bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of Multiple Individual Primary Cardiovascular Events Using Pooled Cohorts
Authors: Sussman Jeremy B. , Whitney Rachael T. , Burke James F. , Hayward Rodney A. , Galecki Andrzej , Sidney Stephen , Allen Norrina Bai , Gottesman Rebecca F. , Heckbert Susan R. , Longstreth William T. , Psaty Bruce M , Elkind Mitchell S.V. , Levine Deborah A. 
Published: August 2023

AbstractIntroductionMost current clinical risk prediction scores for cardiovascular disease prevention use a composite outcome. Risk prediction scores for specific cardiovascular events could identify people who are at higher risk for some events than others informing personalized care and trial recruitment. We sought to predict risk for multiple different events, describe how those risks differ, and examine if these differences could improve treatment priorities.MethodsWe used participant-level data from five cohort studies. We included participants between 40 and 79 years old who had no history of myocardial infarction (MI), stroke, or heart failure (HF). We made separate models to predict 10-year rates of first atherosclerotic cardiovascular disease (ASCVD), first fatal or nonfatal MI, first fatal or nonfatal stroke, new-onset HF, fatal ASCVD, fatal MI, fatal stroke, and all-cause mortality using established ASCVD risk factors. To limit overfitting, we used elastic net regularization with alpha = 0.75. We assessed the models for calibration, discrimination, and for correlations between predicted risks for different events. We also estimated the potential impact of varying treatment based on patients who are high risk for some ASCVD events, but not others.ResultsOur study included 24,505 people; 55.6% were women, and 20.7% were non-Hispanic Black. Our models had C-statistics between 0.75 for MI and 0.85 for HF, good calibration, and minimal overfitting. The models were least similar for fatal stroke and all MI (0.58). In 1,840 participants whose risk of MI but not stroke or all-cause mortality was in the top quartile, we estimate one blood pressure-lowering medication would have a 2.4% chance of preventing any ASCVD event per 10 years. A moderate-strength statin would have a 2.1% chance. In 1,039 participants who had top quartile risk of stroke but not MI or mortality, a blood pressure-lowering medication would have a 2.5% chance of preventing an event, but a moderate-strength statin, 1.6%.ConclusionWe developed risk scores for eight key clinical events and found that cardiovascular risk varies somewhat for different clinical events. Future work could determine if tailoring decisions by risk of separate events can improve care.
Trends in cardiac arrest mortality in the US, 1999-2020
Authors: Gonuguntla Karthik , Chobufo Muchi Ditah , Shaik Ayesha , Patel Neel , Penmetsa Mouna , Thyagaturu Harshith , Taha Amro , Alharbi Anas , Sattar Yasar , Balla Sudarshan 
Published: August 2023

AbstractImportanceCardiac arrest affects over 600,000 in the US. Despite large-scale public health and educational initiatives, survival rates are lower in certain racial and socioeconomic groups.ObjectiveTo examine the trends in annual rates of cardiac arrests mortality among adults stratified by age, race, and gender in the U.S.DesignA county-level cross-sectional longitudinal study using death data from the Centres for Disease Control and Prevention’s (CDC) Wide-Ranging Online Data for Epidemiologic Research (WONDER) database from 1999 to 2020.SettingUsing the multiple causes of death dataset from the CDC’s WONDER database, cardiac arrests were identified using the International Classification of Diseases (ICD), tenth revision, clinical modification codes.ParticipantsIndividuals aged 15 years or more whose death was attributed to cardiac arrest.ExposuresCalendar year.Main outcomes and measuresNational trends in annual mortality from cardiac arrest in select demographic groups and at the state level.ResultsBetween 1999 and 2020, the annual cardiac arrest related AAMR (CA-MR) declined through 2019 (132.9 to 89.7 per 100,000 residents, followed by an increase in 2020 (104.5 per 100,000). White patients constituted 82% of all deaths and 51% were female. The overall CA-MR during the study period was 104.48 per 100,000 persons. The CA-MR was higher for men as compared with women (123.5 vs. 89.7 per 100,000) and higher for Black as compared with White adults (154.4 vs. 99.1 per 100,000).Conclusion and relevanceCA-MR in the overall population has declined, followed by an increase in 2020, which is likely the impact of COVID-19 pandemic. There were also significant racial and sex differences in mortality rates.Visual AbstractVisual representation of cardiac arrest-related mortality and the impact of social vulnerability index on mortality rates42Key PointsQuestionWhat are the temporal trends on cardiac arrest-related deaths in the United States (U.S.)?FindingsIn this national cross-sectional study spanning 22 years, there was an overall declining trend in cardiac arrest mortality across all age groups, gender, race, and regions. However, in 2020 there was an increase in the rates of cardiac arrest mortality, likely due to the COVID-19 pandemic. There was also a state-level variation in cardiac arrest mortality, with certain states showing an increase in mortality rates.MeaningThere was an overall reduction in the age-adjusted mortality rates due to cardiac arrest. This decrease in mortality rate was consistent across all genders, races, and US regions. There was also significant racial and sex differences in mortality rates.
Probing efficient microbial CO2utilization through metabolic and process modeling
Authors: de Vries Philip J. Gorter , Mol Viviënne , Sonnenschein Nikolaus , Jensen Torbjørn Ølshøj , Nielsen Alex Toftgaard 
Published: August 2023

