bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adherence to the EAT-Lancet Healthy Reference Diet in relation to Coronary Heart Disease, All-Cause Mortality Risk and Environmental Impact: Results from the EPIC-NL Cohort
Authors: Colizzi Chiara , Harbers Marjolein C , Vellinga Reina E , Verschuren WM Monique , Boer Jolanda MA , Temme Elisabeth HM , van der Schouw Yvonne T 
Published: July 2021

AbstractObjectivesTo construct a diet-score measuring the level of adherence to the Healthy Reference Diet (HRD), to explore whether adherence to the HRD is associated with coronary heart disease (CHD), all-cause mortality risk, and to calculate its environmental impact.DesignProspective cohort study.SettingThe Dutch contribution to the European Prospective Investigation into Cancer and Nutrition (EPIC-NL).Participants37,349 adults (20-70y) without CHD at baseline.Main outcome measuresPrimary outcomes were incident CHD and all-cause mortality. Secondary outcomes were greenhouse gas emission (GHGE), land use, blue water use, freshwater eutrophication, marine eutrophication, and terrestrial acidification.ResultsDuring a median 15.3-year follow-up, 2,543 cases of CHD occurred, and 5,648 individuals died from all causes. The average HRD-score was 73 (SD=10). High adherence to the HRD was associated with a 15% lower risk of CHD (hazard ratio 0.85, 95% confidence interval 0.75 to 0.96), as well as a 17% lower risk of all-cause mortality (hazard ratio 0.83, 95% confidence interval 0.77 to 0.90) in multivariable-adjusted models. Better adherence to the HRD was associated with lower environmental impact from GHGE (β= -0.10 kg CO2-eq, 95% confidence interval -0.13 to -0.07), land use (β= -0.11 m2per year, 95% confidence interval -0.12 to -0.09), freshwater eutrophication (β= -0.000002 kg P-eq, 95% confidence interval -0.000004 to -0.000001), marine eutrophication (β= -0.00035 kg N-eq, 95% confidence interval -0.00042 to -0.00029), and terrestrial acidification (β = -0.004 kg SO2-eq, 95% confidence interval -0.004 to -0.003), but with higher environmental impact from blue water use (β=0.044 m3, 95% confidence interval 0.043 to 0.045).ConclusionHigh adherence to the HRD was associated with lower risk of CHD and all-cause mortality. Additionally, increasing adherence to the HRD could lower some aspects of the environmental impact of diets, but attention is needed for the associated increase in blue water use.
The relationship between Lipoprotein A and other lipids with prostate cancer risk: A multivariable Mendelian randomisation study
Authors: Ioannidou Anna , Watts Eleanor L , Perez-Cornago Aurora , Platz Elizabeth A , Mills Ian G , Key Timothy J , Travis Ruth C ,   The PRACTICAL consortium, CRUK, BPC3, CAPS, PEGASUS, Tsilidis Konstantinos K , Zuber Verena 
Published: July 2021

AbstractBackgroundNumerous epidemiological studies have investigated the role of blood lipids in prostate cancer (PCa) risk though findings remain inconclusive to date. The ongoing research has mainly involved observational studies which are often prone to confounding. This study aimed to identify the relationship between genetically predicted blood lipid concentrations and PCa.Methods and FindingsData for low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides (TG), apolipoprotein A (apoA) and B (apoB), lipoprotein A (Lp(a)) and PCa were acquired from genome-wide association studies in UK Biobank and the PRACTICAL consortium, respectively. We used a two-sample Mendelian randomisation (MR) approach with both univariable and multivariable (MVMR) models and utilised a variety of robust methods and sensitivity analyses to assess the possibility of MR assumptions violation. No association was observed between genetically predicted concentrations of HDL, TG, apoA and apoB and PCa risk. Genetically predicted LDL concentration was positively associated with total PCa in the univariable analysis but adjustment for HDL, TG and Lp(a) led to a null association. Genetically predicted concentration of Lp(a) was associated with higher total PCa risk in the univariable (ORweighted median per sd = 1.091; 95% CI 1.028-1.157; P=0.004) and MVMR analyses after adjustment for the other lipid traits (ORIVW per sd = 1.068; 95% CI 1.005-1.134; P = 0.034). Genetically predicted Lp(a) was also associated with advanced (MVMR ORIVW per sd = 1.078; 95% CI 0.999-1.163; P=0.055) and early age onset PCa (MVMR ORIVW per sd = 1.150; 95% CI 1.015,1.303; P = 0.028). Although multiple estimation methods were utilized to minimize the effect of pleiotropic traits, the presence of any unmeasured pleiotropy cannot be excluded and may limit our findings.ConclusionsWe observed that genetically predicted Lp(a) concentrations are associated with an increased PCa risk. Future studies are required to understand the underlying biological pathways of this finding, as it may inform PCa prevention through Lp(a)-lowering strategies.
Altered DNA methylation pattern characterizes the peripheral immune cells of patients with autoimmune hepatitis
Authors: Zachou Kalliopi , Arvaniti Pinelopi , Lyberopoulou Aggeliki , Sevdali Eirini , Speletas Matthaios , Ioannou Maria , Koukoulis George K. , Renaudineau Yves , Dalekos George N. 
Published: July 2021

