bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dietary choline intake is necessary to prevent systems-wide organ pathology and reduce Alzheimer’s disease hallmarks
Authors: Dave Nikhil , Judd Jessica M. , Decker Annika , Winslow Wendy , Sarette Patrick , Espinosa Oscar V. , Sandler Jessica , Bilal Alina , Tallino Savannah , McDonough Ian , Winstone Joanna K , Blackwood Erik A. , Glembotski Christopher , Karr Timothy , Velazquez Ramon 
Published: August 2022

AbstractEvidence suggests that environmental factors may contribute to Alzheimer’s disease (AD). The B-like vitamin choline plays key roles in body- and brain-related functions. Choline produced endogenously by the phosphatidylethanolamine N-methyltransferase (PEMT) enzyme in the liver is not sufficient for adequate physiological functions, necessitating daily dietary intake. ∼90% of Americans don’t reach the recommended daily choline intake. Thus, it’s imperative to determine whether dietary deficiency increases disease outcomes. Here, we placed 3xTg-AD, a model of AD, and non-transgenic (NonTg) control mice on either a sufficient choline (ChN) or choline deficient (Ch-; choline deficiency) diet from 3 to 12 (early to late adulthood) months of age. Ch- reduced plasma choline and acetylcholine levels, increased weight, and impaired both glucose metabolism and motor function in NonTg, with 3xTg-AD mice showing greater deficits. Tissue analyses showed cardiac and liver pathology, and elevated Amyloid-β and phosphorylated tau in the hippocampus and cortex of 3xTg-AD Ch- mice. Unbiased proteomic analyses revealed Ch- altered hippocampal networks associated with microtubule function and postsynaptic membrane regulation. In plasma, Ch- altered protein networks associated with insulin metabolism, mitochondrial function, and inflammation. Collectively, our data highlight that dietary choline intake is necessary to prevent systems-wide organ pathology and reduce AD hallmark pathologies.
Inline SAXS-coupled chromatography under extreme hydrostatic pressure
Authors: Miller Robert , Cummings Cody , Huang Qingqiu , Ando Nozomi , Gillilan Richard E. 
Published: August 2022

AbstractAs continuing discoveries highlight the surprising abundance and resilience of deep ocean and subsurface microbial life, the effects of extreme hydrostatic pressure on biological structure and function have attracted renewed interest. Biological small angle X-ray scattering (BioSAXS) is a widely used method of obtaining structural information from biomolecules in solution under a wide range of solution conditions. Due to its ability to reduce radiation damage, remove aggregates, and separate monodisperse components from complex mixtures, size-exclusion chromatography coupled SAXS (SEC-SAXS) is now the dominant form of BioSAXS at many synchrotron beamlines. While BioSAXS can currently be performed with some difficulty under pressure with non-flowing samples, it has not been clear how, or even if, continuously flowing SEC-SAXS, with its fragile media-packed columns, might work in an extreme high-pressure environment. Here we show, for the first time, that reproducible chromatographic separations coupled directly to high-pressure BioSAXS can be achieved at pressures up to at least 100 MPa and that pressure-induced changes in folding and oligomeric state and other properties can be observed. The apparatus described here functions at a range of temperatures (0° C - 50° C), expanding opportunities for understanding biomolecular rules of life in deep ocean and subsurface environments.
Insplico: Effective computational tool for studying intron splicing order genome-wide with short and long RNA-seq reads
Authors: Gohr Andre , Torres-Méndez Antonio , Bonnal Sophie , Irimia Manuel 
Published: August 2022

