties. This paper investigates robust formation control of multi-UAV systems using control barrier functions (CBFs). We first propose a novel formation law to drive groups of UAVs into formations with communication graphs that satisfy the [Formula: see text]-robustness. With such a law, all the normal UAVs in the formation are capable of executing a given resilient consensus protocol, and achieving convergence in the presence of malicious attackers. Then, we present a control law that facilitates the establishment of UAV formations, in which the communication graphs satisfy p-fraction robustness. Finally, simulation examples are given to verify the effectiveness of the proposed formation control laws.
Relationship between fault transmissivity, flow dimensions and effective hydraulic conductivity in siliceous mudstone of the Wakkanai Formation around the Horonobe Underground Research Laboratory in Japan
Authors: Ozaki Yusuke , Ishii Eiichi
Published: May 2024

Effective hydraulic conductivity is typically used to evaluate groundwater flow in faulted/fractured media. Estimating effective hydraulic conductivity relies on modelling the transmissivity and hydraulic connectivity of faults/fractures using a large dataset. As an alternative to evaluating hydraulic connectivity, flow dimension is an easily available and quantitative indicator of fault/fracture hydraulic connectivity. However, the flow dimension has not been used as much quantitatively to evaluate the effective hydraulic conductivity. This study demonstrates how flow dimensions in poorly self-sealed faults directly relate to effective hydraulic conductivities. Effective hydraulic conductivities of massive siliceous mudstone of the Wakkanai Formation around the Horonobe Underground Research Laboratory (URL) in Japan were analysed by simulation with long-term (>10 years) data of hydraulic pressure and inflow during the construction and operation of the URL. The estimated effective hydraulic conductivities varied from
c
. 10
−8
to
c
. 10
−11
 m s
−1
with an increase in depth from
c
. 250 to
c
. 600 m. The fault local transmissivities and flow dimensions from packer tests varied from
c
. 10
−6
to
c
. 10
−10
 m
2
 s
−1
and from
c
. 2.0 or more to
c
. 1.0 with increasing depth, respectively. When applying the Landau–Lifshitz–Matheron formula to calculate the fault effective transmissivities, these variations correlate well and the estimated effective hydraulic conductivities are sound.
Eurasian Arctic Rifted Margin Composite Tectono-Sedimentary Element
Authors: Abdelmalak Mohamed Mansour , Minakov Alexander , Meza-Cala Juan Camilo , Faleide Jan Inge , Gaina Carmen , Drachev Sergey S.
Published: May 2024

The Eurasian Arctic Rifted Margin (EARM) spans a poorly studied transition region between the Eurasian continental shelf and the deep-water Nansen Basin. It is a conjugate margin to the Lomonosov Ridge, as both domains were united before the opening of the oceanic Eurasia Basin. The EARM is considered as a Composite Tectono-Sedimentary Element (CTSE) consisting of two individual tectono-sedimentary elements (TSEs): (1) an undefined group of poorly known pre-rift Mesozoic and Paleozoic sedimentary successions; and (2) Late Cretaceous–Paleocene synrift strata. The latter are bounded by a
c.
56 Ma break-up unconformity and are overlain by the Eurasia Basin prograded margin TSE, which is not included in EARM. In the absence of drilled wells, we utilize multichannel seismic reflection (MCS) data for seismic stratigraphic correlations with nearby, better-explored, areas. The EARM CTSE is subdivided into three along-strike segments (from west to east): Svalbard–Barents Sea, the North Kara Sea and the Taimyr–Laptev Sea. Across-strike, the EARM CTSE is composed of a proximal zone of stretched crust characterized by normal faulting and a relatively narrow distal transition zone that may contain unroofed serpentinized mantle. The lack of drilled wells makes it challenging to evaluate the petroleum potential of the CTSE, although some indications of a working petroleum system presence exist.
Compiler-Driven FPGA Virtualization with SYNERGY
Authors: Landgraf Joshua , Yang Tiffany , Lin Will , Rossbach Christopher J. , Schkufza Eric
Published: May 2024

