bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide association meta-analysis of spontaneous coronary artery dissection reveals common variants and genes related to artery integrity and tissue-mediated coagulation
Authors: Adlam David , Berrandou Takiy-Eddine , Georges Adrien , Nelson Christopher P. , Giannoulatou Eleni , Henry Joséphine , Ma Lijiang , Blencowe Montgomery , Turley Tamiel N. , Yang Min-Lee , Braund Peter S. , Sadeg-Sayoud Ines , Iismaa Siiri E. , Kosel Matthew L. , Zhou Xiang , Hamby Stephen E. , Cheng Jenny , Liu Lu , Tarr Ingrid , Muller David W.M. , d’Escamard Valentina , King Annette , Brunham Liam R. , Baranowska-Clarke Ania A. , Debette Stéphanie , Amouyel Philippe , Olin Jeffrey W. , Patil Snehal , Hesselson Stephanie E. , Junday Keerat , Kanoni Stavroula , Aragam Krishna , Butterworth Adam S. ,   CARDIoGRAMPlusC4D,   MEGASTROKE,   International stroke genetics consortium (ISGC) intracranial aneurysm working group, Tweet Marysia S. , Gulati Rajiv , Combaret Nicolas ,   DISCO register investigators, Kadian-Dodov Daniella , Kalman Jon , Fatkin Diane , Saw Jacqueline , Webb Tom R. , Hayes Sharonne N. , Yang Xia , Ganesh Santhi K. , Olson Timothy M. , Kovacic Jason C. , Graham Robert M. , Samani Nilesh J. , Bouatia-Naji Nabila 
Published: July 2022

AbstractSpontaneous coronary artery dissection (SCAD) is an understudied cause of acute myocardial infarction primarily affecting women. It is not known to what extent SCAD is genetically distinct from other cardiovascular diseases, including atherosclerotic coronary artery disease (CAD). Through a meta-analysis of genome-wide association studies including 1917 cases and 9292 controls of European ancestry, we identified 17 risk loci, including 12 new, with odds ratios ranging from 2.04 (95%CI 1.77-2.35) on chr21 to 1.25 (95%CI 1.16-1.35) on chr4. A locus on chr1 containing the tissue factor gene (F3), which is involved in blood coagulation cascade, appears to be specific for SCAD risk. Prioritized genes were mainly expressed in vascular smooth muscle cells and fibroblasts of arteries and are implicated predominantly in extracellular matrix biology (e.g. COL4A1/A2, HTRA1 and TIMP3). We found that several variants associated with SCAD had diametrically opposite associations with CAD suggesting that shared biological processes contribute to both diseases but through different mechanisms. We also demonstrated an inferred causal role for high blood pressure, but not other CAD risk factors, in SCAD. Our findings provide novel pathophysiological insights involving arterial integrity and tissue-mediated coagulation in SCAD and set the stage for future specific therapeutics and prevention for this disease.
Reproducibility of neuroimaging studies of brain disorders with hundreds -not thousands- of participants
Authors: Libedinsky Ilan , Helwegen Koen , Dannlowski Udo , Fornito Alex , Repple Jonathan , Zalesky Andrew ,   Alzheimer’s Disease Neuroimaging Initiative,   Alzheimer’s Disease Repository Without Borders Investigators, Breakspear Michael , van den Heuvel Martijn P. 
Published: July 2022

AbstractAn important current question in neuroimaging concerns the sample sizes required for producing reliable and reproducible results. Recent findings suggest that brain-wide association studies (BWAS) linking neuroimaging features with behavioural phenotypes in the general population are characterised by (very) weak effects and consequently need large samples sizes of 3000+ to lead to reproducible findings. A second, important goal in neuroimaging is to study brain structure and function under disease conditions, where effects are likely much larger. This difference in effect size is important. We show by means of power calculations and empirical analysis that neuroimaging studies in clinical populations need hundreds -and not necessarily thousands-of participants to lead to reproducible findings.
Phosphorylation of aldose-6-phosphate reductase from Prunus persica leaves
Authors: Hartman Matías D. , Rojas Bruno E. , Ferrero Danisa M. L. , Leyva Alejandro , Durán Rosario , Iglesias Alberto A. , Figueroa Carlos M. 
Published: July 2022

