bluuebunny/crossref_metadata_2025 huggingface dataset:
Transitions of blood immune endotypes and improved outcome by anakinra in COVID-19 pneumonia: an analysis of the SAVE-MORE randomized controlled trial
Authors: Kyriazopoulou Evdoxia , Hasin-Brumshtein Yehudit , Midic Uros , Poulakou Garyfallia , Milionis Haralampos , Metallidis Simeon , Astriti Myrto , Fragkou Archontoula , Rapti Aggeliki , Taddei Eleonora , Kalomenidis Ioannis , Chrysos Georgios , Angheben Andrea , Kainis Ilias , Alexiou Zoi , Castelli Francesco , Serino Francesco Saverio , Bakakos Petros , Nicastri Emanuele , Tzavara Vasiliki , Ioannou Sofia , Dagna Lorenzo , Dimakou Katerina , Tzatzagou Glykeria , Chini Maria , Bassetti Matteo , Kotsis Vasileios , Tsoukalas Dionysios G. , Selmi Carlo , Konstantinou Alexandra , Samarkos Michael , Doumas Michael , Masgala Aikaterini , Pagkratis Konstantinos , Argyraki Aikaterini , Akinosoglou Karolina , Symbardi Styliani , Netea Mihai G. , Panagopoulos Periklis , Dalekos George N. , Liesenfeld Oliver , Sweeney Timothy E. , Khatri Purvesh , Giamarellos-Bourboulis Evangelos J.
Published: March 2024

Background

Endotype classification may guide immunomodulatory management of patients with bacterial and viral sepsis. We aimed to identify immune endotypes and transitions associated with response to anakinra (human interleukin 1 receptor antagonist) in participants in the SAVE-MORE trial.

Methods

Adult patients hospitalized with radiological findings of PCR-confirmed severe pneumonia caused by SARS-CoV-2 and plasma-soluble urokinase plasminogen activator receptor levels of ≥ 6 ng/ml in the SAVE-MORE trial (NCT04680949) were characterized at baseline and days 4 and 7 of treatment using a previously defined 33-messenger RNA classifier to assign an immunological endotype in blood. Endpoints were changes in endotypes and progression to severe respiratory failure (SRF) associated with anakinra treatment.

Results

At baseline, 23.2% of 393 patients were designated as inflammopathic, 41.1% as adaptive, and 35.7% as coagulopathic. Only 23.9% were designated as the same endotype at days 4 and 7 compared to baseline, while all other patients transitioned between endotypes. Anakinra-treated patients were more likely to remain in the adaptive endotype during 7-day treatment (24.4% vs. 9.9%; p < 0.001). Anakinra also protected patients with coagulopathic endotype at day 7 against SRF compared to placebo (27.8% vs. 55.9%; p = 0.013).

Conclusion

We identify an association between endotypes defined using blood transcriptome and anakinra therapy for COVID-19 pneumonia, with anakinra-treated patients shifting toward endotypes associated with a better outcome, mainly the adaptive endotype.

Trial registration ClinicalTrials.gov, NCT04680949, December 23, 2020.
The exceptions that prove the rule—a historical view of bedaquiline susceptibility
Authors: Miotto Paolo , Cirillo Daniela M. , Schön Thomas , Köser Claudio U.
Published: March 2024

In the accompanying study, Nimmo and colleagues estimated the dates of emergence of mutations in mmpR5 (Rv0678), the most important resistance gene to the anti-tuberculosis drug bedaquiline, in over 3500 geographically diverse Mycobacterium tuberculosis genomes. This provided important insights to improve the design and analysis of clinical trials, as well as the World Health Organization catalogue of resistance mutations, the global reference for interpreting genotypic antimicrobial susceptibility testing results.
Epigenetic age acceleration and risk of aortic valve stenosis: a bidirectional Mendelian randomization study
Authors: Pan Wanqian , Huang Qi , Zhou Le , Lin Jia , Du Xiaojiao , Qian Xiaodong , Jiang Tingbo , Chen Weixiang
Published: March 2024

Background

Aortic valve stenosis (AVS) is the most prevalent cardiac valve lesion in developed countries, and pathogenesis is closely related to aging. DNA methylation-based epigenetic clock is now recognized as highly accurate predictor of the aging process and associated health outcomes. This study aimed to explore the causal relationship between epigenetic clock and AVS by conducting a bidirectional Mendelian randomization (MR) analysis.

Methods

Summary genome-wide association study statistics of epigenetic clocks (HannumAge, HorvathAge, PhenoAge, and GrimAge) and AVS were obtained and assessed for significant instrumental variables from Edinburgh DataShare (n = 34,710) and FinnGen biobank (cases = 9870 and controls = 402,311). The causal association between epigenetic clock and AVS was evaluated using inverse variance weighted (IVW), weighted median (WM), and MR-Egger methods. Multiple analyses (heterogeneity analysis, pleiotropy analysis, and sensitivity analysis) were performed for quality control assessment.

Results

The MR analysis showed that the epigenetic age acceleration of HorvathAge and PhenoAge was associated with an increased risk of AVS (HorvathAge: OR = 1.043, P = 0.016 by IVW, OR = 1.058, P = 0.018 by WM; PhenoAge: OR = 1.058, P = 0.005 by IVW, OR = 1.053, P = 0.039 by WM). Quality control assessment proved our findings were reliable and robust. However, there was a lack of evidence supporting a causal link from AVS to epigenetic aging.

