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571b8b9e35c0647a7e7ecd88ff29ae8a_0
Functional Genetic Variants in DC-SIGNR Are Associated with Mother-to-Child Transmission of HIV-1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2752805/ Boily-Larouche, Geneviève; Iscache, Anne-Laure; Zijenah, Lynn S.; Humphrey, Jean H.; Mouland, Andrew J.; Ward, Brian J.; Roger, Michel 2009-10-07 DOI:10.1371/journal....
571b8b9e35c0647a7e7ecd88ff29ae8a_1
Abstract: BACKGROUND: Mother-to-child transmission (MTCT) is the main cause of HIV-1 infection in children worldwide. Given that the C-type lectin receptor, dendritic cell-specific ICAM-grabbing non-integrin-related (DC-SIGNR, also known as CD209L or liver/lymph node–specific ICAM-grabbing non-integrin (L-SIGN)), can i...
571b8b9e35c0647a7e7ecd88ff29ae8a_2
factors. The implicated H1 and H3 haplotypes share two single nucleotide polymorphisms (SNPs) in promoter region (p-198A) and intron 2 (int2-180A) that were associated with increased risk of both IU (P = 0.045 and P = 0.003, respectively) and IP (P = 0.025, for int2-180A) HIV-1 infection. The promoter variant reduced t...
571b8b9e35c0647a7e7ecd88ff29ae8a_3
Text: Without specific interventions, the rate of HIV-1 mother-tochild transmission (MTCT) is approximately 15-45% [1] . UNAIDS estimates that last year alone, more than 400,000 children were infected worldwide, mostly through MTCT and 90% of them lived in sub-Saharan Africa. In the most heavilyaffected countries, such...
571b8b9e35c0647a7e7ecd88ff29ae8a_4
alternative interventions to antiretroviral therapy for transmission prevention.
571b8b9e35c0647a7e7ecd88ff29ae8a_5
Dendritic cell-specific ICAM-grabbing non-integrin-related (DC-SIGNR, also known as CD209L or liver/lymph node-specific ICAM-grabbing non-integrin (L-SIGN)) can interact with a plethora of pathogens including HIV-1 and is expressed in placental capillary endothelial cells [2] . DC-SIGNR is organized in three distinct d...
571b8b9e35c0647a7e7ecd88ff29ae8a_6
Given the presence of DC-SIGNR at the maternal-fetal interface and its interaction with HIV-1, we hypothesized that it could influence MTCT of HIV-1. To investigate the potential role of DC-SIGNR in MTCT of HIV-1, we carried out a genetic association study of DC-SIGNR in a well-characterized cohort of HIV-infected moth...
571b8b9e35c0647a7e7ecd88ff29ae8a_7
Samples consisted of stored DNA extracts obtained from 197 mother-child pairs co-enrolled immediately postpartum in the ZVITAMBO Vitamin A supplementation trial (Harare, Zimbabwe) and followed at 6 weeks, and 3-monthly intervals up to 24 months. The ZVITAMBO project was a randomized placebocontrolled clinical trial tha...
571b8b9e35c0647a7e7ecd88ff29ae8a_8
by ELISA and confirmed by Western Blot. Infants were considered to be infected if they were HIV-1 seropositive at 18 months or older and had two or more positive HIV-1-DNA polymerase chain reaction (PCR) results at earlier ages. 100 infants were considered to be uninfected as they were ELISA negative at 18 months or ol...
571b8b9e35c0647a7e7ecd88ff29ae8a_9
considered to be infected during the PP period. In the analysis comparing the 3 different modes of MTCT, 12 HIV-1-infected infants were excluded because the PCR results were not available at 6 weeks of age. Full methods for recruitment, baseline characteristics collection, laboratory procedures have been described else...
571b8b9e35c0647a7e7ecd88ff29ae8a_10
The nucleotide sequence variation of the entire promoter, coding and part of 39-UTR regions of DC-SIGNR gene in the study population was determined previously [7] . Haplotype reconstruction was performed using Bayesian statistical method implemented in PHASE [8] , version 2.1.1, using single nucleotide polymorphism (SN...
