bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic panel analysis of the EU's fiscal reaction function with threshold effects
Authors: Mamatzakis Emmanuel 
Published: March 2024

AbstractThis study contributes to the ongoing reform of the EU's economic governance, particularly about fiscal performance. We opt for a fiscal reaction function of the cyclically adjusted primary balance. Given concerns over underlying endogeneity and heterogeneity across countries we employ a threshold dynamic analysis. The findings confirm that the fiscal policy in the EU has been procyclical overall. However, we identify two regimes of output gap. Fiscal policy has been countercyclical for EU member states in the higher output gap regime while EU member states follow a procyclical fiscal policy in the lower regime. We reveal also that the endogenous debt‐to‐GDP ratio threshold is at 75.6% for the EU and 78.7% for the Euro area, which notably exceeds the EU Treaty's reference value of 60%. Fiscal rules and fiscal councils mitigate procyclical fiscal policies, being more effective for low debt countries. In terms of policy implications, the identified fiscal thresholds and variability across countries warrant a higher degree of fiscal coordination in the EU, particularly in the Euro area.
Factors affecting the compliance of hepatocellular carcinoma screening among high‐risk populations: A systematic review and meta‐analysis
Authors: Feng Ge‐hui , Yue Qian‐qian , Zhao Ke‐hao , Peng Tong , Tang Tian , Sun Ying‐xue , Meng Xin‐ru , Huang Li‐li , Zeng Xi , Zeng Ying 
Published: March 2024

AbstractBackgroundHepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the third leading cause of cancer mortality. HCC has high morbidity, high mortality, and low survival rates. Screening is one of the most significant methods of lowering incidence and death while also increasing survival.ObjectivesThe aim of this study was to identify the facilitators and barriers to participation in HCC screening among high‐risk populations.MethodsA comprehensive and systematic search was undertaken in PubMed, Web of Science, MEDLINE, EMBACE, EBSCOhost and the Cochrane Library. A combination of synonyms of the keywords including HCC, screening, factors and adherence were used for searching. Studies addressing the facilitators and barriers to HCC screening compliance in at‐risk individuals were included. Data were synthesized using Review Manager version 5.4. A random/fixed effects model meta‐analysis was performed to estimate the pooled data and expressed with odds ratio (OR) and 95% confidence interval (CI).ResultsA total of seven articles met the inclusion criteria. Qualitative (n = 1) and quantitative (n = 6) studies using various types of surgery were conducted. The most commonly mentioned barriers were insufficient knowledge and awareness of HCC screening, unawareness of the necessity for early detection of HCC and lack of physician recommendation. A meta‐analysis of seven studies showed that individuals with a family history of HCC increased screening uptake by nearly three times (OR: 2.69, 95% CI: 1.93, 3.75). Other most frequently reported facilitators include age, education level, and perceived risk et al.ConclusionsMany barriers to HCC screening were found. Meanwhile, this review points out that improving the awareness of high‐risk populations toward HCC screening is expected to enhance compliance, thereby promoting early diagnosis of liver cancer, reducing mortality, and alleviating the burden of HCC.
Endophytic Fungi‐Mediated Defense Signaling in Maize: Unraveling the Role of WRKY36 in Regulating Immunity against Spodoptera frugiperda
Authors: Batool Raufa , Xuelian Gou , Hui Dong , Xiuzhen Long , Umer Muhammad Jawad , Rwomushana Ivan , Ali Abid , Attia Kotb A. , Jingfei Guo , Zhenying Wang 
Published: March 2024

