bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scaling SARS-CoV-2 Wastewater Concentrations to Population Estimates of Infection
Authors: Kaplan Edward H. , Zulli Alessandro , Sanchez Marcela , Peccia Jordan 
Published: July 2021

AbstractMonitoring the progression of SARS‐CoV‐2 outbreaks requires accurate estimates of infection rates. Estimation methods based on observed cases are biased due to changes in testing over time. Here we report an approach based upon scaling daily concentrations of SARS‐CoV‐2 RNA in wastewater to infections that produces representative estimates due to the consistent population contribution of fecal material to the sewage collection system.
Positive Mental Training in patients with Multiple Sclerosis experiencing psychological distress: A Preliminary Randomised Controlled Trial
Authors: Murray Katy , Melchiorre Giulia , Dobbin Alastair , Welch Killian A 
Published: July 2021

AbstractIntroductionPsychological distress is a major issue in multiple sclerosis (MS), having a significant impact on quality of life. Antidepressants are generally unhelpful for subsyndromal symptomatology, and psychological treatment approaches often not accessible or too cognitively demanding for some patients. There is an urgent need for low-cost interventions to improve wellbeing in MS.MethodsThis was a pilot randomised controlled trial (RCT) of Positive Mental Training (PosMT), a low intensity intervention providing training in positivity, optimism and resilience previously shown to improve anxious and depressive symptomotology. 28 patients with MS were randomised to the intervention and 30 to the control group.ResultsFollow-up data was obtained from 39 patents. The majority of participants receiving PosMT reported that they had used the intervention, with few reporting side effects. The intervention group reported a significant improvement in self-rated health as measured by the EuroQual visual analogue scale, F(4,34) = 3.204, p = 0.025, R2 = 0.274.DiscussionThis preliminary RCT found that PosMT in its current form could be used by patients with MS with little difficulty. Despite the small size of the study, allocation to the intervention was found to be associated with a significant improvement in self-rated health. Given the low cost of PosMT and its easy availability (it can simply be downloaded from a website), this pilot RCT suggests it could be a useful tool for MS patients. We believe this intervention warrants further study, ideally in a large multi-centre RCT.
Association between willingness to receive the COVID-19 vaccine and sources of health information among Japanese workers: a cohort study
Authors: Hiraoka Ko , Nagata Tomohisa , Mori Takahiro , Ando Hajime , Hino Ayako , Tateishi Seiichiro , Tsuji Mayumi , Matsuda Shinya , Fujino Yoshihisa ,   for the CORoNaWork project
Published: July 2021

AbstractBackgroundIt is important to achieve herd immunity by vaccinating as many people as possible to end the COVID-19 pandemic. We investigated the relationship between willingness to receive vaccination and sources of health information among those who did not want to be vaccinated against COVID-19.MethodsThis prospective cohort study collected data using a self-administered questionnaire survey. The baseline survey was conducted during December 22–25, 2020, and the follow-up survey during February 18–19, 2021. Participants were aged 20–65 years and worked at the time of the baseline survey (N = 33,087). After excluding 6,051 invalid responses, we included responses from 27,036 participants at baseline. In total, 19,941 people responded to the follow-up survey (74% follow-up rate). We excluded 7,415 participants who answered “yes” to the question “If a COVID-19 vaccine becomes available, would you like to get it?” in the baseline survey. We finally analyzed 12,526 participants.ResultsThe odds ratio for change in willingness to be vaccinated from “no” to “yes” differed by source of health information. Compared with workers that used TV as a source of information, significantly fewer people who reported getting information from the Internet and friends/colleagues were willing to get the vaccine.ConclusionsIt is important to approach workers who do not watch TV when implementing workplace vaccination programs. It is likely that willingness to be vaccinated can be increased through an active company policy whereby the top management recommend vaccination, coupled with an individual approach by occupational health professionals.Trial registrationNot applicable.
Spontaneous Mutants of Streptococcus sanguinis with Defects in the Glucose-PTS Show Enhanced Post-Exponential Phase Fitness
Authors: Zeng Lin , Walker Alejandro R. , Lee Kyulim , Taylor Zachary A. , Burne Robert A. 
Published: July 2021

