bluuebunny/crossref_metadata_2025_split huggingface dataset:
Magnetic activated cell-sorting identifies a unique lung microbiome community associated with disease states
Authors: Dunlap Daniel G. , Yang Libing , Qin Shulin , Ries John , Li Kelvin , Fitch Adam , Huang Laurence , McVerry Bryan J. , Methé Barbara A. , Morris Alison 
Published: June 2021

AbstractRationaleThe advent of culture-independent, next-generation DNA sequencing has led to discovery of distinct lung bacterial communities. Studies of lung microbiome taxonomy often reveal only subtle differences between health and disease, but microbial host response may distinguish members of similar communities in different populations.ObjectivesMagnetic-activated cell sorting (MACS) has been applied to the gut microbiome to identify numbers and types of bacteria eliciting a humoral response. We adapted this technique to examine populations of immunoglobulin-bound bacteria and investigate the lung microbiota in HIV as a representative disease.Methods42 people living with HIV (PLWH) and 22 HIV-uninfected individuals underwent bronchoalveolar lavage (BAL). We separated immunoglobulin G-bound bacteria using MACS and sequenced the 16S rRNA gene on the Illumina MiSeq platform. We analyzed sequences and quantified BAL cytokines and bacterial rRNA copy numbers.Measurements and Main ResultsImmunoglobulin G-bound bacteria were detectable in the healthy lung microbiota. Comparison of raw BAL by HIV status showed no significant taxonomic differences, but the immunoglobulin-bound lung microbiota differed by HIV status with greater abundance of Pseudomonas in PLWH. BAL cytokine levels were also higher in PLWH, which correlated with increased quantity of immunoglobulin G-bound bacteria.ConclusionsWe report a novel application of magnetic-activated cell sorting to identify immunoglobulin G-bound bacteria in the lung. This technique identified distinct bacterial communities which differed in composition from raw BAL, revealing differences in health and disease not detected by traditional analyses. Cytokine response was also associated with differential immunoglobulin binding of lung bacteria, suggesting functional importance of these communities.
Clinical cholera surveillance sensitivity in Bangladesh and implications for large-scale disease control
Authors: Hegde Sonia T. , Lee Elizabeth C. , Khan Ashraful Islam , Lauer Stephen A. , Islam Md. Taufiqul , Bhuiyan Taufiqur Rahman , Lessler Justin , Azman Andrew S. , Qadri Firdausi , Gurley Emily S. 
Published: June 2021

AbstractIntroductionA surveillance system that is sensitive to detecting high burden areas is critical for achieving widespread disease control. In 2014, Bangladesh established a nationwide, facility-based cholera surveillance system for Vibrio cholerae infection. We sought to measure the sensitivity of this surveillance system to detect cases to assess whether cholera elimination targets outlined by the Bangladesh national control plan can be adequately measured.MethodsWe overlaid maps of nationally-representative annual V. cholerae seroincidence onto maps of the catchment areas of facilities where confirmatory laboratory testing for cholera was conducted, and identified its spatial complement as surveillance greyspots, areas where cases likely occur but go undetected. We assessed surveillance system sensitivity and changes to sensitivity given alternate surveillance site selection strategies.ResultsWe estimated that 69% of Bangladeshis (111.7 million individuals) live in surveillance greyspots, and that 23% (25.5 million) of these individuals live in areas with the highest V. cholerae infection rates.ConclusionsThe cholera surveillance system in Bangladesh has the ability to monitor progress towards cholera elimination goals among 31% of the country’s population, which may be insufficient for accurately measuring progress. Increasing surveillance coverage, particularly in the highest risk areas, should be considered.
Reduced risk of placental parasitaemia associated with complement fixation on Plasmodium falciparum by antibodies among pregnant women
Authors: Opi D. Herbert , Boyle Michelle J. , McLean Alistair , Reiling Linda , Chan Jo-Anne , Stanisic Danielle I. , Ura Alice , Mueller Ivo , Fowkes Freya J. , Rogerson Stephen J. , Beeson James G. 
Published: June 2021

