bluuebunny/crossref_metadata_2025_split huggingface dataset:
MRP8/14 serum levels as diagnostic markers for systemic juvenile idiopathic arthritis in children with prolonged fever
Authors: Park Carolin , Miranda-Garcia María , Berendes Rainer , Horneff Gerd , Kuemmerle-Deschner Jasmin , Ganser Gerd , Huppertz Hans-Iko , Minden Kirsten , Haas Johannes-Peter , Jansson Annette F , Borte Michael , Schuetz Catharina , Oommen Prasad , Frosch Michael , Schlueter Bernhard , Richter-Unruh Annette , Kessel Christoph , Hinze Claas , Wittkowski Helmut , Roth Johannes , Foell Dirk , Holzinger Dirk 
Published: September 2021

Abstract

Objectives
Differential diagnosis in children with prolonged fever is challenging. In particular, differentiating systemic-onset JIA (SJIA) from infectious diseases is difficult. Biomarkers are needed that support the diagnostic work-up. The aim of this study was to validate the usefulness of Myeloid-related protein 8/14 (MRP8/14) measurements in the diagnostic work-up of febrile children and to transfer it to clinical practice.

Methods
Data for 1110 paediatric patients were included and divided into two cohorts: (cohort A) for validation of MRP8/14 test performance with three different testing systems: the experimental ELISA, commercial ELISA and an innovative (point-of-care test) lateral flow immunoassay (LFIA); (cohort B) to validate the diagnostic accuracy with the two latter assays.

Results
In cohort A (n = 940), MRP8/14 was elevated in SJIA (12 110 ± 2650 ng/ml mean ± 95% CI) compared with other diagnoses (including infections and autoinflammatory diseases; 2980 ± 510 ng/ml) irrespective of fever and anti-inflammatory treatment (P &lt; 0.001). In untreated patients with fever (n = 195) MRP8/14 levels in SJIA (19 740 ± 5080 ng/ml) were even higher compared with other diagnoses (4590 ± 1160 ng/ml) (P &lt; 0.001, sensitivity 73%, specificity 90%). In group B1, the performance of the tests was confirmed in untreated patients with fever (n = 170): commercial ELISA (sensitivity 79%, specificity 89%) and LFIA (sensitivity 84%, specificity 81%). Compared with ferritin, IL-18, ESR, soluble IL-2 receptor and procalcitonin, MRP8/14 showed the best accuracy.

Conclusion
MRP8/14 serum analyses have been validated as a helpful tool supporting the diagnosis of SJIA in febrile children. The results could be confirmed with commercial ELISA and LFIA enabling a rapid diagnostic point-of-care screening test.
Resilience, Growth, and Posttraumatic Symptoms among Social Workers Who Are “Doubly Exposed”
Authors: Finklestein Michal , Laufer Avital 
Published: September 2021

Abstract
The current study examined posttraumatic stress (PTS), resilience, and posttraumatic growth (PTG) among social workers (SWs) in Israel exposed to trauma both directly and indirectly through their work. Two groups of SWs were examined: SWs with high exposure to rocket attacks (n = 50) and SWs with low exposure to rocket attacks (n = 52). Measures included objective, subjective, and professional exposure; PTS; vicarious traumatization (VT); resilience; and PTG. Differences between the two groups were found regarding objective, subjective, and professional exposure, as well as PTS, VT, and PTG. No differences were found regarding resilience. PTS and PTG were positively associated. An interaction between group and resilience in predicting PTS and PTG was found. In the highly exposed group, resilience was negatively associated with PTS and positively with PTG, whereas for the low-exposed group resilience was not associated with PTS and was negatively associated with PTG. The discussion focuses on the need to understand the role of resilience and PTG in the psychological reaction of SWs to direct as well as indirect trauma; it also weighs the possibility that PTG serves as a salutogenic variable under high-trauma exposure but as an illusionary means of self-enhancement under low-level exposure.
Principal Component Analysis to Distinguish Seizure Liability of Drugs in Human iPS Cell-Derived Neurons
Authors: Ishibashi Y , Odawara A , Kinoshita K , Okamura A , Shirakawa T , Suzuki I 
Published: September 2021