Conclusion

The present MR analysis unveiled a causal association between epigenetic clocks, especially HorvathAge and PhenoAge, with AVS. Further research is required to elucidate the underlying mechanisms and develop strategies for potential interventions.

Graphical abstract
CT-based pancreatic radiomics predicts secondary loss of response to infliximab in biologically naïve patients with Crohn’s disease
Authors: Yang Tian , Feng Jing , Yao Ruchen , Feng Qi , Shen Jun
Published: March 2024

Objectives

Predicting secondary loss of response (SLR) to infliximab (IFX) is paramount for tailoring personalized management regimens. Concurrent pancreatic manifestations in patients with Crohn’s disease (CD) may correlate with SLR to anti-tumor necrosis factor treatment. This work aimed to evaluate the potential of pancreatic radiomics to predict SLR to IFX in biologic-naive individuals with CD.

Methods

Three models were developed by logistic regression analyses to identify high-risk subgroup prone to SLR. The area under the curve (AUC), calibration curve, decision curve analysis (DCA), and integrated discrimination improvement (IDI) were applied for the verification of model performance. A quantitative nomogram was proposed based on the optimal prediction model, and its reliability was substantiated by 10-fold cross-validation.

Results

In total, 184 CD patients were enrolled in the period January 2016 to February 2022. The clinical model incorporated age of onset, disease duration, disease location, and disease behavior, whereas the radiomics model consisted of five texture features. These clinical parameters and the radiomics score calculated by selected texture features were applied to build the combined model. Compared to other two models, combined model achieved favorable, significantly improved discrimination power (AUCcombined vs clinical 0.851 vs 0.694, p = 0.02; AUCcombined vs radiomics 0.851 vs 0.740, p = 0.04) and superior clinical usefulness, which was further converted into reliable nomogram with an accuracy of 0.860 and AUC of 0.872.

Conclusions

The first proposed pancreatic-related nomogram represents a credible, noninvasive predictive instrument to assist clinicians in accurately identifying SLR and non-SLR in CD patients.

Critical relevance statement

This study first built a visual nomogram incorporating pancreatic texture features and clinical factors, which could facilitate clinicians to make personalized treatment decisions and optimize cost-effectiveness ratio for patients with CD.

Key points

• The first proposed pancreatic-related model predicts secondary loss of response for infliximab in Crohn’s disease.

• The model achieved satisfactory predictive accuracy, calibration ability, and clinical value.

• The model-based nomogram has the potential to identify long-term failure in advance and tailor personalized management regimens.

Graphical Abstract
Short cell cycle duration is a phenotype of human epidermal stem cells
Authors: Xiao Tong , Eze Ugomma C , Charruyer-Reinwald Alex , Weisenberger Tracy , Khalifa Ayman , Abegaze Brook , Schwab Gabrielle K , Elsabagh Rasha H , Parenteau T. Richard , Kochanowski Karl , Piper Merisa , Xia Yumin , Cheng Jeffrey B , Cho Raymond J , Ghadially Ruby
Published: March 2024

Background

A traditional view is that stem cells (SCs) divide slowly. Meanwhile, both embryonic and pluripotent SCs display a shorter cell cycle duration (CCD) in comparison to more committed progenitors (CPs).

Methods

We examined the in vitro proliferation and cycling behavior of somatic adult human cells using live cell imaging of passage zero keratinocytes and single-cell RNA sequencing.

Results

We found two populations of keratinocytes: those with short CCD and protracted near exponential growth, and those with long CCD and terminal differentiation. Applying the ergodic principle, the comparative numbers of cycling cells in S phase in an enriched population of SCs confirmed a shorter CCD than CPs. Further, analysis of single-cell RNA sequencing of cycling adult human keratinocyte SCs and CPs indicated a shortening of both G1 and G2M phases in the SC.

Conclusions

Contrary to the pervasive paradigm, SCs progress through cell cycle more quickly than more differentiated dividing CPs. Thus, somatic human adult keratinocyte SCs may divide infrequently, but divide rapidly when they divide. Additionally, it was found that SC-like proliferation persisted in vitro.
Menstrual blood-derived mesenchymal stem cells combined with collagen I gel as a regenerative therapeutic strategy for degenerated disc after discectomy in rats
Authors: Yu Li , Wu Honghao , Zeng Shumei , Hu Xiaojian , Wu Yuxu , Zhou Jinhong , Yuan Li , Zhang Qingqing , Xiang Charlie , Feng Zhiyun
Published: March 2024

Background

Annulus fibrosis (AF) defects have been identified as the primary cause of disc herniation relapse and subsequent disc degeneration following discectomy. Stem cell-based tissue engineering offers a promising approach for structural repair. Menstrual blood-derived mesenchymal stem cells (MenSCs), a type of adult stem cell, have gained attention as an appealing source for clinical applications due to their potential for structure regeneration, with ease of acquisition and regardless of ethical issues.

Methods

The differential potential of MenSCs cocultured with AF cells was examined by the expression of collagen I, SCX, and CD146 using immunofluorescence. Western blot and ELISA were used to examine the expression of TGF-β and IGF-I in coculture system. An AF defect animal model was established in tail disc of Sprague-Dawley rats (males, 8 weeks old). An injectable gel containing MenSCs (about 1*106/ml) was fabricated and transplanted into the AF defects immediately after the animal model establishment, to evaluate its repairment properties. Disc degeneration was assessed via magnetic resonance (MR) imaging and histological staining. Immunohistochemical analysis was performed to assess the expression of aggrecan, MMP13, TGF-β and IGF-I in discs with different treatments. Apoptosis in the discs was evaluated using TUNEL, caspase3, and caspase 8 immunofluorescence staining.