AbstractSugar-alcohols are major photosynthates in plants from the Rosaceae family. Expression of the gene encoding aldose-6-phosphate reductase (Ald6PRase), the critical enzyme for glucitol synthesis in rosaceous species, is regulated by physiological and environmental cues. Additionally, Ald6PRase is inhibited by small molecules (hexose-phosphates and inorganic orthophosphate) and oxidizing compounds. This work demonstrates that Ald6PRase from peach leaves is phosphorylated in planta at the N-terminus. We also show in vitro phosphorylation of recombinant Ald6PRase by a partially purified kinase extract from peach leaves containing Ca2+-dependent protein kinases (CDPKs). Moreover, phosphorylation of recombinant Ald6PRase was inhibited by hexose-phosphates, phosphoenolpyruvate and pyrophosphate. We further show that phosphorylation of recombinant Ald6PRase was maximal using recombinant CDPKs. Overall, our results suggest that phosphorylation could fine-tune the activity of Ald6PRase.
Understanding The Role of Heparinoids on the SARS-CoV-2 Spike Protein through Molecular Dynamics Simulations
Authors: Pipitò Ludovico , Reynolds Christopher A. , Deganutti Giuseppe 
Published: July 2022

AbstractThe pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to pose a threat, with an estimated number of deaths exceeding 5 million. SARS-CoV-2 entry into the cell is mediated by its transmembrane spike glycoprotein (S protein), and the angiotensin-converting enzyme 2 (ACE2) receptor on the human cell surface. The extracellular heparan sulphate (EcHS) enhances the S protein binding through a mechanism that is still unknown. Surprisingly, low molecular weight heparin (LMWH) and HS in the disaccharide form (dHS) hinder the S protein binding to ACE2, despite the similarity with EcHS. We investigated the molecular mechanism behind this inhibition through molecular dynamics (MD) simulations to understand the interaction pattern of the heparinoids with S protein and ACE2 receptor.
Local changes dominate variation in biotic homogenization and differentiation
Authors: Blowes Shane A. , McGill Brian , Brambilla Viviana , Chow Cher F. Y. , Engel Thore , Fontrodona-Eslava Ada , Martins Inês S. , McGlinn Daniel , Moyes Faye , Sagouis Alban , Shimadzu Hideyasu , van Klink Roel , Xu Wu-Bing , Gotelli Nicholas J. , Magurran Anne , Dornelas Maria , Chase Jonathan M. 
Published: July 2022

AbstractIt is commonly thought that the biodiversity crisis includes widespread decreases in the uniqueness of different sites in a landscape (biotic homogenization). Using a typology relating homogenization and differentiation to local and regional diversity changes, we synthesize patterns across 283 metacommunities surveyed for 10-91 years, and 54 species checklists (13-500+ years). On average, there is a 0.2% increase in species shared among communities/year (i.e., weak homogenization), but across data sets, differentiation frequently occurs, with no statistically significant change being most common. Local (not regional) diversity frequently underlies composition change, and homogenization is strongly associated with checklist data that have longer durations and large spatial scales. Conservation and management can benefit from the multiscale perspective used here as it disentangles the implications of both the differentiation and homogenization currently unfolding.One-Sentence SummaryBiotic homogenization is most prevalent at large temporal and spatial scales.
Metagenomics and metabarcoding experimental choices and their impact on microbial community characterization in freshwater recirculating aquaculture systems
Authors: Rieder Jessica , Kapopoulou Adamandia , Bank Claudia , Adrian-Kalchhauser Irene 
Published: July 2022

AbstractRecirculating aquaculture systems (RAS) heavily depend on microbial communities to maintain water quality. These communities therefore influence the growth, development, and welfare of farmed fish. With the increasing socio-economic role of fish farming e.g. regarding food security, an in-depth understanding of aquaculture microbial communities is also relevant from a management perspective. However, the data situation regarding the composition of microbial communities within RAS is patchy. Since this is partly ascribed to method choices, there clearly is a need for accurate, standardized, and user-friendly methods to study microbial communities in aquaculture systems.Here, we compare the performance of 16S amplicon sequencing, Pac-Bio long-read amplicon sequencing, and amplification-free shotgun metagenomics in the characterization of microbial communities in two commercial-size RAS fish farms. We show that, even though primer choice affects read quality, diversity, and assigned taxa, distinct primer pairs uncover similar spatio-temporal patterns between sample types, farms, and time points. We find that long-read amplicons underperform regarding quantitative resolution of spatio-temporal patterns, but allow for species-level identification of functional services and pathogens. Finally, shotgun metagenomics data identified fungi, viruses, and bacteriophages, opening avenues for an exploration of natural approaches regarding antipathogenic treatments. Overall, the datasets agreed on major prokaryotic players.In conclusion, different sequencing approaches yield overlapping and highly complementary results, with each contributing data no other approach could. Such a tiered approach therefore constitutes a practical and cost-effective strategy for obtaining the maximum amount of information on aquaculture microbial communities. These data could lead to better farm management practices and at the same time inform basic research on community evolution dynamics.
TLR4 signaling in presence of HIV-induced activation enhances programmed death ligand-1 expression on human plasmacytoid dendritic cells and modulates their function
Authors: Patel Meher , Singh Sukhwinder , Davidow Amy , Dai Jihong , Fitzgerald-Bocarsly Patricia 
Published: July 2022

