bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design and approval of the nutritional warnings’ policy in Peru: Milestones, key stakeholders, and policy drivers for its approval
Authors: Francisco Diez-Canseco , Cavero Victoria , Álvarez-Cano Juan , Saavedra-Garcia Lorena , Taillie Lindsey Smith , Dillman Carpentier Francesca , Miranda J. Jaime 
Published: September 2022

ABSTRACTBackgroundNutritional warnings are used as a public health strategy to prevent increases in obesity prevalence. Peru approved in 2013 and implemented in 2019 a Law requiring nutritional warnings on the marketing and packaging of processed foods high in sugar, sodium, saturated fat, and containing transfat. The complexity behind the implementation of this set of policies over six years provide unique learnings, essential to inform the obesity prevention context, especially when facing strong opposition from powerful stakeholders such as the food industry.AimsDescribe milestones and key stakeholders’ roles and stances during the nutritional warnings policy design in Peru; and identify and analyze the main drivers of policy change that explain its approval.MethodologyIn 2021, interviews were conducted with 25 key informants, advocates and opponents of the policy, closely involved in its design. Interviews were analyzed using the Kaleidoscope Model as a theoretical framework. Relevant policy documents and news were also analyzed.ResultsMilestones for this policy were the approval of the Law, Regulation, and Manual. Policy supporters were mainly from the Congress, civil society organizations, and Health Ministers; whereas opponents came from other parties in the Congress, ministries linked to the economic sector, the food industry, and media. Across the years, warning’s evolved from a single text, to traffic lights, to the approved black octagons. Main challenges included the strong opposition of powerful stakeholders; the lack of agreement for defining the appropriate evidence for nutritional warning parameters and design; and the political instability of the country. Based on the Kaleidoscope Model, the policy successfully targeted a relevant problem (unhealthy eating decisions) and had powerful advocates who effectively used focusing events to reposition the warnings in the policy agenda across the years. Negotiations weakened the policy but led to its approval. Importantly, government veto players were mostly in favor of the policy, which enabled its final approval despite the strong opposition.ConclusionsDespite the strong opposition faced and technical and political difficulties to define the best parameters and warnings’ design, Peru’s nutritional warnings policy was approved. Lessons learned are essential to inform similar and related prevention policies in Peru and elsewhere.
Heparin Does Not Regulate Circulating Human PCSK9
Authors: Xia Vivian Q. , Ong Chui Mei , Zier Lucas S. , MacGregor John S. , Wu Alan H. B. , Chorba John S. 
Published: September 2022

AbstractBackgroundPCSK9 chaperones the hepatic low-density lipoprotein receptor (LDLR) for lysosomal degradation, elevating serum LDL cholesterol and increasing the risk of atherosclerotic heart disease. Though the major effect on the hepatic LDLR comes from secreted PCSK9, the details of PCSK9 reuptake into the hepatocyte remain unclear. In both tissue culture and animal models, heparan sulfate proteoglycans (HSPGs) on hepatocytes act as co-receptors to promote PCSK9 reuptake. We hypothesized that if this PCSK9:HSPG interaction is important in humans, disrupting the interaction with unfractionated heparin (UFH) would acutely displace PCSK9 from the liver and increase plasma PCSK9.MethodsWe obtained remnant plasma samples from 160 subjects undergoing cardiac catheterization before and after administration of intravenous UFH. PCSK9 levels were determined using a commercial ELISA.ResultsMedian plasma PCSK9 concentrations were 113 ng/ml prior to UFH and 119 ng/ml afterwards. This difference was not significantly different (p = 0.83, 95% CI of difference: −6.23 to 6.31 ng/ml). Tests for equivalence provided 95% confidence that UFH administration would not raise PCSK9 levels by more than 4.7% of the baseline value. No predefined subgroups exhibited an effect of UFH on circulating PCSK9.ConclusionAdministration of UFH does not result in a clinically meaningful effect on circulating PCSK9 in humans. These results suggest that disruption of the PCSK9:HSPG interaction does not affect PCSK9 reuptake into the liver. Further, they cast doubt on the clinical utility of disrupting the PCSK9:HSPG interaction as a therapeutic strategy for PCSK9 inhibition.Graphical AbstractClinical PerspectiveWhat is new?Prior tissue culture and animal data suggest that PCSK9 interacts with hepatic heparan sulfate proteoglycans to enter the liver and raise cholesterol levelsWe found no evidence that heparin, a competitive inhibitor of heparan sulfate proteoglycans, acutely affects PCSK9 in humansWhat are the clinical implications?Heparin is unlikely to be successfully repurposed as a PCSK9 inhibitor
Appetitive mapping of the human nucleus accumbens
Authors: Parker Jonathon J. , Rolle Cammie E. , Shivacharan Rajat S. , Barbosa Daniel A. N. , Feng Austin , Huang Yuhao , Kakusa Bina W. , Prieto Tom , Jaffe Richard A. , Williams Nolan R. , Halpern Casey H. 
Published: September 2022