Results

Coculturing MenSCs with AF cells demonstrated ability to express collagen I and biomarkers of AF cells. Moreover, the coculture system presented upregulation of the growth factors TGF-β and IGF-I. After 12 weeks, discs treated with MenSCs gel exhibited significantly lower Pffirrmann scores (2.29 ± 0.18), compared to discs treated with MenSCs (3.43 ± 0.37, p < 0.05) or gel (3.71 ± 0.29, p < 0.01) alone. There is significant higher MR index in disc treated with MenSCs gel than that treated with MenSCs (0.51 ± 0.05 vs. 0.24 ± 0.04, p < 0.01) or gel (0.51 ± 0.05 vs. 0.26 ± 0.06, p < 0.01) alone. Additionally, MenSCs gel demonstrated preservation of the structure of degenerated discs, as indicated by histological scoring (5.43 ± 0.43 vs. 9.71 ± 1.04 in MenSCs group and 10.86 ± 0.63 in gel group, both p < 0.01), increased aggrecan expression, and decreased MMP13 expression in vivo. Furthermore, the percentage of TUNEL and caspase 3-positive cells in the disc treated with MenSCs Gel was significantly lower than those treated with gel alone and MenSCs alone. The expression of TGF-β and IGF-I was higher in discs treated with MenSCs gel or MenSCs alone than in those treated with gel alone.

Conclusion

MenSCs embedded in collagen I gel has the potential to preserve the disc structure and prevent disc degeneration after discectomy, which was probably attributed to the paracrine of growth factors of MenSCs.
Automated molecular structure segmentation from documents using ChemSAM
Authors: Tang Bowen , Niu Zhangming , Wang Xiaofeng , Huang Junjie , Ma Chao , Peng Jing , Jiang Yinghui , Ge Ruiquan , Hu Hongyu , Lin Luhao , Yang Guang
Published: March 2024

Chemical structure segmentation constitutes a pivotal task in cheminformatics, involving the extraction and abstraction of structural information of chemical compounds from text-based sources, including patents and scientific articles. This study introduces a deep learning approach to chemical structure segmentation, employing a Vision Transformer (ViT) to discern the structural patterns of chemical compounds from their graphical representations. The Chemistry-Segment Anything Model (ChemSAM) achieves state-of-the-art results on publicly available benchmark datasets and real-world tasks, underscoring its effectiveness in accurately segmenting chemical structures from text-based sources. Moreover, this deep learning-based approach obviates the need for handcrafted features and demonstrates robustness against variations in image quality and style. During the detection phase, a ViT-based encoder-decoder model is used to identify and locate chemical structure depictions on the input page. This model generates masks to ascertain whether each pixel belongs to a chemical structure, thereby offering a pixel-level classification and indicating the presence or absence of chemical structures at each position. Subsequently, the generated masks are clustered based on their connectivity, and each mask cluster is updated to encapsulate a single structure in the post-processing workflow. This two-step process facilitates the effective automatic extraction of chemical structure depictions from documents. By utilizing the deep learning approach described herein, it is demonstrated that effective performance on low-resolution and densely arranged molecular structural layouts in journal articles and patents is achievable.
Time-varying graph learning from smooth and stationary graph signals with hidden nodes
Authors: Ye Rong , Jiang Xue-Qin , Feng Hui , Wang Jian , Qiu Runhe , Hou Xinxin
Published: March 2024

Learning graph structure from observed signals over graph is a crucial task in many graph signal processing (GSP) applications. Existing approaches focus on inferring static graph, typically assuming that all nodes are available. However, these approaches ignore the situation where only a subset of nodes are available from spatiotemporal measurements, and the remaining nodes are never observed due to application-specific constraints, resulting in time-varying graph estimation accuracy declines dramatically. To handle this problem, we propose a framework that consider the presence of hidden nodes to identify time-varying graph. Specifically, we assume that the graph signals are smooth and stationary on the graphs and only a small number of edges are allowed to change between two consecutive graphs. With these assumptions, we present a challenging time-varying graph inference problem, which models the influence of hidden nodes in terms of estimating the graph-shift operator matrices that have a form of graph Laplacian. Moreover, we emphasize similar edge pattern (column-sparsity) between different graphs. Finally, our method is evaluated on both synthetic and real-world data. The experimental results demonstrate the advantage of our method when compared to existing benchmarking methods.
Routing networking technology based on improved ant colony algorithm in space-air-ground integrated network
Authors: Nie Wuzhou , Chen Yong , Wang Yuhao , Wang Peizheng , Li Meng , Ning Lei
Published: March 2024