ABSTRACTAlthough splicing occurs largely co-transcriptionally, the order by which introns are removed does not necessarily follow the order in which they are transcribed. Whereas several genomic features are known to influence whether or not an intron is spliced before its downstream neighbour, multiple questions related to intron splicing order (ISO) remain unanswered. Here, we present Insplico, the first standalone tool to quantify ISO that works with both short and long read sequencing technologies. We first demonstrate its applicability and effectiveness recapitulating previously reported patterns, while unveiling overlooked biases associated with long read sequencing. We next show that ISO around individual exons is remarkably constant across cell and tissue types and even upon major spliceosomal disruption, and it is evolutionarily conserved between human and mouse brains. We also establish a set of universal features associated with ISO patterns across various animal and plant species. Finally, we used Insplico to investigate ISO in the context of tissue-specific exons, particularly focusing on SRRM4-dependent microexons. We found that the majority of such microexons have non-canonical ISO, in which the downstream intron is spliced first, and we revealed two potential modes of SRRM4 regulation of microexons related to their ISO and various splicing-related features. Insplico is available on gitlab.com/aghr/insplico.
Extending Janus lectins architecture: characterization and application to protocells
Authors: Notova Simona , Siukstaite Lina , Rosato Francesca , Vena Federica , Audfray Aymeric , Bovin Nicolai , Landemarre Ludovic , Römer Winfried , Imberty Anne 
Published: August 2022

AbstractSynthetic biology is a rapidly growing field with applications in biotechnology and biomedicine. Through various approaches, remarkable achievements, such as cell and tissue engineering, have been already accomplished. In synthetic glycobiology, the engineering of glycan binding proteins is being developed for producing tools with precise topology and specificity. We developed the concept of chimeric lectins, i.e., Janus lectin, with increased valency, and additional specificity. The novel engineered lectin, assembled as a fusion protein between the β-propeller domain from Ralstonia solanacearum and the β-trefoil domain from fungus Marasmius oreades, is specific for fucose and α-galactose and its unique protein architecture allows to bind these ligands simultaneously. The protein activity was tested with glycosylated giant unilamellar vesicles, resulting in the formation of proto-tissue-like structures through cross-linking of such protocells. The synthetic protein binds to H1299 lung epithelial cancer cells by its two domains. The biophysical properties of this new construct were compared with the two already existing Janus lectins, RSL-CBM40 and RSL-CBM77Rf. Denaturation profiles of the proteins indicate that the fold of each has a significant role in protein stability and should be considered during protein engineering.
Microsporidian obligate intracellular parasites subvert autophagy of infected mammalian host cells to promote their own growth
Authors: Panek Johan , Sendra Kacper , Glenwright Helen , Kosta Gregor , Korolchuk Viktor I. , Hirt Robert P. 
Published: August 2022

AbstractIntracellular pathogens such as Microsporidia can interact with host proteostasis pathways such as autophagy. Previous work done inCaenorhabditis elegansdemonstrated involvement of autophagy in controlling Microsporidian proliferation through ubiquitin labelling of the parasite and subsequent degradation by autolysomes. However, it remains unknown if such mechanisms also play the role in mammalian models. Here we used immunochemistry assays, super-resolution fluorescence microscopy, and modulation of the host’s autophagy flux through siRNA silencing and chemical agents to elucidate how Microsporidia interact with host mammalian cell autophagy flux. We show that despite targeting by early autophagy markers (ubiquitin and p62); the host cell was not able to complete autophagy-mediated removal ofEncephalitozoon cuniculi. Furthermore, instead of helping to control Microsporidia proliferation, the induction of autophagy dramatically increased proliferation of two Microsporidian species in two different mammalian cell models. Finally, we showed that the reduction of the autophagy flux using siRNA treatment or gut microbiota-derived metabolites known to be important for the intestinal epithelium homeostasis was able to reduce the parasite proliferation. Taken together, our results indicate that Microsporidia infecting mammalian cells not only developed strategies to evade the host autophagy but also evolved way to divert the autophagy flux to promote their own growth.
Environmentalism as an independent dimension of political preferences
Authors: KENNY JOHN , LANGSÆTHER PETER EGGE 
Published: August 2022

AbstractEnvironmental issues are an important aspect of party competition and voters’ political preferences. Yet political behaviour research often considers environmental attitudes as a component of a broader ‘second‐dimension’ and either subsumes it into this or omits it. Using data from the fifth wave of the European Values Study, we demonstrate through factor analysis that environmentalism loads as a separate dimension across Western Europe, that environmentalism has somewhat different social predictors and that it has important associations with party preference that differ from those of other second dimension issues. Our findings have crucial implications. Firstly, not accounting for environmentalism in studies of political behaviour misses an important part of the picture. Secondly, subsuming environmentalism into a broader ‘cultural’ dimension may lead to incomplete conclusions about both social predictors and the electoral consequences of political attitudes and values. Thus, allowing for a separate environmental dimension opens up novel perspectives on political representation in Western democracies.
Dedicated nursing care pathway improved management of opioid‐poisoned patients in the emergency department: A before–after observational study
Authors: Isoardi Katherine , Learmont Benjamin , Horan Benjamin , Isbister Geoffrey 
Published: August 2022