571b8b9e35c0647a7e7ecd88ff29ae8a_11
transcription factors binding sites using the TRANSFAC database.
571b8b9e35c0647a7e7ecd88ff29ae8a_12
Luciferase reporter assays using pGL2-Basic vector were performed in order to investigate the functional effect of mutations on DC-SIGNR promoter activity. Genomic DNA from subjects homozygous for the promoter variants and WT was amplified from nucleotide position 2715 to 21 and cloned between the BglII and HindIII mul...
571b8b9e35c0647a7e7ecd88ff29ae8a_13
post-transfection. Firefly luciferase activity was normalized to Renilla luciferase activity. 0 mg, 0,5 mg or 1 mg CMV-Tat vector was transfected with LTR-Luc as a positive control in these experiments. We carried out lucierase assays in triplicate in three independent experiments. Results are expressed as mean6 standa...
571b8b9e35c0647a7e7ecd88ff29ae8a_14
First-term placental tissues were obtained from abortions following voluntary interruption of pregnancy at CHUM Hôpital Saint-Luc (Montreal, Canada). Tissues from 3 H1 (associated with MTCT of HIV-1) and 3 H15 (wild-type) homozygous haplotypes were used to analyse possible differences in isoform expression. Total place...
571b8b9e35c0647a7e7ecd88ff29ae8a_15
Gel Extraction Kit (Qiagen Canada inc, Mississauga, ON, Canada) and cloned using the TOPO TA Cloning Kit for sequencing (Invitrogen). For each placenta, 15 different clones were randomly selected and amplified with M13 primers and sequenced with ABI PRISM 3100 capillary automated sequencer (Applied Biosystems, Foster C...
571b8b9e35c0647a7e7ecd88ff29ae8a_16
Quantitative expression of DC-SIGNR isoforms 1,5 mg of placental RNA was reverse transcribed using 2.5 mM of Oligo dT 20 and Expand RT in 20 ml volume according to the manufacturer (Roche Applied Science). 15 ng of total cDNA in a final volume of 20 ml was used to perform quantitative real-time PCR using Universal Expr...
571b8b9e35c0647a7e7ecd88ff29ae8a_17
Standard curves (50-500 000 copies per reaction) were generated using serial dilution of a full-length DC-SIGNR or commercial GAPDH (Invitrogen) plasmid DNA. All qPCR reactions had efficiencies ranging from 99% to 100%, even in the presence of 20 ng of non-specific nucleic acids, and therefore could be compared. The co...
571b8b9e35c0647a7e7ecd88ff29ae8a_18
Results are expressed as mean6S.E.M.
571b8b9e35c0647a7e7ecd88ff29ae8a_19
Statistical analysis was performed using the GraphPad PRISM 5.0 for Windows (GraphPad Software inc, San Diego, CA, USA). Differences in baseline characteristics and genotypic frequencies of haplotypes or htSNPs were compared between groups using the x 2 analysis or Fisher's exact test. Logistic regression analysis was ...
571b8b9e35c0647a7e7ecd88ff29ae8a_20
Written informed consent was obtained from all mothers who participated in the study and the ZVITAMBO trial and the investigation reported in this paper were approved by The
571b8b9e35c0647a7e7ecd88ff29ae8a_21
We carried out an association study of DC-SIGNR polymorphism in 197 infants born to untreated HIV-1-infected mothers recruited in Harare, Zimbabwe. Among them, 97 infants were HIV-1-infected and 100 infants remained uninfected. Of the 97 HIV-1-infected infants, 57 were infected IU, 11 were infected IP, and 17 were infe...
571b8b9e35c0647a7e7ecd88ff29ae8a_22
Fifteen haplotype-tagged SNPs (htSNPs) corresponding to the 15 major DC-SIGNR haplotypes ( Figure 1 ) described among Zimbabweans [7] were genotyped in our study samples (Tables S2 and S3 ). H1 (31%) and H3 (11%) were the most frequent haplotypes observed (Figure 1 ). Being homozygous for the H1 haplotype was associat...
