bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overexpression of tousled-like kinase 2 predicts poor prognosis in HBV-related hepatocellular carcinoma patients after radical resection
Authors: Liu Bang , Lu Ling-Ling , Yu Li , Mei Xuan , Liu Jia , Zheng Jiao-Long , Zhou Xiao-Ling , Lin Hai-Yan , Zhu Xiu-Ling , Li Dong-Liang 
Published: January 2024

Background: Tousled-like kinase 2 (TLK2) is integral to DNA repair, replication, and cell cycle regulation, crucial for maintaining genome stability and integrity. However, the expression and prognostic value of TLK2 in hepatitis B viral (HBV) -related hepatocellular carcinoma (HCC) remains unclear.Methods: We examined TLK2 expression and prognostic implications in pan-cancer by using diverse databases. Subsequently, TLK2 expression in HBV-related HCC tissues and adjacent tissues was assessed using quantitative real-time PCR and immunohistochemistry. The prognostic value of TLK2 was assessed through ROC curves, time-dependent ROC curves, Cox regression, Kaplan-Meier curve, and decision curve analysis. Additionally, analyses of immune infiltration, protein-protein interactions, key molecules of tumor-related signaling pathways, molecular subtypes, and TLK2-associated differentially expressed genes (DEGs) were conducted, along with GO/KEGG and GSEA enrichment analyses.Results: TLK2 expression was significantly higher in HCC tissues compared to adjacent tissues and correlated with gender, AFP levels, albumin-bilirubin (ALBI) grade, microvascular invasion (MVI), maximum tumor diameter, tumor number, and TNM stage. TLK2 overexpression emerged as an independent risk factor for overall survival (OS) and recurrence-free survival (RFS) in HBV-related HCC patients. An integrated OS nomogram model, incorporating TLK2, age, ALBI grade, MVI, and tumor number, displayed enhanced prognostic capability (C-index: 0.765, 95% CI: 0.732–0.798) in predicting OS and has a higher net benefit than the TNM stage. Moreover, TLK2 expression correlated closely with immune cell infiltration and key molecules of signaling pathways. Functional enrichment analyses highlighted significant associations with DNA duplex unwinding, double-strand break repair, DNA replication, cell cycle, E2F targets, G2M checkpoint, and MYC targets V1.Conclusion: TLK2 is notably overexpressed in HBV-related HCC and emerges as a promising prognostic biomarker, necessitating further validation.
Low pre-existing endemic human coronavirus (HCoV-NL63)-specific T cell frequencies are associated with impaired SARS-CoV-2-specific T cell responses in people living with HIV
Authors: Ng’uni Tiza L. , Musale Vernon , Nkosi Thandeka , Mandolo Jonathan , Mvula Memory , Michelo Clive , Karim Farina , Moosa Mohomed Yunus S. , Khan Khadija , Jambo Kondwani Charles , Hanekom Willem , Sigal Alex , Kilembe William , Ndhlovu Zaza M. 
Published: January 2024

BackgroundUnderstanding how HIV affects SARS-CoV-2 immunity is crucial for managing COVID-19 in sub-Saharan populations due to frequent coinfections. Our previous research showed that unsuppressed HIV is associated with weaker immune responses to SARS-CoV-2, but the underlying mechanisms are unclear. We investigated how pre-existing T cell immunity against an endemic human coronavirus HCoV-NL63 impacts SARS-CoV-2 T cell responses in people living with HIV (PLWH) compared to uninfected individuals, and how HIV-related T cell dysfunction influences responses to SARS-CoV-2 variants.MethodsWe used flow cytometry to measure T cell responses following PBMC stimulation with peptide pools representing beta, delta, wild-type, and HCoV-NL63 spike proteins. Luminex bead assay was used to measure circulating plasma chemokine and cytokine levels. ELISA and MSD V-PLEX COVID-19 Serology and ACE2 Neutralization assays were used to measure humoral responses.ResultsRegardless of HIV status, we found a strong positive correlation between responses to HCoV-NL63 and SARS-CoV-2. However, PLWH exhibited weaker CD4+ T cell responses to both HCoV-NL63 and SARS-CoV-2 than HIV-uninfected individuals. PLWH also had higher proportions of functionally exhausted (PD-1high) CD4+ T cells producing fewer proinflammatory cytokines (IFNγ and TNFα) and had elevated plasma IL-2 and IL-12(p70) levels compared to HIV-uninfected individuals. HIV status didn’t significantly affect IgG antibody levels against SARS-CoV-2 antigens or ACE2 binding inhibition activity.ConclusionOur results indicate that the decrease in SARS-CoV-2 specific T cell responses in PLWH may be attributable to reduced frequencies of pre-existing cross-reactive responses. However, HIV infection minimally affected the quality and magnitude of humoral responses, and this could explain why the risk of severe COVID-19 in PLWH is highly heterogeneous.
Immune response following a two-dose schedule of bivalent HPV vaccination among girls and boys
Authors: Middeldorp Marit , Duijster Janneke W. , van de Kassteele Jan , van der Klis Fiona R.M. , de Melker Hester E. 
Published: January 2024