Abstract
Screening for drug discovery targeting the central nervous system requires the establishment of efficient and highly accurate toxicity test methods that can reduce costs and time while maintaining high throughput using the function of an in vitro neural network. In particular, an evaluation system using a human-derived neural network is desirable in terms of species difference. Despite the attention, the microelectrode array (MEA) is attracting among the evaluation systems that can measure in vitro neural activity, an effective analysis method for evaluation of toxicity and mechanism of action has not yet been established. Here we established analytical parameters and multivariate analysis method capable of detecting seizure liability of drugs using MEA measurement of human iPS cell-derived neurons. Using the spike time series data of all drugs, we established periodicity as a new analytical parameter. Periodicity has facilitated the detection of responses to seizurogenic drugs, previously difficult to detect with conventional analytical parameters. By constructing a multivariate analytical method that identifies a parameter set that achieves an arbitrary condition, we found that the parameter set comprising total spikes, maximum frequency (MF), inter- MF interval (IMFI), coefficient of variance of IMFI, and periodicity can uniformly detect the seizure liability of seizurogenic drugs with different mechanisms of action. Seizurogenic drugs were suggested to increase the regularity of the network burst in MEA measurements in human iPS cell-derived neurons.
A primer on rhythm quantification for fish sounds: a Mediterranean case study
Authors: Burchardt Lara S. , Picciulin Marta , Parmentier Eric , Bolgan Marta 
Published: September 2021

We have used a lately established workflow to quantify rhythms of three fish sound types recorded in different areas of the Mediterranean Sea. So far, the temporal structure of fish sound sequences has only been described qualitatively. Here, we propose a standardized approach to quantify them, opening the path for assessment and comparison of an often underestimated but potentially critical aspect of fish sounds. Our approach is based on the analysis of inter-onset-intervals (IOIs), the intervals between the start of one sound element and the next. We calculate exact beats of a sequence using Fourier analysis and IOI analysis. Furthermore, we report on important parameters describing the variability in timing within a given sound sequence. Datasets were chosen to depict different possible rhythmic properties:Sciaena umbrasounds have a simple isochronous—metronome-like—rhythm. The /Kwa/ sound type emitted byScorpaena spp.has a more complex rhythm, still presenting an underlying isochronous pattern. Calls ofOphidion rocheimales present no rhythm, but a random temporal succession of sounds. This approach holds great potential for shedding light on important aspects of fish bioacoustics. Applications span from the characterization of specific behaviours to the potential discrimination of yet not distinguishable species.
An Analysis of SARS-CoV-2 Vaccine Breakthrough Infections and Associated Clinical Outcomes
Authors: Kerwin Heather , Briggs Rex , Nair-Desai Sameer , Gorzalski Andrew , Pandori Mark , Friedhoff Stefanie , Tsai Thomas C. 
Published: September 2021

AbstractUnderstanding the rate and clinical features associated with vaccine breakthrough infections (VBT) is of critical public health importance. Recent evidence on VBT in Barnstable County, Massachusetts, has prompted guidance on masking for vaccinated individuals in areas of high community-level transmission.1 Additional data is needed to better understand the prevalence and rate of VBT infections. Using detailed disease investigation data from Washoe County, Nevada we sought to assess the rate of symptomatic infection and serious illness among VBT cases compared to non-vaccinated individuals with COVID-19. From February 12 - July 29, 2021, the Washoe County Health District identified and traced 6,128 out of 6,399 reported cases across the sample period. 338 (5.5%) of all cases were identified as breakthrough infections, and 289 (86%) vaccinated individuals had symptomatic infections. Severe clinical outcomes were infrequent with 17 hospitalizations (5% of VBT) and no deaths. Cycle threshold values were not statistically different between vaccinated and unvaccinated individuals.
Quantitative interpretation of Sedia LAg Assay test results after HIV diagnosis
Authors: Sempa Joseph , Grebe Eduard , Welte Alex 
Published: September 2021