571b8b9e35c0647a7e7ecd88ff29ae8a_23
ex4RPT, int5+7C) ( Figure 1 ). Of these, the p-198A and int2-180A variants were significantly associated with MTCT of HIV-1 (Table S2 ). In the unadjusted regression analysis, homozygous infants for the p-198A and int2-180A variants had increased risk of IU (OR: 2.07 P = 0.045, OR: 3.78, P = 0.003, respectively) and IP...
571b8b9e35c0647a7e7ecd88ff29ae8a_24
Alternative splicing of the DC-SIGNR gene in the placenta produces both membrane-bound and soluble isoform repertoires [3] . The relative proportion of membrane bound and soluble DC-SIGNR could plausibly influence the susceptibility to HIV-1 infection [11] . We therefore hypothesized that the DC-SIGNR mutations associa...
571b8b9e35c0647a7e7ecd88ff29ae8a_25
We cloned DC-SIGNR from placental tissues by RT-PCR from 3 homozygous H1 samples containing both the DC-SIGNR p-198AA and int2-180AA variants associated with HIV-1 transmission and 3 homozygous wild-type (WT) (p-198CC, int2-180GG) samples. Fifteen clones per sample were randomly selected for sequencing. As expected, we...
571b8b9e35c0647a7e7ecd88ff29ae8a_26
of membrane-bound isoforms in placental tissues of the H1 homozygotes appears to be lower than that observed in samples from WT individuals ( Figure S1 ). The deletion of exon 3 was confirmed by sequencing and we hypothesize that the skipping of exon 3, could be due to the presence of the int2-180A mutation observed in...
571b8b9e35c0647a7e7ecd88ff29ae8a_27
a significantly lower proportion of membrane-bound DC-SIGNR (18%) compared to that in WT individuals (36%) (P = 0.004) ( Figure 2B ) suggesting that exon 3 skipping happens more frequently in presence of the DC-SIGNR int2-180A variant associated with MTCT of HIV-1.
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The DC-SIGNR int2-180A variant is always transmitted with the promoter mutation p-198A (Figure 1 ). In the unadjusted regression analysis, the p-198A variant was significantly associated with IU but not with IP and PP HIV-1 transmission (Table 3) . Computational transcription factor binding site analysis predicts Table...
571b8b9e35c0647a7e7ecd88ff29ae8a_29
absolute number of total and membrane-bound DC-SIGNR transcripts in the H1 homozygote and wild-type placental samples as described earlier. The total number of DC-SIGNR transcripts was determined to be 6856213 (DC-SIGNR copies6S.E.M per 10 5 GAPDH copies) in the placental samples from homozygous H1 infants and was 4-fo...
571b8b9e35c0647a7e7ecd88ff29ae8a_30
= 19256495.3, P = 0.03) ( Figure 3C ). Therefore, DC-SIGNR p-198A and int2-180A mutations associated with MTCT of HIV-1 significantly decreased the level of total placental DC-SIGNR transcripts, disproportionately affecting the membrane-bound isoform production. Table 3 . Associations between infant DC-SIGNR promoter p...
571b8b9e35c0647a7e7ecd88ff29ae8a_31
Our genetic results, supported by expression assay in placenta, suggest the involvement of DC-SIGNR in MTCT of HIV-1. Homozygosity for the haplotype H1 was associated with IU transmission in the unadjusted regression analysis. However, the association disappeared after adjustment was made for the maternal factors presu...
571b8b9e35c0647a7e7ecd88ff29ae8a_32
the association disappeared after adjustment was made for the maternal viral load. Nevertheless, we showed that this mutation reduces DC-SIGNR transcriptional activity in vitro and produces lower level of DC-SIGNR transcripts in placental tissues in combination with the int2-180A variant. Since int2-180A is always tran...
571b8b9e35c0647a7e7ecd88ff29ae8a_33
The majority of IU transmission occurs during the last trimester of pregnancy (reviewed in [12] ). Full-term placenta samples were not available for the current study and the expression assays were performed on first-term placental tissues. A previous study looking at DC-SIGNR placental isoforms repertoire in full-term...
