bluuebunny/crossref_metadata_2025_split huggingface dataset:
OASL suppresses infectious bursal disease virus replication by targeting VP2 for degrading through the autophagy pathway
Authors: Wang Suyan , Xu Zhuangzhuang , Liu Yongzhen , Yu Mengmeng , Zhang Tao , Liu Peng , Qi Xiaole , Chen Yuntong , Meng Lingzhai , Guo Ru , Zhang Li , Fan Wenrui , Gao Li , Duan Yulu , Zhang Yanping , Cui Hongyu , Gao Yulong 
Published: April 2024

ABSTRACT

Infectious bursal disease (IBD) is an acute and fatal immunosuppressive disease caused by infectious bursal disease virus (IBDV). As an obligate intracellular parasite, IBDV infection is strictly regulated by host factors. Knowledge on the antiviral activity and possible mechanism of host factors might provide the theoretical basis for the prevention and control of IBD. In this study, RNA-sequencing results indicated that many host factors were induced by IBDV infection, among which the expression levels of OASL (2´,5´-oligadenylate synthetase-like protein) was significantly upregulated. OASL overexpression significantly inhibited IBDV replication, whereas OASL knockdown promoted IBDV replication. Interestingly, the antiviral ability of OASL was independent of its canonical enzymatic activity, i.e., OASL targeted viral protein VP2 for degradation, depending on the autophagy receptor p62/SQSTM1 in the autophagy pathway. Additionally, the 316 lysine (K) of VP2 was the key site for autophagy degradation, and its replacement with arginine disrupted VP2 degradation induced by OASL and enhanced IBDV replication. Importantly, our results for the first time indicate a unique and potent defense mechanism of OASL against double-stranded RNA virus by interaction with viral proteins, which leads to their degradation.

IMPORTANCE
OASL (2´,5´-oligadenylate synthetase-like protein) exhibits broad-spectrum antiviral effects against single-stranded RNA viruses in mammals, potentially serving as a promising target for novel antiviral strategies. However, its role in inhibiting the replication of double-stranded RNA viruses (dsRNA viruses), such as infectious bursal disease virus (IBDV), in avian species remains unclear. Our findings indicated a unique and potent defense mechanism of OASL against dsRNA viruses. It has been previously shown in mammals that OASL inhibits virus replication through increasing interferon production. The groundbreaking aspect of our study is the finding that OASL has the ability to interact with IBDV viral protein VP2 and target it for degradation and thus exerts its antiviral effect. Our results reveal the interaction between avian natural antiviral immune response and IBDV infection. Our study not only enhances our understanding of bird defenses against viral infections but can also inform strategies for poultry disease management.
Trends in work-related respiratory diseases attributed to nickel, chromium and cobalt in the UK: descriptive findings from The Health and Occupation Research (THOR) network 1996–2019
Authors: Iskandar Ireny Y K , Gawkrodger David J , Byrne Laura , Gittins Matthew , Carder Melanie , Fishwick David , van Tongeren Martie 
Published: April 2024