AbstractBackgroundTesting for ‘recent HIV infection’ is common in surveillance, where only population-level estimates (of incidence) are reported. Typically, ‘recent infection’ is a category, obtained by applying a threshold on an underlying continuous biomarker from some laboratory assay(s). Somehow interpreting the biomarker values obtained for individual subjects, for example interpreting them as estimates of the date of infection, has obvious potential applications in the context of studies of early infection, and has also for some years attracted significant interest as an extra component of post-test counselling and treatment initiation. The applicable analyses have typically run aground on the complexity of the full biomarker growth model, which is in principle a non-linear mixed-effects model of unknown structure, the fitting of which seems infeasible from realistically obtainable data.MethodsIt is known that to estimate Mean Duration of Recent Infection (MDRI) at a given value of the recent/non-recent -infection discrimination threshold, one may compress the full biomarker growth model into a relation capturing the probability of a recent test result as a function of time since infection. Noting that the time-derivative (gradient) of this curve (for a value of threshold – h) is identical to the formal likelihood relevant to Bayesian inference of the infection date, for a subject yielding an assay result * h * on the date of their first positive HIV test. This observation bypasses the need for fitting a complex detailed biomarker growth model. Using publicly available data from the CEPHIA collaboration, we calculated curves for a range of thresholds for the Sedia Lag assay and performed Bayesian inference of infection data, given a uniform prior implied by a last negative and first positive test.ResultsWe demonstrate the generation of posteriors for infection date, for patients with various delays between their last negative and first positive HIV test, and a range of LAg assay results (ODn) hypothetically obtained on the date of the first positive result.ConclusionDepending on the last-negative / first-positive interval, there is a range of ODn values that yields posteriors significantly different from the uniform prior one would be left with based merely on interval censoring. Hence, a LAg ODn obtained on the date of, or soon after, diagnosis contains potentially significant information about infection dating. It seems worth analysing other assays with meaningful dynamic range, especially tests already routinely used in primary HIV diagnosis (for example chemiluminescent assays and reader/cartridge lateral flow tests which admit objective variable line intensity readings) which have a sufficient dynamic range that corresponds to a clinically meaningful range of times-since-infection that are worth distinguishing from each other.
Depressive symptoms are associated with cigarette smoking among tuberculosis patients in Botswana
Authors: Jones-Patten Alexandria , Wang Qiao , Molebatsi Keneilwe , Novotny Thomas E. , Siddiqi Kamran , Modongo Chawangwa , Zetola Nicola M. , Mbongwe Bontle , Shin Sanghyuk S. 
Published: September 2021

AbstractBackgroundResearchers have increasingly recognized the adverse effects of smoking on tuberculosis (TB) outcomes. Smoking may be a maladaptive coping mechanism for depression and anxiety among TB patients; however, this association has not yet been investigated.Design/MethodsWe conducted a cross-sectional study among newly diagnosed TB patients between January and December 2019 in Gaborone, Botswana, and evaluated factors associated with cigarette smoking. Using the Patient Health Questionnaire-9 and the Zung Self-Rating Anxiety scale, we collected depression and anxiety scores, respectively; scores of ≥10 indicate depression and scores of ≥36 indicate anxiety. We performed Poisson regression analyses with robust variance to examine whether depression and anxiety were associated with smoking.ResultsOne hundred and eighty participants with TB were enrolled from primary health clinics. Among all enrollees, depression was reported in 46 (27.1%) participants, while anxiety was reported in 60 (44.4%) participants. Overall, 45 (25.0%) participants reported current smoking, and the median number of cigarettes per day was 10. Depressive symptoms were associated with a higher prevalence of smoking (aPR: 1.82; 95% CI = 1.11, 3.01) after adjusting for sex, HIV status, food insecurity, anxiety, and income. The association between anxiety symptoms and cigarette smoking did not reach statistical significance (aPR 1.26; 95% CI: 0.78-2.05).ConclusionsWe found the association between depressive symptoms and smoking among TB patients in Botswana to be significant and the association between anxiety symptoms and cigarette smoking insignificant. Future studies should further investigate these associations when addressing TB care.
Alterations in resting-state activity and functional connectivity in children with 22q11.2 deletion syndrome
Authors: Doherty Joanne L. , Cunningham Adam C. , Chawner Samuel J.R.A. , Moss Hayley M. , Dima Diana C. , Linden David E. J. , Owen Michael J. , van den Bree Marianne B.M. , Singh Krish D. 
Published: September 2021