ABSTRACTThere is strong evidence for the putative role of the nucleus accumbens (NAc) in appetitive motivation. A first-in-human feasibility trial of responsive deep brain stimulation (rDBS) for loss of control eating provided a rare opportunity to examine the physiologic and structural underpinnings of NAc function in a human participant with dysregulated appetition. Patient-specific probabilistic tractography was supplemented by intraoperative microelectrode recordings and stimulation testing to confirm appetitive circuit engagement. Personalized visual stimuli we used to provoke and map appetitive units within the NAc, prior to the surgical implantation of a rDBS system, which was safe, feasible, and well-tolerated. Ambulatory patient-triggered recordings provide ongoing electrophysiologic surveillance of NAc activity time-locked to eating behavior in the real-world. This technique described provides a proof-of-concept for utilizing simultaneous intracranial activity and real-time appetitive responses to guide implantation of a rDBS system to treat loss of control eating.
The impact of access to financial services on mitigating COVID-19 mortality globally
Authors: Watkins Todd A. , Nguyen Khue , Ali Hamza , Gummakonda Rishikesh , Pelman Jacques , Taracena Brianna 
Published: September 2022

ABSTRACTThe COVID-19 pandemic has disproportionately affected different social and demographic groups, deepening the negative health implications of social and economic inequalities and highlighting the importance of social determinants of health. Despite a deep literature on pandemic-related disparities, specifically regarding social determinants and health outcomes, the influence of the accessibility of financial services on health outcomes during COVID-19 remains largely unexplored. Modeling (pre-omicron) COVID-19 mortality across 142 nations, we assess the impact of national-level usage and access to formal financial services. Two financial access indexes constructed through principal component analysis capture (1) usage of and access to formal financial tools and (2) reliance on alternative and informal financial tools. On average, nations with higher pre-pandemic use of and access to formal financial services had substantially lower population mortality risk from COVID-19, controlling for key population health, demographic, and socioeconomic covariates. The scale of effect is similar in magnitude—but opposite in direction—to major risk factors identified in previous literature, such as lung cancer, hypertension, and income inequality. Findings suggest that financial services deserve greater attention both in the public health literature related to COVID-19 and more broadly in policy discussions about fostering better public health overall.
Chilean bee diversity: Contrasting patterns of species and phylogenetic turnover along a large-scale ecological gradient
Authors: Marshall Leon , Ascher John S. , Villagra Cristian , Beaugendre Amaury , Herrera Valentina , Henríquez-Piskulich Patricia , Vera Alejandro , Vereecken Nicolas J. 
Published: September 2022

