bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alterations in Sarcopenia Index are Associated with Inflammation, Gut and Oral Microbiota among Heart Failure, Left Ventricular Assist Device and Heart Transplant Patients
Authors: Yuzefpolskaya Melana , Bohn Bruno , Ladanyi Annamaria , Pinsino Alberto , Braghieri Lorenzo , Carey Matthew R. , Clerkin Kevin , Sayer Gabriel T. , Latif Farhana , Koji Takeda , Uriel Nir , Nandakumar Renu , Uhlemann Anne-Catrin , Colombo Paolo C. , Demmer Ryan T. 
Published: September 2023

ABSTRACTBackgroundSarcopenia, characterized by loss of muscle mass and function, is prevalent in heart failure (HF) and associated with poor outcomes. We investigated alterations in sarcopenia index (SI), a surrogate marker of skeletal muscle mass, in HF, left ventricular assist device (LVAD) and heart transplant (HT) and assessed its relationship with inflammation and digestive tract (gut and oral) microbiota.MethodsWe enrolled 460 HF, LVAD and HT patients. Repeated measures pre and post procedures were obtained in a subset of LVAD and HT patients. Sarcopenia index (serum Creatinine/Cystatin C) and inflammatory biomarkers (C-reactive protein, interleukin-6, tumor necrosis factor-alpha) were measured in 271 and 622 blood samples, respectively. Gut and saliva microbiota were assessed via 16S rRNA sequencing among 335 stool and 341 saliva samples. Multivariable regression models were used to assess the relationship between SI and i) New York Heart Association class; ii) pre-vs. post-LVAD or HT; iii) biomarkers of inflammation and microbial diversity.ResultsMedian (interquartile range) ln-SI was −0.13(−0.32,0.05). Ln-SI decreased across worsening HF class, further declined within the 1-month after LVAD and HT and rebounded over time to the levels of symptomatic HF. Ln-SI demonstrated an inverse correlation with inflammation (r=-0.28, p<0.0001), and a positive correlation with gut (r=0.26, p<0.0001) and oral microbial diversity (r=0.24, p<0.0001). Presence of the gut taxaRoseburia inulinivoranswas associated with increased SI.ConclusionsSI levels decreased in symptomatic HF and remained decreased long-term after LVAD and HT. SI levels covaried with inflammation, gut and oral microbiota in a similar fashion.
From Fossils to Living Canids: Two Contrasting Perspectives on Biogeographic Diversification
Authors: Porto Lucas M. V. , Maestri Renan , Janzen Thijs , Etienne Rampal S. 
Published: September 2023

ABSTRACTThe Canidae are an ecologically important group of dog-like carnivores that arose in North America and spread across the planet around 10 million years ago. The current distribution patterns of species, coupled with their phylogenetic structure, suggest that Canidae diversification may have occurred at varying rates across different biogeographic areas. However, such extant-only analyses undervalued the group’s rich fossil history because of a limitation in method’s development. Current State-dependent Speciation and Extinction (SSE) models are (i) often parameter-rich which hinders reliable application to relatively small clades such as the Caninae (the only extant subclade of the Canidae consisting of 36 extant species); and (ii) often assume as possible states only the states that extant species present. Here we extend the SSE method SecSSE to apply to phylogenies with extinct species as well (111 Caninae species) and compare the results to those of analyses with the extant-species-only phylogeny. The results on the extant-species tree suggest that distinct diversification patterns are related to geographic areas, but the results on the complete tree do not support this conclusion. Furthermore, our extant-species analysis yielded an unrealistically low estimate of the extinction rate. These contrasting findings suggest that information from extinct species is different from information from extant species. A possible explanation for our results is that extinct species may have characteristics (causing their extinction), which may be different from the characteristics of extant species that caused them to be extant. Hence, we conclude that differences in biogeographic areas probably did not contribute much to the variation in diversification rates in Caninae.
Evolution of hierarchical switching pattern in antigenic variation ofPlasmodium falciparumunder variable host immunity
Authors: Iragavarapu Gayathri Priya , Varsha HJ , Vembar Shruthi Sridhar , Ghosh Bhaswar 
Published: September 2023