BackgroundOccupational exposure to metals can be associated with respiratory diseases which can adversely affect the individual’s health, finances and employment. Despite this, little is known about the incidence of these respiratory conditions over prolonged periods of time.AimsThis study aimed to investigate the trends in the incidence of work-related respiratory diseases attributed to nickel, chromium and cobalt in the UK.MethodsCases of occupational respiratory diseases caused by nickel, chromium or cobalt reported to Surveillance of Work-related and Occupational Respiratory Disease (SWORD), the UK-based surveillance scheme between 1996 and 2019 (inclusive), were extracted and grouped into six 4-year time periods. Cases were characterised by causative metal exposure, occupational and industrial sector. Incidence rates diseases (adjusted for physician participation and response rate) were calculated using ONS employment data.ResultsOf cases reported to SWORD during the study period, 1% (173 actual cases) of respiratory problems were attributed to nickel, chromium or cobalt. Diagnoses of asthma compromised the largest proportion of diagnoses (74.4%), followed by lung cancer (8.9%) and pneumoconiosis (6.7%). Cases had a mean age of 47 years (SD 13); 93% were men. The annual incidence fell from 1.6 per million employed in the first 4-year period, to 0.2 in the most recent period.ConclusionsOver 24 years, a decline in the incidence of metal-related occupational respiratory diseases was observed in the UK. This could be attributed to improvements in working conditions which resulted in reduced metal exposure but could also be due to closure of industries that might have generated case returns.
Performance evaluation of a self-administered point-of-care test for anal HPV screening in PrEP users: data from a community-based PrEP service
Authors: Biasioli Lorenzo , Rossotti Roberto , Tavelli Alessandro , De Bona Anna , Tincati Camilla , Calzavara Daniele , Vinti Pietro , Baiguera Chiara , D’Amico Federico , Nava Alice , Repossi Roberto , Bossolasco Simona , Muccini Camilla , Mulè Giovanni , Tesoro Daniele , d'Arminio Monforte Antonella , Cernuschi Massimo 
Published: April 2024

Objectives
In this study, we compared the performance of a self-administered point-of-care test (POCT) for anal human papillomavirus (HPV) screening with laboratory gold-standard test in pre-exposure prophylaxis (PrEP) users and evaluated its feasibility.

Methods
We enrolled PrEP users from a local community-based PrEP service. Each participant self-collected an anal swab to test anal HPV with a PCR POCT capable of detecting 14 high-risk HPV genotypes. Anonymous questionnaires on self-sampling feasibility were completed. Participants were then referred to local clinics to undergo standard viral genotyping. Concordance between POCT and gold-standard test was measured with absolute agreement and Cohen’s kappa. Receiver operating characteristic (ROC) curves were used to calculate POCT sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV).

Results
179 subjects got a valid POCT result, most of them men (98.3%) and men who have sex with men (90.4%). 68.2% tested positive for at least one high-risk HPV genotype on POCT. 150 feasibility questionnaires were collected: 92.7% of compilers found the self-swab easy to perform. For 178 subjects, a gold-standard test valid result was also available: 77% tested positive for at least one high-risk HPV genotype. The median time elapsed between the two tests was 9.8 months, due to COVID-19-related service interruptions. Agreement between POCT and gold-standard test was 79.3% (Cohen’s kappa=0.49). POCT showed a sensitivity of 81.0%, a specificity of 73.8%, a PPV of 91.0% and an NPV of 54.4%.

Conclusions
POCT showed a moderate agreement with gold-standard test and a discrete sensitivity and specificity, suggesting that it could be a useful and feasible additional tool for HPV screening, especially in low-resource and community-based settings.
The distribution of tree biomass carbon within the Pacific Coastal Temperate Rainforest, a disproportionally carbon dense forest
Authors: Carter Trevor A. , Buma Brian 
Published: April 2024

Spatially explicit global estimates of forest carbon storage are typically coarsely scaled. While useful, these estimates do not account for the variability and distribution of carbon at management scales. We asked how climate, topography, and disturbance regimes interact across and within geopolitical boundaries to influence tree biomass carbon, using the perhumid region of the Pacific Coastal Temperate Rainforest, an infrequently disturbed carbon dense landscape, as a test case. We leveraged permanent sample plots in southeast Alaska and coastal British Columbia and used multiple quantile regression forests and generalized linear models to estimate tree biomass carbon stocks and the effects of topography, climate, and disturbance regimes. We estimate tree biomass carbon stocks are either 211 (SD = 163) Mg C ha−1 or 218 (SD = 169) Mg C ha−1. Natural disturbance regimes had no correlation with tree biomass but logging decreased tree biomass carbon and the effect diminished with increasing time since logging. Despite accounting for 0.3% of global forest area, this forest stores between 0.63% and 1.07% of global aboveground forest carbon as aboveground live tree biomass. The disparate impact of logging and natural disturbance regimes on tree biomass carbon suggests a mismatch between current forest management and disturbance history.
Kinetic modeling of a Sznajd opinion model on social networks
Authors: Liao Jie , Yang Xiongfeng 
Published: April 2024