AbstractMicrobial gas fermentation is proving to be a promising technology to upcycle carbon-rich waste gasses into value-added biochemicals, though production yields of varied products are currently limited. Through the holistic pairing of process modeling with host agnostic black box metabolic modeling, here we investigate an efficient thermophilic CO2upcycling process, based on acetogenic carbon utilization. From a process engineering perspective, higher temperatures were found to favor overall gas transfer rates, even with lower gas solubility, particularly for the more expensive and often limiting H2gas. Metabolically, for growth coupled products, thermophilic production favors higher product yields as a result of a higher maintenance energy input. A process simulation for acetate production in a large-scale bubble column reactor predicts an optimal feed gas composition of approximately 9:1 mol H2to mol CO2and a process with higher production yields and rates at higher temperatures. To assess the expansion of the product portfolio beyond acetate, both a product volatility analysis and a metabolic pathway model were implemented.In-siturecovery of volatile products is shown to be within range for acetone but challenging due to the extensive evaporation of water, while the production of more valuable compounds is energetically unfavorable compared to acetate. We discuss alternative approaches to overcome these challenges to utilize acetogenic CO2fixation for the production of a wider range of carbon negative chemicals.
Activation of cannabinoid CB2 receptors by (−)-cannabichromene but not (+)-cannabichromene
Authors: Udoh Michael , Santiago Marina , Haneef Syed , Rodger Alison , Marlowe Charles K. , Barr Philip J. , Connor Mark 
Published: August 2023

AbstractIntroductionCannabichromene (CBC) is a minor constituent of Cannabis that is a selective cannabinoid CB2 receptor agonist and activator of TRPA1. To date, it has not been shown whether (−)-CBC, (+)-CBC (or both) can mediate these effects. In this study we investigate the activity of the CBC enantiomers at CB1, CB2 and TRPA1in vitro.Materials and MethodsCBC enantiomers were purified from synthetic CBC by chiral chromatography, and their optical activity was confirmed by spectroscopy. Human CB1 and CB2 receptor activity was measured using a fluorescent assay of membrane potential in stably transfected AtT20 cells. TRPA1 activation was measured using a fluorescent assay of intracellular calcium in stably transfected HEK293 cells.Results(−)-CBC activated CB2 with an EC50of 1.5 µM, to a maximum of 60 % of CP55940. (+)-CBC did not activate CB2 at concentrations up to 30 µM. Only 30 µM (−)– CBC produced detectable activation of CB1, (+)-CBC was inactive. Both (−)-CBC and (+)– CBC activated TRPA1; at 30 µM (−)-CBC produced an activation 50% of that of the reference agonist cinnamaldehyde (300 µM), 30 µM (+)-CBC activated TRPA1 to 38% of the cinnamaldehyde maximum.DiscussionIt is unclear whether (−)-CBC is the sole or even the predominant enantiomer of CBC enzymatically synthesized inCannabis. This study shows that (−)-CBC is the active isomer at CB2 receptors, while both isomers activate TRPA1. The results suggest that medicinal preparations of CBC that target cannabinoid receptors would be most effective when (−)-CBC is the dominant isomer.
Lysosomal release of amino acids at ER three-way junctions regulates transmembrane and secretory protein mRNA translation
Authors: Choi Heejun , Liao Ya-Cheng , Yoon Young J. , Grimm Jonathan , Lavis Luke D. , Singer Robert H. , Lippincott-Schwartz Jennifer 
Published: August 2023

