bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effective high-throughput RT-qPCR screening for SARS-CoV-2 infections in children
Authors: Dewald Felix , Suárez Isabelle , Johnen Ronja , Grossbach Jan , Moran-Tovar Roberto , Steger Gertrud , Joachim Alexander , Rubio Gibran Horemheb , Fries Mira , Behr Florian , Kley Joao , Lingnau Andreas , Kretschmer Alina , Gude Carina , Beazes-Flores Guadelupe , del Valle David Laveaga , Roblero-Hernandez Alberto , Magana-Cerino Jesus , Hernandez Adriana Torres , Ruiz-Quinones Jesus , Schega Konstantin , Linne Viktoria , Junker Lena , Wunsch Marie , Heger Eva , Knops Elena , Di Cristanziano Veronica , Meyer Meike , Hünseler Christoph , Weber Lutz T. , Lüers Jan-Christoffer , Quade Gustav , Wisplinghoff Hilmar , Tiemann Carsten , Zotz Rainer , Jomaa Hassan , Pranada Arthur , Herzum Ileana , Cullen Paul , Schmitz Franz-Josef , Philipsen Paul , Kirchner Georg , Knabbe Cornelius , Hellmich Martin , Buess Michael , Wolff Anna , Kossow Annelene , Niessen Johannes , Jeworutzki Sebastian , Schräpler Jörg-Peter , Lässig Michael , Dötsch Jörg , Fätkenheuer Gerd , Kaiser Rolf , Beyer Andreas , Rybniker Jan , Klein Florian 
Published: February 2022

AbstractSystematic SARS-CoV-2 testing is a valuable tool for infection control and surveillance. However, broad application of high sensitive RT-qPCR testing in children is often hampered due to unpleasant sample collection, limited RT-qPCR capacities and high costs. Here, we developed a high-throughput approach (‘Lolli-Method’) for SARS-CoV-2 detection in children, combining non-invasive sample collection with an RT-qPCR-pool testing strategy. SARS-CoV-2 infections were diagnosed with sensitivities of 100% and 93.9% when viral loads were >106 copies/ml and >103 copies/ml in corresponding Naso-/Oropharyngeal-swabs, respectively. For effective application of the Lolli-Method in schools and daycare facilities, SEIR-modeling indicated a preferred frequency of two tests per week. The developed test strategy was implemented in 3,700 schools and 698 daycare facilities in Germany, screening over 800,000 individuals twice per week. In a period of 3 months, 6,364 pool-RT-qPCRs tested positive (0.64%), ranging from 0.05% to 2.61% per week. Notably, infections correlated with local SARS-CoV-2 incidences and with a school social deprivation index. Moreover, in comparison with the alpha variant, statistical modeling revealed a 36.8% increase for multiple (≥2 children) infections per class following infections with the delta variant. We conclude that the Lolli-Method is a powerful tool for SARS-CoV-2 surveillance and infection control in schools and daycare.
Measuring patient centeredness with German language Patient-Reported Experience Measures (PREM) – a systematic review and qualitative analysis according to COSMIN
Authors: Mihaljevic André L. , Dörr-Harim Colette , Kalkum Eva , Strunk Guido 
Published: February 2022