AbstractObjectiveAIH is a chronic liver disease of unknown aetiology with favourable response to immunosuppression. Little is known about the impact of methylation modifications on disease pathogenesis.Design10 patients with AIH at diagnosis (time-point 1; tp1), 9 with primary biliary cholangitis (PBC) and 10 healthy controls (HC) were investigated. 8/10 AIH patients were also investigated following biochemical remission (time-point 2; tp2). Peripheral CD19(+)- and CD4(+)-cells were isolated to study global DNA methylation (5mC)/hydroxymethylation (5hmC) by ELISA and mRNA of DNA methylation (DNMT1/3A/3B)/hydroxymethylation enzymes (TET1/2/3) by quantitative RT-PCR. Epigenome wide association study (EWAS) was performed in CD4(+)-cells (Illumina HumanMethylation 850K array) in AIH and HC. Differences in total 5mC/5hmC state between AIH-tp1 and HC were also assessed by immunohistochemistry (IHC) on paraffin embedded liver sections.ResultsReduced TET1 and increased DNMT3A mRNA levels characterized CD19(+) and CD4(+) lymphocytes from AIH-tp1 patients compared to HC and PBC respectively, without affecting global DNA 5mC/5hmC. In AIH-tp1, CD4(+) DNMT3A expression was negatively correlated with serum IgG (p=0.03). In remission (AIH-tp2), DNMT3A decreased in both CD19(+) and CD4(+)-cells (p=0.02, p=0.03, respectively). EWAS in CD4(+)-cells from AIH patients confirmed important modifications in genes implicated in immune responses (HLA-DP, TNF, lnRNAs and CD86). IHC confirmed increased 5hmC staining of periportal infiltrating lymphocytes in AIH-tp1.ConclusionAltered expression of TET1 and DNMT3A, characterizes peripheral immune cells in AIH. DNMT3A is associated with disease activity and decreased following therapeutic response. Gene specific DNA methylation modifications affect immunologic pathways that may play an important role in AIH pathogenesis.Summary boxWhat is already known?Autoimmune hepatitis (AIH) is a non-resolving chronic liver disease of unknown aetiology and favourable response to immunosuppression. Since the interplay between the genetic background and the environment seems to be fundamental for AIH pathogenesis, epigenetic modifications may be of particular importance.What are the new findings?We found characteristic alterations of DNA methylation in peripheral immune cells of AIH patients, which were associated with disease activity and modified by immunosuppressive treatment.How might it impact on clinical practice in the foreseeable future?These results provide the first evidence that epigenetics play a role in AIH pathogenesis, which may have therapeutic implications for the management of the disease.
Diversity and distribution of sulfur metabolism in the human gut microbiome and its association with colorectal cancer
Authors: Wolf Patricia G. , Cowley Elise S. , Breister Adam , Matatov Sarah , Lucio Luke , Polak Paige , Ridlon Jason M. , Gaskins H. Rex , Anantharaman Karthik 
Published: July 2021

