bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disruption of HIF1Α translational control attenuates the HIF-dependent hypoxic response and solid tumour formationin vivo
Authors: Hunter Jill E , McHugh Oliver , Ecclestone Gabrielle B , Child Fraser , Mearns Hannah , Robson Georgia , Dadzie Molly , Rocha Sonia , Perkins Neil D , Kenneth Niall S 
Published: November 2022

ABSTRACTAdaptation to reduced oxygen availability is mediated by the hypoxia-inducible factor (HIF) family of transcription factors. The activity and availability of HIF proteins is primarily driven by the stability of the HIF alpha subunits. However, it is becoming increasingly apparent that preferential translation of HIF1α mRNA is also necessary for full activation of the HIF1-dependent hypoxic response. Consequently, the mechanisms controlling HIF1α translation are of equivalent importance to the proline hydroxylase-dependent degradation pathways. Here we investigate the role of the 5’UTR of the HIF1α mRNA in controlling preferential translation of endogenous HIF1α in hypoxic cells. CRISPR/Cas9-mediated genetic deletion of the 5’ UTR of HIF1α results in reduced HIF1α levels following hypoxia, without alteration in mRNA or protein stability. HIF1α mRNA lacking the 5’UTR was efficiently translated in adequately oxygenated cells but this was inhibited during hypoxia, consistent with the global block on protein synthesis. The HIF1α translational defect observed in cells missing the 5’UTR led to reduced viability in hypoxic conditionsin vitroand an impaired ability to form solid tumours in murine xenografts. Prevention of preferential HIF1α translation limits the duration and intensity of the HIF-dependent hypoxic response and disrupts the formation of solid tumours. Together these results demonstrate the importance of translation control over HIF1α and suggest that strategies to inhibit preferential HIF1α protein translation in hypoxic cancer cells will be an effective strategy to limit the growth of solid hypoxic tumours.
Autophagy limits inflammatory gene expression through targeting of nuclear p65/RelA by LC3 and p62 for lysosomal degradation
Authors: Brischetto Cristina , Mucka Patrick , Kaergel Eva , Scheidereit Claus 
Published: November 2022

AbstractThe interplay between NF-κB signaling and autophagy regulates inflammatory signaling in different cellular contexts and in response to different stimuli. The impairment of this crosstalk may play a role in chronic inflammation and in tumorigenesis. However, the molecular mechanism by which these two pathways interact to regulate the inflammatory response remains elusive. By using biochemical analysis and imaging techniques, we characterized the interaction of the endogenous autophagic marker LC3 and NF-κB/p65 in response to different stress conditions. Following irradiation or TNFα stimulation, nuclear accumulation of LC3 strongly co-localized with p65, suggesting that nuclear p65 is targeted for autophagic degradation. Mechanistically, we showed that the nuclear p65-LC3 interaction is mediated by ubiquitination of the same p65, which is recognized by the cargo receptor p62, resulting in its cytoplasmic export and lysosomal proteolysis. Accordingly, autophagy inhibition by depletion of the essential autophagy geneATG16L1selectively stabilizes nuclear p65, in turn enhancing NF-κB gene expression of pro-inflammatory cytokine. Our results revealed a novel molecular mechanism that modulates the NF-κB inflammatory response through nuclear sequestration of the NF-κB/p65 subunit by autophagy proteins. These findings are of importance for developing novel therapeutic strategies against chronic inflammatory diseases displaying defective autophagy and constitutive NF-κB activity.
The Longitudinal Analysis of Convergent Antibody VDJ Regions in SARS-CoV-2 Positive Patients Using RNA-seq
Authors: Liu Kate J. , Zelazowska Monika A. , McBride Kevin M. 
Published: November 2022

