bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of the salience network in cognitive and affective deficits
Authors: Schimmelpfennig Jakub , Topczewski Jan , Zajkowski Wojciech , Jankowiak-Siuda Kamila
Published: March 2023

Analysis and interpretation of studies on cognitive and affective dysregulation often draw upon the network paradigm, especially the Triple Network Model, which consists of the default mode network (DMN), the frontoparietal network (FPN), and the salience network (SN). DMN activity is primarily dominant during cognitive leisure and self-monitoring processes. The FPN peaks during task involvement and cognitive exertion. Meanwhile, the SN serves as a dynamic “switch” between the DMN and FPN, in line with salience and cognitive demand. In the cognitive and affective domains, dysfunctions involving SN activity are connected to a broad spectrum of deficits and maladaptive behavioral patterns in a variety of clinical disorders, such as depression, insomnia, narcissism, PTSD (in the case of SN hyperactivity), chronic pain, and anxiety, high degrees of neuroticism, schizophrenia, epilepsy, autism, and neurodegenerative illnesses, bipolar disorder (in the case of SN hypoactivity). We discuss behavioral and neurological data from various research domains and present an integrated perspective indicating that these conditions can be associated with a widespread disruption in predictive coding at multiple hierarchical levels. We delineate the fundamental ideas of the brain network paradigm and contrast them with the conventional modular method in the first section of this article. Following this, we outline the interaction model of the key functional brain networks and highlight recent studies coupling SN-related dysfunctions with cognitive and affective impairments.
Microglia and astrocytes underlie neuroinflammation and synaptic susceptibility in autism spectrum disorder
Authors: Xiong Yue , Chen Jianhui , Li Yingbo
Published: March 2023

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder with onset in childhood. The mechanisms underlying ASD are unclear. In recent years, the role of microglia and astrocytes in ASD has received increasing attention. Microglia prune the synapses or respond to injury by sequestrating the injury site and expressing inflammatory cytokines. Astrocytes maintain homeostasis in the brain microenvironment through the uptake of ions and neurotransmitters. However, the molecular link between ASD and microglia and, or astrocytes remains unknown. Previous research has shown the significant role of microglia and astrocytes in ASD, with reports of increased numbers of reactive microglia and astrocytes in postmortem tissues and animal models of ASD. Therefore, an enhanced understanding of the roles of microglia and astrocytes in ASD is essential for developing effective therapies. This review aimed to summarize the functions of microglia and astrocytes and their contributions to ASD.
Explaining cocktail party effect and McGurk effect with a spiking neural network improved by Motif-topology
Authors: Jia Shuncheng , Zhang Tielin , Zuo Ruichen , Xu Bo
Published: March 2023

Network architectures and learning principles have been critical in developing complex cognitive capabilities in artificial neural networks (ANNs). Spiking neural networks (SNNs) are a subset of ANNs that incorporate additional biological features such as dynamic spiking neurons, biologically specified architectures, and efficient and useful paradigms. Here we focus more on network architectures in SNNs, such as the meta operator called 3-node network motifs, which is borrowed from the biological network. We proposed a Motif-topology improved SNN (M-SNN), which is further verified efficient in explaining key cognitive phenomenon such as the cocktail party effect (a typical noise-robust speech-recognition task) and McGurk effect (a typical multi-sensory integration task). For M-SNN, the Motif topology is obtained by integrating the spatial and temporal motifs. These spatial and temporal motifs are first generated from the pre-training of spatial (e.g., MNIST) and temporal (e.g., TIDigits) datasets, respectively, and then applied to the previously introduced two cognitive effect tasks. The experimental results showed a lower computational cost and higher accuracy and a better explanation of some key phenomena of these two effects, such as new concept generation and anti-background noise. This mesoscale network motifs topology has much room for the future.
Tracking functional network connectivity dynamics in the elderly
Authors: Wu Kaichao , Jelfs Beth , Mahmoud Seedahmed S. , Neville Katrina , Fang John Q.
Published: March 2023

Introduction

Functional magnetic resonance imaging (fMRI) has shown that aging disturbs healthy brain organization and functional connectivity. However, how this age-induced alteration impacts dynamic brain function interaction has not yet been fully investigated. Dynamic function network connectivity (DFNC) analysis can produce a brain representation based on the time-varying network connectivity changes, which can be further used to study the brain aging mechanism for people at different age stages.

Method

This presented investigation examined the dynamic functional connectivity representation and its relationship with brain age for people at an elderly stage as well as in early adulthood. Specifically, the resting-state fMRI data from the University of North Carolina cohort of 34 young adults and 28 elderly participants were fed into a DFNC analysis pipeline. This DFNC pipeline forms an integrated dynamic functional connectivity (FC) analysis framework, which consists of brain functional network parcellation, dynamic FC feature extraction, and FC dynamics examination.

Results

The statistical analysis demonstrates that extensive dynamic connection changes in the elderly concerning the transient brain state and the method of functional interaction in the brain. In addition, various machine learning algorithms have been developed to verify the ability of dynamic FC features to distinguish the age stage. The fraction time of DFNC states has the highest performance, which can achieve a classification accuracy of over 88% by a decision tree.

Discussion

The results proved there are dynamic FC alterations in the elderly, and the alteration was found to be correlated with mnemonic discrimination ability and could have an impact on the balance of functional integration and segregation.
The association of energy and macronutrient intake at breakfast and cardiovascular disease in Chinese adults: From a 14-year follow-up cohort study
Authors: Du Xiaoan , Yang Ru , Ma Mengdi , Ke Songqing , Zheng Jie , Tan Xiaodong
Published: March 2023

Background

We aimed to examine the associations between energy and macronutrient intakes at breakfast and the incidence of cardiovascular events among Chinese adults.