In this paper, we study a kinetic modeling of opinion formation on social networks in which the distribution function depends on both the opinion and the connectivity of the agents. The opinion exchange process is governed by a Sznajd-type model with three opinions, [Formula: see text], 0, and the social network is represented statistically with connectivity denoting the number of contacts of a given individual. It is commonly accepted that, in social networks, the opinion of the agents with a higher connectivity, i.e. a larger number of followers, is more convincing than that of the agents with a lower number of followers. By the kinetic modeling approach, we derived the asymptotic mean opinion of a social network in terms of the initial opinion and the connectivity of the agents. The present work extends the result in [N. Loy, M. Raviola and A. Tosin, Opinion polarisation in social networks, Phil. Trans. R. Soc. A 380, 20210158 (2021)] where only binary opinions, [Formula: see text], were considered, that indecisive people who cannot make a clear choice between [Formula: see text] are allowed in this study.
A technique for preserving network structure in randomized Hi-C data
Authors: Sizovs Andrejs , Melkus Gatis , Rucevskis Peteris , Silina Sandra , Lace Lelde , Celms Edgars , Viksna Juris 
Published: April 2024

Chromatin interaction data are frequently analyzed as a network to study several aspects of chromatin structure. Hi-C experiments are costly and there is a need to create simulated networks for quality assessment or result validation purposes. Existing tools do not maintain network properties during randomization. We propose an algorithm to modify an existing chromatin interaction graph while preserving the graphs most basic topological features — node degrees and interaction length distribution. The algorithm is implemented in Python and its open-source code as well as the data to reproduce the results are available on Github.
GPR1 and CMKLR1 Control Lipid Metabolism to Support the Development of Clear Cell Renal Cell Carcinoma
Authors: Wang Dazhi , Mahmud Iqbal , Thakur Vijay S. , Tan Sze Kiat , Isom Daniel G. , Lombard David B. , Gonzalgo Mark L. , Kryvenko Oleksandr N. , Lorenzi Philip L. , Tcheuyap Vanina T. , Brugarolas James , Welford Scott M. 
Published: April 2024

Abstract
Clear cell renal cell carcinoma (ccRCC), the most common type of kidney cancer, is largely incurable in the metastatic setting. ccRCC is characterized by excessive lipid accumulation that protects cells from stress and promotes tumor growth, suggesting that the underlying regulators of lipid storage could represent potential therapeutic targets. Here, we evaluated the regulatory roles of GPR1 and CMKLR1, two G protein–coupled receptors of the protumorigenic adipokine chemerin that is involved in ccRCC lipid metabolism. Both genetic and pharmacologic suppression of either receptor suppressed lipid formation and induced multiple forms of cell death, including apoptosis, ferroptosis, and autophagy, thereby significantly impeding ccRCC growth in cell lines and patient-derived xenograft models. Comprehensive lipidomic and transcriptomic profiling of receptor competent and depleted cells revealed overlapping and unique signaling of the receptors granting control over triglyceride synthesis, ceramide production, and fatty acid saturation and class production. Mechanistically, both receptors enforced suppression of adipose triglyceride lipase, but each receptor also demonstrated distinct functions, such as the unique ability of CMKLR1 to control lipid uptake through regulation of sterol regulatory element–binding protein 1c and the CD36 scavenger receptor. Treating patient-derived xenograft models with the CMKLR1-targeting small molecule 2-(α-naphthoyl) ethyltrimethylammonium iodide (α-NETA) led to a dramatic reduction in tumor growth, lipid storage, and clear-cell morphology. Together, these findings provide mechanistic insights into lipid regulation in ccRCC and identify a targetable axis at the core of the histologic definition of this tumor that could be exploited therapeutically.
Significance: Extracellular control of lipid accumulation via G protein receptor–mediated cell signaling is a metabolic vulnerability in clear cell renal cell carcinoma, which depends on lipid storage to avoid oxidative toxicity.
Association of Ideal Cardiovascular Health in Youth with Cancer Risk in Adulthood: A Cardiovascular Risk in Young Finns Study
Authors: Niemelä Jussi , Nuotio Joel , Laitinen Tomi T. , Kähönen Mika , Hutri Nina , Lehtimäki Terho , Jokinen Eero , Tossavainen Päivi , Laitinen Tomi P. , Heinonen Olli J. , Dwyer Terence , Pahkala Katja , Rovio Suvi P. , Viikari Jorma , Raitakari Olli , Juonala Markus 
Published: April 2024