BackgroundThis longitudinal cohort study describes the kinetics in antibody levels after two doses of the bivalent human papillomavirus (HPV) vaccine in girls (birth cohort 2001) vaccinated in the routine Dutch vaccination program at 12 years of age, up to 7.5 years post-vaccination. Also, the antibody response one month post-vaccination of the first cohort of boys (birth cohort 2012, vaccinated at 10 years of age) eligible for HPV vaccination in the Netherlands is presented.MethodBlood samples and questionnaire data were collected of girls and boys. HPV type-specific antibody concentrations (LU/mL) against HPV16/18/31/33/45/52/58 were assessed using a validated virus-like particle (VLP) multiplex immunoassay. For girls, antibody decays over time were modelled using the modified power-law decay model and the exponential decay model.ResultsThe Geometric Mean Concentrations (GMCs) remained higher for HPV16/18 than for HPV types 31, 33, 45, 52, and 58 among girls up to 7.5 years post-vaccination. The antibody levels of HPV16 and HPV18 reached plateau values of 482 and 159 LU/mL, respectively. Mathematical modelling showed that the half-life values of HPV16/18 were 2.4- to 4.5-fold higher compared with the half-life values of the other HPV types. Among boys (aged 10 years), the GMC for HPV16 was significantly higher than among girls one month post-vaccination (aged 12 years).ConclusionThe GMCs of all HPV types declined over time, although the GMCs of HPV16/18 remained relatively high up to 7.5 years post-vaccination. The GMCs for HPV16/18 among boys were at least equally high as the GMCs among girls at one month post-vaccination. Further follow-up of the cohort of boys is needed to gain knowledge on long-term immune responses of young boys following bivalent HPV vaccination.
Quantifying zoobenthic blue carbon storage across habitats within the Arctic’s Barents Sea
Authors: Souster Terri A. , Barnes David K. A. , Primicerio Raul , Jørgensen Lis Lindal 
Published: January 2024

IntroductionThe Arctic sea ice extent in September (when it is at its lowest) has declined 13% Q10 per decade, and the Arctic Ocean is becoming a more Atlantic-influenced system. Rapid climate-forced changes are taking place in many high-latitude marine ecosystems. The Barents Sea is one such high-latitude shelf ecosystem, between approximately 70° and 80°N in the Norwegian Arctic. The purpose of the current study was to estimate zoobenthic blue carbon across multiple habitats within the Barents Sea (trough, basin, shelf, and shallows), potentially providing values to aid ecosystem-based management of these areas under future climate change scenarios.MethodWe tested this by capture and analysis of 947 high-resolution (each 405.7 × 340.6 mm, 12 MB, 5 megapixels) seabed images at 17 sites with latitudinal cline, linked to a collection of corresponding oceanographic data. Biotas within these images were identified to one of the 14 functional groups and the density was calculated. Mean stored carbon per individual was assigned by ash mass (AM) and ash-free dry mass (AFDM) of individuals caught within Agassiz trawl deployments at the same sites.ResultsTrough sites, except for one site (B16), have a low quantity of zoobenthic blue carbon compared with the shallow, shelf, and basin habitats.DiscussionThe results of a previous study focused entirely on trough habitats and are therefore difficult to scale up as the basis for a meaningful estimate of across-habitat zoobenthic blue carbon in the Barents Sea. Compared with the trough and the basin, the shelf and shallow habitats of the Barents Sea are also subjected to more trawling events through demersal fisheries and showed higher zoobenthic blue carbon stock values.
Diagnostic accuracy of OGUS, Southend halo score and halo count in giant cell arteritis
Authors: Conticini Edoardo , Falsetti Paolo , Al Khayyat Suhel Gabriele , Grazzini Silvia , Baldi Caterina , Bellisai Francesca , Gentileschi Stefano , Bardelli Marco , Fabiani Claudia , Cantarini Luca , Dasgupta Bhaskar , Frediani Bruno 
Published: January 2024

