bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and Mitigation of High-Risk Pregnancy with the Community Maternal Danger Score Mobile Application in Gboko, Nigeria
Authors: Bola Rajan , Ujoh Fanan , Lett Ronald 
Published: August 2021

AbstractIntroductionNigeria constitutes 1% of the world’s population yet accounts for 10% of global maternal mortality. Risk analyses within rural regions of Nigeria are not routinely conducted, yet could help inform access to skilled birth care. The objectives of this study were to assess the proportion of women at risk for mortality or morbidity in Benue State, Nigeria by analysing data collected during routine antenatal visits and through the Community Maternal Danger Score (CMDS), a validated risk-analysis tool.MethodsTwo cohorts, comprised of pregnant women presenting to primary healthcare centres within Gboko, Benue State between 2015-2017 and 2020-2021, were included in this study. The 2015-2017 cohort had their risk assessed retrospectively through analysis of routinely collected data. Identification of risk was based on their age, parity, and disease status (HIV and diabetes). The 2020-2021 cohort had their risk assessed prospectively using the CMDS.ResultsRoutinely collected data from 2015-2017 demonstrated that up to 14.9% of women in Gboko were at risk for mortality or morbidity. The CMDS reported that up to 21.5% of women were at a similar level of risk; a significant difference of 6.6% (p=0.006). The CMDS was more efficient in obtaining and assessing this data, and the identification was available in real-time for midwives and pregnant women.ConclusionRoutine data collected in Gboko identifies a high proportion of pregnant women at risk for mortality or morbidity. The CMDS is an evidence-based risk analysis tool that expands on this assessment by also estimating individual and community-level risk, which allows for more efficient mitigation and prevention strategies of maternal mortality.
Overcoming the pitfalls of NGS-based molecular diagnosis of Shwachman-Diamond syndrome
Authors: Peng Xiaomin , Dong Xinran , Wang Yaqiong , Wu Bingbing , Wang Huijun , Lu Wei , Xiao Feifan , Yang Lin , Li Gang , Zhou Wenhao , Liu Bo , Lu Yulan 
Published: August 2021

AbstractPurposeShwachman-Diamond syndrome (SDS) is predominately caused by biallelic mutations in the SBDS gene and is characterized by exocrine pancreatic insufficiency, skeletal abnormalities and pancytopenia. Gene conversion between SBDS and its pseudogene SBDSP1 is the major cause. We established an efficient approach, HapICE, to infer the haplotype of SBDS based on short-read next-generation sequencing (NGS).MethodsHapICE based on the Expectation-Maximization algorithm was developed to detect variants in exon 2 of SBDS arising from gene conversion. We retrospectively analyzed two common pathogenic variants (c.183_184delinsCT and c.258+2T>C) in suspected SDS patients and compared the results with those from conventional NGS analysis.ResultsIn 47 SDS high-risk individuals and 64 available parents, HapICE improved the diagnostic rate by 27.7% compared with conventional methods and revealed 100% (95% CI: 92.5%-100%) concordance with Sanger sequencing. In addition to eighteen patients having consistent genetic results by both methods, HapICE further reported 8 patients with more accurate variant detection and 13 cases with the c.183_184delinsCT variant missing by conventional methods. HapICE also showed better performance in screening for carrier and wild-type status.ConclusionWe have developed a novel SBDS variant detection tool through regular NGS data that demonstrated precise variant detection performance in clinical scenarios.
Misinformation can prevent the suppression of epidemics
Authors: Sontag Andrei , Rogers Tim , Yates Christian 
Published: August 2021

AbstractThe effectiveness of non-pharmaceutical interventions, such as mask-wearing and social distancing, as control measures for pandemic disease relies upon a conscientious and well-informed public who are aware of and prepared to follow advice. Unfortunately, public health messages can be undermined by competing misinformation and conspiracy theories, spread virally through communities that are already distrustful of expert opinion. In this article, we propose and analyse a simple model of the interaction between disease spread and (mis-) information dynamics in a heterogeneous population composed of both trusting individuals who seek quality information and will take precautionary measures, and distrusting individuals who are susceptible to misinformation. We show that, as the density of the distrusting population increases, the model passes through a phase transition to a state in which major outbreaks cannot be suppressed. Our work highlights the urgent need for effective measures to combat the spread of misinformation.
GWAS meta-analysis reveals dual neuronal and immunological etiology for pain susceptibility
Authors: Mocci Evelina , Ward Kathryn , Dorsey Susan G. , Ament Seth A. 
Published: August 2021