Abstract

Background:
Lifestyle factors may affect cancer risk. This study aimed to identify whether the American Heart Association ideal cardiovascular health (ICH) score and its individual variables in youth are associated with subsequent cancer incidence.

Methods:
This study comprised participants of the Cardiovascular Risk in Young Finns Study free of cancer at the analysis baseline in 1986 (n = 1,873). The baseline age was 12 to 24 years, and the follow-up occurred between 1986 and 2018.

Results:
Among 1,873 participants (mean age 17.3 ± 4.1 years; 53.4% females at baseline), 72 incident cancer cases occurred during the follow-up (mean follow-up time 31.4 ± 3.4 years). Baseline ICH score was not associated with future cancer risk (HR, 0.96; 95% confidence interval, 0.78–1.12 per 1-point increment). Of individual ICH score variables, ideal physical activity (PA) was inversely associated with cancer incidence [age- and sex-adjusted HR, 0.45 (0.23–0.88) per 1-category change (nonideal/ideal)] and remained significant in the multivariable-adjusted model, including body mass index, smoking, diet, and socioeconomic status. A continuous PA index at ages 9 to 24 years and moderate-to-vigorous PA in youth were also related to decreased cancer incidence (P &lt; 0.05). Body mass index, smoking, diet, total cholesterol, glucose, and blood pressure were not related to cancer risk. Of the dietary components, meat consumption was associated with cancer incidence (P = 0.023).

Conclusions:
These findings indicate that higher PA levels in youth are associated with a reduced subsequent cancer incidence, whereas the American Heart Association’s ICH score in youth does not.

Impact:
This finding supports efforts to promote a healthy lifestyle and encourages PA during childhood, yielding a subsequent healthier life.
A Cohort Study to Evaluate Genetic Predictors of Aromatase Inhibitor Musculoskeletal Symptoms: Results from ECOG-ACRIN E1Z11
Authors: Stearns Vered , Jegede Opeyemi A. , Chang Victor T.-S. , Skaar Todd C. , Berenberg Jeffrey L. , Nand Ranveer , Shafqat Atif , Jacobs Nisha L. , Luginbuhl William , Gilman Paul , Benson Al B. , Goodman Judie R. , Buchschacher Gary L. , Henry N. Lynn , Loprinzi Charles L. , Flynn Patrick J. , Mitchell Edith P. , Fisch Michael J. , Sparano Joseph A. , Wagner Lynne I. 
Published: April 2024

Abstract

Purpose:
Aromatase inhibitor (AI)–associated musculoskeletal symptoms (AIMSS) are common and frequently lead to AI discontinuation. SNPs in candidate genes have been associated with AIMSS and AI discontinuation. E1Z11 is a prospective cohort study designed to validate the association between 10 SNPs and AI discontinuation due to AIMSS.