AbstractGenetic truncations in a gene encoding a putative glucose-PTS protein (manL, EIIABMan) were identified in subpopulations of two separate laboratory stocks of Streptococcus sanguinis SK36; the mutants had reduced PTS activities on glucose and other monosaccharides. Using an engineered mutant of manL and its complemented derivative, we showed that the ManL-deficient strain had improved bacterial viability in stationary phase and was better able to inhibit the growth of the dental caries pathogen Streptococcus mutans. Transcriptional analysis and biochemical assays suggested that the manL mutant underwent reprograming of central carbon metabolism that directed pyruvate away from production of lactate, increasing production of hydrogen peroxide (H2O2) and excretion of pyruvate. Addition of pyruvate to the medium enhanced the survival of SK36 in overnight cultures. Meanwhile, elevated pyruvate levels were detected in the cultures of a small, but significant percentage (∼10%), of clinical isolates of oral commensal bacteria. Furthermore, the manL mutant showed higher expression of the arginine deiminase system than the wild type, which enhanced the ability of the mutant to raise environmental pH when arginine was present. Significant discrepancies in genome sequence were identified between strain SK36 obtained from ATCC and the sequence deposited in GenBank. As the conditions that are likely associated with the emergence of spontaneous manL mutations, i.e. excess carbohydrates and low pH, are those associated with caries development, we propose that the glucose-PTS strongly influences commensal-pathogen interactions by altering the production of ammonia, pyruvate, and H2O2.ImportanceA health-associated dental microbiome provides a potent defense against pathogens and diseases. Streptococcus sanguinis is an abundant member of a health-associated oral flora that antagonizes pathogens by producing hydrogen peroxide. There is a need for a better understanding of the mechanisms that allow bacteria to survive carbohydrate-rich and acidic environments associated with the development of dental caries. We report the isolation and characterization of spontaneous mutants of S. sanguinis with impairment in glucose transport. The resultant reprograming of central metabolism in these mutants reduced the production of lactic acid and increased pyruvate accumulation; the latter enables these bacteria to better cope with hydrogen peroxide and low pH. The implications of these discoveries in the development of dental caries are discussed.
Exploring relationships between drought and epidemic cholera in Africa using generalised linear models
Authors: Charnley Gina E C , Kelman Ilan , Green Nathan , Hinsley Wes , Gaythorpe Katy A M , Murray Kris A 
Published: July 2021

AbstractBackgroundTemperature and precipitation are known to affectVibrio choleraeoutbreaks. Despite this, the impact of drought on outbreaks has been largely understudied. Africa is both drought and cholera prone and more research is needed in Africa to understand cholera dynamics in relation to drought.MethodsHere, we analyse a range of environmental and socioeconomic covariates and fit generalised linear models to publicly available national data, to test for associations with several indices of drought and make cholera outbreak projections to 2070 under three scenarios of global change, reflecting varying trajectories of CO2emissions, socio-economic development, and population growth.ResultsThe best-fit model implies that drought is a significant risk factor for African cholera outbreaks, alongside positive effects of population, temperature and poverty and a negative effect of freshwater withdrawal. The projections show that following stringent emissions pathways and expanding sustainable development may reduce cholera outbreak occurrence in Africa, although these changes were spatially heterogeneous.ConclusionsDespite an effect of drought in explaining recent cholera outbreaks, future projections highlighted the potential for sustainable development gains to offset drought-related impacts on cholera risk. Future work should build on this research investigating the impacts of drought on cholera on a finer spatial scale and potential non-linear relationships, especially in high-burden countries which saw little cholera change in the scenario analysis.
HIV Testing Uptake and Late Diagnosis among Urban Population of Ethiopia: A Multilevel Modeling Approach
Authors: Getaneh Yimam , Ayalew Jemal , Abate Ebba , Tayachew Adamu , Lulseged Sileshi , Shao Yiming 
Published: July 2021