FPGAs are increasingly common in modern applications, and cloud providers now support on-demand FPGA acceleration in datacenters. Applications in datacenters run on virtual infrastructure, where consolidation, multi-tenancy, and workload migration enable economies of scale that are fundamental to the provider's business. However, a general strategy for virtualizing FPGAs has yet to emerge. While manufacturers struggle with hardware-based approaches, we propose a compiler/runtime-based solution called Synergy. We show a compiler transformation for Verilog programs that produces code able to yield control to software atsub-clock-tickgranularity according to the semantics of the original program. Synergy uses this property to efficiently support core virtualization primitives: suspend and resume, program migration, and spatial/temporal multiplexing, on hardware which is availabletoday.We use Synergy to virtualize FPGA workloads across a cluster of Intel SoCs and Xilinx FPGAs on Amazon F1. The workloads require no modification, run within 3--4x of unvirtualized performance, and incur a modest increase in FPGA fabric usage.
Data management for continuous learning in EHR systems
Authors: Bellandi Valerio , Ceravolo Paolo , Maggesi Jonatan , Maghool Samira
Published: May 2024

To gain a comprehensive understanding of a patient’s health, advanced analytics must be applied to the data collected by electronic health record (EHR) systems. However, managing and curating this data requires carefully designed workflows. While digitalization and standardization enable continuous health monitoring, missing data values and technical issues can compromise the consistency and timeliness of the data. In this paper, we propose a workflow for developing prognostic models that leverages the SMART BEAR infrastructure and the capabilities of the Big Data Analytics (BDA) engine to homogenize and harmonize data points. Our workflow improves the quality of the data by evaluating different imputation algorithms and selecting one that maintains the distribution and correlation of features similar to the raw data. We applied this workflow to a subset of the data stored in the SMART BEAR repository and examined its impact on the prediction of emerging health states such as cardiovascular disease and mild depression. We also discussed the possibility of model validation by clinicians in the SMART BEAR project, the transmission of subsequent actions in the decision support system, and the estimation of the required number of data points.
Developing Time Series Forecasting Models with Generative Large Language Models
Authors: Morales-García Juan , Llanes Antonio , Arcas-Túnez Francisco , Terroso-Sáenz Fernando
Published: May 2024

Nowadays, Generative Large Language Models (GLLMs) have made a significant impact in the field of Artificial Intelligence (AI). One of the domains extensively explored for these models is their ability as generators of functional source code for software projects. Nevertheless, their potential as assistants to write the code needed to generate and model Machine Learning (ML) or Deep Learning (DL) architectures has not been fully explored to date. For this reason, this work focuses on evaluating the extent to which different tools based on GLLMs, such as ChatGPT or Copilot, are able to correctly define the source code necessary to generate viable predictive models. The use case defined is the forecasting of a time series that reports the indoor temperature of a greenhouse. The results indicate that, while it is possible to achieve good accuracy metrics with simple predictive models generated by GLLMs, the composition of predictive models with complex architectures using GLLMs is still far from improving the accuracy of predictive models generated by human data scientists.
Efficient decoding up to a constant fraction of the code length for asymptotically good quantum codes
Authors: Leverrier Anthony , Zémor Gilles
Published: May 2024

We introduce and analyse an efficient decoder for quantum Tanner codes that can correct adversarial errors of linear weight. Previous decoders for quantum low-density parity-check codes could only handle adversarial errors of weight

\(O(\sqrt{n\log n})\)

. We also work on the link between quantum Tanner codes and the Lifted Product codes of Panteleev and Kalachev, and show that our decoder can be adapted to the latter. The decoding algorithm alternates between sequential and parallel procedures and converges in linear time.
Know their Customers: An Empirical Study of Online Account Enumeration Attacks
Authors: Maceiras Maël , Salehzadeh Niksirat Kavous , Bernard Gaël , Garbinato Benoit , Cherubini Mauro , Humbert Mathias , Huguenin Kévin
Published: May 2024