AbstractBackgroundPatient centeredness is an integral part of the quality of care. Patient-reported experience measures (PREMs) are assumed to be an appropriate tool to assess patient-centredness. An evaluation of German-speaking PREMs is lacking.ObjectiveTo perform a systematic review and qualitative analysis of psychometric measurement qualities of German-speaking PREMs.MethodsA systematic literature search was performed in Medline, PsycInfo, CINHAL, Embase, Cochrane database (last search 9th November 2021) for studies describing generic, surgery-or cancer-specific PREMs. Subsequently, questionnaires that were not in German or for which no German translation exists were excluded. Furthermore, questionnaires, that are for healthcare professionals rather than patients as well as disease-specific questionnaires were excluded. Baseline data for all studies was extracted by two independent reviewers. Psychometric measurement qualities of the questionnaires were assessed according to the COSMIN guidelines.ResultsIn total, 3457 abstracts were screened, of which 3345 were excluded. The remaining 112 articles contained 51 PREMs, of which 12 were either developed in or translated into German: 8 generic (NORPEQ, PPE-15, PEACS, HCAHPS, QPPS, DUQUE, PEQ-G, Schoenfelder et al.), 4 cancer-specific (EORTC IN-PATSAT32, PSCC-G, Danish National Cancer Questionnaire, SCCC) and no surgery-specific PREM. None of the PREMs covered all 16 domains patient-centeredness. Overall rating of structural validity was adequate only for PEACS and HCAHPS. High ratings for internal consistency were given for NORPEQ, Schoenfelder et al., PSCC-G and the SCCC. Cross-cultural validity for translated questionnaires was adequate only for the PSCC-G, while reliability was adequately assessed only for the EORTC IN-PATSAT32. Due to a lack of measurement gold standard and minimal important change, criterion validity and measurement invariance could not be assessed Most PREMs showed the expected outcomes for hypotheses testing for construct validity.ConclusionNone of the PREMs has been fully evaluated in German. Based on current evidence, the EORTC IN-PATSAT32 and PSCC-G can be recommended for cancer patients, while HCAHPS, NORPEQ, PPE-15 and PEACS might be used as generic PREMs. Compared to other languages PREM development in German is rudimentary and no comprehensive PREM system is currently available.RegistrationPROSPERO CRD42021276827FundingNone
Profiling of humoral immune responses to norovirus in children across Europe
Authors: Villabruna Nele , Izquierdo-Lara Ray , Schapendonk Claudia M.E. , de Bruin Erwin , Chandler Felicity , Thao Tran Thi Nhu , Westerhuis Brenda M. , van Beek Janko , Sigfrid Louise , Giaquinto Carlo , Goossens Herman , Bielicki Julia A. , Vasconcelos Malte Kohns , Fraaij Pieter L.A. , Koopmans Marion P.G. , de Graaf Miranda 
Published: February 2022

AbstractHuman noroviruses are a major cause of gastroenteritis outbreaks worldwide. The majority of outbreaks and sporadic cases are caused by norovirus genotype GII.4 but 48 capsid genotypes and 60 polymerase genotypes (P-types) have been described, some of which are frequently reported while others are rarely detected. Little is known about the circulation and reservoirs of the less common genotypes. In this study, we have investigated whether children could pose a possible reservoir for undetected circulation of norovirus diversity. We, therefore, tested IgG and IgA responses of sera obtained from 287 children aged <1-month to 5.5-years on a protein microarray against P particles representing 30 norovirus GI and GII genotypes. We further profiled immune responses against the P-type by assessing antigenicity and seroprevalence of the non-structural proteins. The overall seroprevalence was 95.3% in children up to six months old (maternal antibodies), followed by a decrease to 59.6% up to 12 months, and an increase to 84.7% by the age of 5.5 years. We detected antibody responses against all tested genotypes, with the most specific IgG and IgA responses directed against the GII.2, GII.3, GII.4, and GII.6 capsid genotypes, which are the most frequently reported noroviruses in outbreaks. We also detected antibodies against the non-structural proteins p48 and p22 in sera of older children, predominantly against GII genotypes.While we found no evidence to suggest that rarely detected genotypes widely circulate in children, this is the first study to investigate seroprevalence against such a wide variety of human norovirus capsid and polymerase genotypes.ImportanceNorovirus is a leading cause of epidemic acute gastroenteritis, causing severe disease in children, the elderly, and immunocompromised individuals. Although norovirus is a diverse genus of viruses, the majority of reported cases are caused by viruses of the GII.4 genotype. Many of the genotypes are rarely detected and it is unknown where they circulate between outbreaks. Here we investigated the possibility of children posing a reservoir for undetected circulation. While previous serological studies have tested antibodies against a limited set of capsid genotypes, we profiled the antibody repertoire of children against the capsid and the non-structural proteins, representing the known diversity of human noroviruses. While we detected high seroprevalence in children older than one year, we found no evidence to suggest a wide circulation of rare genotypes in children in Europe.
Appropriately smoothing prevalence data to inform estimates of growth rate and reproduction number
Authors: Eales Oliver , Ainslie Kylie E. C. , Walters Caroline E. , Wang Haowei , Atchison Christina , Ashby Deborah , Donnelly Christl A. , Cooke Graham , Barclay Wendy , Ward Helen , Darzi Ara , Elliott Paul , Riley Steven 
Published: February 2022