Space-air-ground integrated networks comprise a multi-level heterogeneous integrated network that combines satellite-based, aerial, and terrestrial networks. With the increasing human exploration of space and growing demands for internet applications, space-air-ground integrated networks have gradually emerged as the direction for communication network development. These networks face various challenges such as extensive coverage, diverse communication node types, low-quality communication links, and simultaneous operation of multiple network protocols. However, the rapid development and widespread application of artificial intelligence and machine learning technologies in recent years have offered new perspectives and solutions for the communication architecture and routing algorithm research within space-air-ground integrated networks. In these networks, not all nodes can typically communicate directly with satellites; instead, a specific set of specialized communication nodes facilitates data communication between aerial and satellite networks due to their superior communication capabilities. Consequently, in contrast to traditional communication architectures, space-air-ground integrated networks, particularly in the terrestrial layer, often need to address challenges related to the diversity of communication node types and low-quality communication links. A well-designed routing approach becomes crucial in addressing these issues. Therefore, this paper proposes an AODV routing network protocol based on an improved ant colony algorithm (AC-AODV), specifically designed for the terrestrial layer within the space-air-ground integrated networks. By integrating information such as the type, energy, and location of communication nodes, this protocol aims to facilitate network communication. The objective is to guide information flow through nodes that are more suitable for communication, either by relaying communication or by connecting with satellites through specialized nodes. This approach alleviates the burden on ordinary nodes within the terrestrial communication network, thereby enhancing the overall network performance. In this protocol, specialized nodes hold a higher forwarding priority than regular nodes. When a source node needs to transmit data, it enters the route discovery phase, utilizing its own type, location, and energy information as heuristic data to calculate forwarding probabilities. Subsequently, it broadcasts route request (RREQ) messages to find the path. Upon receiving the RREQ message, the destination node sends an RREP message for updating information elements and selects the optimal path based on these information elements. Compared to AODV, AC-AODV shows significant improvements in performance metrics such as transmission latency, throughput, energy conversion rate, and packet loss rate.
The impact of school-based creative bibliotherapy interventions on child and adolescent mental health: a systematic review and realist synthesis protocol
Authors: Redman Hayley , Melendez-Torres G. J. , Bethel Alison , Green Judith
Published: March 2024

Background

There is a need to identify evidence-based interventions to be delivered in schools that can be used to improve child and adolescent mental health and wellbeing. Creative bibliotherapy is one proposed intervention. However, there has been, to date, no comprehensive assessment of the evidence for its impact on mental health and wellbeing. To fill this gap, we will conduct a systematic review and realist synthesis.

Methods

A systematic search of the bibliographic databases APA PsycINFO, Medline (via Ovid), CINAHL, ERIC, Education Research Complete (via EBSCOhost) and Web of Science (SCI, SSCI, AHCI, ESCI) for school-based creative bibliotherapy interventions on child and adolescent mental health. Types of study to be included: cohort studies, non-randomised comparative evaluations, randomised controlled trials. The data from all included studies will be summarised descriptively and strength of evidence appraised. This is a potentially large field of practice, with heterogeneous interventions; we will use methods from intervention components analysis to describe and categorise the range of components and approaches used in included interventions. To understand how interventions work and in which contexts, we will use methods from realist synthesis to develop an exploratory account of mechanisms in different settings and for different young people (contexts).

Discussion

Findings will assess the range of evidence for the impact of creative bibliotherapy on child and adolescent mental health and wellbeing, the strength of evidence for the impact identified, and describe potential mechanisms. This review will be useful for a wide range of stakeholders considering implementing or developing interventions using creative bibliotherapy in school-based settings.

Systematic review registration

This protocol was registered at the International Prospective Register of Systematic Reviews (https://www.crd.york.ac.uk/prospero/), registration number CRD42023410333. This review is funded by Wellcome Trust (221457/Z/20/Z).
Existence and multiplicity of solutions for fractional $p_{1}(x,\cdot )\& p_{2}(x,\cdot )$-Laplacian Schrödinger-type equations with Robin boundary conditions
Authors: Zhang Zhenfeng , An Tianqing , Bu Weichun , Li Shuai
Published: March 2024

In this paper, we study fractional$p_{1}(x,\cdot )\& p_{2}(x,\cdot )$p1(x,⋅)&p2(x,⋅)-Laplacian Schrödinger-type equations for Robin boundary conditions. Under some suitable assumptions, we show that two solutions exist using the mountain pass lemma and Ekeland’s variational principle. Then, the existence of infinitely many solutions is derived by applying the fountain theorem and the Krasnoselskii genus theory, respectively. Different from previous results, the topic of this paper is the Robin boundary conditions in$\mathbb{R}^{N}\setminus \overline{\Omega}$RN∖Ω‾for fractional order$p_{1}(x,\cdot )\& p_{2}(x,\cdot )$p1(x,⋅)&p2(x,⋅)-Laplacian Schrödinger-type equations, including concave-convex nonlinearities, which has not been studied before. In addition, two examples are given to illustrate our results.
Network pharmacology and molecular docking analysis on Shenfu Qiangxin indicate mTOR is a potential target to treat heart failure
Authors: Zou Peilin , Li Jiajun , Zhang Yucong , Qian Zonghao , Nie Hao , Yang Ni , Zhang Le , Lin Li , Peng Dewei , Zhang Cuntai
Published: March 2024

Background

Heart failure (HF) is one of the major causes of mortality worldwide with high recurrence rate and poor prognosis. Our study aimed to investigate potential mechanisms and drug targets of Shenfu Qiangxin (SFQX), a cardiotonic-diuretic traditional Chinese medicine, in treating HF.

Methods

An HF-related and SFQX-targeted gene set was established using disease-gene databases and the Traditional Chinese Medicine Systems Pharmacology database. We performed gene function and pathway enrichment analysis and constructed protein–protein interaction (PPI) network to investigate the potential mechanisms. We also performed molecular docking to analyze the interaction patterns between the active compounds and targeted protein.