ABSTRACTBackgroundThe pathogenesis of malaria in pregnancy (MiP) involves accumulation of P. falciparum-infected red blood cells (pRBCs) in the placenta, contributing to poor pregnancy outcomes. Parasite accumulation is primarily mediated by P. falciparum erythrocyte membrane 1 (PfEMP1). Magnitude of IgG to pRBCs has been associated with reduced risk of MiP in some studies, but associations have been inconsistent. Further, antibody effector mechanisms are poorly understood, and the role of antibody complement interactions is unknown.MethodsStudying a longitudinal cohort of pregnant women (n=302) from a malaria-endemic province in Papua New Guinea (PNG), we measured the ability of antibodies to fix and activate complement using placental binding pRBCs and PfEMP1 recombinant domains. We determined antibody-mediated complement inhibition of pRBC binding to the placental receptor, chondroitin sulfate A (CSA) and associations with protection against placental parasitaemia.ResultsSome women acquired antibodies that effectively promoted complement fixation on placental-binding pRBCs. Complement fixation correlated with IgG1 and IgG3 antibodies, which dominated the response. There was, however, limited evidence for membrane attack complex activity or pRBC lysis or killing. Importantly, a higher magnitude of complement fixing antibodies was prospectively associated with reduced odds of placental infection at delivery. Using genetically-modified P. falciparum and recombinant PfEMP1 domains, we found that complement-fixing antibodies primarily targeted a specific variant of PfEMP1 (known as VAR2CSA). Furthermore, complement enhanced the ability of antibodies to inhibit pRBC binding to CSA, which was primarily mediated by complement C1q protein.ConclusionThese findings provide new insights into mechanisms mediating immunity to MiP and reveal potential new strategies for developing malaria vaccines that harness antibody-complement interactions.
Taxon-specific shifts in bacterial and archaeal transcription of dissolved organic matter cycling genes in a stratified fjord
Authors: Pontiller Benjamin , Pérez-Martínez Clara , Bunse Carina , Osbeck Christofer M.G. , González José M. , Lundin Daniel , Pinhassi Jarone 
Published: June 2021

ABSTRACTA considerable fraction of organic matter derived from photosynthesis in the euphotic zone settles into the ocean’s interior, and under way is degraded by diverse microbial consortia that utilize a suite of extracellular enzymes and membrane transporters. Still, the molecular details that regulate carbon cycling across depths remain little explored. As stratification in fjords has made them attractive models to explore patterns in biological oceanography, we here analyzed bacterial and archaeal transcription in samples from five depth layers in the Gullmar Fjord, Sweden. Transcriptional variation over depth correlated with gradients in chlorophyllaand nutrient concentrations. Differences in transcription between sampling dates (summer and early autumn), were strongly correlated with ammonium concentrations, which potentially was linked with a stronger influence of (micro-)zooplankton grazing in summer. Transcriptional investment in carbohydrate-active enzymes (CAZymes) decreased with depth and shifted toward peptidases, partly a result of elevated CAZyme transcription by Flavobacteriales, Cellvibrionales and Synechococcales at 2-25 m and a dominance of peptidase transcription by Alteromonadales and Rhodobacterales from 50 m and down. In particular, CAZymes for chitin, laminarin, and glycogen were important. High levels of transcription of ammonium transporters by Thaumarchaeota at depth (up to 18% of total transcription), along with the genes for ammonia oxidation and CO2-fixation, indicated that chemolithoautotrophy contributed to the carbon flux in the fjord. The taxon-specific expression of functional genes for processing of the marine DOM pool and nutrients across depths emphasizes the importance of different microbial foraging mechanisms across spatiotemporal scales for shaping biogeochemical cycles.IMPORTANCEIt is generally recognized that stratification in the ocean strongly influences both the community composition and the distribution of ecological functions of microbial communities, which in turn are expected to shape the biogeochemical cycling of essential elements over depth. Here we used metatranscriptomics analyses to infer molecular detail on the distribution of gene systems central to the utilization of organic matter in a stratified marine system. We thereby uncovered that pronounced shifts in transcription of genes encoding CAZymes, peptidases, and membrane transporters occurred over depth among key prokaryotic orders. This implies that sequential utilization and transformation of organic matter through the water column is a key feature that ultimately influences the efficiency of the biological carbon pump.
The African swine fever virus protease pS273R inhibits DNA sensing cGAS-STING pathway by targeting IKKε
Authors: Luo Jia , Ni Jinghua , Jiang Sen , Xia Nengwen , Guo Yiwen , Shao Qi , Zhang Jiajia , Cao Qi , Xu Zhenqi , Zheng Wanglong , Chen Nanhua , Zhang Quan , Chen Hongjun , Guo Xiaoyu , Zhu Hongfei , Meurens François , Zhu Jianzhong 
Published: June 2021