AbstractThe time-varying reproduction number (Rt) can change rapidly over the course of a pandemic due to changing restrictions, behaviours, and levels of population immunity. Many methods exist that allow the estimation of Rt from case data. However, these are not easily adapted to point prevalence data nor can they infer Rt across periods of missing data. We developed a Bayesian P-spline model suitable for fitting to a wide range of epidemic time-series, including point-prevalence data. We demonstrate the utility of the model by fitting to periodic daily SARS-CoV-2 swab-positivity data in England from the first 7 rounds (May 2020 – December 2020) of the REal-time Assessment of Community Transmission-1 (REACT-1) study. Estimates of Rt over the period of two subsequent rounds (6-8 weeks) and single rounds (2-3 weeks) inferred using the Bayesian P-spline model were broadly consistent with estimates from a simple exponential model, with overlapping credible intervals. However, there were sometimes substantial differences in point estimates. The Bayesian P-spline model was further able to infer changes in Rt over shorter periods tracking a temporary increase above one during late-May 2020, a gradual increase in Rt over the summer of 2020 as restrictions were eased, and a reduction in Rt during England’ s second national lockdown followed by an increase as the Alpha variant surged. The model is robust against both under-fitting and over-fitting and is able to interpolate between periods of available data; it is a particularly versatile model when growth rate can change over small timescales, as in the current SARS-CoV-2 pandemic. This work highlights the importance of pairing robust methods with representative samples to track pandemics.
The Simple One-step stool processing method for detection of Pulmonary tuberculosis: a study protocol to assess the robustness, stool storage conditions and sampling strategy for global implementation and scale-up
Authors: de Haas Petra , Yenew Bazezew , Diriba Getu , Amare Misikir , Slyzkyi Andrii , Demissie Yohannes , Sherefdin Bihil , Bedru Ahmed , Mengesha Endale , Dememew Zewdu Gashu , Kebede Abebaw , Getahun Muluwork , Tiemersma Edine , Jerene Degu 
Published: February 2022

AbstractBackgroundXpert MTB/RIF Ultra (Xpert-Ultra) provides timely results with good sensitivity and acceptable specificity with stool samples in children for bacteriological confirmation of tuberculosis (TB). This study aims to optimize the Simple One-Step (SOS) stool processing method for testing stool samples using the Xpert-Ultra in children and adults in selected health facilities in Addis Ababa, Ethiopia. The study is designed to assess the robustness of the SOS stool method, to help fine-tune the practical aspects of performing the test and to provide insights in stool storage conditions and sampling strategies before the method can be implemented and scaled in routine settings in Ethiopia as well as globally.Methods and designThe project “painless optimized diagnosis of TB in Ethiopian children” (PODTEC) will be a cross sectional study where three key experiments will be carried out focusing on 1) sampling strategy to investigate if the Xpert-UltraM.tuberculosis(MTB) -positivity rate depends on stool consistency, and if sensitivity can be increased by taking more than one stool sample from the same participant, or doing multiple tests from the same stool sample, 2) storage conditions to determine how long and at what temperature stool can be stored without losing sensitivity, and 3) optimization of sensitivity and robustness of the SOS stool processing method by varying sample processing steps, stool volume, and sampling from the stool-sample reagent mixture.Stool samples will be collected from participants (children and adults) who are either sputum or naso-gastric aspiration (NGA) and/or stool Xpert-Ultra MTB positive depending on the experiment. Stool samples from these participants, recruited from 22 sites for an ongoing related study, will be utilized for the PODTEC experiments. The sample size is estimated will be 50 participants.We will use EpiData for data entry and Stata for data analysis purposes. The main analyses will include computing the loss or gain in the Xpert-Ultra MTB positivity rate, and rates of unsuccessful test results. The differences in the positivity rate regarding testing more than one sample per child, different storage, and processing conditions, will be compared to the baseline (on-site) Xpert-Ultra result.Ethics and disseminationThe protocol was reviewed and approved by the Ethical Review Board of the Ethiopian Public Health Institute (EPHI-IRB) (Protocol no EPHI-IRB-234-2020). The study results will be shared with the national TB program and stakeholders to the benefit of further roll out of the test in a routine Ethiopian setting. The results will also be disseminated in peer-reviewed scientific journals.
Establishing a marine monitoring programme to assess antibiotic resistance: a case study from the Gulf Cooperation Council (GCC) region
Authors: Light Edel , Baker-Austin Craig , Card Roderick M. , Ryder David , Alves Mickael Teixeira , Al-Sarawi Hanan A. , Abdulla Khalil Hasan , Stahl Henrik , AL-Ghabshi Aliya , Ghoribi Majed Al , Balkhy Hanan H. , Joseph Andrew , Hughes Alexandra , Verner-Jeffreys David W. , Lyons Brett P. , Le Quesne Will J.F. 
Published: February 2022