Results

A gene set with 217 genes was identified. The gene function enrichment indicated that SFQX can regulate apoptotic process, inflammatory response, response to oxidative stress and cellular response to hypoxia. The pathway enrichment indicated that most genes were involved in PI3K–Akt pathway. Eighteen hub target genes were identified in PPI network and subnetworks. mTOR was the key gene among hub genes, which are involved in PI3K–Akt pathway. The molecular docking analysis indicated that 6 active compounds of SFQX can bind to the kinase domain of mTOR, which exerted potential therapeutic mechanisms of SFQX in treating HF.

Conclusions

The results of network pharmacology analysis highlight the intervention on PI3K–Akt pathway of SFQX in the treatment of HF. mTOR is a key drug target to help protect myocardium.
Natural variables separate the endemic areas of Clonorchis sinensis and Opisthorchis viverrini along a continuous, straight zone in Southeast Asia
Authors: Zheng Jin-Xin , Zhu Hui-Hui , Xia Shang , Qian Men‐Bao , Nguyen Hung Manh , Sripa Banchob , Sayasone Somphou , Khieu Virak , Bergquist Robert , Zhou Xiao-Nong
Published: March 2024

Background

Clonorchiasis and opisthorchiasis, caused by the liver flukes Clonorchis sinensis and Opisthorchis viverrini respectively, represent significant neglected tropical diseases (NTDs) in Asia. The co-existence of these pathogens in overlapping regions complicates effective disease control strategies. This study aimed to clarify the distribution and interaction of these diseases within Southeast Asia.

Methods

We systematically collated occurrence records of human clonorchiasis (n = 1809) and opisthorchiasis (n = 731) across the Southeast Asia countries. Utilizing species distribution models incorporating environmental and climatic data, coupled machine learning algorithms with boosted regression trees, we predicted and distinguished endemic areas for each fluke species. Machine learning techniques, including geospatial analysis, were employed to delineate the boundaries between these flukes.

Results

Our analysis revealed that the endemic range of C. sinensis and O. viverrini in Southeast Asia primarily spans across part of China, Vietnam, Thailand, Laos, and Cambodia. During the period from 2000 to 2018, we identified C. sinensis infections in 84 distinct locations, predominantly in southern China (Guangxi Zhuang Autonomous Region) and northern Vietnam. In a stark contrast, O. viverrini was more widely distributed, with infections documented in 721 locations across Thailand, Laos, Cambodia, and Vietnam. Critical environmental determinants were quantitatively analyzed, revealing annual mean temperatures ranging between 14 and 20 °C in clonorchiasis-endemic areas and 24–30 °C in opisthorchiasis regions (P < 0.05). The machine learning model effectively mapped a distinct demarcation zone, demonstrating a clear separation between the endemic areas of these two liver flukes with AUC from 0.9 to1. The study in Vietnam delineates the coexistence and geographical boundaries of C. sinensis and O. viverrini, revealing distinct endemic zones and a transitional area where both liver fluke species overlap.

Conclusions

Our findings highlight the critical role of specific climatic and environmental factors in influencing the geographical distribution of C. sinensis and O. viverrini. This spatial delineation offers valuable insights for integrated surveillance and control strategies, particularly in regions with sympatric transmission. The results underscore the need for tailored interventions, considering regional epidemiological variations. Future collaborations integrating eco-epidemiology, molecular epidemiology, and parasitology are essential to further elucidate the complex interplay of liver fluke distributions in Asia.
Advancing the National Immunization Program in an era of achieving universal vaccine coverage in China and beyond
Authors: Chen Shu , Rodewald Lance E. , Du Anna Heng , Tang Shenglan
Published: March 2024

Background

Immunization is a cornerstone of public health. Despite great success, China’s National Immunization Program (NIP) faces challenges, such as the integration of several World Health Organization-recommended vaccines and other systemic issues. The Innovation Laboratory for Vaccine Delivery Research (VaxLab), supported by the Bill & Melinda Gates Foundation and established in 2021 at Duke Kunshan University, focuses on enhancing China’s NIP through research and policy advocacy. This editorial aims to summarize the key findings of the manuscripts published in the collection contributed by VaxLab team and set the future research agenda.

Key findings

The collection contains eleven manuscripts discussing China’s immunization landscape and strategies to improve coverage, particularly for non-NIP vaccines like human papillomavirus vaccine (HPV), pneumococcal conjugate vaccine (PCV), Haemophilus influenzae type b vaccine (Hib), and rotavirus vaccines. Key findings include: (i) The COVID-19 vaccination campaign demonstrated China’s capacity for rapid, large-scale immunization efforts, suggesting potential for broader vaccine coverage improvements; (ii) Efforts in combating cervical cancer through the HPV vaccine indicate progress but also highlight challenges like vaccine supply and equitable access; (iii) The lag in adopting higher-valent paediatric combination vaccines in China needs attention to address regulatory and health system hurdles; (iv) Disparities in access to non-NIP vaccines underscore the need for government initiatives to improve vaccine coverage, especially for remote areas and marginalized populations; (v) Original studies emphasize the influence of caregivers’ knowledge, health workers’ financial incentives, and concerns about vaccine efficacy on immunization rates; (vi) Case studies from the Weifang City of China and Indonesia to introduce PCV offer insights on successful vaccine introduction strategies and the impact of innovative financing and government support.