Methods

There were 12,937 participants from the China Health and Nutrition Survey who met the study criteria and completed six rounds of questionnaires in 1997, 2000, 2004, 2006, 2009, and 2011. Combined weighing methods with 24-h dietary recall were used to measure dietary intake throughout the day. Intakes of macronutrients at breakfast were calculated using energy provided by nutrients as a percentage of breakfast energy. We calculated hazard ratios using a multivariable Cox frailty model with random intercepts to account for household clustering.

Results

During follow-up, we documented 453 (3.6 per 1,000 person-years) major cardiovascular events, 195 (1.5 per 1,000 person-years) myocardial infarctions, and 293 (2.3 per 1,000 person-years) strokes. In Chinese adults, more breakfast carbohydrates or less proteins intake was associated with the reduced risk of cardiovascular diseases. Especially for women, higher intake of breakfast carbohydrates was associated with a lower risk of major cardiovascular events (quintile 5 vs. quintile 1, HR 0.47 [95%CI 0.30–0.74]; ptrend = 0.0008) and stroke (quintile 5 vs. quintile 1, HR 0.48 [95%CI 0.26–0.88]; ptrend = 0.0006). Higher intake of breakfast proteins was associated with a higher risk of major cardiovascular events (quintile 5 vs. quintile 1, HR 1.77 [95%CI 1.12–2.79]; ptrend = 0.1162), myocardial infarction (quintile 5 vs. quintile 1, HR 2.49 [95%CI 1.21–5.11]; ptrend = 0.2641). There was a significant association between breakfast fat intake and cardiovascular diseases in the adult population, but less significant correlation was found in Chinese men or women. Breakfast fat intake was positively associated with the risk of major cardiovascular events (quintile 5 vs. quintile 1, HR 1.74 [95%CI 1.27–2.36]; ptrend = 0.0070), myocardial infarction (quintile 5 vs. quintile 1, HR 2.03 [95%CI 1.23–3.37]; ptrend = 0.0168), and stroke (quintile 5 vs. quintile 1, HR 1.64 [95%CI 1.12–2.41]; ptrend = 0.0732). There was a significant reduction in major cardiovascular events and stroke when breakfast energy intake was moderated, even if the independence of skipping breakfast.

Conclusion

High carbohydrate intake and low protein and fat intake at breakfast may contribute to cardiovascular health while maintaining a moderate energy intake.
Assessing the in vivo ameliorative effects of Lactobacillus acidophilus KLDS1.0901 for induced non-alcoholic fatty liver disease treatment
Authors: Wang Yanbo , Wang Zengbo , Wan Yang , Jin Furong , Shi Xiaodan , Xing Zhishuang , Tian Bo , Li Bailiang
Published: March 2023

Reputed as a significant metabolic disorder, non-alcoholic fatty liver disease (NAFLD) is characterized by high-fat deposits in the liver and causes substantial economic challenges to any country's workforce. Previous studies have indicated that some lactic acid bacteria may effectively prevent or treat NAFLD. Overall, L. acidophilus KLDS1.0901 protected against HFD-induced NAFLD by improving liver characteristics and modulating microbiota composition, and thus could be a candidate for improving NAFLD. This study aimed to assess the protective effects of L. acidophilus KLDS1.0901 on a high-fat diet(HFD)-induced NAFLD. First, hepatic lipid profile and histological alterations were determined to study whether L. acidophilus KLDS1.0901 could ameliorate NAFLD. Then, the intestinal permeability and gut barrier were explored. Finally, gut microbiota was analyzed to elucidate the mechanism from the insights of the gut–liver axis. The results showed that Lactobacillus KLDS1.0901 administration significantly decreased body weight, Lee's index body, fat rate, and liver index. L. acidophilus KLDS1.0901 administration significantly improved lipid profiles by decreasing the hepatic levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) and by increasing the high-density lipoprotein cholesterol (HDL-C) levels. A conspicuous decrease of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum was observed after L. acidophilus KLDS1.0901 administration. Meanwhile, the H&E and Oil Red O-stained staining showed that L. acidophilus KLDS1.0901 significantly reduced liver lipid accumulation of HFD-fed mice by decreasing the NAS score and lipid area per total area. Our results showed that L. acidophilus KLDS1.0901 administration decreased the interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-alpha (TNF-α) concentrations accompanied by the increase of interleukin-10 (IL-10). L. acidophilus KLDS1.0901 administration could improve the intestinal barrier function by upregulating the mRNA levels of occludin, claudin-1, ZO-1, and Muc-2, which were coupled to the decreases of the concentration of LPS and D-lactic acid. Notably, L. acidophilus KLDS1.0901 administration modulated the gut microbiota to a near-normal pattern. Hence, our results suggested that L. acidophilus KLDS1.0901 can be used as a candidate to ameliorate NAFLD.
Associations between waist circumference and executive function among Chinese Tibetan adolescents living at high altitude
Authors: Liu Yuan , Zhang Feng , Gan Leimin , Shi Lijuan , Yin Xiaojian , Guo Yaru , Sun Pengwei
Published: March 2023

Background

Associations between body composition and execution function (EF) were currently studied in low altitude (LA) areas. However, the research on the correlation between waist circumference (WC) and EF among adolescents living at high altitude (HA) was limited.

