bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sleep disorders as risk factors for calcific aortic stenosis
Authors: El Jamal Nadim , Brooks Thomas G. , Skarke Carsten , FitzGerald Garret A. 
Published: November 2024

AbstractBackgroundCircadian disruption and sleep disorders have been shown to increase the risk for many cardiovascular diseases. Their association specifically with valvular heart disease, however, is inconclusive.MethodsWe leveraged large electronic health record datasets (the TriNetX network and the AllofUs study) to test whether sleep disorders are a risk factor for calcific aortic stenosis (AS). We fitted Cox proportional hazards models to quantify the risk of future incidence of AS in patients with sleep disorders. We also explored clinical laboratory test datasets for biochemical signals that might explain the association, running mediation analyses.ResultsIn our fully adjusted Cox models, we find that having any sleep disorder increases the risk for the future incidence of AS (HR: 1.15 95% CI: 1.13-1.18). Changes in lipid profile mediate a proportion of that association.ConclusionSleep disorders are associated with an increased risk of AS incidence. That association is independent of classical cardiovascular risk factors even though dyslipidemia plays a large role in mediating this risk.
Monogenic Parkinson’s Disease and the Impact ofAPOEE4: A Case-Control Study
Authors: Kmiecik Matthew J. , Holmes Michael V. , Fontanillas Pierre , Riboldi Giulietta M. , Schneider Ruth B. , Shi Jingchunzi , Guan Anna , Tat Susana , Stagaman Keaton , Gottesman Josh , Hinds David A. , Tung Joyce Y. ,   23andMe Research Team, Aslibekyan Stella , Norcliffe-Kaufmann Lucy 
Published: November 2024

AbstractImportanceThe lack of information on progression, phenoconversion, and risk of dementia in a large genotyped sample impedes reliable enrichment for early interventional trials in Parkinson’s disease (PD).ObjectiveTo investigate PD penetrance, risk, motor/non-motor phenotypes, andAPOEallele effects inLRRK2G2019S andGBAN370S carriers.DesignObservational longitudinal case-control self-report survey study.SettingA US population-based study cohort enrolled in the 23andMe, Inc. and Fox Insight Genetic Substudy (FIGS) databases.ParticipantsThe total cohort included 7,586,842 participants (n=35,163 PD; 27% of PD cases from FIGS); 8,791LRRK2G2019S carriers (565 with PD), 37,427GBAN370S carriers (524 with PD), 244 dual carriers (37 with PD), and 7.5 million non-carriers (34,037 with PD).Exposure(s)LRRK2G2019S,GBAN370S,APOEE2/E3/E4 alleles and PD polygenic risk scores (PRS).Main Outcome(s) and Measure(s)Cumulative incidence of PD was estimated using Kaplan-Meier and accelerated failure time models. Relative odds of developing motor and non-motor symptoms were calculated using logistic regression models according to genetic exposure. Impact of theAPOEalleles was estimated in a dose-dependent analysis.ResultsBy the age of 80 years, the cumulative incidence of PD was 43% for dual carriers, 32% forLRRK2G2019S carriers, 6% forGBAN370S carriers, and 3% for non-carriers. Higher PRS was associated with increased penetrance of the variants and earlier time to PD diagnosis. Motor symptoms were similar inLRRK2G2019S,GBAN370S, and non-carriers with PD.GBAN370S PD was associated with the highest burden of non-motor symptoms, including REM sleep behavior disorder and cognitive/memory deficits, andLRRK2G2019S the lowest.APOEE4 dosage was associated with greater odds of developing hallucinations and cognitive decline in addition to carrier status.Conclusions and RelevanceOur findings support the use of genetic screening—includingLRRK2G2019S,GBAN370S,APOEE4, and PRS—to enrich candidate selection for neuroprotective trials and better define outcome measures based on genetic risk factors.
Study on the Intervention of α-Lipoic Acid in Patients with Type 2 Diabetes Mellitus after CAG or PCI Compared with Contrast-Induced Nephropathy
Authors: Wu Aijie , Li Chunyao , Wang Pingping , Shi Wenlu , Zhu Jiaojiao , Zhang Zhengjun , Chen Dapeng , Zhang Ting 
Published: November 2024