AbstractThe var genes family encoding the variants of the erythrocyte membrane protein ofPlasmodium falciparumis crucial for virulence of the parasite inside host. The transcriptional output of the var genes switches from one variant to other in a mutually exclusive fashion. It is proposed that a biased hierarchical switching pattern optimizes the growth and survival of the parasite inside the host. Apart from the hierarchical switching pattern, it is also well established that the intrinsic switching rates vary widely among the var genes. The centromeric protein like Var2csa is much more stable than the genes located at the telomeric and sub-telomeric regions of the chromosomes. In this study, we explored the evolutionary advantage achieved through selecting variable switching rates. Our theoretical analysis based on a mathematical model coupled with single cell RNA-seq data suggests that the variable switching rate is beneficial when cells expressing different variants are deferentially amenable to be cleared by the immune response. In fact, the variants which are cleared by the immune systems more efficiently are more stably expressed compared to a variant attacked by the immune system much less vigorously. The cells turn off expression of the variant quickly which is not cleared very efficiently. The evolutionary simulation shows that this strategy maximizes the growth of the parasite population under the presence of immune attack by the host. In corroboration with the result, we observed that stable variant has higher binding affinity to IgM from experimental data. Our study provides an evolutionary basis of widely variable switching rates of the var genes inPlasmodium falciparum.
Using neural biomarkers to personalize dosing of vagus nerve stimulation
Authors: Berthon Antonin , Wernisch Lorenz , Stoukidi Myrta , Thornton Michael , Tessier-Lariviere Olivier , Fortier-Poisson Pascal , Mamen Jorin , Pinkney Max , Lee Susannah , Sarkans Elvijs , Annecchino Luca , Appleton Ben , Garsed Philip , Patterson Bret , Gonshaw Samuel , Jakopec Matjaz , Shunmugam Sudhakaran , Edwards Tristan , Tukiainen Aleksi , Jennings Joel , Lajoie Guillaume , Hewage Emil , Armitage Oliver 
Published: September 2023

AbstractBackgroundVagus nerve stimulation (VNS) is an established therapy for treating a variety of chronic diseases, such as epilepsy, depression, obesity, and for stroke rehabilitation. However, lack of precision and side-effects have hindered its efficacy and extension to new conditions.ObjectiveTo achieve a better understanding of the relationship between VNS parameters and neural and physiological responses to enable the design of personalized dosing procedures to improve precision and efficacy of VNS therapies.MethodsWe used biomarkers from recorded evoked neural activity and short-term physiological responses (throat muscle, cardiac and respiratory activity) to understand the response to a wide range of VNS parameters in anaesthetised pigs. Using signal processing, Gaussian processes (GP) and parametric regression models we analyse the relationship between VNS parameters and neural and physiological responses.ResultsFirstly, we observe inter-subject variability for both neural and physiological responses. Secondly, we illustrate how considering multiple stimulation parameters in VNS dosing can improve the efficacy and precision of VNS therapies. Thirdly, we describe the relationship between different VNS parameters and the evoked neural activity and show how spatially selective electrodes can be used to improve fibre recruitment. Fourthly, we provide a detailed exploration of the relationship between the activations of neural fibre types and different physiological effects, and show that recordings of evoked neural activity are powerful biomarkers for predicting the short-term physiological effects of VNS. Finally, based on these results, we discuss how recordings of evoked neural activity can help design VNS dosing procedures that optimize short-term physiological effects safely and efficiently.ConclusionUnderstanding of evoked neural activity during VNS provide powerful biomarkers that could improve the precision, safety and efficacy of VNS therapies.
Structural and mechanistic characterization of bifunctional heparan sulfate N-deacetylase-N-sulfotransferase 1
Authors: Mycroft-West Courtney J. , Abdelkarim Sahar , Duyvesteyn Helen M. E. , Gandhi Neha S. , Skidmore Mark A. , Owens Raymond J. , Wu Liang 
Published: September 2023