Objective

We sought to explore the association between WC and EF in Chinese Tibetan adolescents aged 13–18 years in HA areas.

Methods

After excluding invalid data and extreme values, 1,228 participants (583 boys and 645 girls) were eventually included. The areas of Lhasa (average elevation of 3650 m), Nagqu (4500 m), Qamdo (3500 m), and Nyingchi (3100 m) in China were chosen as study sites. Participants completed tasks to measure inhibitory control, working memory, and cognitive flexibility. The predictive association between WC and EF was explored by One-way ANOVA, Pearson correlation, and linear regression analysis.

Results

After controlling for concomitant variables, the reaction time (RT) of responding to inhibitory control (difference incongruent and congruent), working memory (1-back, 2-back), and cognitive flexibility (heterogeneous, difference in heterogeneous and homogeneous) stimuli in subjects with WC ≥ 85th percentile was longer than that in those with WC of the 15th percentile or below [by 1.785 ms (95% CI: 0.078, 3.491), 208.734 ms (95% CI: 96.886, 320.582), 106.679 ms (95% CI: 16.485, 196.873), 82.307 ms (95% CI: 19.171, 145.442), and 58.397 ms (95% CI: 0.343,116.452), respectively], (P < 0.05).

Conclusion

After adjustment for concomitant variables, WC was significantly positively associated with the RT of inhibitory control, working memory, and cognitive flexibility among Chinese Tibetan adolescents in HA areas.
Validation and discussion of clinical practicability of the 2022 graded prognostic assessment for NSCLC adenocarcinoma patients with brain metastases in a routine clinical cohort
Authors: Schröder C. , Windisch P. , Lütscher J. , Zwahlen D. R. , Förster R.
Published: March 2023

Introduction

The goal of this analysis is to validate the 2022 graded prognostic assessment (GPA) for patients with brain metastases from adenocarcinoma of the lung and to discuss its clinical practicability.

Methods/material

137 patients with adenocarcinoma of the lung were included in this analysis. The disease specific GPA for NSCLC, Lung-molGPA and the GPA for NSCLC adenocarcinoma were calculated. Overall survival was calculated for each GPA group. Additionally, expected and actual OS in the prognostic groups of the GPA available at the time of the patients’ diagnosis was compared.

Results

Median overall survival (OS) from diagnosis of brain metastases was 15 months (95% confidence interval (CI) 9.7–20.3 months). The median OS in the three individual prognostic groups was 7 months for GPA 0-1, 16 months for GPA 1.5-2, 33 months for GPA 2.5-3 and not reached for GPA 3.5-4 (p<0.001). Median survival times for the individual groups were similar to those published in the original GPA publication. Regarding the expected and actual OS when using the available GPA at the time of diagnosis there was an underestimation of survival of more than 3 months for all except the worst prognosis group.

Conclusion

We were able to validate the 2022 GPA for NSCLC adenocarcinoma patients with brain metastases in a similar cohort from a non-academic center. However, the practical applicability regarding the expected median OS might be limited due to the constantly evolving treatment landscape and the consecutive improvement in overall survival.
GE11-antigen-loaded hepatitis B virus core antigen virus-like particles efficiently bind to TNBC tumor
Authors: Zhang Long , Tang Lin , Jiang Yongsheng , Wang Chenou , Huang Lijiang , Ding Ting , Zhang Tinghong , Li Huaqiong , Xie Longteng
Published: March 2023

Purpose

This study aimed to explore the possibility of utilizing hepatitis B core protein (HBc) virus-like particles (VLPs) encapsulate doxorubicin (Dox) to reduce the adverse effect caused by its off-target and toxic side effect.

Methods

Here, a triple-negative breast cancer (TNBC) tumor-targeting GE11-HBc VLP was constructed through genetic engineering. The GE11 peptide, a 12-amino-acid peptide targeting epidermal growth factor receptor (EGFR), was inserted into the surface protein loops of VLPs. The Dox was loaded into HBc VLPs by a thermal-triggered encapsulation strategy. The in vitro release, cytotoxicity, and cellular uptake of TNBC tumor-targeting GE11-HBc VLPs was then evaluated.

Results

These VLPs possessed excellent stability, DOX loading efficiency, and preferentially released drug payload at high GSH levels. The insertion of GE11 targeting peptide caused improved cellular uptake and enhanced cell viability inhibitory in EGFR high-expressed TNBC cells.

Conclusion

Together, these results highlight DOX-loaded, EGFR-targeted VLPs as a potentially useful therapeutic choice for EGFR-overexpressing TNBC.
The correlation between tic disorders and allergic conditions in children: A systematic review and meta-analysis of observational studies
Authors: Chang Ying , Zhang Ying , Bai Yifan , Lin Run , Qi Yaping , Li Min
Published: March 2023

Aim

To evaluate the correlation between tic disorders and allergies and to inform strategies for the treatment and prevention of tic disorders.

Methods

We conducted online searches of the MEDLINE, Embase, Cochrane, CNKI, CBM, WanFang, and VIP Information databases. Case-control studies and cohort studies related to tic disorders and allergic conditions were searched. Two researchers screened the literature, extracted data, and evaluated quality in strict accordance with the predetermined retrieval strategy and inclusion criteria. Finally, RevMan 5.4 software was used to conduct a meta-analysis. We used the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach to rating the certainty of evidence about each allergy outcome as high, moderate, low, or very low.