AbstractObjectiveOpioid overdose is increasing and accounts for two‐thirds of poisoning deaths. Opioid induced respiratory depression is life‐threatening and can be under‐recognised even in the hospital setting. We aimed to evaluate the effect of a care pathway on the management of opioid‐poisoned patients.MethodsThis is a before–after observational study following the introduction of a nursing care pathway for opioid‐poisoned patients presenting to ED. Medical records were retrospectively reviewed pre (6‐month period 1 year prior) and post (9‐month period following) the introduction of the pathway. The primary outcome was the proportion of documented episodes of respiratory depression (respiratory rate <10 or oxygen saturation <93% on room air) receiving naloxone. Secondary outcomes were time to naloxone, number of documented observations (first 4 h) and length of stay.ResultsThere were 111 patients included in the study, 61 pre‐intervention and 50 post‐intervention (35 followed the pathway). A significantly larger proportion of patients received naloxone for respiratory depression when the pathway was used (134/200 [67%] vs 34/118 [29%], difference 38%, 95% CI 28–48%). The median time to naloxone was similar (pathway 28.5 min vs no pathway 35 min, difference −6.5 min, 95% CI −19 to 12 min). Documentation increased when the pathway was used (12.0 observations/presentation vs 7.5 observations/presentation, difference 4.5 observations/patient, 95% CI 2.1–7.0 observations/patient). Length of stay was similar (pathway 16.7 h vs no pathway 15.3 h, difference 1.4 h, 95% CI −2.4 to 5.9 h).ConclusionsFollowing the introduction of a dedicated opioid poisoning nursing care pathway, naloxone delivery and observation documentation increased. A care pathway may improve ED management of opioid poisoning.
Association of serum uric acid with all‐cause and cardiovascular mortality among adults with nonalcoholic fatty liver disease
Authors: Yang Sisi , Ye Ziliang , Liu Mengyi , Zhang Yanjun , Wu Qimeng , Zhou Chun , Zhang Zhuxian , He Panpan , Zhang Yuanyuan , Li Huan , Liu Chengzhang , Qin Xianhui 
Published: August 2022

AbstractAimThe association between serum uric acid (SUA) and mortality from cardiovascular diseases (CVDs) in nonalcoholic fatty liver disease (NAFLD) participants remains uncertain. We aim to investigate the relations of SUA with the risk of CVD mortality among adults with and without NAFLD.MethodsUsing data from National Health and Nutrition Examination Survey (NHANES) 1999–2014, a total of 17,858 participants were recruited. Of these, 5767 had a US Fatty Liver Index (USFLI) ≥30 and were classified as having NAFLD. Death information was obtained from the National Death Index until 2015.ResultsDuring a mean follow‐up of 8.3 years, 427 participants died from CVD. Overall, there was a positive association between SUA and CVD mortality among participants with NAFLD (per SD μmol/L increment, adjusted hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.16–1.68). Accordingly, among those with NAFLD, when SUA was assessed as quartiles, compared with those in the first quartile, a significantly higher risk of CVD mortality was found in participants in the fourth quartile (adjusted HR, 2.69; 95% CI, 1.51–4.80). However, there was no significant association between SUA and CVD mortality among participants without NAFLD (per SD μmol/L increment, adjusted HR, 1.01; 95% CI, 0.83–1.22). Similar trends were found for all‐cause mortality. Similar results were also found when using FLI ≥ 60 to define NAFLD.ConclusionsIn a large and nationally representative sample of US adults, a higher SUA was significantly associated with a higher risk of CVD mortality among participants with NAFLD, but not in those without NAFLD.
Long‐term variability in spawning stock age structure influences climate–recruitment link for Barents Sea cod
Authors: Ottersen Geir , Holt Rebecca E. 
Published: August 2022