AbstractThe severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has infected over 600 million individuals and caused over 6.5 million deaths. To understand the immune response individuals have from the SARS-CoV-2 infection, we studied the immunoglobulins against the virus’s antigens. The diversified complementarity determining region 3 (CDR3) can be used to characterize an antibody. We downloaded four public RNA-seq data sets that were collected be-tween March 2020 and March 2022 from the Gene Expression Omnibus (GEO) in our longitudinal analysis. In total, there were 269 SARS-CoV-2 positive patients and 26 negative patients who served as a control group. Samples were grouped based on their SARS-CoV-2 variant type and/or the time they were collected. Among 629,137 immunoglobulin V(D)J sequences identified by reconstructing the V(D)J sequences, we found 1011 common V(D)Js (same V gene, J gene and CDR3 sequences in each SARS-CoV-2 positive group) shared by more than one patient in each group and no common V(D)Js were from the negative control group. In our clustering analysis, we identified 129 convergent clusters from the SARS-CoV-2 positive groups. One of these convergent clusters matched the protein sequence of crystal 3D structures of the antibodies against SARS-CoV-2 in the Protein Data Bank (PDB). In our longitudinal analysis between the Alpha and Omicron variant, we found 2.7% of common CDR3s were shared although the longitudinal profiling of common V(D)Js was variant specific. Although diverse immunoglobulin profiles were observed, the convergence of common V(D)Js suggests that there exists antibodies with similar antigenic specificities across patients in different groups over various stages of the pandemic.
Value relevance of book values, earnings, and future earnings: evidence by time, life cycle stage, and market uncertainty
Authors: Boonlert-U-Thai Kriengkrai , Schaberl Philipp 
Published: November 2022

PurposeThe purpose of this study is to investigate the role of book values, earnings, and future earnings in equity valuation by time, life cycle stage, and market uncertainty using samples of USA and Japanese companies.Design/methodology/approachThis study employs Lubberink and Willett (2021) methodology in using log-linear models to estimate the value relevance of accounting numbers and follows Schaberl (2016) approach to measure %incremental value relevance. The study also includes future earnings in a basic valuation model (Ohlson, 1995) to explore the extent to which stock prices are forward looking.FindingsThis study finds a significant increase by time in the relative value relevance of a combined model with book values and earnings and a combined model with future earnings for both countries. However, the incremental value relevance of book values, earnings, and future earnings remain stable over time. The results by life cycle stage indicate that incremental value relevance of future earnings and earnings are more (less) pronounced for firms in the intro (mature) life cycle stage while the incremental value relevance of book values is highest for firms in the decline stage for both countries. The results by market uncertainty indicate that firms with high market uncertainty display higher incremental value relevance of book values for both countries. The results on future earnings are mixed as USA (Japan) firms with high (low) market uncertainty display more (less) incremental value relevance of future earnings.Practical implicationsThe findings in this study enhance the merits of two basic financial statements (balance sheet and income statement) in a firm's equity valuation for potential investors and existing shareholders and document an additional role of future earnings information in reflecting a firm's stock price, which is beyond what book values and current earnings have already contributed.Originality/valueThis is the first study that uses log-linear models to estimate the value relevance of accounting numbers and investigates value relevance of accounting information in three views: time, life cycle stage, and market uncertainty.
Why, where and how are organizations using blockchain in their supply chains? Motivations, application areas and contingency factors
Authors: Ahmed Wafaa A.H. , MacCarthy Bart L. , Treiblmaier Horst 
Published: November 2022

PurposeBlockchain is increasingly being considered for applications in operations and supply chain management. However, evidence from practice is still scarce on why, where and how organizations seek to apply the technology in the supply chain across different industries. The study develops a comprehensive framework to enhance understanding of the application areas of blockchain technology in the supply chain, as well as organizations' motivations in seeking blockchain solutions and relevant contingency factors influencing applications.Design/methodology/approachThe authors investigate 50 use cases of blockchain applications in the supply chain, covering six industries. Contingency theory is applied in conducting a qualitative textual and correlation analysis to identify and compare blockchain adoption motivations, application areas and contingency factors across different industries.FindingsThe analysis develops an evidence-based framework that captures ten principal motivations in seeking blockchain solutions, three main blockchain application areas along with important application sub-categories and five clusters of contingency factors that influence blockchain deployment and its uses in different industrial sectors.Research limitations/implicationsThe study expands the limited cross-sectoral research on blockchain applications and motivations in the supply chain. Using contingency theory, it presents a comprehensive framework that captures the drivers and factors relating to blockchain adoption in the supply chain in a nomological network. The study lays the foundation for further theoretical perspectives and empirical research to investigate relevant sectoral characteristics and their importance for different types of blockchain application in the supply chain.Practical implicationsThe study informs practitioners about potential supply chain application areas that can be enhanced through blockchain technology, taking account of the specific characteristics of their products, business and manufacturing processes, supply network configurations, industry standards, regulations and market demand.Originality/valueThe study is the first to provide cross-sectoral evidence on the relevance of organizations' motivations and numerous contingency factors on blockchain application areas in the supply chain.
Functional assembly of grassland plant species in native communities in Spain and recipient communities in California
Authors: Galán Díaz Javier , Vilà Montserrat , Parker Ingrid M. , de la Riva Enrique G. 
Published: November 2022