Results

We obtained seven eligible studies involving eight allergic conditions. The following allergic conditions were significantly associated with the presence of a tic disorder: asthma (OR = 1.90, 95% CI = 1.57–2.30, P < 0.001), allergic rhinitis (OR = 2.61, 95% CI = 1.90–3.57, P < 0.001), allergic conjunctivitis (OR = 3.65, 95% CI = 1.53–8,67, P = 0.003), eczema (OR = 3.87, 95% CI = 2.24–6.67, P < 0.001) and food allergy (OR = 2.79, 95% CI = 1.56–4.99, P < 0.001). There was no significant correlation between atopic dermatitis, urticaria, drug allergy, and tic disorder.

Conclusion

The occurrence of tic disorders may be associated with the presence of certain allergic disorders. However, whether allergy is one of the causes of tic disorders remains unclear.

Systematic review registration

The registration number for this systematic review is PROSPERO: CRD42021231658.
Echocardiography parameters used in identifying right ventricle dysfunction in preterm infants with early bronchopulmonary dysplasia: A scoping review
Authors: Muhsen Wisam , Nestaas Eirik , Hosking Joanne , Latour Jos M.
Published: March 2023

Background

Bronchopulmonary Dysplasia (BPD) is a chronic condition that affects preterm infants and is associated with long-term complications. Haemodynamic effects of BPD can lead to right ventricular (RV) dysfunction.

Objective

To synthesise and map the evidence of echo parameters used in identifying RV dysfunction in the first two weeks-after-birth (WAB) of preterm infants with early BPD.

Information Sources

This scoping review included the databases: Medline, CINAHL, PubMed, EMBASE, Scopus, ProQuest, Web of Science, Cochrane Library, JBI Evidence-Based Practise and Gray Literature.

Search Strategy

The search utilised Boolean operators and descriptors registered in Medical Subject Headings.

Inclusion and exclusion criteria

Included were studies utilising echo parameters to examine RV function in preterm infants with early BPD in the first two WAB.

Synthesis of results

The results are presented as a map of the extracted findings in a tabular format with a narrative summary.

Results

Eight studies were included. Differences were observed in the number and timing of echo scans performed in the first two WAB and the variations in the echo parameters used to compare preterm infants with and without early BPD. Only echo scans performed at the end of the first WAB, demonstrated significant differences in the echo parameters measurements between preterm infants with and without BPD. Studies using RV Myocardial Performance Index (MPI) to identify RV-dysfunction associated with early BPD demonstrated similar findings. The Pulsed-Wave Doppler technique identified differences in RV-MPI between preterm infants with and without BPD, while Tissue-Doppler-Imaging did not demonstrate similar results. Speckle tracking can measure strain (S) and strain rate (SR) and diagnose RV-dysfunction. However, the findings of studies that utilised speckle tracking varied. Finally, two of the included studies added blood tests to their diagnostic model of early BPD, which was able to demonstrate significant differences in blood test results between BPD-affected and control preterm infants.

Conclusion

BPD could adversely affect the myocardium function of the RV; these negative influences can be captured in the first two WAB. However, there are still knowledge gaps regarding the appropriate number, timing and the most suitable echo parameters to assess RV function.
Importance of modelling hERG binding in predicting drug-induced action potential prolongations for drug safety assessment
Authors: Farm Hui Jia , Clerx Michael , Cooper Fergus , Polonchuk Liudmila , Wang Ken , Gavaghan David J. , Lei Chon Lok
Published: March 2023

Reduction of the rapid delayed rectifier potassium current (IKr) via drug binding to the human Ether-à-go-go-Related Gene (hERG) channel is a well recognised mechanism that can contribute to an increased risk of Torsades de Pointes. Mathematical models have been created to replicate the effects of channel blockers, such as reducing the ionic conductance of the channel. Here, we study the impact of including state-dependent drug binding in a mathematical model of hERG when translating hERG inhibition to action potential changes. We show that the difference in action potential predictions when modelling drug binding of hERG using a state-dependent model versus a conductance scaling model depends not only on the properties of the drug and whether the experiment achieves steady state, but also on the experimental protocols. Furthermore, through exploring the model parameter space, we demonstrate that the state-dependent model and the conductance scaling model generally predict different action potential prolongations and are not interchangeable, while at high binding and unbinding rates, the conductance scaling model tends to predict shorter action potential prolongations. Finally, we observe that the difference in simulated action potentials between the models is determined by the binding and unbinding rate, rather than the trapping mechanism. This study demonstrates the importance of modelling drug binding and highlights the need for improved understanding of drug trapping which can have implications for the uses in drug safety assessment.
Economic evaluation of five first-line PD-(L)1 inhibitors for treating non-squamous non-small cell lung cancer in China: A cost-effectiveness analysis based on network meta-analysis
Authors: Chen Xi , Zhao Mingye , Tian Lei
Published: March 2023

Background and objective: Non-small cell lung cancer (NSCLC) is one of the most malignant cancer types that causes substantial economic burden in China. This study aimed to evaluate the cost-effectiveness of five first-line anti-PD-(L)1 treatments, including sintilimab, camrelizumab, atezolizumab, pembrolizumab and sugemalimab with each combined with chemotherapy, for treating advanced non-squamous NSCLC (nsq-NSCLC) from Chinese healthcare system perspective.

Methods: Clinical data were obtained from the following clinical trials, namely, ORIENT-11, CameL, IMpower132, KEYNOTE-189 and GEMSTONE-302. A network meta-analysis was performed based on fractional polynomial models. We constructed a partitioned survival model with a three-week cycle length and a lifetime horizon to derive the incremental cost-effectiveness ratio (ICER). We performed one-way sensitivity analysis and probablistic sensitivity analysis to test the robustness. Additionally, two scenario analyses were undertaken to investigate the impact of Patient Assistant Program on the economic conclusion and to explore potential uncertainty associated with population representativeness of the global trial.