AbstractHeparan sulfate (HS) polysaccharides are major constituents of the extracellular matrix, involved in myriad structural and signaling processes. Mature HS polysaccharides contain complex, non-templated patterns of sulfation and epimerization, which mediate interactions with diverse protein partners. Complex HS modifications form around initial clusters of glucosamine-N-sulfate (GlcNS) on nascent polysaccharide chains, but the mechanistic basis underpinning incorporation of the GlcNS modification itself into HS remains unclear. We have determined cryo-electron microscopy structures of human N-deacetylase-N-sulfotransferase (NDST)1, the bifunctional enzyme responsible for initial GlcNS modification of HS. Our structures reveal the architecture of both NDST1 deacetylase and sulfotransferase catalytic domains, alongside a previously unreported non-catalytic N-terminal domain. Surprisingly, the two catalytic domains of NDST1 adopt an unusual back-to-back topology that limits direct cooperativity. Binding analyses, aided by novel activity modulating nanobodies, suggest that sulfotransferase domain substrate anchoring initiates the NDST1 catalytic cycle, providing a plausible mechanism for cooperativity despite spatial domain separation. Our data shed light on key determinants of NDST1 activity, and describe tools to probe NDST1 functionin vitroandin vivo.
Hsa_circ_0005397 could promote hepatocellular carcinoma progression and metastasis through EIF4A3
Authors: Yuan Liu-Xia , Luo Mei , Liu Ruo-Yu , Wang Hui-Xuan , Ju Lin-Ling , Wang Feng , Cao Li-Ya , Wang Zhong-Cheng , Chen Lin 
Published: September 2023

AbstractPurposeThe purpose was to explore the expression and potential mechanism of hsa_circ_0005397 in hepatocellular carcinoma metabolism.MethodsThe quantitative real-time PCR (qPCR) was used to measure the expression of hsa_circ_0005397 and EIF4A3. The specificity of primers was confirmed by agarose gel electrophoresis. The ROC curve was draw to analysis clinical value. The actinomycin D assay and Nuclear and Cytoplasmic Extraction assay were utilized to evaluate the characteristic of hsa_circ_0005397. The CCK-8 and colony formation assays were performed to detect cell proliferation. The flow cytometry analysis was used to detect the cycle distribution. The transwell assays and Xenograft tumor model were conducted to explore cell metabolism. The RNA-binding proteins of hsa_circ_0005397 in HCC were explored in bioinformatics websites. The relationship between hsa_circ_0005397 and EIF4A3 was verified by RIP assays and rescue experiments.ResultsHsa_circ_0005397 and EIF4A3 were overexpressed in HCC. Through ROC analysis, hsa_circ_0005397 shown a big role in diagnosis and prognosis. Hsa_circ_0005397 was stable and almost distributed in the cytoplasm. The upregulation of hsa_circ_0005397 generally resulted in stronger proliferative ability, clonality, metastatic potency of HCC cells, while downregulation of hsa_circ_0005397 yielded opposite results. Tumor volume and size were notably reduced while downregulation of hsa_circ_0005397, showing significant difference in tumor growth. EIF4A3 was the RNA-binding protein of hsa_circ_0005397, the expression of hsa_circ_0005397 decreased equally when depletion of EIF4A3.Knockdown of EIF4A3 could reverse the function on HCC progression.ConclusionsHsa_circ_0005397 could promote the progression of hepatocellular carcinoma through EIF4A3. These research findings may present a novel clinical value for HCC.
Altered DNA methylation underlies monocyte dysregulation and innate exhaustion memory in sepsis
Authors: Caldwell Blake A. , Wu Yajun , Wang Jing , Li Liwu 
Published: September 2023