Abstract

A major aim in invasion ecology is to understand the role of exotic species in plant communities. Whereas most studies have explored the traits of exotic species in the context of the introduced community, functional comparisons of entire assemblages of species in their native and introduced communities have rarely been analysed. Taking advantage of the unidirectional invasion of plant species of European origin (i.e. colonizers) into California, this study aims to investigate the relative importance of plant traits, environmental factors and invasion status in biological invasions.

We compared the functional structure (i.e. trait composition and diversity) along resource availability gradients in recipient and native Mediterranean grassland communities in California and Spain, respectively. Traits were related to resource use in above‐ground and below‐ground organs and reproductive strategy. We also investigated how niche differences vary along environmental gradients between coexisting colonizer and native species assemblages within communities.

There were clear differences in the functional structure of Mediterranean grassland communities between regions, which were associated with the resource availability gradient. Paradoxically, the most acquisitive communities occurred in resource‐poor sites, highlighting that rapid acquisition and use of resources permit species to cope with environmental stress through stress avoidance. In Spain, colonizer species had greater specific leaf area than non‐colonizers. Yet, differences between colonizer and non‐colonizer species in Spain for other traits were mostly absent and did not change along the gradient. This might be a result of the greater native species richness as a consequence of the agricultural practices that have taken place in Europe for millennia and reflect that the entire species pool of grasslands is adapted to agricultural landscapes. In comparison, in California, colonizer species were more acquisitive in their use of resources than natives under favourable conditions, but functionally converged in resource‐limited sites.

Synthesis. These results underscore that the importance of niche differences between native and colonizer species as a community assembly mechanism is strongly subjected to the influence of habitat filtering. Trait comparisons are context dependent, and a correct interpretation of filtering processes in community assembly requires a regional perspective.
The neutrophil‐to‐lymphocyte ratio represents a systemic inflammation marker and reflects the relationship with 90‐day mortality in non‐cirrhotic chronic severe hepatitis
Authors: Dong Fu Chen , Tan Wen Ting , Wang Xian Bo , Zheng Xin , Huang Yan , Li Bei Ling , Meng Zhong Ji , Gao Yan Hang , Qian Zhi Ping , Liu Feng , Lu Xiao Bo , Shang Jia , Shi Yu , Zheng Yu Bao , Yan Hua Dong , Zhang Yan , Xu Bao Yan , Hou Yi Xin , Zhang Qun , Xiong Yan , Zou Cong Cong , Chen Jun , Huang Ze Bing , Jiang Xiu Hua , Luo Sen , Chen Yuan Yuan , Gao Na , Liu Chun Yan , Yuan Wei , Mei Xue , Li Jing , Li Tao , Zheng Rong Jiong , Zhou Xin Yi , Chen Jin Jun , Deng Guo Hong , Mei Xiang Xiao , Zhang Wei Tuo , Li Hai 
Published: November 2022

ObjectivesTo investigate the relationship between systemic inflammatory response and short‐term mortality in patients with non‐cirrhotic chronic severe hepatitis (CSH) by using several indicators of inflammation including neutrophil‐to‐lymphocyte ratio (NLR), neutrophil (NEU), white blood cell (WBC), platelet‐to lymphocyte ratio (PLR), and monocyte‐to‐lymphocyte ratio (MLR).MethodsData were collected from two prospectively enrolled CATCH‐LIFE noncirrhotic cohorts. Cox regression analysis was used to investigate the association between systemic inflammatory biomarkers and 90‐day liver transplant (LT)‐free mortality. A generalized additive model (GAM) was used to illustrate the quantitative curve relationship between NLR and 90‐day LT‐free mortality. Kaplan–Meier method was used to estimate the 90‐year LT‐free survival.ResultsThe prevalence of CSH was 20.5% (226/1103). The 28‐day and 90‐day LT‐free mortality rates were 17.7% and 26.1%, respectively, for patients with non‐cirrhotic CSH. Patients with no infection accounted for 75.0% of all CSH patients, and NLR was independently associated with 90‐day LT‐free mortality. NLR of 2.9 might be related to disease deterioration in CSH patients without infection.ConclusionsNLR may be an independent risk factor for 90‐day LT‐free mortality in patients with non‐cirrhotic chronic liver disease. A NLR of 2.9 as the cut‐off value can be used to predict disease aggravation in CSH patients without infection.
Vitiligo and systemic sclerosis: Are they associated?– Lessons from a population‐based study
Authors: Kridin Khalaf , Lyakhovitsky Keren , Tzur‐Bitan Dana , Onn Erez , Lyakhovitsky Anna , Zoller Lilach , Cohen Arnon D. 
Published: November 2022