Results: Compared with camrelizumab + chemotherapy, sugemalimab + chemotherapy and atezolizumab + chemotherapy were dominated, and the ICERs generated from sintilimab + chemotherapy and pembrolizumab + chemotherapy were $15,280.83/QALY and $159,784.76/QALY, respectively. Deterministic sensitivity analysis showed that uncertainty around ICERs was mainly driven by HR related parameters derived from NMA and drug price. The probablistic sensitivity analysis suggested that camrelizumab treatment was cost-effective at a willingness-to-pay threshold of 1-time GDP per capita. When the threshold was set as 3-time GDP per capita, sintilimab strategy demonstrated the excellent cost-effective advantage. Sensitivity analysis proved the reliability of base-case results. Results from two scenario analyses indicated that the primary finding was robust.

Conclusion: In current context of Chinese healthcare system, sintilimab + chemotherapy appeared to be cost-effective for the treatment of nsq-NSCLC compared with sugemalimab, camrelizumab, pembrolizumab as well as atezolizumab combined with chemotherapy.
Precision sirolimus dosing in children: The potential for model-informed dosing and novel drug monitoring
Authors: Shen Guofang , Moua Kao Tang Ying , Perkins Kathryn , Johnson Deron , Li Arthur , Curtin Peter , Gao Wei , McCune Jeannine S.
Published: March 2023

The mTOR inhibitor sirolimus is prescribed to treat children with varying diseases, ranging from vascular anomalies to sporadic lymphangioleiomyomatosis to transplantation (solid organ or hematopoietic cell). Precision dosing of sirolimus using therapeutic drug monitoring (TDM) of sirolimus concentrations in whole blood drawn at the trough (before the next dose) time-point is the current standard of care. For sirolimus, trough concentrations are only modestly correlated with the area under the curve, with R2 values ranging from 0.52 to 0.84. Thus, it should not be surprising, even with the use of sirolimus TDM, that patients treated with sirolimus have variable pharmacokinetics, toxicity, and effectiveness. Model-informed precision dosing (MIPD) will be beneficial and should be implemented. The data do not suggest dried blood spots point-of-care sampling of sirolimus concentrations for precision dosing of sirolimus. Future research on precision dosing of sirolimus should focus on pharmacogenomic and pharmacometabolomic tools to predict sirolimus pharmacokinetics and wearables for point-of-care quantitation and MIPD.
Therapeutic implications of current Janus kinase inhibitors as anti-COVID agents: A review
Authors: Jain Nem Kumar , Tailang Mukul , Jain Hemant Kumar , Chandrasekaran Balakumar , Sahoo Biswa Mohan , Subramanian Anandhalakshmi , Thangavel Neelaveni , Aldahish Afaf , Chidambaram Kumarappan , Alagusundaram M. , Kumar Santosh , Selvam Palani
Published: March 2023

Severe cases of COVID-19 are characterized by hyperinflammation induced by cytokine storm, ARDS leading to multiorgan failure and death. JAK-STAT signaling has been implicated in immunopathogenesis of COVID-19 infection under different stages such as viral entry, escaping innate immunity, replication, and subsequent inflammatory processes. Prompted by this fact and prior utilization as an immunomodulatory agent for several autoimmune, allergic, and inflammatory conditions, Jakinibs have been recognized as validated small molecules targeting the rapid release of proinflammatory cytokines, primarily IL-6, and GM-CSF. Various clinical trials are under investigation to evaluate Jakinibs as potential candidates for treating COVID-19. Till date, there is only one small molecule Jakinib known as baricitinib has received FDA-approval as a standalone immunomodulatory agent in treating critical COVID-19 patients. Though various meta-analyses have confirmed and validated the safety and efficacy of Jakinibs, further studies are required to understand the elaborated pathogenesis of COVID-19, duration of Jakinib treatment, and assess the combination therapeutic strategies. In this review, we highlighted JAK-STAT signalling in the pathogenesis of COVID-19 and clinically approved Jakinibs. Moreover, this review described substantially the promising use of Jakinibs and discussed their limitations in the context of COVID-19 therapy. Hence, this review article provides a concise, yet significant insight into the therapeutic implications of Jakinibs as potential anti-COVID agents which opens up a new horizon in the treatment of COVID-19, effectively.
Anoikis-related long non-coding RNA signatures to predict prognosis and small molecular drug response in cervical cancer
Authors: Liang Hao , Xiang Lan , Wu Huan , Liu Yang , Tian Wei , Zeng Jianhua
Published: March 2023

Background: Cervical cancer (CC) is a major health threat to females, and distal metastasis is common in patients with advanced CC. Anoikis is necessary for the development of distal metastases. Understanding the mechanisms associated with anoikis in CC is essential to improve its survival rate.

Methods: The expression matrix of long non-coding RNAs (lncRNAs) from cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) patients was extracted from The Cancer Genome Atlas (TCGA), and highly relevant anoikis-related lncRNAs (ARLs) were identified by the single sample gene set enrichment analysis (ssGSEA) method. ARLs-related molecular subtypes were discerned based on prognosis-related ARLs. ARLs-related prognostic risk score (APR_Score) was calculated and risk model was constructed using LASSO COX and COX models. In addition, we also assessed immune cell activity in the immune microenvironment (TME) for both subtypes and APR_Score groups. A nomogram was utilized for predicting improved clinical outcome. Finally, this study also discussed the potential of ARLs-related signatures in predicting response to immunotherapy and small molecular drugs.