AbstractAfrican swine fever virus (ASFV), a large and complex cytoplasmic double-stranded DNA virus, has developed multiple strategies to evade the antiviral innate immune responses. Cytosolic DNA arising from invading ASFV is mainly detected by the cyclic GMP-AMP synthase (cGAS) and then triggers a series of innate immune responses to prevent virus invasion. However, the immune escape mechanism of ASFV remains to be fully clarified. The pS273R of ASFV is a member of the SUMO-1-specific protease family and is crucial for valid virus replication. In this study, we identified pS273R as a suppressor of cGAS-STING pathway mediated type I interferon (IFN) production by ASFV genomic open reading frame screening. The pS273R was further confirmed as an inhibitor of IFN production as well as its downstream antiviral genes in cGAS-STING pathway. Mechanistically, pS273R greatly decreased the cGAS-STING signaling by targeting IKKε but not TBK1 and pS273R was found to disturb the interaction between IKKε and STING through its interaction with IKKε. Further, mutational analyses revealed that pS273R antagonized the cGAS-STING pathway by enzyme catalytic activity, which may affect the IKKε sumoylation state required for the interaction with STING. In summary, our results revealed for the first time that pS273R acts as an obvious negative regulator of cGAS-STING pathway by targeting IKKε via its enzymatic activity, which shows a new immune evasion mechanism of ASFV.ImportanceAfrican swine fever (ASF) is a devastating disease for domestic pigs and wild boar and the pathogen ASFV is a cytoplasmic double-stranded DNA virus. The innate immune cGAS-STING-IFN signaling pathway exerts a critical role in sensing ASFV infection. However, the functions of half ASFV encoded 150 plus proteins are still unknown and the evasion against the cGAS-STING pathway is not resolved. In our study, via ASFV genomic open reading frame (ORF) screening, we found that 29 ASFV proteins could inhibit cGAS-STING signaling pathway, with pS273R showing the most obvious inhibitory effect. Surprisingly, pS273R was found to antagonize the cGAS-STING signaling by targeting IKKε. Moreover, the pS273R enzyme activity is required for its ability to inhibit the cGAS-STING pathway. Our findings deepen the understanding of the immune evasion mechanism of ASFV, which will provide a support for the development of safe and effective ASFV vaccines.
Developing and testing an arts-based, digital knowledge translation tool for parents about childhood croup
Authors: Scott Shannon D. , Le Anne , Hartling Lisa 
Published: June 2021

AbstractCroup is a common viral illness affecting 80,000 children annually in Canada. Between 7-31% of children seen in an ED for croup are admitted to hospital due to health care provider apprehension. However, over 60% of children with croup experience mild symptoms that can be safely managed at home. Emerging evidence suggests that initiatives targeting healthcare consumers (i.e., patients, parents, families) can inform decision making and shape treatment expectations. Previous research demonstrates that innovative media are superior to traditional standard health sheets for transferring information to consumers.The purpose of this project was to develop, refine, and test the usability of a whiteboard animation video for parents about childhood croup. Parents rated the tools highly across all usability items, suggesting that creative tools developed using multi-method development processes can help facilitate the uptake of health information in parents.
Predictive targeting of mitochondrial metabolism in Acute Myeloid Leukemia patients with a lipoic acid analog
Authors: Reid Michael A. , Bose Shree , Pladna Kristin M , Anderson Rebecca , Mikhael Peter G. , Xiao Zhengtao , Dai Ziwei , Liu Shiyu , Liu Juan , Pardee Timothy S. , Locasale Jason W. 
Published: June 2021