AbstractSeed priming with beneficial endophytic fungi is an emerging sustainable strategy for enhancing plant resistance against insect pests. This study examined the effects of Beauvaria bassiana Bb20091317 and Metarhizium rileyi MrCDTLJ1 fungal colonization on maize growth, defence signalling, benzoxazinoid levels and gene expression. The colonization did not adversely affect plant growth but reduced larval weights of Spodoptera frugiperda. Maize leaves treated with M. rileyi exhibited higher levels of jasmonic acid, jasmonoyl‐Isoleucine, salicylic acid, and indole acetic acid compared to control. B. bassiana and M. rileyi accelerated phytohormone increase upon S. frugiperda herbivory. Gene expression analysis revealed modulation of benzoxazinoid biosynthesis genes. We further elucidated the immune regulatory role of the transcription factor zmWRKY36 using virus‐induced gene silencing (VIGS) in maize. zmWRKY36 positively regulates maize immunity against S. frugiperda, likely by interacting with defense‐related proteins. Transient overexpression of zmWRKY36 in tobacco‐induced cell death, while silencing in maize reduced chitin‐triggered reactive oxygen species burst, confirming its immune function. Overall, B. bassiana and M. rileyi successfully colonized maize, impacting larval growth, defense signalling, and zmWRKY36‐mediated resistance. This sheds light on maize‐endophyte‐insect interactions for sustainable plant protection.
Children's help‐seeking expectations during preschool years: The effects of situational stress levels and help‐seekers’ competence
Authors: Jia Chenglong , Xia Xuan , Shen Yuan , Wang Jingmei , Qin Jinliang 
Published: March 2024

AbstractHelp‐seeking is a common strategy for children to cope with daily stress. However, little is known as to how children make help‐seeking expectations during early development. The current study examined the effects of situational stress levels and help‐seekers’ competence on children's expectations of help‐seeking behavior and willingness from age 4 to 6. We manipulated situational stress levels and help‐seekers’ competence in a social expectation task. Children were tested to determine their expectations of help‐seeking behavior and willingness. Two hundred and twenty‐one Han Chinese children aged 4–6 from a city in East China participated in this study. We found that 5‐ to 6‐year‐olds expected the incompetent help‐seekers to seek support more than the competent help‐seekers regardless of situational stress levels. However, 4‐ to 5‐year‐olds made expectations as such only in the low‐stress condition. These results suggest that both situational stress levels and help‐seekers’ competence influence 4‐ to 6‐year‐old children's help‐seeking expectations, and the influence varies across ages.
Characteristics, predictors and consequences of tuberculosis treatment interruption: A multicentre retrospective cohort study
Authors: Oh Ai Ling , Makmor‐Bakry Mohd , Islahudin Farida , Ting Chuo Yew , Chan Swee Kim , Tie Siew Teck 
Published: March 2024

AbstractObjectivesTreatment interruption is associated with poor tuberculosis (TB) treatment outcomes and increased drug resistance. To address the issue, we aimed to investigate the characteristics, predictors and consequences of treatment interruption.MethodsWe conducted a retrospective cohort study by retrieving 4 years (2018–2021) of TB patients' records at 10 public health clinics in Sarawak, Malaysia. Adult patients (≥18 years) with drug‐susceptible TB were selected. Treatment interruption was defined as ≥2 weeks of cumulative interruption during treatment. The Chi‐square test, Mann–Whitney U test, Kaplan–Meier and Cox proportional hazards regression were used to analyse the data, with p < 0.05 being considered statistically significant.ResultsOut of 2953 eligible patients, 475 (16.1%) experienced TB treatment interruption. Interruptions were most frequent during the intensive phase (46.9%, n = 223), with the greatest risk within the first 4 weeks of treatment. The median time to interruption was 2 weeks in the intensive phase and the cumulative interruption probability at the end of the intensive phase was 12.9%. Notably, treatment interruption occurred during both intensive and continuation phases for 144 patients (30.3%), while the remaining 108 (22.7%) experienced interruptions only during the continuation phase with a median time to interruption of 16 weeks. Three predictors were identified to increase the risk of treatment interruption: adverse drug reaction (aHR = 8.53, 95% Cl: 6.73–10.82), smoking (aHR = 2.67, 95% Cl: 2.03–3.53) and illicit drug use (aHR = 1.88, 95% Cl: 1.03–3.45). Conversely, underlying diabetes was associated with a reduced likelihood of treatment interruption (aHR = 0.72, 95% Cl: 0.58–0.90). Treatment interruption led to significant differences in treatment restarts (62.3% vs. 0.7%), changes in medications (47.8% vs. 4.9%), prolonged treatment duration (247 days [IQR = 105] vs. 194 days [IQR = 44.3]) and lower successful outcomes (86.5% vs. 99.9%).ConclusionUnderstanding the temporal characteristics, predictors and negative consequences of treatment interruption can guide the development of time‐relevant approaches to mitigate the problem.
Liouville theorems and optimal regularity in elliptic equations
Authors: Tortone Giorgio 
Published: March 2024