AbstractThe World Health Organization considers antimicrobial resistance as one of the most pressing global issues which poses a fundamental threat to human health, development, and security. Due to demographic and environmental factors, the marine environment of the Gulf Cooperation Council (GCC) region may be particularly susceptible to the threat of antimicrobial resistance. However, there is currently little information on the presence of AMR in the GCC marine environment to inform the design of appropriate targeted surveillance activities. The objective of this study was to develop, implement and conduct a rapid regional baseline monitoring survey of the presence of AMR in the GCC marine environment, through the analysis of seawater collected from high-risk areas across four GCC states: (Bahrain, Oman, Kuwait, and the United Arab Emirates). 560 Escherichia coli strains were analysed as part of this monitoring programme between December 2018 and May 2019. Multi-drug resistance (resistance to three or more structural classes of antimicrobials) was observed in 32.5% of tested isolates. High levels of reduced susceptibility to ampicillin (29.6%), nalidixic acid (27.9%), tetracycline (27.5%), sulfamethoxazole (22.5%) and trimethoprim (22.5%) were observed. Reduced susceptibility to the high priority critically important antimicrobials: azithromycin (9.3%), ceftazidime (12.7%), cefotaxime (12.7%), ciprofloxacin (44.6%), gentamicin (2.7%) and tigecycline (0.5%), was also noted. A subset of 173 isolates was whole genome sequenced, and high carriage rates of qnrS1 (60/173) and blaCTX-M-15 (45/173) were observed, correlating with reduced susceptibility to the fluoroquinolones and third generation cephalosporins, respectively. This study is important because of the resistance patterns observed, the demonstrated utility in applying genomic-based approaches to routine microbiological monitoring, and the overall establishment of a transnational AMR surveillance framework focussed on coastal and marine environments.
From Volume to Value: Comparative value, quality, and cost between three treatment modalities for early childhood caries
Authors: Okuji David , Jivraj Ashiana , Wu Yinxiang 
Published: February 2022

AbstractContextIn recent decades there has been a shift from a reimbursement system based upon treatment “volume” to “value.”AimsTo compare value, quality, and cost of three treatment modalities for early childhood caries: surgical care with and without general anesthesia, and non-surgical care with disease management.Settings and DesignThrough an analytical, observational, cross-sectional design, data was collected from 487 pediatric subjects treated at health centers in seven states. Nearly 95% of the subjects were beneficiaries of the United States government Medicaid health insurance program, which supports families with low socioeconomic status.Methods and MaterialQuality was measured with a Parental-Reported Symptom and Service Quality questionnaire, adapted from the validated Early Child Oral Health Impact Scale, Child-Oral Impacts on Daily Performance, and Dental Consumer Assessments of Healthcare Providers and Systems surveys. Cost was measured by the labor cost for clinicians and adjusted by total relative value units for all treatment procedures. Value was calculated as the quotient of the weighted quality score and the adjusted cost, multiplied by a coefficient.Statistical AnalysisValue comparisons were analyzed using chi-square, ANOVA, and likelihood ratio tests.ResultsChildren treated with non-surgical, disease management had significantly higher parental-perceived quality, lower cost, and higher value when compared to the two surgical treatment modalities.ConclusionsDentists should consider that non-surgical treatment yields higher “value” than surgical treatments for the management of early childhood caries. Payers and consumers would benefit by comparing treatment “value” when choosing institutions and providers for the management of early childhood caries.
Tissue specific dual RNA-seq defines host-parasite interplay in murine visceral leishmaniasis caused by Leishmania donovani and Leishmania infantum
Authors: Forrester Sarah , Goundry Amy , Dias Bruna Torres , Leal-Calvo Thyago , Moraes Milton Ozório , Kaye Paul M. , Mottram Jeremy C. , Lima Ana Paula C. A. 
Published: February 2022