ABSTRACTInnate immune memory is the process by which pathogen exposure elicits cell-intrinsic states to alter the strength of future immune challenges. Such altered memory states drive monocyte dysregulation during sepsis, promoting pathogenic behavior characterized by pro-inflammatory, immunosuppressive gene expression in concert with emergency hematopoiesis. Epigenetic changes, notably in the form of histone modifications, have been shown to underlie innate immune memory, but the contribution of DNA methylation to this process remains poorly understood. Using anex vivosepsis model, we discovered broad changes in DNA methylation throughout the genome of exhausted monocytes, including at several genes previously implicated as major drivers of immune dysregulation during sepsis and Covid-19 infection (e.g.Plac8). Methylome alterations are driven in part by Wnt signaling inhibition in exhausted monocytes, and can be reversed through treatment with DNA methyltransferase inhibitors, Wnt agonists, or immune training molecules. Importantly, these changes are recapitulated in septic mice following cecal slurry injection, resulting in stable changes at critical immune genes that support the involvement of DNA methylation in acute and long-term monocyte dysregulation during sepsis.
DESCRIPTION OF THE METABOLIC SYNDROME AND ITS INDIVIDUALIZED RISK IN A LATIN AMERICAN COHORT OF GERIATRIC PATIENTS WITH HYPOTHYROIDISM
Authors: Dulcey Sarmiento Luis Andres , Theran Leon Juan Sebastián , Gomez Jaime , Parales Strauch Rafael Guillermo , Caltagirone Raimondo , Blanco Pimiento Edgar Camilo , Ciliberti Artavia María Paula , Martinez Juan Camilo , Peña Valentina Cabrera , Amaya Maria Camila , Vargas Jorge Luis , Lizcano Angie , Quintero Aldahir , Mayorca Juan Camilo , Hernandez Carlos , Cala Maria Alejandra 
Published: September 2023

AbstractIntroductionIt is still discussed whether hypothyroidism as an independent risk factor for cardiovascular events. Our objective was to evaluate the association between hypothyroidism and the risks of cardiovascular events and mortality through 3 stratification systems.MethodsA retrospective study was carried out by reviewing medical records in the period of January 2015 - December 2017 in a South American hospital. Patients had fasting total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and plasma glucose were included. Quantitative variables are presented as mean ± standard deviation or median (interquartile range) according to their distribution, and qualitative variables as percentages. Student’s test was performed to assess the differences between two variables. all statistical analyzes of the database results were performed with (SPSS for Windows, v.20.1; Chicago, IL).ResultsThe present study has demonstrated metabolic syndrome criteria present in patients diagnosed with hypothyroidism in a high proportion. The male gender was 32% compared to the female 68%. The Framingham equation classified a higher percentage of women patients with hypothyroidism as low cardiovascular risk compared to the PROCAM and SCORE equations. Item was found that there was a greater cardiovascular risk in those patients with still uncontrolled hypothyroidism profile, showing a statistical correlation of this alteration for the 3 stratification systems used.ConclusionsHypothyroidism is a risk factor for cardiovascular disease. Uncontrolled hypothyroidism in the present study is associated with greater adverse outcomes in the medium and long term, the present study warns about the need to better characterize this patient cohorts.
Observational Study of Repeat Immunoadsorption (RIA) in Post-COVID ME/CFS Patients with Elevated ß2-Adrenergic Receptor Autoantibodies – an Interim Report
Authors: Stein Elisa , Heindrich Cornelia , Wittke Kirsten , Kedor Claudia , Kim Laura , Freitag Helma , Krueger Anne , Toelle Markus , Scheibenbogen Carmen 
Published: September 2023

AbstractThere is increasing evidence for an autoimmune aetiology in post-infectious Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). SARS-CoV-2 has now become the main trigger for ME/CFS. We have already conducted two small proof-of-concept studies of IgG depletion by immunoadsorption (IA) in post-infectious ME/CFS, which showed efficacy in most patients. This observational study aims to evaluate the efficacy of IA in patients with post-COVID-19 ME/CFS. The primary objective is to assess the improvement in functional ability. Due to the urgency of finding therapies for post-Covid-Syndrome (PCS), we report here the interim results of the first ten patients with seven responders defined by an increase of between 10 and 35 points in the Short-Form 36 Physical Function (SF36-PF) at week four after IA. The results of this observational study will provide the basis for patient selection for a randomised controlled trial (RTC) including sham apheresis and for a RTC combining IA with B-cell depletion therapy.
Alcohol consumption and heavy episodic drinking within different types of drinking occasion in Great Britain: An event-level latent class analysis
Authors: Holmes John , Sasso Alessandro , Alava Mónica Hernández , Neves Rita Borges , Stevely Abigail K , Warde Alan , Meier Petra S 
Published: September 2023