AbstractBackgroundThe epidemiological relationship of vitiligo with systemic sclerosis (SSc) remains to be precisely evaluated.ObjectiveTo investigate the bidirectional association between vitiligo and SSc.MethodsA population‐based study was carried out to compare vitiligo patients (n = 20,851) with age‐, sex‐ and ethnicity‐matched control subjects (n = 102,475) regarding the incidence of new‐onset and the prevalence of preexisting SSc. Adjusted hazard ratios (HRs) and adjusted odds ratios (ORs) were calculated by the Cox regression and logistic regression, respectively.ResultsThe incidence rate of new‐onset SSc was calculated at 2.4 (95% CI, 1.6–3.4) and 0.4 (95% CI, 0.3–0.6) cases per 10,000 person‐years among patients with vitiligo and controls, respectively. Patients with vitiligo had an increased risk of SSc (fully adjusted HR, 5.37; 95% CI, 3.03–9.54; p < 0.001). Correspondingly, a history of SSc predicted elevated odds of developing vitiligo (fully adjusted OR, 2.09; 95% CI, 1.23–3.55; p = 0.006). Relative to other patients with vitiligo, those with vitiligo and comorbid SSc were older and had a higher prevalence of ischaemic heart disease, hyperlipidaemia, and hypertension.ConclusionsA robust bidirectional association exists between vitiligo and SSc. This knowledge is valuable for physicians managing patients with both conditions. Patients with vitiligo and comorbid SSc might be monitored for cardiovascular and metabolic comorbidities.
Erbu Zhuyu decoction improves endometrial angiogenesis via uterine natural killer cells and the PI3K/Akt/eNOS pathway a mouse model of embryo implantation dysfunction
Authors: Shen Mengmeng , Liu Yanfeng , Ma Xiaona , Zhu Qingwen 
Published: November 2022

AbstractBackgroundWe investigated the effect of Erbu Zhuyu decoction (EBZY) on angiogenesis via uterine natural killer (uNK) cells and the PI3K/Akt/eNOS pathway in embryo implantation dysfunction (EID) mice.MethodsPregnant mice were randomly divided into blank, model, EBZY, progynova, and aspirin groups. Uteri were excised on the 5th day of pregnancy for analysis.ResultsMice in the model group showed pale uteri, a reduced implantation rate, and lower expression levels of phosphatidylinositol‐3‐kinase (PI3K), protein kinase B (Akt), endothelial nitric oxide synthase (eNOS) and nitric oxide (NO). Compared to the model group, implantation rates in the medium‐dose and high‐dose groups of EBZY were significantly higher (P < .05), PI3K and Akt mRNA expression levels in the low‐dose group were significantly higher (P < .05, P < .01), and the expression of p‐PI3K, p‐Akt, and p‐eNOS proteins in all treatment groups were significantly increased (P < .01, P < .05). The expression of NO was significantly increased in the low‐dose and high‐dose groups (P < .01, P < .05, respectively). The level of p‐Akt protein in the high‐dose group was significantly higher than those in the other treatment groups (P < .01, P < .05). There was no significant difference in the density of uNK cells (P > .05).ConclusionsEBZY facilitated embryo implantation in EID mice by enhancing endometrial angiogenesis via activation of the PI3K/Akt/eNOS pathway, at least in part. There was no evidence to indicate that EBZY could adjust the expression of uNK.
Significant histological disease of patients with chronic hepatitis B virus infection in the grey zone
Authors: Wang Jian , Yan Xiaomin , Zhu Li , Liu Jiacheng , Qiu Yuanwang , Li Yiguang , Liu Yilin , Xue Ruifei , Zhan Jie , Jiang Suling , Geng Yu , Wan Yawen , Li Ming , Mao Minxin , Gao Dongmei , Yin Shengxia , Tong Xin , Xia Juan , Ding Weimao , Chen Yuxin , Li Jie , Zhu Chuanwu , Huang Rui , Wu Chao 
Published: November 2022