AbstractHuman Plasmacytoid dendritic cells (pDC) only comprise a minute fraction of human mononuclear leukocytes, but are important anti-viral responders that mediate both innate as well as adaptive immune responses. Persistent activation of pDC enhances HIV pathogenesis by promoting immune suppressive mechanisms such as T regulatory cells. It is therefore important to identify the sources of pDC activation in the context of HIV infection. HIV-associated disruption of gut mucosa associated lymphoid tissue introduces normal flora-lipopolysaccharide (LPS) into systemic circulation, which exacerbates HIV-induced immune activation. We report here that pDC are capable of mediating functional TLR4 signaling upon LPS stimulation, and that pDC of HIV-infected individuals have enhanced TLR4 expression compared to healthy individuals. How TLR4 signaling affects pDC function in HIV infection has not been examined before. Hence we examined the influence of TLR4 signaling in presence of HIVstimulation on pDC and found that it not only potentiated HIV-induced activation but also strongly up-regulated Programmed death ligand-1 (PD-L1) expression and Interleukin-6 synthesis. TLR4 signaling specifically up-regulated PD-L1 expression on activated pDC in presence of HIV stimulation. LPS and HIV co-stimulated pDC demonstrated enhanced migratory potential and repressed T cell proliferation. Together, these results suggest that in the setting of HIV infection enhancement of pDC immune suppressive mechanisms such as PD-L1 may be an outcome of HIV-associated immune activation potentiated by TLR4 signaling.
High exposure variance enables candidate biomarker detection in a small EWAS of methylmercury-exposed Peruvian adults
Authors: Weinhouse Caren , Perez Luiza , Ryde Ian , Goodrich Jaclyn M. , Miranda J. Jaime , Hsu-Kim Heileen , Murphy Susan K. , Meyer Joel N. , Pan William K. 
Published: July 2022

I.AbstractBackgroundEpigenome-wide association studies (EWAS) are a highly promising approach that can inform precision environmental health. However, current EWAS are underpowered for biomarker detection and increasing sample sizes will require substantial resources. Therefore, alternative approaches for identifying candidate biomarkers through EWAS are critical for moving the field forward.ObjectivesTo provide proof-of-principle that maximizing exposure variance in EWAS by selecting participants from disproportionately exposed global populations enables effective candidate biomarker detection, even in small sample sizes.MethodsWe profiled genome-wide DNA methylation using Illumina Infinium MethylationEPIC BeadChip in whole blood from N=32 individuals from Madre de Dios, Peru with high methylmercury (MeHg) exposure due to artisanal and small-scale gold mining. We compared DNA methylation in N=16 individuals with high (>10 μg/g) vs. N=16 individuals with low (<1 μg/g) total hair mercury (a proxy for methylmercury exposure), matched on age and sex.ResultsWe identified nine differentially methylated CpG sites (FDR<0.05), including several with known links to MeHg toxicity. The most significantly different CpG site was in an intronic enhancer of theSLC5A7gene, which encodes the L-type amino acid transporter 1 (LAT1) that facilitates MeHg transport into protein-rich tissue, including muscle and brain. Our Gene Ontology and transcription factor motif enrichment analyses identified differential methylation of genes involved in several outcomes with established links to MeHg, including immune response, neurotoxicity, and type 2 diabetes (T2D) risk. Last, we identified candidate epigenetic biomarkers of PUFA-mediated protection against MeHg toxicity.DiscussionHere, we show that a small EWAS on samples with high MeHg exposure variance can detect candidate differentially methylated CpGs and pathways of interest relevant to MeHg biology. Similar EWAS in global populations with known high exposure variance can be leveraged to develop targeted, custom sequencing panels and microarrays limited to replicated, validated biomarkers of a given exposure.
Daily movement behaviours and cognition in mid-life: A cross-sectional compositional analysis of the 1970 British Cohort Study
Authors: Mitchell JJ , Blodgett JM , Chastin S , Jefferis BJ , Wannamethee G , Hamer M 
Published: July 2022