AbstractOne-third of the mammalian proteome is comprised of transmembrane and secretory proteins that are synthesized on endoplasmic reticulum (ER). Here, we investigate the spatial distribution and regulation of mRNAs encoding these membrane and secretory proteins (termed “secretome” mRNAs) through live cell, single molecule tracking to directly monitor the position and translation states of secretome mRNAs on ER and their relationship to other organelles. Notably, translation of secretome mRNAs occurred preferentially near lysosomes on ER marked by the ER junction-associated protein, Lunapark. Knockdown of Lunapark reduced the extent of secretome mRNA translation without affecting translation of other mRNAs. Less secretome mRNA translation also occurred when lysosome function was perturbed by raising lysosomal pH or inhibiting lysosomal proteases. Secretome mRNA translation near lysosomes was enhanced during amino acid deprivation. Addition of the integrated stress response inhibitor, ISRIB, reversed the translation inhibition seen in Lunapark knockdown cells, implying an eIF2 dependency. Altogether, these findings uncover a novel coordination between ER and lysosomes, in which local release of amino acids and other factors from ER-associated lysosomes patterns and regulates translation of mRNAs encoding secretory and membrane proteins.
Elucidating the activation mechanism for GBP1 oligomerization
Authors: Weismehl Marius , Chu Xiaofeng , Kutsch Miriam , Lauterjung Paul , Herrmann Christian , Kudryashev Misha , Daumke Oliver 
Published: August 2023

AbstractThe dynamin-related human guanylate-binding protein 1 (GBP1) mediates host defense against microbial pathogens. Upon GTP binding and hydrolysis, auto-inhibited GBP1 monomers dimerize and assemble into soluble and membrane-bound oligomers, which are crucial for innate immune responses. How higher-order GBP1 oligomers are built from dimers and how assembly is coordinated with nucleotide-dependent conformational changes has remained elusive. Here, we present cryo-electron microscopy-based structural data of the soluble and membrane-bound GBP1 oligomers demonstrating that GBP1 assembles in an outstretched dimeric conformation. We identify a surface-exposed helix in the large GTPase domain, which contributes to the oligomerization interface, and probe its nucleotide- and dimerization-dependent movements facilitating the formation of an antimicrobial protein coat on a Gram-negative bacterial pathogen. Our results reveal a sophisticated activation mechanism for GBP1 in which nucleotide-dependent structural changes coordinate dimerization, oligomerization, and membrane binding to allow encapsulation of pathogens with an antimicrobial protein coat.
Adaptation of theSpalax galilitranscriptome to life under hypoxia may hold a key to a complex phenotype including longevity and cancer resistance
Authors: Poetzsch G. , Jelacic L. , Bicker A. , Balling M. , Hellmann L. , Dammer L. , Andrade-Navarro M.A. , Shams I. , Avivi A. , Hankeln T. 
Published: August 2023

AbstractThe muroid rodentNannospalax galili(syn.Spalax) is adapted to life in underground burrows and tolerates acute exposure to severe hypoxia. Adaptation to hypoxia is correlated with delayed onset of ageing and resistance against tumour formation.Spalaxbecomes five to seven times older than its relatives, the mouse and rat, without displaying signs of ageing or developing ageing-related disorders like cancer. Investigating and understanding adapted genes and gene regulatory networks ofSpalaxmight pinpoint novel strategies to maintain an extended healthy phenotype in humans. Here we analysed and compared RNA-Seq data of liver, kidney and spleen ofSpalaxand rat subjected to 6% O2or normoxia. We identified differentially expressed genes and pathways common to multiple organs inSpalaxand rat. Body-wide differences betweenSpalaxand rat affected biological processes like cell death, defence against reactive oxygen species (ROS), DNA repair, energy metabolism, immune response and angiogenesis, which altogether might play a crucial role inSpalax’s adaptation to life under oxygen deprivation. In all organs, mRNA expression of genes associated with genome stability maintenance and DNA repair was elevated inSpalaxcompared to rat, accompanied by a lower gene expression of genes associated with aerobic energy metabolism and proinflammatory processes. These transcriptomic changes might be accountable for the extraordinary lifespan ofSpalaxand its cancer resistance. Our results reveal gene regulatory networks that become candidates for the investigation of the molecular bases that underlie the complex phenotype ofSpalax.
Hierarchical Assembly of Single-Stranded RNA
Authors: Pietrek Lisa M. , Stelzl Lukas S. , Hummer Gerhard 
Published: August 2023