ABSTRACTChronic pain is at epidemic proportions in the United States, represents a significant burden on our public health system and is coincident with a growing opioid crisis. While numerous genetic risk factors have been identified, its genetic basis remains poorly understood. Here, we conducted a meta-analysis of genome-wide association study (GWAS) summary statistics from seventeen pain susceptibility traits in the UK Biobank. This analysis revealed 99 genome-wide significant risk loci, of which 62 have not been previously associated with a pain-related trait. Risk loci were enriched for genes involved in neurological and inflammatory pathways. Two-sample Mendelian randomization indicated that depression, neuroticism, and immunological traits mediate many of these effects. These analyses double the number of known risk loci for pain susceptibility and support dual causation from neuronal and immunological genes, providing leads toward targets for novel pain medications.
Development of affinity beads-based in vitro metal-ligand binding assay reveals dominant cadmium affinity of thiol-rich small peptides phytochelatins beyond glutathione
Authors: Uraguchi Shimpei , Nagai Kenichiro , Naruse Fumii , Otsuka Yuto , Ohshiro Yuka , Nakamura Ryosuke , Takanezawa Yasukazu , Kiyono Masako 
Published: August 2021

AbstractFor a better understanding of metal-ligand interaction and its function in cells, we developed an easy, sensitive, and high-throughput method to quantify ligand-metal(loid) binding affinity under physiological conditions by combining ligand-attached affinity beads and inductively coupled plasma-optical emission spectrometry (ICP-OES). Glutathione (GSH) and two phytochelatins (PC2 and PC3, small peptides with different numbers of free thiols) were employed as model ligands and attached to hydrophilic beads. The principle of the assay resembles that of affinity purification of proteins in biochemistry: metals binding to the ligand on the beads and the rest in the buffer are separated by a spin-column and quantified by ICP-OES. The binding assay using the GSH-attached beads and various metal(loid)s suggested the different affinity of the metal-GSH interactions, in accordance with the order of the Irving–Williams series and the reported stability constants. The binding assay using PC2 or PC3-attached beads suggested positive binding between PCs and Ni(II), Cu(II), Zn(II), Cd(II), and As(III) in accordance with the number of thiols in PC2 and PC3. We then conducted the competition assay using Cd(II), Mn(II), Fe(II), Cu(II), and Zn(II) and the results suggested a better binding affinity of PC2 with Cd(II) than with the essential metals. Another competition assay using PC2 and GSH suggested a robust binding affinity between PCs and Cd(II) compared to GSH and Cd(II). These results suggested the dominance of PC-Cd complex formation in vitro, supporting the physiological importance of PCs for the detoxification of cadmium in vivo. We also discuss the potential application of the assay.
Sex differences in incidence and mortality of bloodstream infections. Results from the population-based HUNT study in Norway
Authors: Mohus Randi Marie , Gustad Lise T. , Furberg Anne Sofie , Moen Martine Kjølberg , Liyanarachi Kristin Vardheim , Askim Åsa , Åsberg Signe E. , DeWan Andrew T. , Rogne Tormod , Simonsen Gunnar Skov , Nilsen Tom Ivar Lund , Åsvold Bjørn Olav , Damås Jan Kristian , Solligård Erik 
Published: August 2021