AbstractVisceral leishmaniasis is associated with hepato-splenomegaly and altered immune and haematological parameters in both pre-clinical animal models and humans. We studied mouse experimental visceral leishmaniasis caused by Leishmania infantum and Leishmania donovani in BALB/c mice using dual RNA-seq to investigate the transcriptional response of host and parasite in liver and spleen. We identified only 4 species-specific parasite expressed genes (SSPEGs; log2FC >1, FDR <0.05) in the infected spleen, and none in the infected liver. For the host transcriptome, we found 789 differentially expressed genes (DEGs; log2FC >1, FDR <0.05) in the spleen that were common to both infections, with IFNγ signaling and complement and coagulation cascade pathways highly enriched, and an additional 286 and 186 DEGs that were selective to L. donovani and L. infantum infection respectively. Among those, there were network interactions between genes of amino acid metabolism and PPAR signaling in L. donovani infection and increased IL1β and positive regulation of fatty acid transport in L. infantum infection, although no pathway enrichment was observed. In the liver, there were 1939 DEGs in mice infected with either L. infantum or L. donovani in comparison to uninfected mice, and the most enriched pathways were IFNγ signaling, neutrophil mediated immunity, complement and coagulation, cytokine-chemokine responses and hemostasis. Additionally, 221 DEGs were selective in L. donovani and 429 DEGs in L. infantum infections. These data show that the host response for these two visceral leishmaniasis infection models is broadly similar, and ∼10% of host DEGs vary in infections with either parasite species.ImportanceVisceral leishmaniasis (VL) is caused by two species of Leishmania parasites, L. donovani in the Old World and L. infantum in the New World and countries bordering the Mediterranean. Although cardinal features such as hepato-splenomegaly and alterations in blood and immune function are evident, clinical presentation may vary by geography, with for example severe bleeding often associated with VL in Brazil. Although animal models of both L. donovani and L. infantum have been widely used to study disease pathogenesis, a direct side-by-side comparison of how these parasites species impact the infected host and/or how they might respond to the stresses of mammalian infection has not been previously reported. Identifying common and distinct pathways to pathogenesis will be important to ensure that new therapeutic or prophylactic approaches will be applicable across all forms of VL.
Regulation of mannitol metabolism inEnterococcus faecalisand association withparEF0409toxin-antitoxin locus function
Authors: Anbalagan Srivishnupriya , Sadlon Jessie , Weaver Keith 
Published: February 2022

AbstractTheparEF0409type I toxin-antitoxin locus is situated between genes for two paralogous mannitol-family phosphoenolpyruvate phosphotransferase systems (PTS). In order to address the possibility thatparEF0409function was associated with sugar metabolism, genetic and phenotypic analyses were performed on the flanking genes. It was found that the genes were transcribed as two operons; the downstream operon essential for mannitol transport and metabolism and the upstream operon performing a regulatory function. In addition to genes for the PTS components, the upstream operon encodes a gene similar tomtlR, the key regulator of mannitol metabolism in other Gram-positive bacteria. We confirmed that this gene is essential for regulation of the downstream operon and identified putative phosphorylation sites required for carbon catabolite repression and mannitol-specific regulation. Genomic comparisons revealed that this dual operon organization of mannitol utilization genes is uncommon in enterococci and that association with a toxin-antitoxin system is unique toE. faecalis. Finally, we consider possible links betweenparEF0409function and mannitol utilization.ImportanceEnterococcus faecalisis both a common member of the human gut microbiota and an opportunistic pathogen. Its evolutionary success is partially due to its metabolic flexibility: in particular, its ability to import and metabolize a wide variety of sugars. While a large number of phosphoenolpyruvate phosphotransferase sugar transport systems have been identified in theE. faecalisgenome bioinformatically, the specificity and regulation of most of these systems remains undetermined. Here we characterize a complex system of two operons flanking a type I toxin-antitoxin system required for the transport and metabolism of the common dietary sugar mannitol. We also determine the phylogenetic distribution of mannitol utilization genes in the enterococcal genus and discuss the significance of association with toxin-antitoxin systems.