Internet users possess accounts on dozens of online services where they are often identified by one of their e-mail addresses. They often use the same address on multiple services and for communicating with their contacts. In this paper, we investigate attacks that enable an adversary (e.g., company, friend) to determine (stealthily or not) whether an individual, identified by their e-mail address, has an account on certain services (i.e., an
account enumeration attack
). Such attacks on
account privacy
have serious implications as information about one’s accounts can be used to (1) profile them and (2) improve the effectiveness of phishing. We take a multifaceted approach and study these attacks through a combination of experiments (63 services), surveys (318 respondents), and focus groups (13 participants). We demonstrate the high vulnerability of popular services (93.7%) and the concerns of users about their account privacy, as well as their increased susceptibility to phishing e-mails that impersonate services on which they have an account. We also provide findings on the challenges in implementing countermeasures for service providers and on users’ ideas for enhancing their account privacy. Finally, our interaction with national data protection authorities led to the inclusion of recommendations in their developers’ guide.
Electroanalytical Exploration of Li Loss at the Solid Electrolyte-Anode Interface in Anode-Free Batteries with Polymer Electrolytes
Authors: Sahore Ritu , Mayer Alexander , Steinle Dominik , Counihan Michael J. , Chen Xi Chelsea , Tepavcevic Sanja , Bresser Dominic , Westover Andrew S.
Published: May 2024

Li loss during cycling at the solid electrolyte∣anode interface strongly determines the cycle life of anode-free solid-state batteries (SSBs). Here, this loss is probed electroanalytically for polymer electrolyte (PE)-based SSBs in anode-free coin cells with practical pressures. A wide range of parameters expected to impact the measured average coulombic efficiency (CE) were explored to estimate the expected range of performance. These factors include PE type, cycling profiles, current collector type, and the presence of a thin Li seed layer. Low CE values in the ∼50%–85% range are observed for all electrolytes and test conditions. Other than the electrolyte type, a strong dependence of the CE on the electrochemical cycling profile and the type of metallic current collector is observed. Compared to the anode-free setup, the presence of a thin (5 μm) Li seed layer did not improve the average CE for two out of three PEs, suggesting its presence to be a weak contributor in minimizing the Li loss. This work provides baseline data on the Li losses in low-pressure anode-free configuration cells with PEs.
A Solid-State Reaction in a Vapor Chamber: Synthesis of Bi2(MoO4)3 Nanorods as High-Capacity Anode for Lithium-Ion Batteries
Authors: Tran Huu Ha , Luu Quang Huy , Nguyen Thi Thuy Trang , Le Thi Bich Ngoc , Nguyen Se Chin , Vo Ngoc Tra My , Minh Nguyen Thu , Nguyen Van Thang , Nguyen Phi Hung , Tran Van Man , Vo Vien
Published: May 2024

Conversion- and alloying-type materials have been investigated as alternatives to intercalating graphite anodes of lithium-ion batteries for recent decades. However, the electrochemical pulverization and limitations in large-scale production of metal oxides prohibit them from practical applications. This work provided an ambient solid-state reaction accelerated by water vapor for synthesizing Bi2(MoO4)3 nanorods combined with carbon under mild-condition ball-milling for composite fabrication. The obtained composite performs superior electrochemical performance: a delivered capacity of 802.2 mAh·g−1 after 300 cycles at a specific current of 500 mA·g−1 with a retention of 82.3%. This improvement was ascribed to the better accommodation to volume variation and reinforced physical contact raised by one-dimensional morphology and ball-milling treatment. The complex conversion-intercalation-alloying mechanism of the lithium-ion storage in Bi2(MoO4)3 anode was also clarified using cyclic voltammetry and ex situ X-ray photoelectron spectroscopy results.
Effect of menstrual cycle and menopause on human gastric electrophysiology
Authors: Lim Alexandria H. , Varghese Chris , Sebaratnam Gabrielle H. , Schamberg Gabriel , Calder Stefan , Gharibans Armen A. , Andrews Christopher N. , Foong Daphne , Ho Vincent , Ishida Shunichi , Imai Yohsuke , Wise Michelle R. , O’Grady Greg
Published: May 2024