AbstractBackgroundExpanding HIV testing and early diagnosis requires a better understanding of determinants to uptake and late diagnosis. We investigated factors contributing to HIV testing uptake and late diagnosis.ObjectiveThe aim of this study was to determine level of HIV Testing Uptake and Late Diagnosis among Urban Population of EthiopiaDesignWe used data from the Ethiopian Population Based HIV Impact assessment in Ethiopia (EPHIA), conducted in 2017/18. EPHIA was a nationally-representative, cross-sectional and household-based study, conducted in urban Ethiopia which used a two-stage cluster sampling design with stratification into small and large urban areas. The EPHIA data were collected from 19,136 adults aged 15 to 64 years. For current study, we considered self-reports first diagnosis to estimate the testing uptake and also consider HIV LAg avidity Vs Viral Load Vs plasma Antiretroviral drug level algorithm to categorize the late diagnosis. In this analysis, a 2-level multilevel mixed-effect logistic regression model was employed using STATA v16. The effects of individual-level predictors were quantified by the estimates from the fixed-effect part of the model with a p-value less than 0.05 or 95% CI.ResultBy the year 2017/18, overall 29.4% of people living with HIV (PLHIV) were never tested in urban Ethiopia. Never tested male was significantly higher (32.4%; 95%: 31.0, 33.9) than females (26.4%; 95%: 25.3, 27.5) while it ranged from 28.3% to 47.8% among 45–54 and 15–24 years, respectively. By the same study period, 25.9% (95% CI: 21.7, 30.2) of PLHIV were lately diagnosed and male was significantly higher (36.8%; 95%: 28.0, 46.6) than females (20.8%; 95%: 17.3, 24.9). Late HIV diagnosis was also heterogeneous by various age group categories. Late diagnosis varies by region which ranged from 38.1% in the Gambella to 5.8% in Benishangul Gumuz. HIV testing uptake and late diagnosis was also significantly affected by alcohol use, income and educational status.ConclusionEthiopia was behind the global target for HIV testing uptake. Late diagnosis of HIV constituted one-quarter of all testing HIV positive, and this was significantly higher among adult males. HIV testing offer and early diagnosis strategy need to focus on addressing geographically highly affected regions, and male and young adolescent age groups. The widowed population group, which is highly affected by HIV, and has low level of testing uptake, may require due attention by the HIV program. It is also suggested that HIV care and treatment programs provide a focus to the disadvantaged populations, especially those with limited education and low income.
Social determinants of health exacerbate disparities in COVID-19 illness severity and lasting symptom complaints
Authors: Thomason Moriah E. , Hendrix Cassandra L. , Werchan Denise , Brito Natalie H. 
Published: July 2021

AbstractBACKGROUNDIncreasing reports of long-term symptoms following COVID-19 infection, even among mild cases, necessitates systematic investigation into the prevalence and type of lasting illness. Notably, there is limited data regarding the influence of social determinants of health, like perceived discrimination and economic stress, which may exacerbate COVID-19 health risks. The primary goals of this study are to test the bearing of subjective experiences of discrimination, financial security, and quality of care on illness severity and lasting symptom complaints.METHODS1,584 recovered COVID-19 patients that experienced mild to severe forms of the disease provided information about their illness, medical history, lasting symptoms, and psychosocial information. Prevalence data isolated differences in patients infected early versus late in the pandemic. Path analyses examined hypothesized associations between discrimination, illness severity, and lasting symptoms. Post hoc logistic regressions tested social determinants hypothesized to predict neurological, cognitive, or mood symptoms.RESULTS70.6% of patients reported presence of one or more lasting symptoms after recovery. Neural systems were especially impacted, and 19.4% and 25.1% of patients reported mood or cognitive/memory complaints, respectively. Path models demonstrated that frequency and stress about experiences of discrimination predicted increased illness severity and increased lasting symptom count, even when adjusting for sociodemographic factors and mental/physical health comorbidities. Notably, this effect was specific to stress related to discrimination, and did not extend to general stress levels. Further, perceived but not objective socioeconomic status (SES) was associated with increased lasting symptom complaints after recovery. Finally, associations between discrimination and illness differed with individual perceptions about quality of medical care.CONCLUSIONSLasting symptoms after recovery from COVID-19 are highly prevalent and neural systems are significantly impacted. Importantly, psychosocial factors (perceived discrimination and perceived SES) can exacerbate individual health risk. This study provides actionable directions for improved health outcomes by establishing that sociodemographic risk and medical care influence near and long-ranging health outcomes.
Taller height and risk of coronary heart disease and cancer: a within-sibship Mendelian randomization study
Authors: Howe Laurence J , Brumpton Ben , Rasheed Humaira , Åsvold Bjørn Olav , Willer Cristen J , Smith George Davey , Davies Neil M 
Published: July 2021