Patients and Methods:
Postmenopausal women with stage I to III hormone receptor–positive breast cancer received anastrozole 1 mg daily and completed patient-reported outcome measures to assess AIMSS (Stanford Health Assessment Questionnaire) at baseline, 3, 6, 9, and 12 months. We estimated that 40% of participants would develop AIMSS and 25% would discontinue AI treatment within 12 months. Enrollment of 1,000 women with a fixed number per racial stratum provided 80% power to detect an effect size of 1.5 to 4. SNPs were found in ESR1 (rs2234693, rs2347868, and rs9340835), CYP19A1 (rs1062033 and rs4646), TCL1A (rs11849538, rs2369049, rs7158782, and rs7159713), and HTR2A (rs2296972).

Results:
Of the 970 evaluable women, 43% developed AIMSS and 12% discontinued AI therapy within 12 months. Although more Black and Asian women developed AIMSS than White women (49% vs. 39%, P = 0.017; 50% vs. 39%, P = 0.004, respectively), the AI discontinuation rates were similar across groups. None of the SNPs were significantly associated with AIMSS or AI discontinuation in the overall population or in distinct cohorts. The OR for rs2296972 (HTR2A) approached significance for developing AIMSS.

Conclusions:
We were unable to prospectively validate candidate SNPs previously associated with AI discontinuation due to AIMSS. Future analyses will explore additional genetic markers, patient-reported outcome predictors of AIMSS, and differences by race.
Integrating Multisector Molecular Characterization into Personalized Peptide Vaccine Design for Patients with Newly Diagnosed Glioblastoma
Authors: Johanns Tanner M. , Garfinkle Elizabeth A.R. , Miller Katherine E. , Livingstone Alexandra J. , Roberts Kaleigh F. , Rao Venkata Lakshmi P. , Dowling Joshua L. , Chicoine Michael R. , Dacey Ralph G. , Zipfel Gregory J. , Kim Albert H. , Mardis Elaine R. , Dunn Gavin P. 
Published: April 2024

Abstract

Purpose:
Outcomes for patients with glioblastoma (GBM) remain poor despite multimodality treatment with surgery, radiation, and chemotherapy. There are few immunotherapy options due to the lack of tumor immunogenicity. Several clinical trials have reported promising results with cancer vaccines. To date, studies have used data from a single tumor site to identify targetable antigens, but this approach limits the antigen pool and is antithetical to the heterogeneity of GBM. We have implemented multisector sequencing to increase the pool of neoantigens across the GBM genomic landscape that can be incorporated into personalized peptide vaccines called NeoVax.

Patients and Methods:
In this study, we report the findings of four patients enrolled onto the NeoVax clinical trial (NCT0342209).

Results:
Immune reactivity to NeoVax neoantigens was assessed in peripheral blood mononuclear cells pre- and post-NeoVax for patients 1 to 3 using IFNγ-ELISPOT assay. A statistically significant increase in IFNγ producing T cells at the post-NeoVax time point for several neoantigens was observed. Furthermore, a post-NeoVax tumor biopsy was obtained from patient 3 and, upon evaluation, revealed evidence of infiltrating, clonally expanded T cells.

Conclusions:
Collectively, our findings suggest that NeoVax stimulated the expansion of neoantigen-specific effector T cells and provide encouraging results to aid in the development of future neoantigen vaccine–based clinical trials in patients with GBM. Herein, we demonstrate the feasibility of incorporating multisector sampling in cancer vaccine design and provide information on the clinical applicability of clonality, distribution, and immunogenicity of the neoantigen landscape in patients with GBM.
A Machine Learning Algorithm Facilitates Prognosis Prediction and Treatment Selection for Barcelona Clinic Liver Cancer Stage C Hepatocellular Carcinoma
Authors: Han Ji W. , Lee Soon K. , Kwon Jung H. , Nam Soon W. , Yang Hyun , Bae Si H. , Kim Ji H. , Nam Heechul , Kim Chang W. , Lee Hae L. , Kim Hee Y. , Lee Sung W. , Lee Ahlim , Chang U I. , Song Do S. , Kim Seok-Hwan , Song Myeong J. , Sung Pil S. , Choi Jong Y. , Yoon Seung K. , Jang Jeong W. 
Published: April 2024

Abstract

Purpose:
Given its heterogeneity and diverse clinical outcomes, precise subclassification of Barcelona Clinic Liver Cancer stage C (BCLC-C) hepatocellular carcinoma (HCC) is required for appropriately determining patient prognosis and selecting treatment.