Results: Three ARLs-related subtypes were identified from TCGA-CESC (AC1, AC2, and AC3), with AC3 patients having the highest ARG scores, higher angiogenesis scores, and the worst prognosis. AC3 had lower immune cell scores in TME but higher immune checkpoint gene expression and higher potential for immune escape. Next, we constructed a prognostic risk model consisting of 7-ARLs. The APR_Score exhibited a greater robustness as an independent prognostic indicator in predicting prognosis, and the nomogram was a valuable tool for survival prediction. ARLs-related signatures emerged as a potential novel indicator for immunotherapy and small molecular drug selection.

Conclusion: We firstly constructed novel ARLs-related signatures capable of predicting prognosis and offered novel ideas for therapy response in CC patients.
Increased expression of glutathione peroxidase 3 prevents tendinopathy by suppressing oxidative stress
Authors: Furuta Haruka , Yamada Mari , Nagashima Takuya , Matsuda Shuichi , Nagayasu Kazuki , Shirakawa Hisashi , Kaneko Shuji
Published: March 2023

Tendinopathy, a degenerative disease, is characterized by pain, loss of tendon strength, or rupture. Previous studies have identified multiple risk factors for tendinopathy, including aging and fluoroquinolone use; however, its therapeutic target remains unclear. We analyzed self-reported adverse events and the US commercial claims data and found that the short-term use of dexamethasone prevented both fluoroquinolone-induced and age-related tendinopathy. Rat tendons treated systemically with fluoroquinolone exhibited mechanical fragility, histological change, and DNA damage; co-treatment with dexamethasone attenuated these effects and increased the expression of the antioxidant enzyme glutathione peroxidase 3 (GPX3), as revealed via RNA-sequencing. The primary role of GPX3 was validated in primary cultured rat tenocytes treated with fluoroquinolone or H2O2, which accelerates senescence, in combination with dexamethasone or viral overexpression of GPX3. These results suggest that dexamethasone prevents tendinopathy by suppressing oxidative stress through the upregulation of GPX3. This steroid-free approach for upregulation or activation of GPX3 can serve as a novel therapeutic strategy for tendinopathy.
Characterization of olfactory sensory neurons in the striped ambrosia beetle Trypodendron lineatum
Authors: Biswas Twinkle , Yuvaraj Jothi Kumar , Hansson Bill S. , Löfstedt Christer , Anderbrant Olle , Andersson Martin N.
Published: March 2023

Introduction:The striped ambrosia beetleTrypodendron lineatum(Coleoptera, Curculionidae, Scolytinae) is a major forest pest in the Holarctic region. It uses an aggregation pheromone and host and non-host volatiles to locate suitable host trees, primarily stressed or dying conifer trees. The beetles bore into the xylem and inoculate spores of their obligate fungal mutualistPhialophoropsis ferrugineainside their excavated egg galleries, with the fungus serving as the main food source for the developing larvae. Olfactory sensory neuron (OSN) responses to pheromones and host volatiles are poorly understood inT. lineatumand other ambrosia beetles, and nothing is known about potential responses to fungal volatiles.

Methods:We screened responses of OSNs present in 170 antennal olfactory sensilla using single sensillum recordings (SSR) and 57 odor stimuli, including pheromones, host and non-host compounds, as well as volatiles produced byP. ferrugineaand fungal symbionts of other scolytine beetles.

Results and Discussion:Thirteen OSN classes were characterized based on their characteristic response profiles. An OSN class responding to the aggregation pheromone lineatin was clearly the most abundant on the antennae. In addition, four OSN classes responded specifically to volatile compounds originating from the obligate fungal mutualist and three responded to non-host plant volatiles. Our data also show thatT. lineatumhas OSN classes tuned to pheromones of other bark beetles. Several OSN classes showed similar response profiles to those previously described in the sympatric bark beetleIps typographus, which may reflect their shared ancestry.
Genetic analysis and QTL mapping of aroma volatile compounds in the apple progeny ‘Fuji’ × ‘Cripps Pink’
Authors: Yang Shunbo , Yu Jing , Yang Huijuan , Zhao Zhengyang
Published: March 2023

Aroma is an essential trait for apple fruit quality, but the understanding of biochemical mechanisms underlying aroma formation is still limited. To better characterize and assess the genetic potential for improving aroma quality for breeding, many efforts have been paid to map quantitative trait loci (QTLs) using a saturated molecular linkage map. In the present study, aroma profiles in ripe fruit of F1 population between ‘Fuji’ and ‘Cripps Pink’ were evaluated by gas chromatography-mass spectrometry (GC-MS) over 2019 and 2020 years, and the genetics of volatile compounds were dissected. In total, 38 volatile compounds were identified in ‘Fuji’ × ‘Cripps Pink’ population, including 23 esters, 3 alcohols, 7 aldehydes and 5 others. With the combination of aroma phenotypic data and constructed genetic linkage map, 87 QTLs were detected for 15 volatile compounds on 14 linkage groups (LGs). Among them, a set of QTLs associated with ester production identified and confirmed on LG 6. A candidate gene MdAAT6 in the QTL mapping interval was detected. Over-expression of MdAAT6 in tomato and apple fruits showed significantly higher esters accumulation compared to the control, indicating it was critical for the ester production. Our results give light on the mode of inheritance of the apple volatilome and provide new insights for apple flavor improvement in the future.
A trait-based framework for seagrass ecology: Trends and prospects
Authors: Moreira-Saporiti Agustín , Teichberg Mirta , Garnier Eric , Cornelissen J. Hans C. , Alcoverro Teresa , Björk Mats , Boström Christoffer , Dattolo Emanuela , Eklöf Johan S. , Hasler-Sheetal Harald , Marbà Nuria , Marín-Guirao Lázaro , Meysick Lukas , Olivé Irene , Reusch Thorsten B. H. , Ruocco Miriam , Silva João , Sousa Ana I. , Procaccini Gabriele , Santos Rui
Published: March 2023