AbstractThe objective of this paper is to establish a connection between the problem of optimal regularity among solutions to elliptic partial differential equations with measurable coefficients and the Liouville property at infinity. Initially, we address the two‐dimensional case by proving an Alt–Caffarelli–Friedman‐type monotonicity formula, enabling the proof of optimal regularity and the Liouville property for multiphase problems. In higher dimensions, we delve into the role of monotonicity formulas in characterizing optimal regularity. By employing a hole‐filling technique, we present a distinct “almost‐monotonicity” formula that implies Hölder regularity of solutions. Finally, we explore the interplay between the least growth at infinity and the exponent of regularity by combining blow‐up and ‐convergence arguments.
FGF2 gene's antisense protein, NUDT6, plays a depressogenic role by promoting inflammation and suppressing neurogenesis without altering FGF2 signalling
Authors: Uzay Burak , Bahadır‐Varol Aslıhan , Hökelekli Fatma Özlem , Yılmaz Murat , Esen Emre Cem , Başar Koray , Ayhan Yavuz , Dalkara Turgay , Eren‐Koçak Emine 
Published: March 2024

AbstractFibroblast growth factor‐2 (FGF2) is involved in the regulation of affective behaviour and shows antidepressant effects through the Akt and extracellular signal regulated kinase (ERK) 1/2 pathways. Nudix hydrolase 6 (NUDT6) protein is encoded from FGF2 gene's antisense strand and its role in the regulation of affective behaviour is unknown. Here, we overexpressed NUDT6 in the hippocampus and investigated its behavioural effects and the underlying molecular mechanisms affecting the behaviour. We showed that increasing hippocampal NUDT6 results in depression‐like behaviour in rats without changing FGF2 levels or activating its downstream effectors, Akt and ERK1/2. Instead, NUDT6 acted by inducing inflammatory signalling, specifically by increasing S100 calcium binding protein A9 (S100A9) levels, activating nuclear factor‐kappa B‐p65 (NF‐κB‐p65), and elevating microglia numbers along with a reduction in neurogenesis. Our results suggest that NUDT6 could play a role in major depression by inducing a proinflammatory state. This is the first report of an antisense protein acting through a different mechanism of action than regulation of its sense protein. The opposite effects of NUDT6 and FGF2 on depression‐like behaviour may serve as a mechanism to fine‐tune affective behaviour. Our findings open up new venues for studying the differential regulation and functional interactions of sense and antisense proteins in neural function and behaviour, as well as in neuropsychiatric disorders.
imageKey points
Hippocampal overexpression of nudix hydrolase 6 (NUDT6), the antisense protein of fibroblast growth factor‐2 (FGF2), increases depression‐like behaviour in rats.
Hippocampal NUDT6 overexpression triggers a neuroinflammatory cascade by increasing S100 calcium binding proteinA9 (S100A9) expression and nuclear NF‐κB‐p65 translocation in neurons, in addition to microglial recruitment and activation.
Hippocampal NUDT6 overexpression suppresses neurogenesis.
NUDT6 exerts its actions without altering the levels or downstream signalling pathways of FGF2.
The Impact of the Fluid–Solid Coupling Behavior of Macro and Microstructures in the Spiral Cochlea on Hearing
Authors: Zhao Zhengshan , Liang Junyi , Yao Wenjuan 
Published: March 2024