This study evaluates gastric electrophysiology in relation to the menstrual cycle using a novel noninvasive high-resolution methodology, revealing substantial variations in gastric activity with menstrual cycling and menopause. Gastric slow-wave frequency is significantly higher in the luteal versus follicular menstrual phase. Computational modeling predicts that this difference translates to higher rates of gastric mixing and liquid emptying in the luteal phase, which is consistent with previous experimental data evaluating menstrual cycling effects on gastric emptying.
Novel 5-HT7 receptor antagonists modulate intestinal immune responses and reduce severity of colitis
Authors: Kwon Yun Han , Blass Benjamin E. , Wang Huaqing , Grondin Jensine A. , Banskota Suhrid , Korzekwa Kenneth , Ye Min , Gordon John C. , Colussi Dennis , Blattner Kevin M. , Canney Daniel J. , Khan Waliul I.
Published: May 2024

This study demonstrates that the novel highly selective 5-HT7 receptor antagonists, MC-170073 and MC-230078, significantly alleviated the severity of colitis across models of experimental colitis. These findings suggest that inhibition of 5-HT7 receptor signaling by these new antagonists may serve as an alternative mode of treatment to diminish symptomology in those with inflammatory bowel disease.
NF-κB/RelA signaling in secretoglobin progenitors mediates plasticity and MMP-induced barrier disruption in house dust mite-induced allergic asthma
Authors: Skibba Melissa E. , Brasier Allan R.
Published: May 2024

Allergic asthma from house dust mite (HDM) allergy causes substantial morbidity. This study examines the dynamic changes in small airway epithelial cells in a mouse model of HDM exposure. Our findings indicate that NF-κB/RelA signaling mediates matrix metalloproteinase production, disrupting the epithelial barrier resulting in allergic sensitization. Our findings bring new insight into mechanisms for epithelial cell-state change in the allergen response, creating a potential therapeutic pathway for maintaining barrier function in asthma.
Effect of estrogen receptor α on cardiopulmonary adaptation to chronic developmental hypoxia in a rat model
Authors: Severyn Nicholas T. , Esparza Patricia , Gao Huanling , Mickler Elizabeth A. , Albrecht Marjorie E. , Fisher Amanda J. , Yakubov Bahktiyor , Cook Todd G. , Slaven James E. , Walts Avram D. , Tepper Robert S. , Lahm Tim
Published: May 2024

By exposing novel loss-of-function estrogen receptor alpha (Erα) mutant rats to a novel model of human high-altitude exposure, we demonstrate that ERα has subtle but inconsistent effects on endpoints relevant to cardiopulmonary adaptation to chronic hypoxia. Given that we observed some histologic, sex, and genotype differences, further research into cell-specific effects of ERα during hypoxia-induced cardiopulmonary adaptation is warranted.
Antenatal creatine supplementation reduces persistent fetal lung inflammation and oxidative stress in an ovine model of chorioamnionitis
Authors: Choi Y. Jane , Williams Ellen , Dahl Mar Janna , Amos Sebastian E. , James Christopher , Bautista Angelo P. , Kurup Veena , Musk Gabrielle C. , Kershaw Helen , Arthur Peter G. , Kicic Anthony , Choi Yu Suk , Terrill Jessica R. , Pillow J. Jane
Published: May 2024

We evaluated the effect of antenatal creatine supplementation to reduce pulmonary inflammation and oxidative stress in the fetal lamb lungs arising from lipopolysaccharide (LPS)-induced chorioamnionitis. Fetal creatine supplementation increased lung creatine content and had no adverse effects on systemic fetal physiology and overall lung architecture. Importantly, fetuses that received creatine had significantly lower levels of inflammation and oxidative stress in the lungs, suggesting an anti-inflammatory and antioxidant benefit of creatine.
Elastin-derived peptides favor type 2 innate lymphoid cells in chronic obstructive pulmonary disease
Authors: Lahire Sarah , Fichel Caroline , Rubaszewski Océane , Lerévérend Cédric , Audonnet Sandra , Visneux Vincent , Perotin Jeanne-Marie , Deslée Gaëtan , Le Jan Sébastien , Potteaux Stéphane , Le Naour Richard , Pommier Arnaud
Published: May 2024