AbstractObjectiveTo examine the effect of sex on risk of bloodstream infections (BSI) and BSI mortality and to assess to what extent known risk factors for BSI mediate this association in the general population.ParticipantsThe prospective, population-based HUNT2 Survey (1995-97) in Norway invited 93,898 inhabitants ≥20 years in the Nord-Trøndelag region, whereof 65,237 (69.5%) participated. 46.8% of the participants were men.ExposuresSex and potential mediators between sex and BSI; health behaviours (smoking, alcohol consumption), education attainment, cardiovascular risk factors (systolic blood pressure, non-HDL cholesterol, body mass index) and previous or current comorbidities.Main outcome measuresSex differences in risk of first-time BSI, BSI mortality (death within first 30 days after a BSI), BSI caused by the most frequent bacteria, and the impact of known BSI risk factors as mediators.ResultsWe documented a first-time BSI for 1,840 (2.9%) participants (51.3% men) during a median follow-up of 14.8 years. Of these, 396 (0.6%) died (56.6% men). Men had 41% higher risk of any first-time BSI (95% confidence interval (CI), 28 to 54%) than women. An estimated 34% of the excess risk of BSI in men was mediated by known BSI risk factors. The hazard ratio (HR) with 95% CI for BSI due to S. aureus was 2.09 (1.28 to 2.54), S. pneumoniae 1.36 (1.05 to 1.76), and E. coli 0.97 (0.84 to 1.13) in men vs women. BSI related mortality was higher in men compared to women with HR 1.87 (1.53 to 2.28).ConclusionsThis large population-based study show that men have higher risk of BSI than women. One-third of this effect was mediated by known risk factors for BSI. This raises important questions regarding sex specific approaches to reduce the burden of BSI.
Infection inhibiting effect of RT-PCR testing-isolation in COVID-19 - a case study of Hiroshima and Fukuoka in Japan -
Authors: Maki Kazuo 
Published: August 2021

AbstractA simple method of estimating the effect of reverse transcription polymerase chain reaction (RT-PCR) testing-isolation on the restraint of infection of COVID-19 is proposed. The effect is expressed as the ratio χ of the reproductive number to that in the case that no isolation measure would be taken. The method was applied in the case of the third infection wave (from December, 2020 to February, 2021) of Hiroshima and Fukuoka in Japan. The ratio χ was estimated to be 0.78 to 0.84 and 0.86 to 0.9 in Hiroshima and Fukuoka, respectively. It is also shown that the reduction of χ by 0.07 would have reduced at least 50% of total infected patients during the third infection wave in Fukuoka.
Uncovering the gastrointestinal passage, intestinal epithelial cellular uptake and AGO2 loading of milk miRNAs in neonates using xenomiRs as tracers
Authors: Weil Patrick Philipp , Reincke Susanna , Hirsch Christian Alexander , Giachero Federica , Aydin Malik , Scholz Jonas , Jönsson Franziska , Hagedorn Claudia , Nguyen Duc Ninh , Thymann Thomas , Pembaur Anton , Orth Valerie , Wünsche Victoria , Jiang Ping-Ping , Wirth Stefan , Jenke Andreas C. W. , Sangild Per Torp , Kreppel Florian , Postberg Jan 
Published: August 2021

AbstractBackgroundHuman breast milk has a high microRNA (miRNA) content. It remains unknown whether and how milk miRNAs might affect intestinal gene regulation and homeostasis of the developing microbiome after initiation of enteral nutrition. However, this requires that relevant milk miRNA amounts survive gastrointestinal passage, are taken up by cells, and become available to the RNA interference (RNAi) machinery. It seems important to dissect the fate of these miRNAs after oral ingestion and gastrointestinal passage.ObjectiveOur goal was to analyze the potential transmissibility of milk miRNAs via the gastrointestinal system in neonate humans and a porcine modelin vivoto contribute to the discussion whether milk miRNAs could influence gene regulation in neonates and thus might vertically transmit developmental relevant signals.DesignWe performed cross-species profiling of miRNAs via deep-sequencing and utilized dietary xenobiotic taxon-specific milk miRNA (xenomiRs) as tracers in human and porcine neonates, followed by functional studies in primary human fetal intestinal epithelial cells (HIEC-6) using Ad5-mediated miRNA-gene transfer.ResultsMammals share many milk miRNAs yet exhibit taxon-specific miRNA fingerprints. We traced bovine-specific miRNAs from formula-nutrition in human preterm stool and 9 days after onset of enteral feeding in intestinal cells of preterm piglets. Thereafter, several xenomiRs accumulated in the intestinal cells. Moreover, few hours after introducing enteral feeding in preterm piglets with supplemented reporter miRNAs (cel-miR-39-5p/-3p), we observed their enrichment in blood serum and in AGO2-immunocomplexes from intestinal biopsies.ConclusionsMilk-derived miRNAs survived gastrointestinal passage in human and porcine neonates. Bovine-specific miRNAs accumulated in intestinal cells of preterm piglets after enteral feeding with bovine colostrum/formula. In piglets, colostrum supplementation with cel-miR-39-5p/-3p resulted in increased blood levels of cel-miR-39-3p and argonaute RISC catalytic component 2 (AGO2) loading in intestinal cells. This suggests the possibility of vertical transmission of miRNA signaling from milk through the neonatal digestive tract.
Loss of full-length dystrophin expression results in major cell-autonomous abnormalities in proliferating myoblasts
Authors: Gosselin Maxime R. F. , Mournetas Virginie , Borczyk Malgorzata , Verma Suraj , Occhipinti Annalisa , Róg Justyna , Bozycki Lukasz , Korostynski Michal , Robson Samuel C. , Angione Claudio , Pinset Christian , Górecki Dariusz C. 
Published: August 2021