Abstract
The cilia of the outer hair cells (OHCs) are the key microstructures involved in cochlear acoustic function, and their interactions with lymph in the cochlea involve complex, highly nonlinear, coupled motion and energy conversions, including macroscopic fluid–solid coupling. Recent optical measurements have shown that the frequency selectivity of the cochlea at high sound levels is entirely mechanical and is determined by the interactions of the hair bundles with the surrounding fluid. In this paper, an analytical mathematical model of the spiral cochlea containing macro- and micromeasurements was developed to investigate how the phonosensitive function of OHCs' motions is influenced by the macrostructural and microstructural fluid–solid coupling in the spiral cochlea. The results showed that the macrostructural and microstructural fluid–solid coupling exerted the radial forces of OHCs through the flow field, deflecting the cilia and generating frequency-selective properties of the microstructures. This finding showed that microstructural frequency selectivity arises from the radial motions of stereocilia hair bundles and enhances the hearing of sound signals at specific frequencies. It also implied that the macrostructural and microstructural fluid–solid couplings influence the OHCs' radial forces and that this is a key factor in the excitation of ion channels that enables their activity in helping the brain to detect sound.
Reduction of Disk Friction Loss by Applying a Fin to the Back of a Centrifugal Impeller
Authors: Maeda Satoshi , Sano Takeshi , Miyagawa Kazuyoshi , Sakai Kento 
Published: March 2024

Abstract
It is well known that the ratio of disk friction loss of low specific speed pumps is large. When the specific speed is 100 min−1, m3/min, m or less, the disk friction loss increases remarkably. In this study, focusing on the clearance flow from the diffuser outlet to the impeller outlet (This is called the outward flow) behind the centrifugal pump, a fin was installed on outer diameter side of the rotating wall on the back side of a centrifugal pump as a countermeasure, and the influence of changes in velocity distribution near the wall on disk friction loss was investigated by torque measurements, velocity measurement, and computational fluid dynamics (CFD) analysis. As a result, it was clarified that disk friction loss is decreasing by installing the fin in both torque measurements and CFD results, because the clearance flow is separated by fin and circumferential velocity is increased in the wake region of the fin in both measurements and CFD. In addition, it was clarified that disk friction coefficient (normalized torque) can be expressed as a function of the inlet swirl ratio and Reynolds number. Also, prediction equation is derived for each shape (with and without fin). According to the equation, it was found that disk friction loss reduction effect by installing a fin becomes larger when Reynolds number and the inlet swirl ratio are small.
A panel of janus kinase inhibitors identified with anti-inflammatory effects protect mice from lethal influenza virus infection
Authors: Yu Yang , Chen Si , Zhang Haonan , Duan Yuanyuan , Li Zhuogang , Jiang Lefang , Cao Weihua , Peng Qun , Chen Xulin 
Published: March 2024

ABSTRACT

Influenza remains a significant threat to public health. In severe cases, excessive inflammation can lead to severe pneumonia or acute respiratory distress syndrome, contributing to patient morbidity and mortality. While antivirals can be effective if administered early, current anti-inflammatory drugs have limited success in treating severe cases. Therefore, discovering new anti-inflammatory agents to inhibit influenza-related inflammatory diseases is crucial. Herein, we screened a drug library with known targets using a human monocyte U937 infected with the influenza virus to identify novel anti-inflammatory agents. We also evaluated the anti-inflammatory effects of the hit compounds in an influenza mouse model. Our research revealed that JAK inhibitors exhibited a higher hit rate and more potent inhibition effect than inhibitors targeting other drug targets
in vitro
. Of the 22 JAK inhibitors tested, 15 exhibited robust anti-inflammatory activity against influenza virus infection
in vitro
. Subsequently, we evaluated the efficacy of 10 JAK inhibitors using an influenza mouse model and observed that seven provided protection ranging from 40% to 70% against lethal influenza virus infection. We selected oclacitinib as a representative compound for an extensive study to further investigate the
in vivo
therapeutic potential of JAK inhibitors for severe influenza-associated inflammation. Our results revealed that oclacitinib effectively suppressed neutrophil and macrophage infiltration, reduced pro-inflammatory cytokine production, and ultimately mitigated lung injury in mice infected with lethal influenza virus without impacting viral titer. These findings suggest that JAK inhibitors can modulate immune responses to influenza virus infection and may serve as potential treatments for influenza.