Elastin-derived peptides, generated following alveolar degradation during emphysema in patients with COPD, are able to influence the response of type 2 innate lymphoid cells. We show that the orientation of innate lymphoid cells in patients with COPD is shifted toward a type 2 profile and that elastin peptides are indirectly participating in that shift through their influence of macrophages, which in turn impact innate lymphoid cells.
Low-volume ventilation of preinjured lungs degrades lung function via stress concentration and progressive alveolar collapse
Authors: Zimmermann Richard , Roeder Franziska , Ruppert Clemens , Smith Bradford J. , Knudsen Lars
Published: May 2024

Low-volume mechanical ventilation in the presence of high surface tension-induced microatelectases leads to the degradation of lung mechanical function via the progressive loss of alveoli. Microatelectases grow at the interfaces of collapsed and open alveoli. Here, stress concentrations might cause injury and alveolar instability. Accumulation of small amounts of alveolar edema can be found in a fraction of partly collapsed alveoli but, in this model, alveolar flooding is not a major driver for degradation of lung mechanics.
Simultaneous, Dual Continuous Venovenous Haemodiafiltration as Salvage Therapy for Severe Sodium Valproate Intoxication
Authors: Hussan Aminah , Hasan Ifrah , El-Hayani Reem , Zahra Moustafa Shebl
Published: May 2024

Sodium valproate overdose leads to CNS depression, cerebral oedema, and severe metabolic acidosis in cases of severe toxicity. Extracorporeal removal, specifically through intermittent haemodialysis, is recommended, though not always tolerated by or accessible to haemodynamically unstable patients in intensive care units. We present a case of a male in his mid‐twenties presenting following a massive, intentional overdose of 13 g of sodium valproate over 7 hours, with an initial valproate blood concentration of 975 μg/ml (normal 50‐100 μg/ml). He was hypoxic and severely acidotic on arrival and was given fluids and L‐carnitine according to TOXBASE guidelines. This resulted in only marginal improvement to his acidosis. Once transferred to our intensive care unit, the patient was started on inotropic support followed by continuous venovenous hemofiltration (CVVHDF) at the maximum effluent rate of 60 ml/kg/hr. Due to his persisting metabolic acidosis and worsening hyperlacataemia, dual CVVHDF was started by adding another filter in series after 26 hours, increasing the maximum effluent rate to 96 ml/kg/hr. The patient remained on dual CVVHDF for 31 hours, during which his acidosis and lactate showed considerable improvement, and he was subsequently stepped down to single‐filter CVVHDF for a further 20 hours until complete resolution of his acidosis. This case report recognises dual CVVHDF as a viable salvage therapy for severe sodium valproate overdose by facilitating the achievement of a higher effluent flow rate compared to what can be accomplished with single‐filter CVVHDF.
Immune-Enhancing Activity of Vitis coignetiae Extract via Increasing Cytokine and Natural Killer Cell Activity in Splenocytes and Cyclophosphamide-Induced Immunosuppressed Rats
Authors: Park Young Mi , Lee Hak Yong , Shin Dong Yeop , Jeong Han Na , Hwang Hai Min , Park Hyo Yeon , Kim Suk Hun , Kim Min Ji , Kang Hee Joo , Kim Jin Hee , Kim Myung-sunny , Yang Hye Jeong , Kim Min Jung , Kim Jae Gon
Published: May 2024