AbstractDuchenne muscular dystrophy (DMD) affects myofibers and muscle stem cells (SC), causing progressive muscle degeneration and repair defects. It was not known whether dystrophic myoblasts—the effector cells of muscle growth and regeneration—are affected. Using a combination of transcriptomic, molecular, functional analyses, and genome-scale metabolic modelling, we demonstrate, for the first time, convergent cell-autonomous abnormalities in primary mouse and human dystrophic myoblasts. In Dmdmdxmouse myoblasts lacking full-length dystrophin transcripts, the expression of 170 other genes was significantly altered. Myod1 (p=2.9e-21) and key muscle genes controlled by MyoD (Myog, Mymk, Mymx, epigenetic regulators, ECM interactors, calcium signalling and fibrosis genes) were significantly downregulated. Gene ontology enrichment analysis indicated significant alterations in genes involved in muscle development and function. These transcriptomic abnormalities translated into functional alterations such as increased proliferation (p=3.0e-3), reduced chemotaxis towards both sera-rich (p=3.8e-2) and cytokine-containing medium (p=1.0e-2), and significantly accelerated differentiation in 3D organotypic cultures. These altered myoblast functions are essential for muscle regeneration. The defects were caused by the loss of expression of full-length dystrophin, as strikingly similar and not exacerbated alterations were also observed in dystrophin-nullDmdmdx-βgeomyoblasts. Corresponding abnormalities were identified in an established dystrophic mouse muscle (SC5) cell line and human DMD primary myoblasts, confirming universal, cross-species and cell-autonomous nature of these defects. The genome-scale metabolic analysis in human DMD myoblasts indicated significant alteration in the rate of glycolysis/gluconeogenesis (log2FC = 4.8), leukotriene metabolism (log2FC = 4.754), mitochondrial beta-oxidation of branched-chain, odd-chain, and di-unsaturated fatty acids (n-6) (log2FC = -1.187, log2FC = -0.8295 and log2FC = -0.655). These results demonstrate the disease continuum: DMD defects in satellite cells cause myoblast dysfunctions affecting muscle regeneration, which is essential to counteract myofiber loss. Contrary to the established belief, our data demonstrate that typical DMD alterations occur in myoblasts, making these cells a novel therapeutic target for the treatment of this lethal disease.
Innate and adaptive immunity to transfused allogenic red blood cells in mice requires MyD88
Authors: Soldatenko Arielle , Hoyt Laura R. , Xu Lan , Calabro Samuele , Lewis Steven M. , Gallman Antonia E. , Hudson Krystalyn E. , Stowell Sean R. , Luckey Chance J. , Zimring James C. , Liu Dong , Santhanakrishnan Manjula , Hendrickson Jeanne E. , Eisenbarth Stephanie C. 
Published: August 2021

AbstractRed blood cell (RBC) transfusion therapy is essential for the survival of patients with hematological disorders such as sickle cell anemia. A potentially fatal complication of transfusion is development of non-ABO alloantibodies to polymorphic RBC antigens, yet mechanisms of alloantibody formation remain unclear. Human and mouse RBCs acquire a “storage lesion” prior to transfusion, which in mice contributes to immunogenicity. We previously reported that mouse splenic dendritic cells (DCs) are required for RBC alloimmunization and are activated by sterile and leukoreduced mouse RBCs after storage. Yet how syngeneic RBCs activate innate immune pathways to induce DC activation is unknown. We now show that DC activation to transfused RBCs occurs regardless of alloantigen presence, suggesting that RBC damage induced during storage triggers innate immune receptors. We discovered an unexpected dependence of RBC alloimmunization on the Toll-like receptor (TLR) signaling adaptor molecule MyD88. TLRs are a class of pattern recognition receptors (PRRs) that regulate DC activation and signal through two adaptor molecules, MyD88 and TRIF. We show that the inflammatory cytokine response, DC activation, and the subsequent alloantibody response to transfused syngeneic RBCs require MyD88 but not TRIF, suggesting a restricted set of PRRs are responsible for sensing RBCs and triggering alloimmunization.
Infection increases activity via Toll dependent and independent mechanisms in Drosophila melanogaster
Authors: Vincent Crystal M. , Beckwith Esteban J. , Pearson William H. , Kierdorf Katrin , Gilestro Giorgio , Dionne Marc S. 
Published: August 2021