AbstractObjectiveTo investigate the effect of α-lipoic acid on contrast-induced nephropathy (CIN) in diabetic patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI).MethodsPatients diagnosed with type 2 diabetes mellitus and coronary heart disease scheduled for CAG or PCI treatment at the Department of Cardiovascular Medicine, General Hospital of Ningxia Medical University from February 1, 2021, to August 30, 2023, were recruited. After obtaining informed consent, patients were allocated into three groups: α-lipoic acid group (38 cases), adequate hydration group (60 cases), and routine hydration group (104 cases).The primary outcome observed was the incidence of CIN, and secondary endpoints included changes in SCr, TBiL, and GGT 72 hours after contrast agent administration.ResultsThe incidence of CIN in the α-lipoic acid group was 2.63% (1/38), 1.67% (1/60) in the adequate hydration group, and 4.81% (5/104) in the routine hydration group, with no statistically significant difference among the three groups (p=0.544). After PCI or CAG, SCr levels decreased slightly more in the α-lipoic acid group compared to the adequate hydration group, while the routine hydration group showed an increase, but the differences were not statistically significant (p> 0.05).Conclusionα-Lipoic acid has a certain improvement effect on renal function indicators (Scr) after CAG or PCI, but it did not demonstrate a significant preventive effect on CIN. Adequate hydration showed greater reduction in oxidative stress damage after CAG or PCI compared to α-lipoic acid and routine hydration.
Inflammation-associated monocytes express ACOD1 to curtail inflammatory behaviour in IBD and experimental colitis
Authors: Jones Gareth-Rhys , Drury Broc , Alegbe Tobi , Krzak Monika , Hegarty Lizi M , Raine Tim , Bryne Adam , Anderson Carl A , Ho Gwo-Tzer , Bain Calum C 
Published: November 2024

AbstractMonocytes are essential for replenishing homeostatic macrophages in the intestine. However, they also accumulate in significant numbers when intestinal homeostasis is disrupted in diseases, such as inflammatory bowel disease (IBD). The molecular pathways governing monocyte behaviour across these different contexts remain poorly understood. Here, we profile the monocyte / macrophage compartment in human IBD using single-cell RNA sequencing and identify a discrete population of monocytes that accumulate in IBD, which we term inflammation associated monocytes (IAMs). These can be identified by the expression of CD319, CD274 and CCRL2, and demonstrate increased expression of IBD susceptibility genes. By performing cross-species analysis, we show an analogous population of IAMs accumulate during chemically induced colitis in mice. Using transgenic fate mapping approaches, we show these cells likely derive from a discrete precursor in the bone marrow (BM) and are locally imprinted to produce heightened IL-1β and TNF in mouse and humans. Importantly, we show that co-incident with a hyper-inflammatory phenotype, these same cells uniquely and specifically express aconitate decarboxylase (ACOD1) in response to local Toll-like receptor (TLR) and interferon (IFN) receptor signalling, to limit unrestricted cytokine production. Thus, the intestinal environment after injury instructs both inflammation and recovery specifically within a transitioning population of monocytes that are absent in health.
Dynamic change of calcium-rich compartments during coccolithophore biomineralization
Authors: Triccas Alexander , Chevrier Daniel M. , Verezhak Mariana , Ihli Johannes , Guizar-Sicairos Manuel , Holler Mirko , Scheffel Andre , Ozaki Noriaki , Chamard Virginie , Wood Rachel , Grünewald Tilman , Nudelman Fabio 
Published: November 2024

AbstractCoccolithophores are abundant marine phytoplankton that produce biomineralized calcite scales, called coccoliths, which sequester substantial amounts of carbon and play a significant role in biogeochemical cycles. However, mechanisms underlying the storage and transport of ions essential for calcification remain unresolved. We used ptychographic X-ray computed tomography under cryogenic conditions to visualize intracellular calcium-rich structures involved in the storage of calcium ions in the coccolithophore speciesChrysotila carterae. During calcification, we observed a range of structures, from small electron-dense bodies within larger compartments, to denser and distributed globular compartments, before returning to small bodies once scale formation is complete. Nanobeam-scanning X-ray fluorescence measurements further revealed these electron-dense bodies are rich in P and Ca (molar ratio of ∼4:1). We infer from the dynamic nature of structures that these bodies are part of required cellular calcium ion transport pathways, a fundamental process critical for understanding the response of coccolithophores to climate change.
Pro-inflammatory Pathways Contribute to Pathogenesis ofClostridioides difficileInfection in a Murine Model - A Spatial Transcriptomics Study
Authors: Ghahari Niloufar , AbdelKhalek Ahmed , Narayanan Sanjeev , Pillai Deepti 
Published: November 2024