Experimental Design:
We recruited 2,626 patients with BCLC-C HCC from multiple centers, comprising training/test (n = 1,693) and validation cohorts (n = 933). The XGBoost model was chosen for maximum performance among the machine learning (ML) models. Patients were categorized into low-, intermediate-, high-, and very high-risk subgroups based on the estimated prognosis, and this subclassification was named the CLAssification via Machine learning of BCLC-C (CLAM-C).

Results:
The areas under the receiver operating characteristic curve of the CLAM-C for predicting the 6-, 12-, and 24-month survival of patients with BCLC-C were 0.800, 0.831, and 0.715, respectively—significantly higher than those of the conventional models, which were consistent in the validation cohort. The four subgroups had significantly different median overall survivals, and this difference was maintained among various patient subgroups and treatment modalities. Immune-checkpoint inhibitors and transarterial therapies were associated with significantly better survival than tyrosine kinase inhibitors (TKI) in the low- and intermediate-risk subgroups. In cases with first-line systemic therapy, the CLAM-C identified atezolizumab–bevacizumab as the best therapy, particularly in the high-risk group. In cases with later-line systemic therapy, nivolumab had better survival than TKIs in the low-to-intermediate-risk subgroup, whereas TKIs had better survival in the high- to very high-risk subgroup.

Conclusions:
ML modeling effectively subclassified patients with BCLC-C HCC, potentially aiding treatment allocation. Our study underscores the potential utilization of ML modeling in terms of prognostication and treatment allocation in patients with BCLC-C HCC.
NSCLC Extracellular Vesicles Containing miR-374a-5p Promote Leptomeningeal Metastasis by Influencing Blood‒Brain Barrier Permeability
Authors: Jin Jie , Cui Yumeng , Niu Huicong , Lin Yanli , Wu Xiaojie , Qi Xuejiao , Bai Kaixuan , Zhang Yu , Wang Youliang , Bu Hui 
Published: April 2024

AbstractLeptomeningeal metastasis (LM) is a devastating complication of advanced non–small cell lung cancer (NSCLC). Its diagnosis and monitoring can be challenging. Recently, extracellular vesicle (EV) miRNAs have become a new noninvasive diagnostic biomarker. The purpose of this study was to examine the clinical value and role of EV miRNAs in NSCLC-LM. Next-generation sequencing analysis revealed that miRNAs with differential expression of EVs in sera of patients with NSCLC with LM and non-LM were detected to identify biological markers for the diagnosis of LM. Cellular and in vivo experiments were conducted to explore the pathogenesis of EV miRNA promoting LM in NSCLC. In the present study, we first demonstrated that the serum level of EV-associated miR-374a-5p in patients with LM of lung cancer was much higher than that in patients without LM and was correlated with the survival time of patients with LM. Further studies showed that EV miR-374a-5p efficiently destroys tight junctions and the integrity of the cerebral microvascular endothelial cell barrier, resulting in increased blood–brain barrier permeability. Mechanistically, miR-374a-5p regulates the distribution of ZO1 and occludin in endothelial cells by targeting γ-adducin, increasing vascular permeability and promoting LM.Implications: These results suggest that serum NSCLC–derived EV miR-374a-5p is involved in premetastatic niche formation by regulating the permeability of the blood–brain barrier to promote NSCLC-LM and can be used as a blood biomarker for the diagnosis and prognosis of NSCLC-LM.