ABSTRACTTargeting metabolism has long been a theory for cancer therapy, but clinical development has been limited by toxicities, compound availability, overall efficacy, and patient specificity1. CPI-613, a lipoic acid analogue that interferes with enzymes involved in mitochondrial metabolism, has demonstrated clinical activity in lethal malignancies including relapsed or therapy refractory Acute Myeloid Leukemias (AMLs)2,3 and Phase III trials are ongoing1. Using metabolomics, we investigated blood and bone marrow samples from a cohort of 29 relapsed or refractory AML patients involved in Phase I and II studies undergoing CPI-613 treatment (NCT01768897, NCT02484391) including 13 that achieved a complete response. We show that CPI-613 treatment in patients induced defined alterations related to the tricarboxylic acid (TCA) cycle and associated redox, anabolic and catabolic metabolism. These findings are consistent with targeting of several ketoacid dehydrogenase (KADH) enzymes that use lipoic acid as a cofactor and are related to mitochondrial metabolism. The alterations were observed systemically but were more pronounced within the leukemic bone marrow microenvironment consistent with its mechanistic target. Machine learning revealed that metabolic status and changes associated with mitochondrial metabolism were predictive of treatment response, indicating that mechanism-based metabolite biomarkers to a targeted metabolic cancer therapy may be feasible. Finally, we confirm using isotope tracing and flux analysis that these effects are due to disruptions to substrate utilization into the mitochondria. Our findings provide evidence that a tolerated, anti-cancer therapeutic can act by targeting mitochondrial metabolism in humans.
Comparing India’s second COVID wave with the first wave – a single-center experience
Authors: Kapoor Mayank , Singh Budha O , Panda Prasan Kumar , Dhanger Pathik , Kataria Anant 
Published: June 2021

AbstractBackgroundThe COVID-19 pandemic has resurfaced in India in the form of a hard-hitting second wave. This study aims to compare the clinical profile of the first wave (April-June 2020) and the second wave (March-May 2021) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a single tertiary care center of India. This will help prioritize the target population group and management strategies in the upcoming third wave if any.MethodsIn this retrospective observational study, we examined the demographic profile, symptoms at presentation, the severity of illness, baseline investigations, treatments received, underlying comorbidities, and outcomes of the COVID-19 patients belonging to the first (W1) and the second wave (W2) of the pandemic in India.FindingsAmong 106 patients in W1 and 104 patients in W2, the age group affected most was 37·1 (SD=16·9) years compared with 50.5 (SD=17.7) years respectively. The baseline oxygen saturation is lower in W2, being 84·0 (13·4) % compared with 91·9 (7·4) % in W1. 70.2 % of the cases belonged to the severe category in W2 compared to 37.5% in W1. W2 patients demonstrated higher transaminase levels [SGOT, 108.3 (99.3) v/s 54.6 (69.3); SGPT, 97.6 (82.3) v/s 58.7 (69.7)] with respect to W1. Similarly, the CT severity score for W2 [29.5 (6.7)] was higher than W1 [23·2 (11·5)][All P<0.05]. The proportion of patients requiring oxygen (81.8% v/s 11.2%), high flow nasal cannula (11.4% v/s 5.6%), non-invasive ventilation (41.2% v/s 1.5%), invasive ventilation (24.5% v/s 0.9%), as well as ICU/HDU admissions (56.4% v/s 12.0%) was higher for W2 as compared with W1. The measured case fatality rate varies from 29% for W2 to 9.6% for W1.InterpretationHigher age, oxygen requirement, ventilator requirement, ICU admission, and organ impairment are more prevalent in the admitted COVID-19 cases during the second wave that has hit India compared to the first wave and associated with more fatalities. Strategy for another wave should be planned accordingly.Key pointsQuestionWhat are the differences between the clinical profile of the first wave (W1) and the second wave (W2) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a single tertiary care center of India?FindingsIn this observational study among 106 patients in W1 (April-June 2020) and 104 patients in W2 (March-May 2021), there were higher proportion of increased age, oxygen requirement, ventilator requirement, ICU admission, and organ impairment in the admitted COVID-19 cases during the second wave.MeaningThe second wave hits India badly than the first wave and associated with more fatalities.
Novel scotoma detection method using time required for fixation to the random targets
Authors: Takahashi Nobuyuki , Saeki Shozo , Kawahara Minoru , Aman Hirohisa , Nakano Eri , Mori Yuki , Miyake Masahiro , Tamura Hiroshi , Tsujikawa Akitaka 
Published: June 2021