571b8b9e35c0647a7e7ecd88ff29ae8a_34
However, the multiple mechanisms involved in trans infection and redundancy among C-type lectin functions make it difficult to determine the actual participation of DC-SIGNR in this mode of infection in vivo [13, 14] . The strong correlation we observed between MTCT of HIV-1 and DC-SIGNR genetic variants producing low ...
571b8b9e35c0647a7e7ecd88ff29ae8a_35
on placental and blood-brain barrier (BBB) endothelial cells [18, 19] . HIV-1 gp120 binding to CCR5 receptor on endothelial cells compromises BBB integrity and enhances monocytes adhesion and transmigration across the BBB [20, 21] . It is thus possible that reduced expression of DC-SIGNR, particularly the membranebound...
571b8b9e35c0647a7e7ecd88ff29ae8a_36
The int2-180A variant contained in the H1 and H3 haplotypes was associated with IP transmission suggesting that DC-SIGNR also affect transmission of HIV-1 during delivery. Little is known about the mechanisms underlying transmission of HIV-1 during delivery. Passage through the birth canal could potentially expose infa...
571b8b9e35c0647a7e7ecd88ff29ae8a_37
transmission, the relatively lower level of DC-SIGNR in the placenta of homozygous infants harbouring the int2-180A variant could promote HIV-1 binding to CCR5 receptor on endothelial cells affecting the placental barrier integrity and facilitating the passage of maternal infected cells in foetal circulation during del...
571b8b9e35c0647a7e7ecd88ff29ae8a_38
Beside DC-SIGNR, other HIV-1 receptors are known to influence MTCT of HIV-1 (reviewed in [24] ). Genetic variants in CCR5 have been shown to influence vertical transmission of HIV-1. CCR5 promoter variants resulting in higher expression of the receptor were associated with increased risk of MTCT of HIV-1 among sub-Saha...
571b8b9e35c0647a7e7ecd88ff29ae8a_39
and non-coding regions has been associated with an increased risk of MTCT of HIV-1 [31, 32] .
571b8b9e35c0647a7e7ecd88ff29ae8a_40
In this study, we demonstrate for the first time, the potential functional impact of DC-SIGNR mutations on its expression in the placenta and in vertical transmission of HIV-1. We believe that the presence of DC-SIGNR at the placental endothelial cell surface may protect infants from HIV-1 infection by capturing virus ...
571b8b9e35c0647a7e7ecd88ff29ae8a_41
Associations between child DC-SIGNR exon 4 repeated region genotypes and mother-to-child HIV-1 transmission.CI, Confidence interval; N, number; NA; not applicable; OR, odds ratio a P-value as determined by the Chi-square test. b Comparison between genotype and all others. Found at: doi:10.1371/journal.pone.0007211.s003...
571b8b9e35c0647a7e7ecd88ff29ae8a_42
variant or p-323A variant were calculated relatively to this value. Data are presented in mean values6S.E.M of three independent experiments performed in triplicate. One-way ANOVA test followed by the Dunnett test for multiple comparison was used to compare the relative luciferase expression of the p-557C and p-323A va...
95a3390d2c839a1ea02a113e1ca4fcb6_0
First Complete Genome Sequence of a French Bovine coronavirus Strain https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5477389/ SHA: eef0ecf5b8e7b179dadaef967e65f2ab68f021e1 Authors: Kin, Nathalie; Guerard, Pauline; Diancourt, Laure; Caro, Valérie; Vabret, Astrid; Ar Gouilh, Meriadeg Date: 2017-05-25 DOI: 10.1128/genomea...
95a3390d2c839a1ea02a113e1ca4fcb6_1
Text: B ovine coronavirus (BCoV) belongs to the Nidovirales order, the Coronaviridae family, the Coronavirinae subfamily, and the Betacoronavirus (https://talk.ictvonline.org/ ICTV/proposals/2008.085-122V.v4.Coronaviridae.pdf). Its genome is a single-stranded, linear, and nonsegmented RNA of around 31 kb. BCoV is respo...