AbstractChile’s isolation and varied climates have driven the evolution of a unique biodiversity with a high degree of endemism. The Mediterranean-type biome of Central Chile is one of 35 global biodiversity hotspots and has been highlighted as one of Chile’s most endangered areas. It is threatened by anthropogenic land use change impacting the integrity of local biomes and associated species. This area holds the most extensive collections of the country with high endemicity regarding native bee species. Characterising habitat requirements of bees is a pressing priority to safeguard them and the ecosystem services they provide.We investigated broad-scale patterns of bee diversity using newly accessible expert-validated datasets comprising digitized specimen records from both Chilean and US collections and novel, expert-validated type specimen data for the bees of Chile. We used a generalised dissimilarity modelling (GDM) approach to explore both compositional and phylogenetic β-diversity patterns across latitudinal, altitudinal, climate and habitat gradients in well-sampled bee assemblages in Central Chile. Using the GDM measures of increasing compositional and environmental dissimilarity we categorised and compared the most important drivers of these patterns and used them to classify ‘wild bee ecoregions’ (WBE) representing unique assemblages.Turnover of bee assemblages was explained primarily by latitudinal variation (proxy for climate) along Chile. However, temperature variations, precipitation and the presence of bare soil also significantly explained the observed patterns. In comparison, we observed less turnover in phylogenetic biodiversity corresponding to spatial gradients. We were able to develop sixde novoecoregions (WBE) all with distinct taxa, endemic lineages, and representative species. The WBE represent distinct spatial classifications but have similarities to existing biogeographical classifications, ecosystems and bioclimatic zones.This approach establishes the baseline needed to prioritise bee species conservation efforts across this global biodiversity hotspot. We discuss the novelty of this classification considering previous biogeographical characterisations and its relevance for assessing conservation priorities for bee conservation. We argue that Chile’s WBE show areas requiring funding for bee species exploration and description, distribution mapping and strengthening of conservation policies.
Suggesting disease associations for overlooked metabolites using literature from metabolic neighbours
Authors: Delmas M. , Filangi O. , Duperier C. , Paulhe N. , Vinson F. , Rodriguez-Mier P. , Giacomoni F. , Jourdan F. , Frainay C. 
Published: September 2022

AbstractIn human health research, metabolic signatures extracted from metabolomics data are a strong-added value for stratifying patients and identifying biomarkers. Nevertheless, one of the main challenges is to interpret and relate these lists of discriminant metabolites to pathological mechanisms. This task requires experts to combine their knowledge with information extracted from databases and the scientific literature.However, we show that a large fraction of metabolites are rarely or never mentioned in the literature. Consequently, these overlooked metabolites are often set aside and the interpretation of metabolic signatures is restricted to a subset of the significant metabolites. To suggest potential pathological phenotypes related to these understudied metabolites, we extend the ‘guilt by association’ principle to literature information by using a Bayesian framework. With this approach, we suggest more than 35,000 associations between 1,047 overlooked metabolites and 3,288 diseases (or disease families). All these newly inferred associations are freely available on the FORUM ftp server (See information at https://github.com/eMetaboHUB/Forum-LiteraturePropagation.).
TheAphelenchoidesgenomes reveal substantial horizontal gene transfers in the last common ancestor of free-living and major plant parasitic nematodes
Authors: Lai Cheng-Kuo , Lee Yi-Chien , Ke Huei-Mien , Lu Min R , Liu Wei-An , Lee Hsin-Han , Liu Yu-Ching , Yoshiga Toyoshi , Kikuchi Taisei , Chen Peichen J. , Tsai Isheng Jason 
Published: September 2022

AbstractAphelenchoides besseyiis a plant-parasitic nematode (PPN) in the Aphelenchoididae family capable of infecting more than 200 plant species.A. besseyiis also a species complex with strains exhibiting varying pathogenicity to plants. We present the genome and annotations of sixAphelenchoidesspecies, four of which belonged to theA. besseyispecies complex. MostAphelenchoidesgenomes have a size of 44.7-47.4 Mb and are amongst the smallest in clade IV, with the exception ofA. fujianensis, which has a size of 143.8 Mb and is the largest. Phylogenomic analysis successfully delimited the species complex intoA. oryzaeandA. pseudobesseyiand revealed a reduction of transposon elements in the last common ancestor ofAphelenchoides. Synteny analyses between reference genomes indicated that three chromosomes inA. besseyiwere derived from fission and fusion events. A systematic identification of horizontal gene transfer (HGT) genes across 27 representative nematodes allowed us to identify two major episodes of acquisition corresponding to the last common ancestor of clade IV or major PPNs, respectively. These genes were mostly lost and differentially retained between clades or strains. Most HGT events were acquired from bacteria, followed by fungi, and also from plants; plant HGT was especially prevalent inBursaphelenchus mucronatus. Our results comprehensively improve the understanding of horizontal gene transfer in nematodes.
Reduced coenzyme Q synthesis confers non-target site resistance to the herbicide thaxtomin A
Authors: Casey Chloe , Köcher Thomas , Champion Clément , Jandrasits Katharina , Mosiolek Magdalena , Bonnot Clémence , Dolan Liam 
Published: September 2022