AbstractClostridioides difficile(C. difficile) is a common cause of antibiotic-induced diarrhea and causes the highest number of nosocomial infections. Only two antibiotics are currently recommended for treatingC. difficileinfection (CDI), which may contribute to unsatisfactory treatment outcomes and an increased likelihood of recurrence.Clostridioides difficileexists as a non-pathogenic member of the human intestinal microbiome in 10-20% of the population, a phenomenon observed in mouse models after infection with bacterial spores. In this study, we aim to evaluate the difference in gene expression between symptomatic and asymptomatic mice after infection withC. difficileusing spatial transcriptomics analysis. We also aim to evaluate the spatial aspect of altered genes between different layers of intestinal mucosa (superficial vs deep) and identify the key pathways. Formalin-fixed paraffin-embedded (FFPE) intestinal sections were utilized for analysis using NanoString™platform to evaluate differential gene expressions in the caecum and colon. The IL-17 pathway, includingLcn2, Cxcl2, andS100a8genes, was significantly upregulated in symptomatic mice. The IL-17 signaling pathway activated downstream signaling through NF-κB and MAPK pathways. Gene expression was significantly altered between the intestinal superficial and deep mucosal layers, highlighting layer-specific differences in gene expression patterns in the intestines of symptomatic and asymptomatic mice. Gene expression patterns in the enteric mucosa explain several clinical signs and lesions in CDI mice.
Illumina Complete Long Read Assay yields contiguous bacterial genomes from human gut metagenomes
Authors: Maghini Dylan G , Darling Aaron E , Monahan Leigh G , Halpern Aaron L , Burke Catherine M , Jaeger Erich , Statham Aaron , Truong Tiffany , Ying Kevin , Schroth Gary P , Bhatt Ami S. 
Published: November 2024

AbstractMetagenomics enables direct investigation of the gene content and potential functions of gut bacteria without isolation and culture. However, metagenome-assembled genomes are often incomplete and have low contiguity due to challenges in assembling repeated genomic elements. Long-read sequencing approaches have successfully yielded circular bacterial genomes directly from metagenomes, but these approaches are low throughput, have high DNA input requirements, and can have high error rates. Illumina has recently launched the Illumina Complete Long Read (ICLR) assay, a new approach for generating kilobase-scale reads with low DNA input requirements and high accuracy. Here, we evaluate the performance of ICLR sequencing for gut metagenomics. We sequenced a microbial mock community and ten human gut microbiome samples with standard, shotgun 2×150 paired-end sequencing, ICLR sequencing, and nanopore long-read sequencing and compared performance in read lengths, assembly contiguity, and bin quality. We find that ICLR human metagenomic assemblies have higher N50 (119.5 ± 24.8 kilobases) than short read assemblies (9.9 ± 4.5 kilobases; p = 0.002), and comparable N50 to nanopore assemblies (91.0 ± 43.8 kilobases; p = 0.32). Additionally, we find that ICLR draft microbial genomes are more complete (94.0% ± 20.6%) than nanopore draft genomes (85.9% ± 23.0%; p≤0.001), and that nanopore draft genomes have truncated gene lengths (924.6 ± 114.7 base pairs) relative to ICLR genomes (954.6 ± 71.5 base pairs; p≤0.001). Overall, we find that ICLR sequencing is a promising method for high-throughput and accurate assembly of microbial genomes from gut metagenomes.ImportanceMetagenomic sequencing allows scientists to directly measure the genome content and structure of microbes residing in complex microbial communities. Traditional short-read metagenomic sequencing methods often yield fragmented genomes, whereas advanced long-read sequencing methods improve genome assembly quality but often suffer from high error rates and are logistically limited due to low throughput and high input requirements. A new method, the Illumina Complete Long Read Assay (ICLR), is capable of generating highly-accurate kilobase-scale sequencing reads with minimal input material. To evaluate the utility of ICLR in metagenomic contexts, we applied short-read, long-read, and ICLR methods to simple and complex microbial communities. We found that ICLR outperforms short-read methods, and yields comparable metagenomic assemblies to standard long-read approaches while requiring less input material. Overall, ICLR represents a high-throughput and efficient solution for assembling complete genomes from complex metagenomes.
Structural basis for growth factor and nutrient signal integration on the lysosomal membrane by mTORC1
Authors: Cui Zhicheng , Esposito Alessandra , Napolitano Gennaro , Ballabio Andrea , Hurley James H. 
Published: November 2024