Plant and fruit extracts exhibit fewer side effects than pharmaceuticals and can display therapeutic qualities. Consequently, they have attracted increased attention among health-conscious individuals, and many studies related to their health-promoting effects are being actively conducted. Vitis coignetiae is well-known for its antioxidant, anti-inflammatory, and anticancer properties. However, the immune-enhancing effects of Vitis coignetiae have not yet been studied. In this study, Vitis coignetiae extract (VCE) increased immune-related activity in Wistar rat splenocytes and cyclophosphamide (Cy)-induced immunosuppressed rats. In splenocytes, VCE was nontoxic up to 300 μg/mL and increased cell viability in the presence of Cy. VCE also recovered Cy-induced decreases in cytokine (tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), interleukin-2 (IL-2), and IL-12) levels and natural killer (NK) cell activity in splenocytes. In Cy-induced immunosuppressed rats, VCE protected against Cy-induced spleen tissue damage and decreases in body and spleen weight, cytokine (TNF-α, IFN-γ, IL-2, and IL-12) levels, and NK cell activity. We also observed recovery of immunoglobulin G (IgG) and IgM levels following VCE treatment. In conclusion, the ability of VCE to restore immune activity from an immunosuppressive state to normal levels suggests its immune-enhancing efficacy. Therefore, VCE may have the potential for application in the development of immune-enhancing functional foods and medicines.
FDA Approval Summary: Ciltacabtagene Autoleucel for Relapsed or Refractory Multiple Myeloma
Authors: Natrajan Kavita , Kaushal Megha , George Bindu , Kanapuru Bindu , Theoret Marc R.
Published: May 2024

In February 2022, the FDA approved ciltacabtagene autoleucel, a chimeric antigen receptor (CAR) T-cell therapy targeting the B-cell maturation antigen, for adult patients with relapsed/refractory multiple myeloma after ≥4 lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. Approval was based on overall response rate (ORR), complete response (CR) rate, and duration of response (DoR) in 97 adult patients in a single-arm, open-label, multicenter phase 2 trial (CARTITUDE-1 [NCT03548207]). Patients received a single infusion of ciltacabtagene autoleucel, preceded by lymphodepleting chemotherapy. Of the 97 patients evaluable, ORR was 97.9% [95% confidence interval (CI), 92.7–99.7] with a stringent CR rate of 78.4% (95% CI, 68.8–86.1). After median follow-up of 18 months, the median DoR was 21.8 months (95% CI, 21.8–not estimable [NE]) in responders (PR or better) and NE (95% CI, 21.8 months–NE) in patients who achieved stringent CR. Serious adverse reactions occurred in 55% of the 97 patients evaluated for safety. Grade 3 or higher cytokine release syndrome (CRS) and neurologic toxicities occurred in 5% and 11% of the patients, respectively, leading to a Risk Evaluation and Mitigation Strategy. Neurologic toxicities included immune effector cell–associated neurologic syndrome, typically seen with CAR-T products, parkinsonism, peripheral neuropathy, cranial nerve palsies, and Guillain–Barré syndrome. One fatal case of hemophagocytic lymphohistiocytosis/macrophage activation syndrome occurred. Prolonged and recurrent grade 3 or 4 cytopenias occurred; a single patient required hematopoietic stem-cell rescue.
Paraneoplastic Hyperthyroidism in Advanced Testicular Non-Seminomatous Germ Cell Tumors: Prevalence and Clinical Management
Authors: Angerer Markus , Hansen Bendix , Wülfing Christian , Dieckmann Klaus-Peter
Published: May 2024