ABSTRACTHerbicide resistance in weeds is a growing threat to global crop production. Non-target site resistance is problematic because a single resistance allele can confer tolerance to many herbicides (cross resistance), and it is often a polygenic trait so it can be difficult to identify the molecular mechanisms involved. Most characterized molecular mechanisms of non-target site resistance are caused by gain-of-function mutations in genes from a few key gene families – the mechanisms of resistance caused by loss-of-function mutations remain unclear. In this study, we first show that the mechanism of non-target site resistance to the herbicide thaxtomin A conferred by loss-of-function of the genePAM16is conserved inMarchantia polymorpha, validating its use as a model species with which to study non-target site resistance. To identify mechanisms of non-target site resistance caused by loss-of-function mutations, we generated 107UV-B mutagenizedM. polymorphaspores and screened for resistance to the herbicide thaxtomin A. We isolated 13 thaxtomin A-resistant mutants and found that 3 mutants carried candidate resistance-conferring SNPs in the MpRTN4IP1Lgene. Mprtn4ip1lmutants are defective in coenzyme Q biosynthesis and accumulate higher levels of reactive oxygen species (ROS) than wild-type plants. Mutants are also defective in thaxtomin A metabolism, consistent with the hypothesis that loss of MpRTN4IP1Lfunction confers non-target site resistance. We conclude that loss of MpRTN4IP1Lfunction is a novel mechanism of non-target site herbicide resistance, and propose that other mutations which increase ROS levels or decrease thaxtomin A metabolism could confer thaxtomin A resistance in the field.AUTHOR SUMMARYModern agriculture relies on herbicides to control weed populations. However, herbicide resistance in weeds threatens the efficacy of herbicides and global crop production, similar to how antibiotic resistance poses a global health threat. Understanding the molecular mechanisms behind herbicide resistance helps to prevent resistance from evolving and to better manage herbicide resistant weeds in the field. Here, we use a forward genetic approach in the model speciesMarchantia polymorphato discover novel mechanisms of herbicide resistance. We report the discovery of a novel mechanism of herbicide resistance caused by loss-of-function mutations in the MpRTN4IP1Lgene. We find that Mprtn4ip1lmutants are resistant to the herbicides thaxtomin A and isoxaben, accumulate higher levels of reactive oxygen species than wild type plants, and are defective in thaxtomin A metabolism. We predict that loss-of-function mutations or treatments that increase reactive oxygen species production could contribute to thaxtomin A tolerance.
Major Histocompatibility Complex class I heavy chains localize in both cytoplasmic and nuclear compartment
Authors: Gómez-Herranz Maria , Dziadosz Alicja , Mikac Sara , Rychłowski Michał , Fahraeus Robin , Marek-Trzonkowska Natalia , Chruściel Elżbieta , Urban-Wójciuk Zuzanna , Papak Ines , Arcimowicz Łukasz , Marjanski Tomasz , Rzyman Witold , Sznarkowska Alicja 
Published: September 2022

AbstractThe Major Histocompatibility Complex class I (MHC-I) molecules present antigenic peptides (AP) to CD8+T cells for self versus non-self recognition. Loading of AP on MHC-I takes place in the endoplasmic reticulum (ER), upon shuttling of cytoplasmic AP substrates to the ER. Understanding of this process has been influenced by the view that MHC-I antigens are produced from the proteasomal degradation of cellular proteins. Recent observations on the intronic and untranslated region-derived peptides as well as on the non-AUG translation products presented on the MHC-I open the possibility that antigenic peptides can derive from pre-spliced mRNAs translated in the nuclear compartment. In this brief report, we show that a fraction of human MHC-I molecules (human leukocyte antigens type A, HLA-A) is present in the nuclei of cells, in the proximity of histone H2B. With this finding, we hope to initiate a new direction of research on the nuclear role of MHC-I and ask whether the loading of antigens can take place in the nuclear compartment.
Genomic erosion in the assessment of species extinction risk and recovery potential
Authors: van Oosterhout Cock , Speak Samuel A. , Birley Thomas , Bortoluzzi Chiara , Percival-Alwyn Lawrence , Urban Lara H. , Groombridge Jim J. , Segelbacher Gernot , Morales Hernán E. 
Published: September 2022