AbstractIMPORTANCEMovement behaviours (e.g. sedentary behaviour (SB), moderate and vigorous physical activity (MVPA), light intensity physical activity (LIPA) and sleep) are linked to cognition, yet the relative importance of each component is unclear, and not yet explored with compositional methodologies.OBJECTIVETo examine how time spent in one behaviour (e.g. SB, MVPA, LIPA, sleep) relative to all others is associated with overall cognition, including executive function and memory.DESIGN, SETTING, AND PARTICIPANTSThe 1970 British Cohort Study (BCS70) is an ongoing prospective birth cohort study of adults born in England, Scotland and Wales in a single week. At age 46, participants wore an accelerometer device and completed cognitive screening. Linear regression was used to examine cross-sectional associations between movement behaviours and cognitive scores, using a compositional approach. Isotemporal substitution was performed to model the effect of reallocating time between components of daily movement on cognition.EXPOSURESA thigh-mounted activPAL accelerometer device was worn without removal for one week. Daily time in SB, MVPA, LIPA and sleep were derived using a validated processing algorithm.MAIN OUTCOMES AND MEASURESStandardised scores of executive function (letter cancellation and verbal fluency), memory (immediate and delayed wordlist recall) and a composite score were derived from computer administered cognitive tasks.RESULTSThe sample comprised 4,481 participants (52% female). Time in MVPA relative to SB, LIPA and sleep was positively associated with cognition after adjustments for education and occupational physical activity, but additional adjustment for health status attenuated associations. SB relative to all other movements was robustly positively associated with cognition. Modelling time reallocation between components revealed a higher cognition percentile after MVPA theoretically replaced just 9 minutes of SB (+1.31; 95% CI: 0.09, 2.50), 7 minutes of LIPA (+1.27; 0.07, 2.46) or 7 minutes of sleep (+1.20; 0.01, 2.39).CONCLUSIONS AND RELEVANCERelative to time spent in other behaviours, more time spent in MVPA and SB was associated with higher cognitive scores. Displacement of MVPA time, given its smaller relative amount, appear most deleterious. Efforts should be made to preserve MVPA time, or reinforce it with time taken from other behaviours.
Systematic comparison of family history and polygenic risk across 24 common diseases
Authors: Mars Nina , Lindbohm Joni V. , Briotta Parolo Pietro della , Widén Elisabeth , Kaprio Jaakko , Palotie Aarno ,   FinnGen, Ripatti Samuli 
Published: July 2022

ABSTRACTFamily history is the standard indirect measure of inherited susceptibility in clinical care, while polygenic risk scores (PRS) have more recently demonstrated potential for more directly capturing genetic risk in many diseases. No studies have systematically compared how these overlap and complement each other across common diseases. Within FinnGen (N=306,418), we leverage family relationships, up to 50 years of nationwide registries, and genome-wide genotyping to examine the interplay of family history and genome-wide PRSs. We explore the dynamic for three types of family history across 24 common diseases: first- and second-degree family history, and parental causes of death. Covering a large proportion of the burden of non-communicable diseases in adults, we show that family history and PRS are independent and not interchangeable measures, but instead provide complementary information of inherited disease susceptibility. The PRSs explained on average 10% of the effect of first-degree family history, and first-degree family history 3% of PRSs, and PRS effects were independent of both early- and late-onset family history. The PRS stratified the risk similarly in individuals with and without family history. In most diseases, including coronary artery disease, glaucoma, and type 2 diabetes, a positive family history with a high PRS was associated with a considerably elevated risk, whereas a low PRS compensated completely for the risk implied by positive family history. This study provides a catalogue of risk estimates for both family history of disease and PRSs, and highlights opportunities for a more comprehensive way of assessing inherited disease risk across common diseases.
Trust in the attending rheumatologist, health-related hope, and medication adherence among Japanese patients with systemic lupus erythematosus: the TRUMP2-SLE project
Authors: Kurita Noriaki , Oguro Nao , Miyawaki Yoshia , Hidekawa Chiharu , Sakurai Natsuki , Ichikawa Takanori , Ishikawa Yuichi , Hayashi Keigo , Shidahara Kenta , Kishida Dai , Yoshimi Ryusuke , Sada Ken-ei , Shimojima Yasuhiro , Yajima Nobuyuki 
Published: July 2022