Conclusion

The articles emphasize the need for government leadership, strategic policymaking, and public awareness to enhance vaccine coverage and equity. The VaxLab will continue strengthening China’s NIP by focusing on vaccine financing, emphasizing diversity, equity, and inclusion, and improving maternal vaccination coverage. Research will extend to Southeast Asian and Western Pacific regions, especially in middle-income countries facing challenges in vaccine financing and delivery. The collective efforts outlined in this collection show a commitment to evolving and adapting immunization strategies to meet global health goals and to provide equitable access to vaccines for all.

Graphical Abstract
Social media-related nightmare — a potential explanation for poor sleep quality and low affective well-being in the social media era?
Authors: Shabahang Reza , Kim Sohee , Aruguete Mara S. , Azadimanesh Pegah , Ghaemi Zahra , Khanzadeh Abbas Ali Hossein , Kakabaraee Keivan , Zsila Ágnes
Published: March 2024

Research has posited that social media use during the day may be reflected in nighttime dreams. Nevertheless, no prior studies have explored frightening, unpleasant dreams arising from social media use. This study introduces the construct of the social media-related nightmare by (a) developing and validating a scale capturing negative-valenced dreams with themes of helplessness, loss of control, inhibition, victimization, and making mistakes in social media, and (b) examining relationships between social media use, social media-related nightmares, sleep quality, and affective well-being. A convenience sample of 595 Iranian adult social media users (Mage = 27.45, SDage = 11.42) reported on social media-related nightmare, social media use integration, anxiety, peace of mind, sleep quality, and nightmare distress. The Social Media-Related Nightmare Scale (SMNS) demonstrated a unidimensional structure with sound psychometric properties. The most common nightmares involved the inability to log in to social media and the disruption of relationships with other users. Social media use intensity predicted frequency of social media-related nightmares. These nightmares were correlated with increased anxiety, lower peace of mind, poor sleep quality, and nightmare distress. Importantly, social media-related nightmares mediated the relationship between social media use intensity and low affective well-being (i.e., anxiety and peace of mind), poor sleeping, and nightmare distress. The findings suggest that social media-related nightmares could be a potential pathway through which social media engagement may lead to affective distress and sleep difficulties.
DNA hypomethylator phenotype reprograms glutamatergic network in receptor tyrosine kinase gene-mutated glioblastoma
Authors: Harachi Mio , Masui Kenta , Shimizu Erika , Murakami Kumiko , Onizuka Hiromi , Muragaki Yoshihiro , Kawamata Takakazu , Nakayama Hisako , Miyata Mariko , Komori Takashi , Cavenee Webster K. , Mischel Paul S. , Kurata Atsushi , Shibata Noriyuki
Published: March 2024

DNA methylation is crucial for chromatin structure and gene expression and its aberrancies, including the global “hypomethylator phenotype”, are associated with cancer. Here we show that an underlying mechanism for this phenotype in the large proportion of the highly lethal brain tumor glioblastoma (GBM) carrying receptor tyrosine kinase gene mutations, involves the mechanistic target of rapamycin complex 2 (mTORC2), that is critical for growth factor signaling. In this scenario, mTORC2 suppresses the expression of the de novo DNA methyltransferase (DNMT3A) thereby inducing genome-wide DNA hypomethylation. Mechanistically, mTORC2 facilitates a redistribution of EZH2 histone methyltransferase into the promoter region of DNMT3A, and epigenetically represses the expression of DNA methyltransferase. Integrated analyses in both orthotopic mouse models and clinical GBM samples indicate that the DNA hypomethylator phenotype consistently reprograms a glutamate metabolism network, eventually driving GBM cell invasion and survival. These results nominate mTORC2 as a novel regulator of DNA hypomethylation in cancer and an exploitable target against cancer-promoting epigenetics.
R2DRV: study protocol for longitudinal assessment of driving after mild TBI in young drivers
Authors: Yang Jingzhen , Stavrinos Despina , Kerwin Thomas , Mrug Sylvie , Tiso Michael , McManus Benjamin , Wrabel Cameron G. , Rundus Christopher , Zhang Fangda , Davis Drew , Swanson Erin M. , Bentley Brett , Yeates Keith Owen
Published: March 2024

Background

Mild traumatic brain injury (mTBI) and traffic-related injuries are two major public health problems disproportionately affecting young people. Young drivers, whose driving skills are still developing, are particularly vulnerable to impaired driving due to brain injuries. Despite this, there is a paucity of research on how mTBI impacts driving and when it is safe to return to drive after an mTBI. This paper describes the protocol of the study, R2DRV, Longitudinal Assessment of Driving After Mild TBI in Young Drivers, which examines the trajectory of simulated driving performance and self-reported driving behaviors from acutely post-injury to symptom resolution among young drivers with mTBI compared to matched healthy drivers. Additionally, this study investigates the associations of acute post-injury neurocognitive function and cognitive load with driving among young drivers with and without mTBI.

Methods

A total of 200 young drivers (ages 16 to 24) are enrolled from two study sites, including 100 (50 per site) with a physician-confirmed isolated mTBI, along with 100 (50 per site) healthy drivers without a history of TBI matched 1:1 for age, sex, driving experience, and athlete status. The study assesses primary driving outcomes using two approaches: (1) high-fidelity driving simulators to evaluate driving performance across four experimental study conditions at multiple time points (within 96 h of injury and weekly until symptom resolution or 8 weeks post-injury); (2) daily self-report surveys on real-world driving behaviors completed by all participants.