ObjectivesUltrasound has a paramount role in the diagnostic assessment of giant cell arteritis (GCA); Southend halo score (HS), halo count (HC), and OMERACT GCA Ultrasonography Score (OGUS) are the first quantitative scores proposed in this setting. The aim of this study was therefore to assess the diagnostic accuracy of these scores in a real-life scenario, as well as to evaluate their optimal cutoff, also with respect to disease extent, sex, and age.MethodsWe retrospectively collected clinical, serological, and US findings of all patients referred for the first time to our vasculitis clinic in the suspicion of GCA.ResultsA total of 79 patients were included, and a definite diagnosis of GCA was made in 43 patients. For OGUS, the ROC curve showed an optimal cut point of 0.81 (sensitivity 79.07% and specificity 97.22%). For HC and HS, the optimal cutoff values were &gt; 1.5 (sensitivity 76.7% and specificity 97.2%) and &gt; 14.5 (sensitivity 74.4% and specificity 97.2%), respectively. No relevant differences were assessed when patients were stratified according to disease extent, age, and sex. Compression sign (CS) was positive in 34 of 38 patients with cranial GCA and negative in all controls and LV-GCA.ConclusionAll three scores display good sensitivity and excellent specificity, although the cutoff was slightly different than proposed. In particular, for OGUS, a threshold of 0.81 could be employed for diagnostic purposes, although it was developed solely for monitoring. Due to its high sensitivity and specificity, CS should be always assessed in all patients referred with a suspicion of cranial GCA.
Induced degeneration and regeneration in aged muscle reduce tubular aggregates but not muscle function
Authors: Vasconcelos Felipe Tadeu Galante Rocha de , Ribeiro Júnior Antonio Fernando , Souza Brandow Willy , Zogbi Isabela de Aquino , Carvalho Laura Machado Lara , Feitosa Letícia Nogueira , Souza Lucas Santos , Saldys Nathália Gagliardi , Ferrari Merari de Fátima Ramires , Vainzof Mariz 
Published: January 2024

IntroductionTubular aggregates (TA) are skeletal muscle structures that arise from the progressive accumulation of sarcoplasmic reticulum proteins. Cytoplasmic aggregates in muscle fibers have already been observed in mice and humans, mainly during aging and muscle disease processes. However, the effects of muscle regeneration on TA formation have not yet been reported. This study aimed to investigate the relationship between degeneration/regeneration and TA in aged murine models. We investigated the presence and quantity of TA in old males from two murine models with intense muscle degeneration and regeneration.MethodsOne murine lineage was a Dmdmdx model of Duchenne muscular dystrophy (n = 6). In the other model, muscle damage was induced by electroporation in C57BL/6J wild-type mice, and analyzed after 5, 15, and 30 days post-electroporation (dpe; n = 15). Regeneration was evaluated based on the quantity of developmental myosin heavy chain (dMyHC)-positive fibers.ResultsThe frequency of fibers containing TA was higher in aged C57BL/6J (26 ± 8.3%) than in old dystrophic Dmdmdx mice (2.4 ± 2%). Comparing the data from induced degeneration/regeneration in normal mice revealed a reduced proportion of TA-containing fibers after 5 and 30 dpe. Normal aged muscle was able to regenerate and form dMyHC+ fibers, mainly at 5 dpe (0.1 ± 0.1 vs. 16.5 ± 2.6%). However, there was no difference in force or resistance between normal and 30 dpe animals, except for the measurements by the Actimeter device, which showed the worst parameters in the second group.DiscussionOur results suggest that TA also forms in the Dmdmdx muscle but in smaller amounts. The intense degeneration and regeneration of the old dystrophic model resulted in the generation of new muscle fibers with a lower quantity of TA. Data from electroporated wild-type mice support the idea that muscle regeneration leads to a reduction in the amount of TA. We suggest that TA accumulates in muscle fibers throughout physiological aging and that regeneration leads to the formation of new fibers without these structures. In addition, these new fibers do not confer functional benefits to the muscle.
Marine fungus Aspergillus c1. sp metabolite activates the HSF1/PGC-1α axis, inducing a thermogenic program for treating obesity
Authors: Rao Yong , Su Rui , Wu Chenyan , Yang Guanyu , Fu Renquan , Wu Junjie , Liang Jinqiang , Liu Jin , Jiang Zhongping , Xu Congjun , Huang Ling 
Published: January 2024