In the last three decades, quantitative approaches that rely on organism traits instead of taxonomy have advanced different fields of ecological research through establishing the mechanistic links between environmental drivers, functional traits, and ecosystem functions. A research subfield where trait-based approaches have been frequently used but poorly synthesized is the ecology of seagrasses; marine angiosperms that colonized the ocean 100M YA and today make up productive yet threatened coastal ecosystems globally. Here, we compiled a comprehensive trait-based response-effect framework (TBF) which builds on previous concepts and ideas, including the use of traits for the study of community assembly processes, from dispersal and response to abiotic and biotic factors, to ecosystem function and service provision. We then apply this framework to the global seagrass literature, using a systematic review to identify the strengths, gaps, and opportunities of the field. Seagrass trait research has mostly focused on the effect of environmental drivers on traits, i.e., “environmental filtering” (72%), whereas links between traits and functions are less common (26.9%). Despite the richness of trait-based data available, concepts related to TBFs are rare in the seagrass literature (15% of studies), including the relative importance of neutral and niche assembly processes, or the influence of trait dominance or complementarity in ecosystem function provision. These knowledge gaps indicate ample potential for further research, highlighting the need to understand the links between the unique traits of seagrasses and the ecosystem services they provide.
Genetic mapping of leaf rust (Puccinia triticina Eriks) resistance genes in six Canadian spring wheat cultivars
Authors: Bokore Firdissa E. , Cuthbert Richard D. , Knox Ron E. , Hiebert Colin W. , Pozniak Curtis J. , Berraies Samia , Ruan Yuefeng , Meyer Brad , Hucl Pierre , McCallum Brent D.
Published: March 2023

The Canada Western Red Spring wheat (Triticum aestivum L.) cultivars AAC Concord, AAC Prevail, CDC Hughes, Lillian, Glenlea, and elite line BW961 express a spectrum of resistance to leaf rust caused by Puccinia triticina Eriks. This study aimed to identify and map the leaf rust resistance of the cultivars using three doubled haploid populations, AAC Prevail/BW961 (PB), CDC Hughes/AAC Concord (HC), and Lillian/Glenlea (LG). The populations were evaluated for seedling resistance in the greenhouse and adult plant disease response in the field at Morden, MB for 3 years and genotyped with the 90K wheat Infinium iSelect SNP array. Genetic maps were constructed to perform QTL analysis on the seedling and field leaf rust data. A total of three field leaf rust resistance QTL segregated in the PB population, five in the HC, and six in the LG population. In the PB population, BW961 contributed two QTL on chromosomes 2DS and 7DS, and AAC Prevail contributed a QTL on 4AL consistent across trials. Of the five QTL in HC, AAC Concord contributed two QTL on 4AL and 7AL consistent across trials and a QTL on 3DL.1 that provided seedling resistance only. CDC Hughes contributed two QTL on 1DS and 3DL.2. Lillian contributed four QTL significant in at least two of the three trials on 2BS, 4AL, 5AL, and 7AL, and Glenlea two QTL on 4BL and 7BL. The 1DS QTL from CDC Hughes, the 2DS from BW961, the 4AL from the AAC Prevail, AAC Concord, and Lillian, and the 7AL from AAC Concord and Lillian conferred seedling leaf rust resistance. The QTL on 4AL corresponded with Lr30 and was the same across cultivars AAC Prevail, AAC Concord, and Lillian, whereas the 7AL corresponding with LrCen was coincident between AAC Concord and Lillian. The 7DS and 2DS QTL in BW961 corresponded with Lr34 and Lr2a, respectively, and the 1DS QTL in CDC Hughes with Lr21. The QTL identified on 5AL could represent a novel gene. The results of this study will widen our knowledge of leaf rust resistance genes in Canadian wheat and their utilization in resistance breeding.
Introducing a new concept: Psychological capital of older people and its positive effect on mental health
Authors: Xin Yaping , Li Dan
Published: March 2023

Objective

This study aimed to explore the structure of psychological capital (PsyCap) and its positive effects on mental health among older people.

Methods

Study 1 used grounded theory to analyze the semi-structured interviewing data of 17 Chinese older people (60–96 years old) to develop a primary PsyCap questionnaire for older people. Study 2, respectively, applied exploratory factor analysis (EFA) with 198 Chinese older people (M= 69.2;SD= 6.685) and confirmatory factor analysis (CFA) with 370 Chinese older people (M= 73.84;SD= 9.416) to test a seven-factor structure for PsyCap. Study 3 used 328 participants (M= 79.73;SD= 9.073) to examine the correlation between PsyCap and mental health.