IMPORTANCE

Antivirals exhibit limited efficacy in treating severe influenza when not administered promptly during the infection. Current steroidal and nonsteroidal anti-inflammatory drugs demonstrate restricted effectiveness against severe influenza or are associated with significant side effects. Therefore, there is an urgent need for novel anti-inflammatory agents that possess high potency and minimal adverse reactions. In this study, 15 JAK inhibitors were identified through a screening process based on their anti-inflammatory activity against influenza virus infection
in vitro
. Remarkably, 7 of the 10 selected inhibitors exhibited protective effects against lethal influenza virus infection in mice, thereby highlighting the potential therapeutic value of JAK inhibitors for treating influenza.
Complete genome sequence of
Gluconobacter frateurii
ML.ISBL3, an endophytic strain isolated from aerial roots of
Syngonium podophyllum
Authors: Lam M. , Leung K. M. , Lai G. K. K. , Leung F. C. C. , Griffin S. D. J. 
Published: March 2024

ABSTRACT

The endophytic strain
Gluconobacter frateurii
ML.ISBL3 was isolated from aerial roots of
Syngonium podophyllum
in Hong Kong. Its complete genome, established through hybrid assembly, comprises a single chromosome of 3,309,710 bp (56.30% G+C).
Comprehensive virulence profiling and evolutionary analysis of specificity determinants in
Staphylococcus aureus
two-component systems
Authors: Ahator Stephen Dela , Wenzl Karoline , Hegstad Kristin , Lentz Christian S. , Johannessen Mona 
Published: March 2024

ABSTRACT

In the
Staphylococcus aureus
genome, a set of highly conserved two-component systems (TCSs) composed of histidine kinases (HKs) and their cognate response regulators (RRs) sense and respond to environmental stimuli, which drive the adaptation of the bacteria. This study investigates the complex interplay between TCSs in
S. aureus
USA300, a predominant methicillin-resistant
S. aureus
strain, revealing shared and unique virulence regulatory pathways and genetic variations mediating signal specificity within TCSs. Using TCS-related mutants from the Nebraska Transposon Mutant Library, we analyzed the effects of inactivated TCS HKs and RRs on the production of various virulence factors,
in vitro
infection abilities, and adhesion assays. We found that the TCSs’ influence on virulence determinants was not associated with their phylogenetic relationship, indicating divergent functional evolution. Using the co-crystallized structure of the DesK-DesR from
Bacillus subtilis
and the modeled structures of the four NarL TCSs in
S. aureus
, we identified interacting residues, revealing specificity determinants and conservation within the same TCS, even from different strain backgrounds. The interacting residues were highly conserved within strains but varied between species due to selection pressures and the coevolution of cognate pairs. This study unveils the complex interplay and divergent functional evolution of TCSs, highlighting their potential for future experimental exploration of phosphotransfer between cognate and non-cognate recombinant HK and RRs.

IMPORTANCE

Given the widespread conservation of two-component systems (TCSs) in bacteria and their pivotal role in regulating metabolic and virulence pathways, they present a compelling target for anti-microbial agents, especially in the face of rising multi-drug-resistant infections. Harnessing TCSs therapeutically necessitates a profound understanding of their evolutionary trajectory in signal transduction, as this underlies their unique or shared virulence regulatory pathways. Such insights are critical for effectively targeting TCS components, ensuring an optimized impact on bacterial virulence, and mitigating the risk of resistance emergence via the evolution of alternative pathways. Our research offers an in-depth exploration of virulence determinants controlled by TCSs in
S. aureus
, shedding light on the evolving specificity determinants that orchestrate interactions between their cognate pairs.