AbstractWe developed a novel scotoma detection system using time required for fixation to the random targets, or the” eye-guided scotoma detection method “. In order to verify the” eye-guided scotoma detection method “, we measured 78 eyes of 40 subjects, and examined the measurement results in comparison with the results of measurement by Humphrey perimetry. The results were as follows: (1) Mariotte scotomas were detected in 100% of the eyes tested; (2) The false-negative rate (the percentage of cases where a scotoma was evaluated as a non-scotoma) was less than 10%; (3) The positive point distribution in the low-sensitivity eyes was well matched. These findings suggested that the novel scotoma detection method in the current study will pave the way for the realization of mass screening to detect pathological scotoma earlier.Author summaryConventional perimeters, such as the Goldmann perimeter and Humphrey perimeter, require experienced examiners and space occupying. With either perimeter, subjects’ eye movements need to be strictly fixed to the fixation target of the device. Other perimeters can monitor fixation and automatically measure the visual field. With the eye-guided scotoma detection method proposed in the current study, subjects feel less burdened since they do not have to fixate on the fixation target of the device and can move their eyes freely. Subjects simply respond to visual targets on the display; then, scotomas can be automatically detected. The novel method yields highly accurate scotoma detection through an algorithm that separates scotomas from non-scotomas.
Estimating the impact of Angelman syndrome on parental productivity in Australia using productivity-adjusted life years
Authors: Hartmanis Sally L , Baker Emma K , Godler David E , Liew Danny 
Published: June 2021

AbstractBackgroundAngelman syndrome (AS) is a rare genetic condition characterised by global developmental delay, including severe to profound intellectual disability. The parents of persons with AS experience increased stress, anxiety and depression. This impacts parents’ career choices and productivity.AimsTo estimate, for the first time, the total productivity lost by the parents of persons with AS over a 10-year period in Australia and the corresponding cost to society.Methods and proceduresA cost-of-illness model with simulated follow-up over a 10-year period was developed, with 2019 as the baseline year, facilitated by a Markov chain of life tables. The prevalence of persons with AS and their parents, the productivity-adjusted life years (PALYs) lost by parents, and the cost to society were estimated. Key data were obtained from a prospective cohort of AS families, peer-reviewed literature, and publicly available sources.Outcomes and resultsThe base-case productivity burden borne by the estimated 330 living parents of the 428 prevalent-persons with AS totalled AUD$45.30 million, corresponding to a loss of 38.42% of PALYs per-parent.Conclusions and implicationsCaring for a child with AS has a significant impact on the productivity of affected parents, with a large associated impact on the broader Australian economy.What this paper adds?Persons with AS require lifelong care and support. Consequently, AS results in a significant socioeconomic impact, borne both by the healthcare system and affected families. This is the first known study to estimate the total impact of caring for a child with AS on parental productivity, as well as the first study known to estimate the PALYs lost by a parental or caregiver population. This study found that caring for a child with AS has a significant impact on the productivity of affected parents, with a large associated impact on the broader Australian economy. At present, the supports available to persons with AS and their families include sleep aids and behavioural therapy. In future, specific therapeutic treatments for AS may become available, with trials underway at present investigating the efficacy and effectiveness of gene therapies for AS. As such, evidence regarding the total socioeconomic impact, including the parental productivity burden, attributable to AS is needed to inform future funding decisions.
Reg4 defenses the intestine against Salmonella infection via binding the flagellin
Authors: Wang Weipeng , Lu Ying , Tian Xinbei , Chen Shanshan , Du Jun , Cai Wei , Xiao Yongtao 
Published: June 2021

AbstractSalmonella Typhimurium is gram-negative flagellated bacteria that can cause food-borne gastroenteritis and diarrhea in humans and animals. The regenerating islet-derived family member 4 (Reg4) is overexpressed in the gastrointestinal tract during intestinal inflammation. However, the role of Reg4 in the intestinal inflammation induced by Salmonella Typhimurium is largely unknown. In this study, we reported for the first time that Reg4 has bactericidal activity against intestinal infection caused by Salmonella Typhimurium. In vivo, Reg4 could reduce the colonization of Salmonella Typhimurium and attenuate intestinal inflammation in the Salmonella Typhimurium-infected model. Additionally, the mice with the epithelial cell specific deletion of Reg4 (Reg4ΔIEC) exhibited more severe intestinal inflammation and more colonization of Salmonella Typhimurium. However, the administration of Reg4 could reverse these negative impacts. In vitro, Reg4 protein was showed to inhibit the growth of Salmonella Typhimurium. We further investigate the function motif of Reg4 and find that the “HDPQK” motif in Reg4 is essential to its bactericidal activity. Reg4 exerted the bactericidal effect by binding to the flagellin of Salmonella Typhimurium and suppressing its motility, adhesion, and invasion to the intestinal epithelia. In conclusion, our findings identify Reg4 as a novel antimicrobial peptide against infection by Salmonella Typhimurium and explore its possible mechanism, which may be of great significance for developing novel agents against flagellated micro pathogens.