AbstractSingle-stranded RNA (ssRNA) plays a major role in the flow of genetic information– most notably in the form of messenger RNA (mRNA)–and in the regulation of biological processes. The highly dynamic nature of chains of unpaired nucleobases challenges structural characterizations of ssRNA by experiments or molecular dynamics (MD) simulations alike. Here we use hierarchical chain growth (HCG) to construct ensembles of ssRNA chains. HCG assembles the structures of protein and nucleic acid chains from fragment libraries created by MD simulations. Applied to homo- and heteropolymeric ssRNAs of different lengths, we find that HCG produces structural ensembles that overall are in good agreement with diverse experiments including nuclear magnetic resonance (NMR), small-angle X-ray scattering (SAXS), and single-molecule Förster resonance energy transfer (FRET). The agreement can be further improved by ensemble refinement using Bayesian inference of ensembles (BioEn). HCG can also be used to assemble RNA structures that combine base-paired and unpaired regions, as illustrated for the 51untranslated region (UTR) of SARS-CoV-2 mRNA.
Diagnostic accuracy of MRI compared to CTPA for pulmonary Embolism : A meta analysis
Authors: Desai Dev H. , Shah Abhijay , Shah Hetvi , Naik Aarya A. , Sadat Sharif Mohammed , Raval Dwija 
Published: August 2023

ABSTRACTBackgroundThis meta-analysis presents a comparison between Computed Tomography Pulmonary Angiography (CTPA) and Magnetic Resonance Angiography (MRA), to diagnose a pulmonary embolism. Computed tomography presents the advantage of imaging the entire thorax, facilitating the diagnosis of conditions that are commonly mistaken for pulmonary embolism, such as pneumonia, aortic dissection, and malignancy. UK and US guidelines have established CT amongst the basic investigations for pulmonary embolism. MRA does not require the use of ionizing radiation or iodinated contrast, thus making it possible for routine use of multiphasic acquisitions as well as for repeated contrast injectionsMethodologyFor the collection of the data, a search was done by two individuals using PubMed, Google Scholar, and Cochrane Library databases for all relevant literature. Full - Text Articles written only in English were considered. Each qualifying paper was independently evaluated by two reviewers. Each article was analyzed for the number of patients, their age, procedure modality, and incidence of the pre decided complications.ResultsThe results also showed a high positive predictive value of 0.947 or 94.7% for MRA in the diagnosis of Pulmonary embolism, as compared with CTPA. Some analyses have marked MRA to have low specificity. These results establish MRA as a respectable alternative for diagnosis of APE, especially in cases when reducing radiation exposure is desired. However, the gold standard of diagnosis remains Computed Tomography Pulmonary Angiography.ConclusionAs the results show, though MRA has high statistical value for the diagnosis of pulmonary embolism, it also has its drawbacks. MRA cannot be used in severely ill patients as it continues to be challenging, with the longer scan times and multiple breath holds that are required in different MR protocols are difficult to follow in these patients. CTPA remains the gold standard for diagnosis of Pulmonary embolism, with MRA as a secondary test used when CTPA is contraindicated.
Diagnostic performance of urinary 5-Hydroxyindoleacetic Acid in acute appendicitis: a systematic review and diagnostic test accuracy meta-analysis
Authors: Arredondo Montero Javier , Bueso Asfura Oscar Emilio , Pérez Riveros Blanca Paola , Rico Jiménez María 
Published: August 2023