AbstractHost behavioural changes are among the most apparent effects of infection. ‘Sickness behaviour’ can involve a variety of symptoms, including anorexia, depression, and changed activity levels. Here we use a real-time tracking and behavioural profiling platform to show that, in Drosophila melanogaster, many systemic bacterial infections cause significant increases in physical activity, and that the extent of this activity increase is a predictor of survival time in several lethal infections. Using various bacteria and D. melanogaster immune and activity mutants, we show that increased activity is driven by at least two different mechanisms. Increased activity after infection with Micrococcus luteus, a Gram-positive bacterium rapidly cleared by the immune response, strictly requires the Toll ligand spätzle and Toll-pathway activity in the fat body and the brain. In contrast, increased activity after infection with Francisella novicida, a Gram-negative bacterium that cannot be cleared by the immune response, is entirely independent of either spätzle or the parallel IMD pathway. The existence of multiple signalling mechanisms by which bacterial infections drive increases in physical activity implies that this effect may be an important aspect of the host response.
Differential proteomic analysis of laser-microdissected penetration glands of avian schistosome cercariae with a focus on proteins involved in host invasion
Authors: Vondráček Oldřich , Mikeš Libor , Talacko Pavel , Leontovyč Roman , Bulantová Jana , Horák Petr 
Published: August 2021

AbstractSchistosome invasive stages, cercariae, leave intermediate snail hosts, penetrate the skin of definitive hosts, and transform to schistosomula migrating to final localization. During invasion, cercariae employ histolytic and other bioactive products of specialized holocrine secretory cells – postacetabular (PA) and circumacetabular (CA) penetration glands. Although several studies attempted to characterize protein composition of the in vitro induced gland secretions in Schistosoma mansoni and Schistosoma japonicum, the results were inconsistent and dependent on the method of sample collection and processing. Products of both gland types mixed during their secretion did not allow localization of identified proteins to a particular gland. Here we compared proteomes of separately isolated cercarial gland cells of the avian schistosome Trichobilharzia szidati employing laser-assisted microdissection and shotgun LC-MS/MS, thus obtaining the largest dataset so far concerning the representation and localization of cercarial penetration gland proteins. We optimized the methods of sample processing with cercarial bodies (heads) first. Alizarin-pre-stained, chemically non-fixed samples provided optimal results of MS analyses, and enabled distinguishing PA and CA glands for microdissection. Using 7.5 × 106 μm3 sample volume per gland replicate, we identified 3347 peptides assigned to 792 proteins, from which 461 occurred in at least 2 of 3 replicates in either gland type (PA = 455, 40 exclusives; CA = 421, 6 exclusives; 60 proteins differed significantly in their abundance between the glands). Peptidases of 5 catalytic types accounted for ca. 8 % and 6 % of reliably identified proteins in PA and CA glands, respectively. Invadolysin, nardilysin, cathepsins B2 and L3, and elastase 2b orthologs were the major gland endopeptidases. Two cystatins and a serpin were highly abundant peptidase inhibitors in the glands. CA glands were rich in venom allergen-like proteins. The assembled total cercarial body proteome included 1631 identified proteins and revealed additional interesting factors possibly related to tissue invasion.HighlightsProteomes of two penetration gland types in schistosome cercariae greatly differPostacetabular glands possess 40 unique proteins and are abundant in hydrolasesCircumacetabular glands posses 6 unique proteins and are rich in VAL proteinsPeptidases make up 8 % of postacetabular and 6 % of circumacetabular gland proteinsCercarial elastase is unique to circumacetabular glands of Trichobilharzia szidatiNote: Supplementary data associated with this article All supplementary data files can be accessed from the following link: http://www.helminthology.cz/supplementary_files.html