ABSTRACTMicrobial sulfidogenesis produces genotoxic hydrogen sulfide (H2S) in the human gut using inorganic (sulfate) and organic (taurine/cysteine/methionine) substrates, however the majority of studies have focused on sulfate reduction using dissimilatory sulfite reductases (Dsr). Recent evidence implicates microbial sulfidogenesis as a potential trigger of colorectal cancer (CRC), highlighting the need for comprehensive knowledge of sulfur metabolism within the human gut. Here we show that microbial sulfur metabolism is more abundant and diverse than previously studied and is statistically associated with CRC. Using ~17,000 bacterial genomes from publicly available stool metagenomes, we studied the diversity of sulfur metabolic genes in 667 participants across different health statuses: healthy, adenoma, and carcinoma. Sulfidogenic genes were harbored by 142 bacterial genera and both organic and inorganic sulfidogenic genes were associated with carcinoma. Significantly, anaerobic sulfite reductases were twice as abundant as dsr. We identified twelve potential pathways for reductive taurine metabolism including novel pathways, and prevalence of organic sulfur metabolic genes indicate these substrates may be the most abundant source of microbially derived H2S. Our findings significantly expand knowledge of microbial sulfur metabolism in the human gut, and highlight key gaps that limit understanding of its potential contributions to the pathogenesis of CRC.
SARS-CoV-2 Nsp14 mediates the effects of viral infection on the host cell transcriptome
Authors: Zaffagni Michela , Harris Jenna M , Patop Ines L , Pamudurti Nagarjuna Reddy , Nguyen Sinead , Kadener Sebastian 
Published: July 2021

SUMMARYViral infection involves complex set of events orchestrated by multiple viral proteins. To identify functions of SARS-CoV-2 proteins, we performed transcriptomic analyses of cells expressing individual viral proteins. Expression of Nsp14, a protein involved in viral RNA replication, provoked a dramatic remodeling of the transcriptome that strongly resembled that observed following SARS-CoV-2 infection. Moreover, Nsp14 expression altered the splicing of more than 1,000 genes and resulted in a dramatic increase in the number of circRNAs, which are linked to innate immunity. These effects were independent of the Nsp14 exonuclease activity and required the N7-guanine-methyltransferase domain of the protein. Activation of the NFkB pathway and increased expression of CXCL8 occurred early upon Nsp14 expression. We identified IMPDH2, which catalyzes the rate-limiting step of guanine nucleotides biosynthesis, as a key mediator of these effects. Nsp14 expression caused an increase in GTP cellular levels, and the effect of Nsp14 was strongly decreased in presence of IMPDH2 inhibitors. Together, our data demonstrate an unknown role for Nsp14 with implications for therapy.
A multi-gene region targeted capture approach to detect plant DNA in environmental samples: A case study from coastal environments
Authors: Foster Nicole R. , van Dijk Kor-jent , Biffin Ed , Young Jennifer M. , Thomson Vicki , Gillanders Bronwyn M. , Jones Alice , Waycott Michelle 
Published: July 2021

AbstractMetabarcoding of plant DNA recovered from environmental samples, termed environmental DNA (eDNA), has been used to detect invasive species, track biodiversity changes and reconstruct past ecosystems. The P6 loop of the trnL intron is the most widely utilized gene region for metabarcoding plants due to the short fragment length and subsequent ease of recovery from degraded DNA, which is characteristic of environmental samples. However, the taxonomic resolution for this gene region is limited, often precluding species level identification. Additionally, targeting gene regions using universal primers can bias results as some taxa will amplify more effectively than others. To increase the ability of DNA metabarcoding to better resolve flowering plant species (angiosperms) within environmental samples, and reduce bias in amplification, we developed a multi-gene targeted capture method that simultaneously targets 20 chloroplast gene regions in a single assay across all flowering plant species. Using this approach, we effectively recovered multiple chloroplast gene regions for three species within artificial DNA mixtures down to 0.001 ng/µL of DNA. We tested the detection level of this approach, successfully recovering target genes for 10 flowering plant species. Finally, we applied this approach to sediment samples containing unknown compositions of environmental DNA and confidently detected plant species that were later verified with observation data. Targeting multiple chloroplast gene regions in environmental samples enabled species-level information to be recovered from complex DNA mixtures. Thus, the method developed here, confers an improved level of data on community composition, which can be used to better understand flowering plant assemblages in environmental samples.
Cystathionine-β-synthase is essential for AKT-induced senescence and suppresses the development of gastric cancers with PI3K/AKT activation
Authors: Zhu Haoran , Chan Keefe T. , Huang Xinran , Blake Shaun , Trigos Anna S. , Anderson Dovile , Creek Darren , De Souza David P. , Wang Xi , Fu Caiyun , Jana Metta , Sanij Elaine , Pearson Richard B , Kang Jian 
Published: July 2021