Discussion

This study will fill critical knowledge gaps by longitudinally assessing driving performance and behaviors in young drivers with mTBI, as compared to matched healthy drivers, from acutely post-injury to symptom resolution. The research strategy enables evaluating how increased cognitive load may exacerbate the effects of mTBI on driving, and how post-mTBI neurocognitive deficits may impact the driving ability of young drivers. Findings will be shared through scientific conferences, peer-reviewed journals, and media outreach to care providers and the public.
Starvation resistance in the nematode Pristionchus pacificus requires a conserved supplementary nuclear receptor
Authors: Theska Tobias , Renahan Tess , Sommer Ralf J.
Published: March 2024

Nuclear hormone receptors (NHRs) are a deeply-conserved superfamily of metazoan transcription factors, which fine-tune the expression of their regulatory target genes in response to a plethora of sensory inputs. In nematodes, NHRs underwent an explosive expansion and many species have hundreds ofnhrgenes, most of which remain functionally uncharacterized. However, recent studies have reported that two sister receptors,Ppa-NHR-1 andPpa-NHR-40, are crucial regulators of feeding-structure morphogenesis in the diplogastrid model nematodePristionchus pacificus. In the present study, we functionally characterizePpa-NHR-10, the sister paralog ofPpa-NHR-1 andPpa-NHR-40, aiming to reveal whether it too regulates aspects of feeding-structure development. We used CRISPR/CAS9-mediated mutagenesis to create small frameshift mutations of this nuclear receptor gene and applied a combination of geometric morphometrics and unsupervised clustering to characterize potential mutant phenotypes. However, we found thatPpa-nhr-10mutants do not show aberrant feeding-structure morphologies. Instead, multiple RNA-seq experiments revealed that many of the target genes of this receptor are involved in lipid catabolic processes. We hypothesized that their mis-regulation could affect the survival of mutant worms during starvation, where lipid catabolism is often essential. Indeed, using novel survival assays, we found that mutant worms show drastically decreased starvation resistance, both as young adults and as dauer larvae. We also characterized genome-wide changes to the transcriptional landscape inP. pacificuswhen exposed to 24 h of acute starvation, and found thatPpa-NHR-10 partially regulates some of these responses. Taken together, these results demonstrate thatPpa-NHR-10 is broadly required for starvation resistance and regulates different biological processes than its closest paralogsPpa-NHR-1 andPpa-NHR-40.
A comprehensive MCDM assessment for economic data: success analysis of maximum normalization, CODAS, and fuzzy approaches
Authors: Baydaş Mahmut , Yılmaz Mustafa , Jović Željko , Stević Željko , Özuyar Sevilay Ece Gümüş , Özçil Abdullah
Published: March 2024

The approach of evaluating the final scores of multi-criteria decision-making (MCDM) methods according to the strength of association with real-life rankings is interesting for comparing MCDM methods. This approach has recently been applied mostly to financial data. In these studies, where it is emphasized that some methods show more stable success, it would be useful to see the results that will emerge by testing the approach on different data structures more comprehensively. Moreover, not only the final MCDM results but also the performance of normalization techniques and data types (fuzzy or crisp), which are components of MCDM, can be compared using the same approach. These components also have the potential to affect MCDM results directly. In this direction, in our study, the economic performances of G-20 (Group of 20) countries, which have different data structures, were calculated over ten different periodic decision matrices. Ten different crisp-based MCDM methods (COPRAS, CODAS, MOORA, TOPSIS, MABAC, VIKOR (S, R, Q), FUCA, and ELECTRE III) with different capabilities were used to better visualize the big picture. The relationships between two different real-life reference anchors and MCDM methods were used as a basis for comparison. The CODAS method develops a high correlation with both anchors in most periods. The most appropriate normalization technique for CODAS was identified using these two anchors. Interestingly, the maximum normalization technique was the most successful among the alternatives (max, min–max, vector, sum, and alternative ranking-based). Moreover, we compared the two main data types by comparing the correlation results of crisp-based and fuzzy-based CODAS. The results were very consistent, and the “Maximum normalization-based fuzzy integrated CODAS procedure” was proposed to decision-makers to measure the economic performance of the countries.
Chronological transitions of hepatocyte growth factor treatment effects in spinal cord injury tissue
Authors: Okano Yuji , Kase Yoshitaka , Suematsu Yu , Nakamura Masaya , Okano Hideyuki
Published: March 2024

Inflammatory responses are known to suppress neural regeneration in patients receiving stem cell-based regenerative therapy for spinal cord injury (SCI). Consequently, pathways involved in neurogenesis and immunomodulation, such as the hepatocyte growth factor (HGF)/MET signaling cascade, have garnered significant attention. Notably, various studies, including our own, have highlighted the enhanced recovery of locomotor functions achieved in SCI animal models by combining HGF pretreatment and human induced stem cell-derived neural stem/progenitor cell (hiPSC-NS/PC) transplantation. However, these studies implicitly hypothesized that the functionality of HGF in SCI would be time consistent and did not elucidate its dynamics. In the present article, we investigated the time-course of the effect of HGF on SCI, aiming to uncover a more precise mechanism for HGF administration, which is indispensable for developing crystallizing protocols for combination therapy. To this end, we performed a detailed investigation of the temporal variation of HGF using the RNA-seq data we obtained in our most recent study. Leveraging the time-series design of the data, which we did not fully exploit previously, we identified three components in the effects of HGF that operate at different times: early effects, continuous effects, and delayed effects. Our findings suggested a concept where the three components together contribute to the acceleration of neurogenesis and immunomodulation, which reinforce the legitimacy of empirically fine-tuned protocols for HGF administration and advocate the novel possibility that the time-inconsistent effects of HGF progressively augment the efficacy of combined therapy.
Detection of femoropopliteal arterial steno-occlusion at MR angiography: initial experience with artificial intelligence
Authors: Nguyen Tri-Thien , Folle Lukas , Bayer Thomas
Published: March 2024

Background

This study evaluated a deep learning (DL) algorithm for detecting vessel steno-occlusions in patients with peripheral arterial disease (PAD). It utilised a private dataset, which was acquired and annotated by the authors through their institution and subsequently validated by two blinded readers.