AbstractTaller people have lower risk of coronary heart disease but higher risk of many cancers. Mendelian randomization studies in unrelated individuals have suggested that these relationships are potentially causal. However, Mendelian randomization estimates from samples of unrelated individuals are sensitive to demography (population stratification, assortative mating) and familial (indirect genetic) effects. Height could influence disease risk via anatomic and physiological effects of height (e.g., number of cells or the bore of arteries) or previous results may have been confounded by early-life environmental factors (e.g., parental socioeconomic position and nutrition).In this study, we performed within-sibship Mendelian randomization analyses using 77,757 siblings, a design robust against demography and indirect genetic effects of parents. Within-sibship Mendelian randomization estimated that one SD taller height lowers odds of coronary heart disease by 14% (95% CI: 3% to 23%) but increases odds of cancer by 18% (95% CI: 3% to 34%). There was some evidence that taller height reduces systolic blood pressure and LDL cholesterol, which may mediate some of the protective effect of taller height on coronary heart disease risk.For the first time, we have demonstrated that purported effects of height on adulthood disease risk are unlikely to be explained by demographic or familial factors, and so likely reflect an individual-level causal effect. Disentangling the mechanisms via which height affects disease risk may improve understanding of the aetiologies of atherosclerosis and carcinogenesis.
Regeneration of Plants from DNA-free Edited Grapevine Protoplasts
Authors: Scintilla Simone , Salvagnin Umberto , Giacomelli Lisa , Zeilmaker Tieme , Malnoy Mickael A. , van der Voort Jeroen Rouppe , Moser Claudio 
Published: July 2021

AbstractCRISPR-Cas technology has widely extended the application fields of genome editing in plant breeding, making possible specific and minimal mutations within a genetic pool. With respect to standard genome editing technologies, CRISPR-Cas machinery can be introduced in the form of ribonucleoproteins (RNPs), thus avoiding the introduction of exogenous DNA into cells. The interest on the application of DNA-free delivery into plant cells is constantly increasing, especially in the case of valuable woody plants elite varieties where CRISPR-Cas9 technology would preserve their genotype, while still resulting into targeted genetic modifications. The use of single cells fits well the requirements of New Breeding Technologies, by ensuring both the CRISPR-Cas DNA-free delivery as RNPs and, since every plant will be regenerated from a single edited cell, the absence of chimerism. However, the use of protoplasts cell culture from woody plants is generally hampered by low editing efficiencies and an unsuccessful regenerative process.We here describe a successful DNA-free methodology to obtain fully edited grapevine plants, regenerated from protoplasts obtained from V. vinifera cv. Crimson seedless L. embryogenic callus. The transfected protoplasts were edited on the Downy Mildew susceptibility gene VvDMR6-2. The regenerated edited plants exhibited homozygous deletions of 1bp or 2bp, and homozygous insertion of 1bp.
A new pipeline for the normalization and pooling of metabolomics data
Authors: Viallon Vivian , His Mathilde , Rinaldi Sabina , Breeur Marie , Gicquiau Audrey , Hemon Bertrand , Overvad Kim , Tjønneland Anne , Rostgaard-Hansen Agnetha Linn , Rothwell Joseph A. , Lecuyer Lucie , Severi Gianluca , Kaaks Rudolf , Johnson Theron , Schulze Matthias B. , Palli Domenico , Agnoli Claudia , Panico Salvatore , Tumino Rosario , Ricceri Fulvio , Verschuren Monique , Engelfriet Peter , Onland Charlotte , Vermeulen Roel , Nøst Therese Haugdahl , Urbarova Ilona , Zamora-Ros Raul , Rodriguez-Barranco Miguel , Amiano Pilar , Huerta José Maria , Ardanaz Eva , Melander Olle , Ottoson Filip , Vidman Linda , Rentoft Matilda , Schmidt Julie A , Travis Ruth C , Weiderpass Elisabete , Johansson Mattias , Dossus Laure , Jenab Mazda , Gunter Marc J , Bermejo Lorenzo , Scherer Dominique , Salek Reza M , Keski-Rahkonen Pekka , Ferrari Pietro 
Published: July 2021