AbstractFish populations may spawn a vast number of offspring, while only a small and highly variable fraction of a new cohort survives long enough to enter into the fisheries as recruits. It is intuitive that the size and state of the spawning stock, the adult part of the fish population, is important for recruitment. Additionally, environmental conditions can greatly influence survival through vulnerable early life stages until recruitment. To understand what regulates recruitment, an essential part of fish population dynamics, it is thus necessary to explain the impact of fluctuations in both spawning stock and environment, including interactions. Here, we examine if the connection between the environment and recruitment is affected by the state of the spawning stock, including biomass, mean age and age diversity. Specifically, we re‐evaluate the hypothesis stating that recruitment from a spawning stock dominated by young fish and few age classes is more vulnerable to environmental fluctuations. We expand upon earlier work on the Barents Sea stock of Atlantic cod, now with data series extended in time both backwards and forwards to cover the period 1922–2019. While our findings are correlative and cannot prove a specific cause and effect mechanism, they support earlier work and strengthen the evidence for the hypothesis above. Furthermore, this study supports that advice to fisheries management should include considerations of environmental status.
Warming does not delay the start of autumnal leaf coloration but slows its progress rate
Authors: Jiang Nan , Shen Miaogen , Ciais Philippe , Campioli Matteo , Peñuelas Josep , Körner Christian , Cao Ruyin , Piao Shilong , Liu Licong , Wang Shiping , Liang Eryuan , Delpierre Nicolas , Soudani Kamel , Rao Yuhan , Montagnani Leonardo , Hörtnagl Lukas , Paul‐Limoges Eugénie , Myneni Ranga , Wohlfahrt Georg , Fu Yongshuo , Šigut Ladislav , Varlagin Andrej , Chen Jin , Tang Yanhong , Zhao Wenwu 
Published: August 2022

AbstractAimInitiation of autumnal leaf senescence is crucial for plant overwintering and ecosystem dynamics. Previous studies have focused on the advanced stages of autumnal leaf senescence and reported that climatic warming delayed senescence, despite the fundamental differences among the stages of senescence. However, the timing of onset of leaf coloration (DLCO), the earliest visual sign of senescence, has rarely been studied. Here, we assessed the response of DLCO to temperature.Location30–75° N in the Northern Hemisphere.Time period2000–2018.Major taxa studiedDeciduous vegetation.MethodsWe retrieved DLCO from high‐temporal‐resolution satellite data, which were then validated by PhenoCam observations. We investigated the temporal changes in DLCO and the relationship between DLCO and temperature by using satellite and ground observations.ResultsDLCO was not significantly (p > .05) delayed between 2000 and 2018 in 94% of the area. DLCO was positively (p < .05) correlated with pre‐DLCO mean daily minimum temperature (Tmin) in only 9% of the area, whereas the end of leaf coloration (DLCE) was positively correlated with pre‐DLCE mean Tmin over a larger area (34%). Further analyses showed that warming slowed the progress of leaf coloration. Interestingly, DLCO was less responsive to pre‐DLCO mean Tmin in areas where daylength was longer across the Northern Hemisphere, particularly for woody vegetation.Main conclusionsThe rate of progress of coloration is more sensitive to temperature than its start date, resulting in an extension of the duration of leaf senescence under warming. The dependence of DLCO response to temperature on daylength indicates stronger photoperiodic control on initiation of leaf senescence in areas with longer daylength (i.e., shorter nights), possibly because plants respond to the length of uninterrupted darkness rather than daylength. This study indicates that the onset of leaf coloration was not responsive to climate warming and provides observational evidence of photoperiod control of autumnal leaf senescence at biome and continental scales.
Outcomes reporting in systematic reviews on non‐surgical root canal treatment: A scoping review for the development of a core outcome set
Authors: Kirkevang Lise‐Lotte , El Karim Ikhlas A. , Duncan Henry Fergus , Nagendrababu Venkateshbabu , Kruse Casper 
Published: August 2022