AbstractBackgroundWhile genetic risk factors for psychiatric and neurodevelopmental disorders have been identified, the neurobiological route from genetic risk to neuropsychiatric outcome remains unclear. 22q11.2 deletion syndrome (22q11.2DS) is a copy number variant (CNV) syndrome associated with high rates of neurodevelopmental and psychiatric disorders including autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD) and schizophrenia. Alterations in neural integration and cortical connectivity have been linked to the spectrum of neuropsychiatric disorders seen in 22q11.2DS and may be a mechanism by which the CNV acts to increase risk. Despite this, few studies have investigated electrophysiological activity and connectivity in this high-risk group.MethodsMagnetoencephalography (MEG) was used to investigate resting-state cortical oscillatory patterns in 34 children with 22q11.2DS and 25 controls aged 10-17 years old. Oscillatory activity and functional connectivity across six frequency bands were compared between groups. Regression analyses were used to explore the relationships between these measures, IQ and neurodevelopmental symptoms.ResultsChildren with 22q11.2DS had atypical oscillatory activity and functional connectivity across multiple frequency bands. In the 22q11.2DS group, low frequency (alpha band) activity was positively associated with cognitive ability, while connectivity was negatively associated with ASD and ADHD symptoms. Frontal high frequency (gamma band) activity and connectivity were positively associated with ASD and ADHD symptoms respectively, while posterior gamma activity was negatively associated with ASD symptoms.ConclusionsThese findings highlight that haploinsufficiency at the 22q11.2 locus alters both local and long-range cortical circuitry, which could be a mechanism underlying neurodevelopmental vulnerability in this high risk group.
Multiplex PCR Assay to Detect High Risk Lineages of Salmonella Typhi and Paratyphi A
Authors: Khokhar Fahad A , Pickard Derek DJ , Dyson Zoe A , Iqbal Junaid , Pragasam Agila K , John Jobin Jacob , Veeraraghavan Balaji , Qamar Farah N , Dougan Gordon , MacQueen Hilary , Rigas Sushila H , Holmes Mark A , Mutreja Ankur 
Published: September 2021

AbstractEnteric fever infections remain a significant public health issue, with up to 20 million infections per year. Increasing rates of antibiotic resistant strains have rendered many first-line antibiotics potentially ineffective. Genotype 4.3.1 (H58) is the main circulating lineage of S. Typhi in many South Asian countries and is associated with high levels of antibiotic resistance. The emergence and spread of extensively drug resistant (XDR) typhoid strains has increased the need for a rapid molecular test to identify and track these high-risk lineages for surveillance and vaccine prioritisation. Current methods require samples to be cultured for several days, followed by DNA extraction and sequencing to determine the specific lineage. We designed and evaluated the performance of a new multiplex PCR assay, targeting S. Paratyphi A as well as the H58 and XDR lineages of S. Typhi on a collection of bacterial strains. Our assay was 100% specific for the identification of lineage specific S. Typhi and S. Paratyphi A, when tested with a mix of non-Typhi Salmonella and non-Salmonella strains. With additional testing on clinical and environmental samples, this assay will allow rapid lineage level detection of typhoid of clinical significance, at a significantly lower cost to whole-genome sequencing. To our knowledge, this is the first report of a SNP-based multiplex PCR assay for the detection of lineage specific serovars of Salmonella Typhi.Data StatementAll supporting data, code and protocols have been provided within the article or through supplementary data files.
SARS-CoV-2 Delta variant of concern in Brazil - multiple introductions, communitary transmission, and early signs of local evolution
Authors: Patané José , Viala Vincent , Lima Loyze , Martins Antonio , Barros Claudia , Marqueze Elaine , Bernardino Jardelina , Moretti Debora , Slavov Svetoslav , Bezerra Rafael , Rodrigues Evandra , Santos Elaine , Brassaloti Ricardo , Cassano Raquel , Mariani Pilar , Kitajima João , Santos Bibiana , Assato Patricia , Costa Felipe , Poleti Mirele , Lesbon Jessika , Chicaroni Elisangela , Banho Cecilia , Sacchetto Lívia , Moraes Marília , Palmieri Melissa , Vilanova Fabiana , Martininghi Maiara , Grotto Rejane , Souza-Neto Jayme , Giovanetti Marta , Alcantara Luiz , Nogueira Maurício , Fukumasu Heidge , Coutinho Luiz , Calado Rodrigo , Kashima Simone , Neto Raul , Covas Dimas , Elias Carolina , Coccuzzo Sandra 
Published: September 2021