AbstractPooling metabolomics data across studies is often desirable to increase the statistical power of the analysis. However, this can raise methodological challenges as several preanalytical and analytical factors could introduce differences in measured concentrations and variability between datasets. Specifically, different studies may use variable sample types (e.g., serum versus plasma) collected, treated and stored according to different protocols, and assayed in different laboratories using different instruments. To address these issues, a new pipeline was developed to normalize and pool metabolomics data through a set of sequential steps: (i) exclusions of the least informative observations and metabolites and removal of outliers; imputation of missing data; (ii) identification of the main sources of variability through PC-PR2 analysis; (iii) application of linear mixed models to remove unwanted variability, including samples’ originating study and batch, and preserve biological variations while accounting for potential differences in the residual variances across studies. This pipeline was applied to targeted metabolomics data acquired using Biocrates AbsoluteIDQ kits in eight case-control studies nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Comprehensive examination of metabolomics measurements indicated that the pipeline improved the comparability of data across the studies. Our pipeline can be adapted to normalize other molecular data, including biomarkers as well as proteomics data, and could be used for pooling molecular datasets, for example in international consortia, to limit biases introduced by inter-study variability. This versatility of the pipeline makes our work of potential interest to molecular epidemiologists.
The HDL particle composition determines its anti-tumor activity in pancreatic cancer
Authors: Bauer Raimund , Kührer Kristina , Udonta Florian , Wroblewski Mark , Ben-Batalla Isabel , Hassl Ingrid , Körbelin Jakob , Röhrl Clemens , Unseld Matthias , Jauhiainen Matti , Hengstschläger Markus , Loges Sonja , Stangl Herbert 
Published: July 2021

AbstractDespite significant efforts in the last years to improve therapeutic options, pancreatic cancer remains a fatal disease and is expected to become the second leading cause of cancer-related deaths in the next decade. Late diagnosis and a complex, fibrotic tumor microenvironment produces a therapeutically hardly approachable situation with rapidly emerging resistance mechanisms. In response to this hostile microenvironment, previous research identified lipid metabolic pathways to be highly enriched in pancreatic ductal adenocarcinoma (PDAC) cells. Thereby, cholesterol uptake and synthesis was shown to promote a growth advantage to, and chemotherapy resistance for PDAC tumor cells. Here, we demonstrate that efficient, net-cholesterol removal from cancer cells, driven by high-density lipoprotein (HDL) mediated efflux, results in a significant PDAC cell growth reduction, apoptosis and a decreased PDAC tumor development in vivo. This effect is driven by an HDL particle composition-dependent interaction with SR-B1 and ABCA1 on cancer cells, two major lipid flux receptors, which differentially regulate cholesterol transport at the plasma membrane. Eventually, we show that pancreatic cancer patients display reduced plasma levels of HDL-cholesterol, directly translating into a reduced cholesterol efflux capacity of patient-derived plasma samples. We conclude that cholesterol depletion from PDAC cells, together with possible interventions that shunt the import and endogenous synthesis pathways of cholesterol, might represent a promising strategy to increase and complement the currently available treatment options to improve the prognosis of patients suffering from PDAC.