AbstractBackgroundStudies related to non‐surgical root canal treatment are amongst the most frequently performed clinical studies in endodontics. However, heterogeneity in reporting outcomes and lack of standardization is a significant challenge to evidence synthesis and guideline development.ObjectivesThe aims of the present scoping review were to (a) identify outcomes reported in systematic reviews evaluating non‐surgical root canal treatment; (b) identify how and when the reported outcomes were measured; (c) assess possible selective reporting bias in the included studies. The information obtained in this study should inform the development of a core outcome set (COS) for non‐surgical root canal treatment.MethodologyStructured literature searches were performed to identify systematic reviews on non‐surgical root canal treatments published in English between January 1990 and December 2020. Two reviewers undertook study selection and data extraction. Outcomes were categorized according to a healthcare taxonomy into five core areas (survival, clinical/physiological changes, life impact, resource use, and adverse events). The outcome measurement tools and length of follow‐up were recorded.ResultsSeventy‐five systematic reviews were included, of which 40 included meta‐analyses. Most reviews reported on physiological and clinical outcomes, primarily pain and/or radiographic assessment of periapical status, and a variety of measurement tools and scales were used. Few reviews focused on tooth survival, life impact, resources, and adverse events. The heterogeneity amongst the reviews was large on all parameters. Less than 40% of the reviews assessed the risk of selective reporting.DiscussionOverall aims of the included reviews were highly heterogenic; thus, outcomes and how they were measured also varied considerably. Patient‐centred outcomes and the use of resources were rarely reported on.ConclusionsMost studies reported on physiological and clinical outcomes, in particular pain and/or radiographic healing. Measurement tools, scales, thresholds, and follow‐up periods varied greatly within each outcome, making comparison across studies complicated. Less than 40% of the reviews assessed risk of selective reporting; thus, selective bias could not be ruled out. The presented information on reported outcomes, measurement tools and scales, and length of follow‐up may guide the planning of future research and inform the development of a COS for non‐surgical root canal treatment.
How toxic is an old friend? A review of the safety of hydroxychloroquine in clinical practice
Authors: Fairley Jessica L. , Nikpour Mandana , Mack Heather G. , Brosnan Maria , Saracino Amanda M. , Pellegrini Marc , Wicks Ian P. 
Published: August 2022

AbstractHydroxychloroquine (HCQ) and its close relative chloroquine (CQ) were initially used as antimalarial agents but are now widely prescribed in rheumatology, dermatology and immunology for the management of autoimmune diseases. HCQ is considered to have a better long‐term safety profile than CQ and is therefore more commonly used. HCQ has a key role in the treatment of connective tissue diseases including systemic lupus erythematosus (SLE), where it provides beneficial immunomodulation without clinically significant immunosuppression. HCQ can also assist in managing inflammatory arthritis, including rheumatoid arthritis (RA). Debate around toxicity of HCQ in COVID‐19 has challenged those who regularly prescribe HCQ to discuss its potential toxicities. Accordingly, we have reviewed the adverse effect profile of HCQ to provide guidance about this therapeutic agent in clinical practice.
Incidence of chronic renal injury in patients undergoing autologous stem cell transplant therapy
Authors: Dawson Chloe , Palfreyman Emma , Parisotto Robin , D'Rozario James 
Published: August 2022

AbstractBackgroundHaemopoietic stem cell transplant (HSCT) is a well‐established treatment option for many haematologic immunologic and oncologic diseases, allowing the safe administration of high‐dose chemotherapy. Increased risk of acute renal injury is associated with HSCT; however, the risk of chronic kidney injury in autologous HSCT remains unclear.AimsThis cohort study investigates the incidence of chronic renal injury and its predisposing factors in a single‐centre population of 139 patients who underwent autologous HSCT.MethodsEstimated glomerular filtration rate (eGFR) was measured at baseline and at 3, 6, 12 and 24 months following autologous stem cell reinfusion and used as a marker of renal dysfunction.ResultsA significant reduction in mean eGFR of patients was observed from baseline (80.62 ± 2.97 mL/min) to 24 months (71.54 ± 4.14 mL/min), independent of primary diagnosis (P = 0.0019). At baseline, 12% of the cohort had stage 3 or worse chronic renal injury and this increased to 38% by 24 months. By univariate analysis, age at baseline greater than the mean of 58 years and the occurrence of acute kidney injury during the peritransplant period emerged as predictive factors for the development of chronic kidney disease at 24 months.ConclusionsThe current results indicate there is an increased incidence of chronic renal injury in patients who have undergone autologous peripheral blood haemopoietic stem cell transplantation therapy and this injury is potentiated by the autologous stem cell transplant procedure.