Background and aims: Obesity is one of the most prevalent diseases worldwide with less ideal approved agents in clinic. Activating the HSF1/PGC-1α axis in adipose tissues has been reported to induce thermogenesis in mice, which presents a promising therapeutic avenue for obesity treatment. The present study aimed to identified novel natural HSF1 activator and evaluated the therapeutic effects of the newly discovered compound on obesity-associated metabolic disorders and the molecular mechanisms of these effects.Methods: Our previous reported HSF1/PGC-1α activator screening system was used to identify novel natural HSF1 activator. The PGC-1α luciferase activity, immunoblot, protein nuclear-translocation, immunofluorescence, chromatin immunoprecipitation assays were used to evaluate the activity of compound HN-001 in activating HSF1. The experiments of mitochondrial number measurement, TG assay and imaging, cellular metabolic assay, gene assays, and CRISPR/Cas 9 were applied for investigating the metabolic effect of HN-001 in C3H10-T1/2 adipocytes. The in vivo anti-obesity efficacies and beneficial metabolic effects of HN-001 were evaluated by performing body and fat mass quantification, plasma chemical analysis, GTT, ITT, cold tolerance test, thermogenesis analysis.Results: HN-001 dose- and time-dependently activated HSF1 and induced HSF1 nuclear translocation, resulting in an enhancement in binding with the gene Pgc-1α. This improvement induced activation of adipose thermogenesis and enhancement of mitochondrial oxidation capacity, thus inhibiting adipocyte maturation. Deletion of HSF1 in adipocytes impaired mitochondrial oxidation and abolished the above beneficial metabolic effects of HN-001, including adipocyte browning induction, improvements in mitogenesis and oxidation capacity, and lipid-lowering ability. In mice, HN-001 treatment efficiently alleviated diet-induced obesity and metabolic disorders. These changes were associated with increased body temperature in mice and activation of the HSF1/PGC-1α axis in adipose tissues. UCP1 expression and mitochondrial biogenesis were increased in both white and brown adipose tissues of HN-001-treated mice.Conclusion: These data indicate that HN-001 may have therapeutic potential for obesity-related metabolic diseases by increasing the capacity of energy expenditure in adipose tissues through a mechanism involving the HSF1/PGC-1α axis, which shed new light on the development of novel anti-obesity agents derived from marine sources.
Chemical composition, antioxidant properties, and antifungal activity of wild Origanum elongatum extracts against Phytophthora infestans
Authors: Hari Amal , Echchgadda Ghizlane , Darkaoui Fatima-Azzahra , Taarji Noamane , Sahri Nihad , Sobeh Mansour , Ezrari Said , Laasli Salah-Eddine , Benjelloun Meryem , Lahlali Rachid 
Published: January 2024

IntroductionPhytophthora infestans, the causative agent of late blight disease, has gained notoriety for its destructive potential, leading to substantial losses in potato yields. Although conventional systemic fungicides have been shown to be effective in controlling plant pathogens, growing environmental concerns have prompted the need for more integrated disease management approaches. Hence, in this study, the effectiveness of wild Origanum elongatum extracts as biopesticides was explored in controlling P. infestans and potentially mitigating its devastating impact in planta.MethodsThe aerial parts of O. elongatum were subjected to sequential extraction using water, hexane, chloroform, and methanol. The obtained extracts were tested in vitro through the poisoned food procedure for their capacity to obstruct P. infestans growth and to defeat potato blight severity in vivo. The phyto-contents (total phenolic content (TPC) and total flavonoid content (TFC)), as well as the antioxidant activities, were spectrophotometrically determined in all extracts, and the phytoconstituents of the most active extract (methanolic extract) were profiled via high-performance liquid chromatography–photodiode array–tandem mass spectrometry (HPLC–PDA–MS/MS).ResultsIn vitro, the complete inhibition rate of the P. infestans was obtained using the methanolic extract at 5 mg/mL, followed by the hexane and chloroform extracts at 10 mg/mL. Interestingly, complete inhibition of the pathogen was achieved upon the application of the aqueous extract at 10 mg/mL. In vivo, the aqueous extract at 25 mg/mL reduced the P. infestans severity rate to 27.25%, while the methanolic extract at 20 mg/mL led to the lowest severity rate. Moreover, the hexane and chloroform extracts impaired the pathogen severity rate to 50% and 41% using 20 mg/mL, respectively. The TPC and TFC in the extracts were variable with high concentrations detected in the methanolic extract with 485.42 mg GAE/g and 58.24 mg QE/g, respectively. In addition, the methanolic extract showed the highest antioxidant activities, while the chloroform extract exhibited the lowest activity. Liquid chromatography (LC)–MS/MS analysis of the methanol extract revealed 56 components from diverse classes. These included organic acids, phenolic acids, flavonoids, tannins, and coumarins.ConclusionThese findings suggest that O. elongatum could be investigated as a potential source of antifungal compounds targeting different phytopathogens.
Comprehensive phenomic and genomic studies of the species, Pectobacterium cacticida and proposal for reclassification as Alcorniella cacticida comb. nov
Authors: Jonca Joanna , Pirhonen Minna , Waleron Michal Mateusz , Gawor Jan , Mrozik Agnieszka , Smoktunowicz Magdalena , Waleron Krzysztof , Waleron Malgorzata 
Published: January 2024