SummaryBackgroundMany patients with chronic hepatitis B (CHB) do not meet the definitions of the traditional natural phases and are classified as being in the grey zone (GZ).AimsTo investigate liver histology, and to establish a management strategy for patients with CHB in the GZ.MethodsThis study included 1043 patients with CHB who underwent liver biopsy. Phases of natural history were determined according to the AASLD 2018 hepatitis B guidance. CHB patients in the GZ were divided into HBeAg‐positive, normal ALT and HBV DNA ≤106 IU/ml (GZ‐A); HBeAg‐positive, elevated ALT and HBV DNA ≤2 × 104 IU/ml (GZ‐B); HBeAg‐negative, normal ALT and HBV DNA ≥2 × 103 IU/ml (GZ‐C) and HBeAg‐negative, elevated ALT and HBV DNA ≤2 × 103 IU/ml (GZ‐D). Significant histological disease was defined as liver inflammation ≥G2 and/or liver fibrosis ≥S2.ResultsTwo hundred and forty two (23.2%) patients were in the GZ. Approximately 72.7% had significant histological disease. HBeAg‐positive GZ CHB patients had a higher proportion of significant histological disease than HBeAg‐negative GZ patients (91.1% vs. 68.5%, p = 0.002). GZ‐D (42.6%) was the dominant category, followed by GZ‐C (38.8%), GZ‐A (10.3%) and GZ‐B (8.3%). The highest proportion of significant histological disease was observed patients in GZ‐B (100.0%), followed by GZ‐A (84.0%), GZ‐D (69.9%) and GZ‐C (67.0%). Prothrombin time (PT) was an independent risk factor of significant histological disease in the HBeAg‐negative GZ.ConclusionsOver 70% of GZ CHB patients had significant histological disease. We recommend antiviral treatment for HBeAg‐positive and HBeAg‐negative GZ CHB patients with high PT.
Elucidating the cellular uptake mechanisms of heptamethine cyanine dye analogues for their use as an anticancer drug‐carrier molecule for the treatment of glioblastoma
Authors: Cooper Elizabeth , Choi Peter J. , Hwang Kihwan , Nam Kyung M. , Kim Chae‐Yong , Shaban Tina , Schweder Patrick , Mee Edward , Correia Jason , Turner Clinton , Faull Richard L. M. , Denny William A. , Noguchi Katsuya , Dragunow Mike , Jose Jiney , Park Thomas I.‐H. 
Published: November 2022

AbstractThe development of chemotherapies for glioblastoma is hindered by their limited bioavailability and toxicity on normal brain function. To overcome these limitations, we investigated the structure‐dependent activity of heptamethine cyanine dyes (HMCD), a group of tumour‐specific and BBB permeable near‐infrared fluorescent dyes, in both commercial (U87MG) and patient‐derived GBM cell lines. HMCD analogues with strongly ionisable sulphonic acid groups were not taken up by patient‐derived GBM cells, but were taken up by the U87MG cell line. HMCD uptake relies on a combination of transporter uptake through organic anion‐transporting polypeptides (OATPs) and endocytosis into GBM cells. The uptake of HMCDs was not affected by p‐glycoprotein efflux in GBM cells. Finally, we demonstrate structure‐dependent cytotoxic activity at high concentrations (EC50: 1–100 μM), likely due to mitochondrial damage‐induced apoptosis. An in vivo orthotopic glioblastoma model highlights tumour‐specific accumulation of our lead HMCD, MHI‐148, for up to 7 days following a single intraperitoneal injection. These studies suggest that strongly ionisable groups like sulphonic acids hamper the cellular uptake of HMCDs in patient‐derived GBM cell lines, highlighting cell line‐specific differences in HMCD uptake. We envisage these findings will help in the design and structural modifications of HMCDs for drug‐delivery applications for glioblastoma.