AbstractObjectivesPoor medication adherence among patients with systemic lupus erythematosus (SLE) is a critical problem associated with adverse outcomes. This study examined the relationship between trust in one’s physician and goal-oriented thinking, hope, and medication adherence among Japanese patients with SLE who were ethnically matched to their physicians.MethodsThis cross-sectional study was conducted in the rheumatology outpatient clinics at five academic centers. Patients with SLE who were prescribed oral medications were included. The main exposure was trust in one’s physician measured via the 5-item Japanese version of the Wake Forest Physician Trust Scale and the 18-item Health-related Hope Scale, with each score ranging from 0 to 100 points. The outcome was medication adherence measured using the 12-item Medication Adherence Scale with scores ranging from 5 to 60 points. A general linear model was created after adjusting for demographics, socioeconomic status, disease activity, disease duration, basic health literacy, depression, medication variables, experiencing adverse effects, and concerns regarding lupus medications.ResultsAltogether, 373 patients with SLE were included. The mean age of the patients was 46.4 years, and among them, 329 (88.2%) were women. Both trust in one’s physician (per 10-point increase: 0.88, 95% confidence interval [95%CI]: 0.53 to 1.24) and the Health-related Hope score (per 10-point increase: 0.64, 95%CI: 0.33 to 0.95) were associated with better medication adherence.ConclusionsPhysician communication to build trust and coaching on self-management to maintain or achieve what is important in the patient’s life and to enhance hope may lead to better medication adherence.Key messagesWhat is already known on this topicThe possible association of loss of trust in the attending physician with medication adherence in systemic lupus erythematosus has been conflicting in previous research, in which the effect of physician–patient racial mismatch has not been considered. The protective role of hope and goal-oriented thinking for mental symptoms has been suggested among patients with SLE.What this study addsThis study revealed that both trust in one’s physician and health-related hope were associated with better medication adherence in Japanese patients who were ethnically matched to their physicians.How this study may affect research, practice, or policyThe results indicated that physician communication to build trust and coaching on self-management to maintain or achieve what is important in the patient’s life may lead to better medication adherence.
Obesity Disrupts Pituitary UPR Leading to NAFLD
Authors: Qian Qingwen , Li Mark , Zhang Zeyuan , Davis Shannon , Rahmouni Kamal , Norris Andrew W. , Cao Huojun , Ding Wen-Xing , Yang Ling 
Published: July 2022

ABSTRACTObesity is the major risk factor for nonalcoholic fatty liver disease (NAFLD), for which effective cures are lacking. Despite the notion that obesity is associated with aberrant levels and action of pituitary hormones that are essential for maintaining hepatic metabolic and inflammatory states, the intrinsic pituitary endocrine abnormalities and their systemic consequences are incompletely defined. By characterizing the impact of diet-induced obesity (DIO) on the pituitary whole tissue and single cell transcriptome, we demonstrated that obesity disrupts pituitary endoplasmic reticulum (ER) homeostasis by suppressing the inositol-requiring enzyme-α (IRE1α)-mediated adaptive unfolded protein response (UPR). We further showed that defective pituitary UPR by IRE1α-deletion in the anterior pituitary strikingly augmented obesity-associated systemic metabolic abnormalities, particularly the NAFLD-associated pathologies. Conversely, enhancing the adaptive UPR in the anterior pituitary, by genetic gain-of-function of spliced X-box binding protein 1 (sXBP1), ameliorated the systemic and hepatic metabolic defects observed in mice with pituitary IRE1α deletion. Intriguingly, disruption of the UPR in the pituitary resulted in impaired hepatic UPR, which was in part due to a defective thyroid hormone receptor (THR)-mediated activation of hepatic Xbp1. In contrast, activation of the hepatic THR signaling improved obesity-associated glucose intolerance and attenuated the impaired hepatic ER homeostasis in anterior pituitary-IRE1α deficient mice. Together, our study provides the first insight into disruption of endocrine signaling-mediated inter-organ UPR communication drives obesity-associated hepatic pathologies. Unraveling these connections might uncover new therapeutic targets for NAFLD and other obesity-associated diseases.