IntroductionPectobacterium cacticida was identified as the causative agent of soft rot disease in cacti. Due to a high potential of spread in the face of global warming, the species poses a significant threat to horticultural and crop industry. The aim of this study was to revise the genomic, physiology and virulence characteristics of P. cacticida and update its phylogenetic position within the Pectobacterium genus.MethodsWhole genome sequences of five P. cacticida strains were obtained and subjected to comprehensive genomic and phylogenomic data analyses. We assessed the presence of virulence determinants and genes associated with host and environmental adaptation. Lipidomic analysis, as well as biochemical and phenotypic assays were performed to correlate genomic findings.ResultsPhylogenomic analysis revealed that P. cacticida forms a distinct lineage within the Pectobacterium genus. Genomic evaluation uncovered 516 unique proteins, most of which were involved in cellular metabolism. They included genes of carbohydrate metabolism and transport and ABC transporters. The main differing characteristics from other Pectobacterium species were the lack of a myo-inositol degradation pathway and the presence of the malonate decarboxylase gene. All tested strains were pathogenic towards Opuntia spp., chicory, Chinese cabbage, and potato, but exhibited only mild pathogenicity towards carrot.DiscussionThis study sheds light into the genomic characteristics of P. cacticida and highlights the pathogenic potential of the species. Unique genes found in P. cacticida genomes possibly enhance the species’ survival and virulence. Based on phylogenomic analyses, we propose the reclassification of P. cacticida to a new genus, Alcorniella comb. nov.
ESport programs in high school: what’s at play?
Authors: Lemay Antoine , Dufour Magali , Goyette Mathieu , Berbiche Djamal 
Published: January 2024

BackgroundA growing number of high schools in Canada offer eSports (ES) in their facilities, which raises concerns regarding this activity’s potential health risks for adolescents.MethodsThe aim of this study is to describe the characteristics of 67 adolescent ES players (ESp) and to compare them to 109 recreational gamers in their high school (nESp). The two groups were compared on (1) sociodemographic and academic characteristics; (2) online and offline activities; (3) psychological characteristics.ResultsResults show that ESp spend more time on online activities and report a higher proportion of problematic gaming compared to the nESp group. ESp report more often that gaming has positive consequences on their physical health and report more often negative consequences on their education compared to the nESp group.ConclusionThese results underscore the importance of screening gaming problems among adolescent ES players. Targeted prevention should be carried out with these teenagers and in order to be adapted, prevention efforts should consider both, the positive and negative consequences that ESp experience from gaming.
White matter hyperintensities in bipolar disorder: systematic review and meta-analysis
Authors: Silva Tânia , Nunes Cesar , Ribeiro Andreia , Santana Isabel , Cerejeira Joaquim 
Published: January 2024

BackgroundWhite matter hyperintensities are lesions of presumed vascular origin associated with Cerebral small vessel disease. WMH are common findings that and are associated with increased risk of cognitive impairment and dementia. A higher prevalence of WMH has been also reported in patients with bipolar disorder (BD), although the evidence is conflicting.ObjectiveTo compare the prevalence of WMH in adults with BD, with the prevalence found in healthy controls.MethodsWe searched the Embase, Medline/PubMed, and references cited in articles retrieved on May 20, 2023. We included case-control studies that compared the prevalence of WMH in adult BD patients with the prevalence of WMH in healthy controls, using T2-weighted magnetic resonance imaging. We performed a meta-analysis using a random-effects method based on the inverse-variance approach.FindingsWe included 22 case-control studies reporting data of 1313 people. The overall rate of WMH was 46.5% in BD patients and 28% in controls (pooled Odds Ratio 2.89, 95% CI 1.76; 4.75). We found a moderate heterogeneity across studies (I2 = 0.49). Publication bias was not significant.InterpretationWe found evidence that BD patients have a higher burden of WMH than healthy controls. Main limitations were impossibility of analyzing gender differences and bipolar type, moderate heterogeneity between studies, non-representative samples, lack of control for major confounders and search in two electronic databases.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023428464