Results

Study 1 identified that PsyCap of older people contains ‘resilience,’ ‘self-efficacy,’ ‘optimism,’ ‘ease and content,’ ‘gratitude and dedication, ‘wisdom,’ and ‘meaning in life’ and generated a primary seven-factor questionnaire. Study 2 proved the overall and internal structure reliability of PsyCap were good (Cronbach’s alphas ranged 0.809 ~ 0.935), and the seven-factor measurement model fitted the data well (χ2/df= 2.07, RMSEA = 0.05, RMR = 0.05, CFI = 0.95, IFI = 0.95, TLI = 0.94, NFI = 0.91). The PsyCap scale was also proved to an excellent convergent validity, discriminant validity, calibration validity, and measurement invariance across different groups. Study 3 found that PsyCap and its seven factors significantly correlated with depression (r= −0.419 ~ −0.163,p< 0.01) after controlling the demographic variables.

Conclusion

These findings provide a reliable and valid assessment for quantitative empirical research of PsyCap among older people and show significant impacts on mental health among older people, which offers new insight into improving mental health from the perspective of positive psychology.
COVID-19 symptoms and compliance: The mediating role of fundamental social motives
Authors: Liu Ruoting , Zheng Xueying , Wang Ziyu , Zhou Mingjie , Weng Jianping , Li Yan-mei , Chen Xuefeng
Published: March 2023

Background

Understanding the compliance of infected individuals and the psychological process underlying compliance during pandemics is important for preventing and controlling the spread of pathogens. Our study investigated whether fundamental social motives mediate the relationship between having infectious disease and compliance.

Methods

An online survey was conducted in March 2020, during the severe phase of the COVID-19 outbreak in China to collect data from 15,758 participants. The survey comprised self-report questionnaires with items pertaining to current symptoms (COVID-19 symptoms, other symptoms or no symptoms), the Fundamental Social Motive Inventory, and measures of compliance. Correlation analysis, linear regression analysis, and structural equation model were used for data analysis.

Results

The participants with COVID-19 symptoms had lower levels of compliance than those without symptoms, and their lower compliance was caused by a decrease in disease avoidance (indirect effect = −0.058, 95% CI = [−0.061, −0.056]) and familial motives (indirect effect = −0.113, 95% CI = [−0.116, −0.062]). Whereas exclusion concern (indirect effect = 0.014, 95% CI = [0.011, 0.017]) suppressed the effects of COVID-19 symptoms on compliance, the effect disappeared in the multiple mediation model, while those of disease avoidance and familial motives remained.

Conclusion

Our findings emphasize the critical role of disease avoidance and familial motives in promoting compliance with public health norms during pandemics and suggest that enhancing these motives may serve as an effective intervention strategy to mitigate noncompliance among potentially infected individuals.
When do supervisors punish subordinates’ unethical pro-organizational behavior: Roles of moral identity and goal congruence with the group
Authors: Gao Feng , Wang Yao , Zhang Jiaojiao
Published: March 2023

Given that unethical pro-organizational behavior (UPB) violates moral standards but benefits the organization at the same time, supervisors’ responses to this behavior could be equivocal although it is supposed to be punished. Previous research, however, has centered on antecedents of UPB, less is known about its consequences, especially how supervisors respond to subordinates’ UPB. Integrating social identity theory with social information processing theory, this paper aims to explain when supervisors perceive subordinate UPB in a negative way, and further engage in negative leading behaviors as punishments for UPB. Results of a multi-wave, multiple-source survey suggest that subordinates’ UPB is most negatively related to supervisors’ trust when supervisors’ moral identity is prominent and goal congruence with the group is low. Furthermore, results show that reduced trust ultimately elicits abusive supervisor behavior. These findings extend understanding of when and why supervisors punish rather than indulge subordinates who act in ethically questionable ways and provide important insights into supervisors’ leading behavior from a bottom-up perspective.
Repeated stage exposure reduces music performance anxiety
Authors: Candia Victor , Kusserow Martin , Margulies Oliver , Hildebrandt Horst
Published: March 2023

Background

High heart rate (HR) and restlessness are two important features of music performance anxiety (MPA). In a case report of a cellist suffering from this condition, we showed that HR and restlessness decreased after repeated live performances of the same musical excerpt, thereby positively modulating objective performance criteria and subjective components. Here, we largely replicate these results in a group of 18 string players reporting MPA.

Methods

Objective measurement devices included a miniaturized electrocardiogram monitor and three 3-axis accelerometer loggers. Subjective measures included the Multidimensional Mental Health Questionnaire (MDBF) and a customized visual analogue scale (VAS) questionnaire for MPA. Non-artistic performance errors were assessed by music experts using a composite score for technical playing errors (i.e., intonation errors, omission of notes, and bowing noise). Data were collected from each study participant during three brief public solo performances of the same musical excerpt, with each performance occurring before a new audience on the same day.

Results

From the 1st to the 3rd performance, HR, VAS, and playing error scores decreased significantly. MDBF (RU scale) showed a significant increase in calmness from the 1st to the 3rd performance on stage. HR and RU, VAS, and RU, as well as bow acceleration and overall duration of playing correlated significantly across participants and performances.

Discussion and conclusion

We conclude that repeated stage exposure significantly reduces HR as well as restlessness and playing errors linked to MPA. Public performances are still successful when HR is significantly higher than during rest periods. These results underscore the importance of stage training to become accustomed to realistic public self-exposure. Musicians – especially students – should consider this component of stage training as an integral part of their practice routine. Therefore, stage training can reduce MPA, promote better live performances and prevent stress-related mental disorders and physical injuries. These result from excessive self-exercise strategies common in musicians experiencing MPA. HR monitoring should be an integral part of evaluating the effectiveness of interventions for better MPA management and efficient performance training.