AbstractThe dissemination of the Delta VOC in Brazil is still unclear, despite the frequent reports of isolated cases from different Brazilian states. In this report we characterize the dissemination of the Delta VOC in Brazil and where the introductions of this lineage fall within the global Delta phylogeny. We also examined the mutational profile of the largest clade within the Brazilian Delta VOCs, with a focus on samples which were obtained in the State of São Paulo, and especially in the city of São Paulo, the largest metropolis of South America, and a national and international transportation hub.
Metabolite-based dietary supplementation in human type 1 diabetes is associated with microbiota and immune modulation
Authors: Bell Kirstine J. , Saad Sonia , Tillett Bree J. , McGuire Helen M. , Bordbar Sara , Yap Yu Anne , Nguyen Long T. , Wilkins Marc R. , Corley Susan , Brodie Shannon , Duong Sussan , Wright Courtney J. , Twigg Stephen , de St Groth Barbara Fazekas , Harrison Leonard C. , Mackay Charles R. , Gurzov Esteban N. , Hamilton-Williams Emma E. , Mariño Eliana 
Published: September 2021

AbstractBackgroundShort-chain fatty acids (SCFAs) produced by the gut microbiota have beneficial anti-inflammatory and gut homeostasis effects and prevent type 1 diabetes (T1D) in mice. Reduced SCFA production indicates a loss of beneficial bacteria, commonly associated with chronic autoimmune and inflammatory diseases, including T1D and type 2 diabetes. Here we addressed whether a metabolite-based dietary supplement has an impact on humans with T1D. We conducted a single-arm pilot-and-feasibility trial with high-amylose maize resistant starch modified with acetate and butyrate (HAMSAB) to assess safety, while monitoring changes in the microbiota in alignment with modulation of the immune system status.ResultsHAMSAB supplement was administered for six weeks with follow-up at 12 weeks in adults with long-standing T1D. Increased concentrations of SCFA acetate, propionate, and butyrate in stools and plasma were in concert with a shift in the composition and function of the gut microbiota. While glucose control and insulin requirements did not change, subjects with the highest SCFA concentrations exhibited the best glycemic control.Bifidobacterium longum,Bifidobacterium adolescentis, and vitamin B7 production correlated with lower HbA1c and basal insulin requirements. Circulating B and T cells developed a more regulatory phenotype post-intervention.ConclusionChanges in gut microbiota composition, function, and immune profile following six weeks of HAMSAB supplementation were associated with increased SCFAs in stools and plasma. The persistence of these effects suggests that targeting dietary SCFAs may be a mechanism to alter immune profiles, promote immune tolerance and improve glycemic control for the treatment of T1D.Trial registrationACTRN12618001391268. Registered 20 August 2018,https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375792
Design and implementation of multiplexed amplicon sequencing panels to serve genomic epidemiology of infectious disease: a malaria case study
Authors: LaVerriere Emily , Schwabl Philipp , Carrasquilla Manuela , Taylor Aimee R. , Johnson Zachary M. , Shieh Meg , Panchal Ruchit , Straub Timothy J. , Kuzma Rebecca , Watson Sean , Buckee Caroline O. , Andrade Carolina M. , Portugal Silvia , Crompton Peter D. , Traore Boubacar , Rayner Julian C. , Corredor Vladimir , James Kashana , Cox Horace , Early Angela M. , MacInnis Bronwyn L. , Neafsey Daniel E. 
Published: September 2021

AbstractMultiplexed PCR amplicon sequencing (AmpSeq) is an increasingly popular application for cost-effective monitoring of threatened species and managed wildlife populations, and shows strong potential for genomic epidemiology of infectious disease. AmpSeq data for infectious microbes can inform disease control in multiple ways, including measuring drug resistance marker prevalence, distinguishing imported from local cases, and determining the effectiveness of therapeutics. We describe the design and comparative evaluation of two new AmpSeq assays for Plasmodium falciparum malaria parasites: a four-locus panel (‘4CAST’) composed of highly diverse antigens, and a 129-locus panel (‘AMPLseq’) composed of drug resistance markers, highly diverse loci for measuring relatedness, and a locus to detect Plasmodium vivax co-infections. We explore the performance of each panel in various public health use cases with in silico simulations as well as empirical experiments. We find that the smaller 4CAST panel performs reliably across a wide range of parasitemia levels without DNA pre-amplification, and could be highly informative for evaluating the number of distinct parasite strains within samples (complexity of infection), and distinguishing recrudescent infections from new infections in therapeutic efficacy studies. The AMPLseq panel performs similarly to two existing panels of comparable size for relatedness measurement, despite differences in the data and approach used for designing each panel. Finally, we describe an R package (paneljudge) that facilitates design and comparative evaluation of AmpSeq panels for relatedness estimation, and we provide general guidance on the design and implementation of AmpSeq panels for genomic epidemiology of infectious disease.