AbstractMany species are facing unprecedented population size declines and deterioration of their environment. This exposes species to genomic erosion, which we define here as the damage inflicted to a species’ genome or gene pool due to a loss of genetic diversity, an increase in expressed genetic load, maladaptation, and/or genetic introgression. The International Union for Conservation of Nature (IUCN) bases its extinction risk assessments on direct threats to population size and habitat. However, it does not assess the long-term impacts of genomic erosion, and hence, it is likely to underestimate the extinction risk of many species. High-quality whole genome sequence data that is currently being generated could help improve extinction risk assessments. Genomic data contains information about a species’ past demography, its genome-wide genetic diversity, the incidence of genetic introgression, as well as the genetic load of deleterious mutations. Computer modelling of these data enables forecasting of population trajectories under different management scenarios. In this Perspective, we discuss the threats posed by genomic erosion. Using evolutionary genomic simulations, we argue that whole genome sequence data provides critical information for assessing the extinction risk and recovery potential of species. Genomics-informed assessments of the extinction risk complement the IUCN Red List, and such genomics-informed conservation is invaluable in guiding species recovery programs in the UN’s Decade on Ecosystem Restoration and beyond.
Allelic and Gene Dosage Effects Involving Uromodulin Aggregates Drive Autosomal Dominant Tubulointerstitial Kidney Disease
Authors: Schiano Guglielmo , Lake Jennifer , Mariniello Marta , Schaeffer Céline , Harvent Marianne , Rampoldi Luca , Olinger Eric , Devuyst Olivier 
Published: September 2022

AbstractMissense mutations in theUMODgene encoding uromodulin cause autosomal dominant tubulointerstitial kidney disease (ADTKD), one of the most common monogenic kidney diseases. A pressing need for ADTKD is to bridge the gap between postulated gain-of-function mutations and organ damage - a prerequisite for therapeutic development. Based on two missenseUMODmutations associated with divergent progression of ADTKD, we generatedUmodC171YandUmodR186Sknock-in mice that showed strong allelic and gene dosage effects, with distinct dynamic pathways impacting on uromodulin trafficking, formation of intracellular aggregates, activation of ER stress, unfolded protein and immune responses, kidney damage and progression to kidney failure. Deletion of the wild-typeUmodallele in heterozygousUmodR186Smice increased the formation of uromodulin aggregates and ER stress, indicating a protective role of wild-type uromodulin. Studies in kidney tubular cells confirmed biochemical differences between distinct uromodulin aggregates, with activation of specific quality control and clearance mechanisms. Enhancement of autophagy by starvation and mTORC1 inhibition decreased the uromodulin aggregates, suggesting a therapeutic strategy. These studies substantiate a model for allelic effects and the role of toxic aggregates in the progression of ADTKD-UMOD, with relevance for toxic gain-of-function mechanisms and for strategies to improve clearance of mutant uromodulin.
SynBOLD-DisCo: Synthetic BOLD images for distortion correction of fMRI without additional calibration scans
Authors: Yu Tian , Cai Leon Y. , Morgan Victoria L. , Goodale Sarah E. , Englot Dario J. , Chang Catherine E. , Landman Bennett A. , Schilling Kurt G. 
Published: September 2022

ABSTRACTThe blood oxygen level dependent (BOLD) signal from functional magnetic resonance imaging (fMRI) is a noninvasive technique that has been widely used in research to study brain function. However, fMRI suffers from susceptibility-induced off resonance fields which may cause geometric distortions and mismatches with anatomical images. State-of-the-art correction methods require acquiring reverse phase encoded images or additional field maps to enable distortion correction. However, not all imaging protocols include these additional scans and thus cannot take advantage of these susceptibility correction capabilities. As such, in this study we aim to enable state-of-the-art distortion correction with FSL’s topup algorithm of historical and/or limited fMRI data that include only a structural image and single phase encoded fMRI. To do this, we use 3D U-net models to synthesize undistorted fMRI BOLD contrast images from the structural image and use this undistorted synthetic image as an anatomical target for distortion correction with topup. We evaluate the efficacy of this approach, named SynBOLD-DisCo (synthetic BOLD images for distortion correction), and show that BOLD images corrected using our approach are geometrically more similar to structural images than the distorted BOLD data and are practically equivalent to state-of-the-art correction methods which require reverse phase encoded data. Future directions include additional validation studies, integration with other preprocessing operations, retraining with broader pathologies, and investigating the effects of spin echo versus gradient echo images for training and distortion correction. In summary, we demonstrate SynBOLD-DisCo corrects distortion of fMRI when reverse phase encoding scans or field maps are not available.