Methods

A single-centre retrospective study analysed 105 magnetic resonance angiography (MRA) images using an EfficientNet B0 DL model. Initially, inter-reader variability was assessed using the complete dataset. For a subset of these images (29 from the left side and 35 from the right side) where digital subtraction angiography (DSA) data was available as the ground truth, the model’s accuracy and the area under the curve at receiver operating characteristics analysis (ROC-AUC) were evaluated.

Results

A total of 105 patient examinations (mean age, 75 years ±12 [mean ± standard deviation], 61 men) were evaluated. Radiologist-DL model agreement had a quadratic weighted Cohen κ ≥ 0.72 (left side) and ≥ 0.66 (right side). Radiologist inter-reader agreement was ≥ 0.90 (left side) and ≥ 0.87 (right side). The DL model achieved a 0.897 accuracy and a 0.913 ROC-AUC (left side) and 0.743 and 0.830 (right side). Radiologists achieved 0.931 and 0.862 accuracies, with 0.930 and 0.861 ROC-AUCs (left side), and 0.800 and 0.799 accuracies, with 0.771 ROC-AUCs (right side).

Conclusion

The DL model provided valid results in identifying arterial steno-occlusion in the superficial femoral and popliteal arteries on MRA among PAD patients. However, it did not reach the inter-reader agreement of two radiologists.

Relevance statement

The tested DL model is a promising tool for assisting in the detection of arterial steno-occlusion in patients with PAD, but further optimisation is necessary to provide radiologists with useful support in their daily routine diagnostics.

Key points

• This study focused on the application of DL for arterial steno-occlusion detection in lower extremities on MRA.

• A previously developed DL model was tested for accuracy and inter-reader agreement.

• While the model showed promising results, it does not yet replace human expertise in detecting arterial steno-occlusion on MRA.

Graphical Abstract
Analysis of the CYP21A2 gene pathogenic variants in CAH patients from Surgut using next-generation sequencing (NGS)
Authors: Osinovskaya Natalia , Vashukova Elena , Tarasenko Olga , Danilova Maria , Glavnova Olga , Sultanov Iskender , Donnikov Maxim , Nasykhova Yulia , Glotov Andrey
Published: March 2024

Background

21-hydroxylase deficiency is present in 90–95% of cases of congenital adrenal hyperplasia (CAH). Eleven major pathogenic variants account for 93% of all identified variants in the CYP21A2 gene in various clinical forms of the disease. Each population has its own range of significant pathogenic variants. We aimed to study the frequency of pathogenic variants in the CYP21A2 gene using NGS technology and real-time PCR in Surgut patients with different clinical forms of CAH. NGS was performed on 70 patients with salt-wasting and non-classical clinical forms of 21-hydroxylase deficiency, verified by direct Sanger sequencing and PCR–RFLP analysis.

Results

Eleven different pathogenic variants were found in 68.57% (48/70) of patients. Among 92.86% (13/14) of patients with salt-wasting CAH, variants were found to be homozygous, with CYP21A2 gene deletion as the most frequent mutation (46.4% or 13/28 alleles). In the group with non-classical CAH, pathogenic variants were identified only in 60.71% (34/56) of patients. V282L was discovered to be the most common variant in heterozygous carriers (45.45%, 15/33). NGS method identified 2 variants that were not determined by the standard method for major mutations detection: p.C170* and p.W22X, accounting for 3% of all known pathogenic variants.

Conclusion

Our data make it possible to clarify the specific spectrum of CYP21A2 gene pathogenic variants in CAH patients from Surgut. The NGS method allows for the identification of rare pathogenic variants (3%) in the CYP21A2 gene that are not included in the conventional PCR–RFLP analysis.
Vacuum-ultraviolet (λ < 200 nm) photodetector array
Authors: Zhu Siqi , Lin Zhuogeng , Wang Zhao , Jia Lemin , Zhang Naiji , Zheng Wei
Published: March 2024

The vacuum-ultraviolet (VUV, 10–200 nm) imaging photodetector (PD) based on the wide bandgap semiconductor (WBGS) can realize a more detailed observation of solar storms than the silicon ones. Here, an 8 × 8 VUV PD array based on the semiconductor AlN with an ultra-wide bandgap is presented, exhibiting the shortest cutoff wavelength (203 nm) reported so far. The PD array with a Pt/AlN/SiC/Ti/Au photovoltaic structure shows an excellent selective response to VUV light, an extremely low dark current density of 2.85 × 10–11 A·cm−2@ -2 V, a responsivity of 0.054 A·W−1@ 0 V and an ultra-short rise time of 13 ns. Also, the clear boundaries and an obvious contrast between light and dark of the VUV image displayed in the imaging measurement indicate the good imaging ability of this PD array, which can be used for the imaging application with high signal-to-noise ratio and high response speed. These results provide rich experience for the development of VUV imaging PDs based on WBGSs both in their fabrication and the practical applications in VUV detection.