ABSTRACTAimsTo update a previous typology of British alcohol drinking occasions using a more recent and expanded dataset and revised modelling procedure. To estimate the average consumption level, prevalence of heavy drinking, and distribution of total alcohol consumption and heavy drinking within and across occasion types.DesignCross-sectional latent class analysis of event-level diary data.SettingGreat Britain, 2019.Cases43,089 drinking occasions reported by 17,821 adult drinkers.MeasurementsThe latent class indicators are characteristics of off-trade only (e.g. home), on-trade only (e.g. bar) and mixed trade (e.g. home and bar) drinking occasions. These describe companions, venue(s) and location, purpose, motivation, accompanying activities, timings, weekday, consumption volume in units (1 UK unit = 8g ethanol) and predominant beverage consumed.FindingsThree latent class models identified four off-trade only occasion types (i.e. latent classes), eight on-trade only occasion types and three mixed-trade occasion types. Mean consumption per occasion varied between 4.4 units inFamily mealsto 17.7 units inBig nights out with pre-loading. Mean consumption exceeded ten units in all mixed-trade occasion types and inOff-trade get togethers, Big nights outandMale friends at the pub. Three off-trade occasion types accounted for 50.8% of all alcohol consumed and 51.8% of heavy drinking occasions:Quiet drink at home alone, Evening at home with partnerandOff-trade get togethers. For thirteen out of fifteen occasion types, more than 25% of occasions involved heavy drinking. Conversely, 41.7% ofBig nights outand 16.4% ofBig nights out with preloadingwere not heavy drinking occasions.ConclusionsAlcohol consumption varies substantially across and within fifteen types of drinking occasion in Great Britain. Heavy drinking is common in most occasion types. However, moderate drinking is also common in types often characterised as heavy drinking practices. Mixed-trade drinking occasions are particularly likely to involve heavy drinking.
The impact of climate change and natural climate variability on the global distribution ofAedes aegypti
Authors: Kaye AR , Obolski U , Sun L , Hurrell JW , Tildesley MJ , Thompson RN 
Published: September 2023

AbstractAedes aegyptispread pathogens affecting humans, including the dengue, Zika and yellow fever viruses. Anthropogenic climate change is altering the spatial distribution ofAe. aegyptiand therefore the locations at risk of vector-borne disease. In addition to climate change, natural climate variability, resulting from internal atmospheric processes and interactions between climate system components (e.g. atmosphere-land, atmosphere-ocean) determines climate outcomes. However, the combined effects of climate change and natural climate variability on futureAe. aegyptispread have not been assessed fully. We developed an ecological model in whichAe. aegyptipopulation dynamics depend on climate variables (temperature and rainfall). We used 100 projections from the Community Earth System Model, a comprehensive climate model that simulates natural climate variability as well as anthropogenic climate change, in combination with our ecological model to generate a range of equally plausible scenarios describing the global distribution of suitable conditions forAe. aegyptiup to 2100. Like other studies, we project the poleward expansion ofAe. aegyptiunder climate change. However, the extent of spread varies considerably between projections, each under the same Shared Socioeconomic Pathway scenario (SSP3-7.0). For example, by 2100, climatic conditions in London may be suitable forAe. aegyptifor between one and five months in the year, depending on natural climate variability. Our results demonstrate that natural climate variability yields different possible futureAe. aegyptispread scenarios. This affects vector-borne disease risks, including the potential for some regions to experience outbreaks earlier than expected under climate change alone.