Introduction: Paraneoplastic hyperthyroidism (PH) has been reported in patients with testicular germ cell tumors (GCTs), sporadically. This disorder is caused by extremely elevated serum levels of beta-human chorionic gonadotropin (bHCG). To date, little is known about the prevalence of PH, and its clinical features are poorly understood. The aim of the present study was to analyze the relative frequency and clinical features of PH in GCTs and evaluate their effects on therapeutic outcomes. Methods: A cohort of 438 patients treated for testicular GCT from 2017 to 2023 was retrospectively analyzed for histology, age, clinical stage, and presence of PH. The clinical features of the patients with PH were evaluated descriptively. The relative frequency of PH was compared among the subgroups using descriptive statistical methods. Results: Three patients with PH were identified; all had clinical symptoms of hyperthyroidism, suppressed serum levels of thyroid-stimulating hormone (TSH), and increased levels of tri-iodothyronin (fT3). All the patients had advanced, metastasized, and non-seminomatous GCTs. Serum bHCG levels ranged from 225,00 U/L to 1,520,000 U/L. The prevalence of PH was 0.7% in the entire GCT population and 60% in those with very high bHCG serum levels. All the patients received standard cisplatin-based chemotherapy along with thyrostatic treatment. The clinical symptoms of the hyperthyroidism rapidly disappeared. TSH levels normalized with decreasing bHCG levels. The PH treatment did not affect the therapeutic outcomes of the patients. Conclusion: PH may occur in 0.7% of all patients with GCT but may be present in up to 60% of patients with very high levels of bHCG. Measuring serum levels of TSH and fT3 should be performed in addition to routine diagnostic measures in all patients with poor prognosis GCTs. Thyrostatic medication is recommended for patients with the clinical symptoms of hyperthyroidism. Early recognition of hyperthyroidism and prompt intervention will reduce comorbidity and help optimize therapeutic outcomes.
Thiazolidinediones Decrease the Recurrence of Intracerebral Hemorrhage in Type 2 Diabetes Mellitus Patients: A Nested Case-Control Study
Authors: Chiu Cheng-Di , Chiu You-Pen , Yip Hei-Tung , Ji Hui-Ru , Cho Der-Yang , Cheng Irene Han-Juo , Chen Cho-Yi
Published: May 2024

Introduction: Preclinical evidence demonstrated the therapeutic potential of thiazolidinediones (TZDs) for the treatment of intracerebral hemorrhage (ICH). The present study conducted an investigation of cerebrovascular and cardiovascular outcomes following ICH in patients with type 2 diabetes mellitus (T2DM) treated with or without TZDs. Methods: This retrospective nested case-control study used data from the Taiwan National Health Insurance Research Database. A total of 62,515 T2DM patients who were hospitalized with a diagnosis of ICH were enrolled, including 7,603 TZD users. Data for TZD non-users were extracted using propensity score matching. Primary outcomes included death and major adverse cardiovascular events (MACEs), which were defined as a composite of ischemic stroke, hemorrhagic stroke (HS), acute myocardial infarction, and congestive heart failure. Patients aged <20 years with a history of traumatic brain injury or any prior history of MACEs were excluded. Results: TZD users had significantly lower MACE risks compared with TZD non-users following ICH (adjusted hazard ratio [aHR]: 0.90, 95% confidence interval [CI]: 0.85–0.94, p < 0.001). The most significant MACE difference reported for TZD users was HS, which possessed lower incidence than in TZD non-users, especially for the events that happened within 3 months following ICH (aHR: 0.74, 95% CI: 0.62–0.89 within 1 month, p < 0.01; aHR: 0.68, 95% CI: 0.54–0.85 between 1 and 3 month). Conclusion: The use of TZD in patients with T2DM was associated with a lower risk of subsequent HS and mortality following ICH.
Long-Term Disinfection in Operating Rooms Affects Skin Microbiota and Metabolites of Medical Personnel
Authors: Yan Yu , Huang Shuzheng , Zeng Yu , Yue Siyuan , Wang Tong , Yuan Lin , Nie Junhui
Published: May 2024

Introduction: Disinfectants play a critical role in reducing healthcare-associated infections by eliminating microorganisms on surfaces. However, prolonged use of disinfectants may adversely affect the skin microflora, essential for skin health and infection prevention. This study investigates the impact of disinfection on the skin microbiota and metabolites of medical personnel in operating rooms, aiming to provide a scientific foundation for safeguarding their skin health. Methods: We conducted 16S sequencing and metabolomic analysis to assess the effects of disinfection on the skin microbiota and metabolites of medical personnel. Samples were collected from operating room personnel after disinfectant exposure to identify changes in microbial communities and metabolite profiles. Results: Our analysis revealed that prolonged use of disinfectants led to alterations in skin microbial communities and microbial metabolites. These alterations included the production of harmful metabolites that could potentially promote skin infections and other health issues among medical personnel. Conclusion: The findings underscore the importance of minimizing disruptions to skin microbiota and metabolites caused by long-term disinfectant use to preserve the overall health of medical personnel. This study provides valuable insights into the relationship between disinfectant use, skin microbiota, and metabolites, highlighting the necessity for further research in this area.