AbstractMechanistic target of rapamycin complex 1 (mTORC1), which consists of mTOR, Raptor, and mLST8, receives signaling inputs from growth factor signals and nutrients. These signals are mediated by the Rheb and Rag small GTPases, respectively, which activate mTORC1 on the cytosolic face of the lysosome membrane. We biochemically reconstituted the activation of mTORC1 on membranes by physiological submicromolar concentrations of Rheb, Rags, and Ragulator. We determined the cryo-EM structure and found that Raptor and mTOR directly interact with the membrane at anchor points separated by up to 230 Å across the membrane surface. Full engagement of the membrane anchors is required for maximal activation, which is brought about by alignment of the catalytic residues in the mTOR kinase active site. The observations show at the molecular and atomic scale how converging signals from growth factors and nutrients drive mTORC1 recruitment to and activation on the lysosomal membrane in a three-step process, consisting of (1) Rag-Ragulator-driven recruitment to within ∼100 Å of the lysosomal membrane, (2) Rheb-driven recruitment to within ∼40 Å, and finally (3) direct engagement of mTOR and Raptor with the membrane. The combination of Rheb and membrane engagement leads to full catalytic activation, providing a structural explanation for growth factor and nutrient signal integration at the lysosome.
Anubis: a multi-level authentication scale for ancient proteins using random forest classification
Authors: Chiang Yun , Nair Bharath Anila Bhuvanendran , Ramsøe Max Emil Ermter , Ravnsborg Tina , Jensen Ole Nørregaard , Collins Matthew James 
Published: November 2024

AbstractDeamidation is a time-dependent, post-translational modification with wide applications in clinical proteomics and palaeoproteomics as ageing indicators and authentication markers. Despite its significance, the use of deamidation for authenticating ancient proteins remains controversial, primarily due to variability in deamidation kinetics and context-specific protein preservation. We proposeAnubis, an open-source, Python-based pipeline to evaluate relative deamidation patterns and authenticate ancient proteins.Anubisleverages random forest classification based on a range of tandem mass spectrometry-based features and physico-chemical characteristics. We use a combination of ancient and experimentally degraded beta-lactoglobulin to demonstrate thatAnubiscan authenticate a putative ancient dairy protein using position-specific deamidation patterns, relative deamidation (asparagine vs. glutamine), and overall modification patterns using trypsin processed in the same batch as a baseline. This multi-level approach addresses the complexities of ancient protein deamidation and paves the way for automated, reliable authentication across different archaeological substrates.
Neutrino roof: Single-scatter cross section ceilings in dark matter direct detection experiments
Authors: Raj Nirmal , Mondal Biprajit 
Published: November 2024

We identify the maximum cross sections probed by single-scatter weakly interacting massive particle (WIMP) searches in dark matter direct detection. Owing to Poisson fluctuations in scatter multiplicity, these ceilings scale logarithmically with mass for heavy dark matter and often lie in regions probed by multiscatter searches. Using a generalized formula for single-scatter event rates we recast WIMP searches by the quintal-to-tonne scale detectors XENON1T, XENONnT, LZ, PANDAX-II, PANDAX-4T, DarkSide-50, and DEAP-3600 to obtain ceilings and floors up to a few 1017  GeV mass and 10−22  cm2 per nucleus cross section. We do this for coherent, geometric, isospin-violating xenophobic and argophobic spin-independent scattering, and neutron-only and proton-only spin-dependent scattering. Future large-exposure detectors would register an almost irreducible background of atmospheric neutrinos that would determine a dark matter sensitivity ceiling that we call the “neutrino roof,” in analogy with the well-studied “neutrino floor.” Accounting for this background, we estimate the reaches of the 10–100 tonne scale DarkSide-20k, DARWIN/XLZD, PANDAX-xT, and Argo, which would probe many decades of unconstrained parameter space up to the Planck mass, as well as of 103–104  tonne scale noble liquid detectors that have been proposed in synergy with neutrino experiments.