AbstractHyperactivation of oncogenic pathways downstream of RAS and PI3K/AKT in normal cells induces a senescence-like phenotype that acts as a tumor-suppressive mechanism that must be overcome during transformation. We previously demonstrated that AKT-induced senescence (AIS) is associated with profound transcriptional and metabolic changes. Here, we demonstrate that human fibroblasts undergoing AIS display increased Cystathionine-β-synthase (CBS) expression and consequent activation of the transsulfuration pathway controlling hydrogen sulfide (H2S) and glutathione (GSH) metabolism. Activated transsulfuration pathway during AIS maintenance enhances the antioxidant capacity, protecting senescent cells from ROS-induced cell death via GSH and H2S. Importantly, CBS depletion allows cells that have undergone AIS to escape senescence and re-enter the cell cycle, indicating the importance of CBS activity in maintaining AIS. Mechanistically, we show this restoration of proliferation is mediated through suppressing mitochondrial respiration and reactive oxygen species (ROS) production and increasing GSH metabolism. These findings implicate a potential tumor-suppressive role for CBS in cells with inappropriately activated PI3K/AKT signaling. Consistent with this concept, in human gastric cancer cells with activated PI3K/AKT signaling, we demonstrate that CBS expression is suppressed due to promoter hypermethylation. CBS loss cooperates with activated PI3K/AKT signaling in promoting anchorage-independent growth of gastric epithelial cells, while CBS restoration suppresses the growth of gastric tumors in vivo. Taken together, we find that CBS is a novel regulator of AIS and a potential tumor suppressor in PI3K/AKT-driven gastric cancers, providing a new exploitable metabolic vulnerability in these cancers.
Tactile suppression stems from sensation-specific sensorimotor predictions
Authors: Führer Elena , Voudouris Dimitris , Lezkan Alexandra , Drewing Knut , Fiehler Katja 
Published: July 2021

SummaryThe ability to sample sensory information with our hands is crucial for smooth and efficient interactions with the world. Despite this important role of touch, tactile sensations on a moving hand are perceived weaker than when presented on the same but stationary hand.1–3 This phenomenon of tactile suppression has been explained by predictive mechanisms, such as forward models, that estimate future sensory states of the body on the basis of the motor command and suppress the associated predicted sensory feedback.4 The origins of tactile suppression have sparked a lot of debate, with contemporary accounts claiming that suppression is independent of predictive mechanisms and is instead akin to unspecific gating.5 Here, we target this debate and provide evidence for sensation-specific tactile suppression due to sensorimotor predictions. Participants stroked with their finger over textured surfaces that caused predictable vibrotactile feedback signals on that finger. Shortly before touching the texture, we applied external vibrotactile probes on the moving finger that either matched or mismatched the frequency generated by the stroking movement. We found stronger suppression of the probes that matched the predicted sensory feedback. These results show that tactile suppression is not limited to unspecific gating but is specifically tuned to the predicted sensory states of a movement.
Gut microbial diversity in stingless bees is linked to host wing size and is influenced by geography
Authors: Liu Hongwei , Hall Mark A. , Brettell Laura E. , Halcroft Megan , Wang Juntao , Nacko Scott , Spooner-Hart Robert , Cook James M , Riegler Markus , Singh Brajesh 
Published: July 2021