ABSTRACTBackgroundThis study aimed to analyze the diagnostic performance of urinary 5-Hydroxyindoleacetic Acid (5-HIAA) in acute appendicitis (AA).MethodsWe conducted a systematic review of the literature in the main databases of medical bibliography. Two independent reviewers selected the articles and extracted relevant data. Methodological quality was assessed using the QUADAS2 index. A synthesis of the results, standardization of the metrics, and a random-effect meta-analysis were performed. Additionally, a diagnostic test accuracy meta-analysis (DTA) was performed.ResultsTwelve studies with data from 1467 participants (724 patients with a confirmed diagnosis of AA and 743 controls) were included in this review. The random-effect meta-analysis of urinary 5-HIAA (AA vs controls) included 7 articles (352 AA and 258 controls) and resulted in a significant mean difference [95% CI] of 23.30 [15.82-30.77] μmol/L (p<0.001). The DTA meta-analysis of urinary 5-HIAA included 8 articles and resulted in a pooled sensitivity [95% CI] of 68.6 [44.1-85.9]% and a pooled specificity [95% CI] of 82 [54.7-94.5]%.ConclusionsAlthough the evidence is heterogeneous and limited, urinary 5-HIAA emerges as a potential non-invasive diagnostic tool for AA. Urinary 5-HIAA does not seem to be a useful biomarker to distinguish between NCAA and CAA. Future prospective studies with a large sample size and a rigorous design are necessary to validate these findings.
Plant TIR domains physically interact with EDS1 family proteins to propagate immune signalling
Authors: Chen Jian , Zhang Xiaoxiao , Bernoux Maud , Rathjen John P. , Dodds Peter N. 
Published: August 2023

AbstractPlant Toll/interleukin-1 receptor/resistance protein (TIR) type nucleotide-binding and leucine-rich repeat immune receptors (NLRs) require Enhanced Disease Susceptibility 1 (EDS1) family proteins and the helper NLRs NRG1 and ADR1 for immune activation. TIR signalling domains possess NADase activity, producing NAM and v-cADPR from NAD+in vitro. However, after TIR activation different small non-cyclic signalling molecules have been detected bound to EDS1/SAG101 and EDS1/PAD4 heterodimers. These molecules have not been detected inin vitroassays or as free moleculesin plantaand it is not clear how they are delivered to the EDS1 complexes. Here we investigate physical and functional interactions between TIR signalling domains, EDS1 family proteins and helper NLRs to clarify these signalling transduction pathways. We show that theNbEDS1-NbSAG101b-NbNRG1 signalling pathway inN. benthamianais necessary and sufficient for cell death signalling induced by six different TIR-containing NLRs from a range of plant species, suggesting this module is likely a universal requirement for TIR-NLR mediated cell death inN. benthamiana. We also find that TIR domains physically interact withNbEDS1,NbPAD4 andNbSAG101in planta, independently of each other. We also find evidence for direct interaction ofNbNRG1 withNbSAG101b via its C-terminal EP domain, but not with other EDS1 family members. These data suggest a model in which physical interaction between activated TIRs and EDS1 signalling complexes facilitates efficient transfer of low abundance products of TIR catalytic activity directly to EDS1 heterocomplexes. The interaction could also alter TIR catalytic activity to favor production of the ligands recognised by EDS1/SAG101 and EDS1/PAD4.
Differences Between Human and Non-Human Primate Theory of Mind: Evidence from Computational Modeling
Authors: Horschler Daniel J. , Berke Marlene D. , Santos Laurie R. , Jara-Ettinger Julian 
Published: August 2023

AbstractCan non-human primates (NHPs) represent other minds? Answering this question has been historically difficult because primates can fail experimental tasks due to a lack of motivation, or succeed through simpler mechanisms. Here we introduce a computational approach for comparative cognition that enables us to quantitatively test the explanatory power of competing accounts. We formalized a collection of theories of NHP social cognition with varying representational complexity and compared them against data from classical NHP studies, focusing on the ability to determine what others know based on what they see. Our results uncovered that, while the most human-like models of NHP social cognition make perfect qualitative predictions, they predict effect sizes that are too strong to be plausible. Instead, theories of intermediate representational complexity best explained the data. At the same time, we show that it is possible for human-like models to capture non-human primate behavior (NHP), as long as we assume that NHPs rely on these representations only about one third of the time. These results show that, in visual perspective taking tasks, NHPs likely draw upon simpler social representations than humans, either in terms of representational complexity, or in terms of use.