Published by the American Physical Society
2024
Social media usage and job performance: a sequential mediation analysis with social capital, self-efficacy, job satisfaction and knowledge sharing
Authors: Kumar Satinder , Rani Pooja 
Published: November 2024

PurposeSocial media use is prevalent today, but there is a possibility that it might go out of control and cause negative consequences. Furthermore, by using social media at work, businesses may develop their networks, communicate in a productive manner and ultimately expand the efficiency. The purpose of this study is to investigate the effect of social media use (SMU) on job performance (JP) through sequential mediators such as social capital dimensions (SC), self-efficacy (SE), job satisfaction (JS) and knowledge sharing (KS) in Indian Public Universities.Design/methodology/approachSerial mediation model has been used in the study to analyse the relationship. Data is collected from teaching faculty (n = 702) who use social media in Indian public universities. The study has assessed the association between variables using structural equation modelling.FindingsThe findings suggest that the dimensions of SC, SE, JS and KS sequentially mediated the effect of SMU on JP. In light of the results, the SMU specifies prerequisites for the development of various dimensions of SC. Similarly, the rest of the mediating constructs further affect the other constructs, which ultimately positively affect JP. The final result shows that the indirect effect between social media use and job performance is positive and significant.Practical implicationsThe study provides practical suggestions for university administration regarding the use of social media for teaching faculty.Originality/valueNo research has been done regarding social media use affecting the job performance of teaching faculty through serial mediation in public universities. In this respect, this study represents an original attempt to conduct such research.
Variation theory as a teaching theory in the theatre classroom
Authors: Ahlstrand Pernilla , Andersson Ninnie 
Published: November 2024

PurposeThe paper presents and discusses an example of findings from a research project. Filmed material from teaching situations in theatre has been the starting point for analysing and planning similar teaching situations in research lessons, where variation theory was used. The aim of using variation theory is to develop teaching practices in the school subject of theatre at upper secondary school level in Sweden.Design/methodology/approachIn the article, one example from the last part of a three-step research project design is discussed. In the third part of the design five research lessons, based on variation theory, were conducted. The starting point for planning the research lessons was teaching situations called didactic interventions, when the teacher interrupts the theatre rehearsals of a stage production and gives response on the student´s acting. The specific situations are used when planning five research lessons based on variation theory. In this paper, one example from one of the research lessons is presented, exemplifying how variation theory has been applied.FindingsThe example shows how variation theory was used in analysing and facilitating teaching in the classroom. The findings suggest that teachers can use variation theory as a way to strengthen the student’s experience of specified objects of learning, in this case, interplay in acting. Another conclusion is that variation theory is helpful when planning whole class teaching situations in the school subject of theatre.Originality/valueThis paper fulfils an identified need to study how to develop teaching practices in the school subject of theatre.
Combined oxygen and glucose oscillations distinctly change the transcriptional and physiological state of Escherichia coli
Authors: Bafna‐Rührer Jonas , Orth Jean V. , Sudarsan Suresh 
Published: November 2024

AbstractEscherichia coli, a common microbial host for industrial bioproduction, experiences a highly dynamic environment in industrial‐scale bioreactors due to significant glucose and oxygen gradients. In this study, we mimic the combined gradients of glucose and oxygen in high‐throughput bioreactors to study the transcriptional response of E. coli to industrial‐scale conditions. Under oscillating oxygen conditions, E. coli formed less biomass and accumulated the anaerobic by‐product acetate. With respect to oxygen‐responsive genes, we found that genes of the TCA cycle and of different electron transport chain complexes were differentially expressed. A global analysis of the expression data revealed that oxygen oscillations had caused a transition towards a catabolite‐repressed state and upregulation of several stress‐related regulatory programs. Interestingly, the transcriptional changes persisted after oxygen limitation stopped. In contrast, the changes we observed due to glucose starvation, such as induction of the stringent response, were primarily transient. Most importantly, we found that effects of combined oxygen and glucose oscillations were distinct from the ones of oxygen and substrate oscillations alone, suggesting an important interplay between the different metabolic regimes in industrial‐scale bioreactors.