SummaryStingless bees are globally important social corbiculate bees, fulfilling critical pollination roles in many ecosystems; however, their gut microbiota, especially fungal communities, are not well characterized to date. We collected 121 bee samples from two species,Tetragonula carbonariaandAustroplebeia australis, across a distance of 1,200 km of eastern Australia, and analysed their gut microbiomes. We found that the gut bacterial richness ofT. carbonariawas influenced by geography (latitude and longitude) and positively correlated to an established fitness indicator in insects; namely, host forewing length/size that relates to flight capacity of stingless bees. We characterized the core microbiomes of the two bees and found that they consisted of the bacterial taxaSnodgrassella, Lactobacillus, Acetobacteraceae andBombella, and the fungal taxa Didymellaceae,Monocilium mucidum, Malassezia restrictaandAureobasidium pullulans. Both host species identity and management (wild or managed) significantly influenced the gut microbial diversity and composition, and similarity between colonies declined as the geographical distance between them increased. This result was also supported by our co-existing network analyses. Overall, we have thoroughly analysed stingless bee gut microbiomes, and provided novel evidence thatT. carbonariabees with larger wings or from more southern populations have higher microbial diversity in their guts.Originality-Significance StatementBeneficial interactions between insects and their microbial symbionts are pivotal for their fitness. In this study, we analysed the gut microbiomes of two stingless bee species,Tetragonula carbonariaandAustroplebeia australis, that are widespread and important pollinators in Australia. We characterized their gut microbiomes and detected a significant positive correlation between gut bacterial richness and host forewing size forT. carbonaria; the first time that gut microbial diversity has been linked to a morphological trait in stingless bees. Furthermore, we found that host species’ identity, management type (wild or managed) and geography all significantly influenced bee gut microbial diversity and composition, and were able to describe both bacterial and fungal core microbial taxa. This study reveals novel understandings of stingless bee gut microbiomes and provides the basis for utilizing microbial strategies to maintain colony health.
Isolation and characterization of a Cyprinid herpesvirus strain YZ01 from apparently healthy goldfish after rising water temperature
Authors: Wang Fengzhi , Xu Ye , Zhou Yi , Ding Chao , Duan Hongan 
Published: July 2021

AbstractA Cyprinid herpesvirus 2 (CyHV-2) strain YZ01 was isolated from an apparently healthy goldfish with history of exposure to CyHV-2 when the water temperature was heated from 3-6□ to 25□. Brain, kidney, spleen (referred to as BKS) and intestine of sick and dead fish as well as crucian carp (CrCB) or goldfish brain cell (GFB) suspensions inoculated with above tissue homogenate were collected for PCR assay.Infected cell layers were prepared into ultrathin sections for transmission electron microscopy. Virus DNA were purified from cell suspensions for whole genome sequencing and analysis. Intestine and mixed brain, kidney and spleen fluid (BKS) of dead goldfish and BKS-infected CrCB suspensions as well as their subsequent passages were tested positive by PCR. Nucleus deformation, lattice-like arrangement of inclusion bodies and various forms of immature and mature virions in the nucleus, cytoplasm and outside of cell membranes were observed. Whole genome analysis of 7 CyHV-2 strains available in GeneBank showed that all strains’ genomes share very high homology while YZ01 was more close to CyHV-2 CNDF-TB2015 and SY-C1 which are classified as C genotype.
Accounting conservatism and income smoothing practices in EU food and drink industry
Authors: Paolone Francesco , Albahloul Mohammad , Tiscini Riccardo 
Published: July 2021

PurposeThe purpose of this paper is to identify the application of the fundamental principle of accounting conservatism within the EU food and drink industry. Furthermore, the authors would also investigate in-depth the above relationship in two different subsamples (income smoothers and non-income smoothers).Design/methodology/approachAll EU-listed companies of the food and drink industry were identified covering the year 2019. Eckel's model was used to classify listed companies as smoothing or non-smoothing, and Basu's model was adopted to test the degree of conditional conservatism.FindingsThe results indicate that conservatism is strongly present in food and drink industry and also in its subindustries. We also showed that non-smoothing firms had higher levels of conditional conservatism in terms of more opportunity to recognize future economic losses because the market could use the stock return data to anticipate future losses contained in the information regarding profits.Research limitations/implicationsOne limitation of this work is the small size of the investigated companies. The authors demonstrate that the likely increased use of conservatism produces better credibility in the EU markets. Practical implications indicate a higher degree of monitoring of the accounting practices adopted by firms. Regulators have to set accounting policies to enhance the quality of the informational environment, investors and shareholders might exercise control over executives' decisions, and lenders might impose contractual clauses requiring the timely disclosure of “bad news.”Originality/valueThis industry is “belted” from any external speculations. This research made it possible also to observe theoretical relationships between the financial information provided by the EU food and drink industry that contributes to the market distinction between smoothers and non-smoothers.