95a3390d2c839a1ea02a113e1ca4fcb6_2
The BCoV/FRA-EPI/CAEN/2014/13 strain was obtained from a fecal sample collected from a 1-week-old calf in Normandy in 2014. The presence of BCoV in the fecal sample was assessed using an in-house reverse transcription-PCR (RT-PCR) targeting the M gene (3). A cDNA library was synthesized using SuperScript III (Invitroge...
95a3390d2c839a1ea02a113e1ca4fcb6_3
the United Arab Emirates (accession no. KF906251), with a nucleotide identity of 99.19%. Conversely, the NS2, HE, S, ns5, and M genes are closely related to the BCoV Bubalus/Italy/179/07-11 strain (accession no. EU019216), with nucleotide identities of 99.88%, 99.45%, 99.02%, 98.79%, and 99.28%, respectively. The E gen...
95a3390d2c839a1ea02a113e1ca4fcb6_4
Multiple-sequence alignment, including 20 BCoVs and 10 clade A betacoronaviruses closely related to BCoV from North America, two DcCoVs from the United Arab Emirates, and two Human coronavirus OC43 (HCoV-OC43) strains from France, was performed using the Muscle algorithm implemented in MEGA7 (4, 5) . The phylogenetic a...
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recombination events could be at the origin of DcCoV.
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Accession number(s). The complete genome sequence sequence of the BCoV/FRA-EPI/CAEN/2014/13 isolate has been deposited in GenBank under the accession number KX982264.
6124f5b1a2cbeeeb156c02325214bb62_0
Species‐specific clinical characteristics of human coronavirus infection among otherwise healthy adolescents and adults https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5820427/ SHA: edfe02a438fa9b667313da8f03614303fc2a4a14 Authors: Bouvier, Monique; Chen, Wei‐Ju; Arnold, John C.; Fairchok, Mary P.; Danaher, Patrick J.;...
6124f5b1a2cbeeeb156c02325214bb62_1
Abstract: Human coronavirus (HCoV) is a known cause of influenza‐like illness (ILI). In a multisite, observational, longitudinal study of ILI among otherwise healthy adolescents and adults, 12% of subjects were PCR‐positive for HCoV. The distribution of species was as follows: HCoV‐OC43 (34%), HCoV‐229E (28%), HCoV‐NL6...
6124f5b1a2cbeeeb156c02325214bb62_2
Highly virulent species of HCoV were responsible for outbreaks of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS); case-fatality rates ranged from 14% to 45%. [1] [2] [3] By contrast, other HCoV species (HCoV-HKU1, HCoV-OC43, HCoV-NL63, and HCoV-229E) are much more prevalent, much l...
6124f5b1a2cbeeeb156c02325214bb62_3
participation. ILI was defined as a temperature ≥100.4°F and sore throat or one of the following respiratory symptoms: cough, sputum production, shortness of breath, or chest pain. Both inpatient and outpatient subjects were eligible to participate. Patients with underlying medical conditions (eg, diabetes, chronic obs...
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symptom score, calculated as the sum of severity scores for earache, runny nose, sore throat, and sneezing, (iii) the lower respiratory symptom score, calculated as the sum of severity scores for cough, difficulty breathing, hoarseness, and chest discomfort, (iv) the gastrointestinal symptom score, calculated as the su...
6124f5b1a2cbeeeb156c02325214bb62_5
There was season-to-season variability in the leading causes of The findings of our study, conducted over a 5-year period at five geographically dispersed sites in the USA, demonstrate that human coronavirus (HCoV) is an important cause of influenza-like illness (ILI) ranged from 4% to 22%. [8] [9] [10] [11] 14 Addit...
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The strengths of this study of HCoV in otherwise healthy adolescents and adults include its multisite and multiyear design, the use of a multiplex diagnostic panel, the prospective collection of symptom data, and the use of a symptom severity scale similar to what has been employed previously. 15 One important limitati...
1df329823dce9b206623e103e9542369_0
One step closer to an experimental infection system for Hepatitis B Virus? --- the identification of sodium taurocholate cotransporting peptide as a viral receptor https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3562259/ SHA: f4f36a8e9fee64d59ccf22b724c7dab345102658 Authors: Chen, Pei-Jer; Wu, T-C Date: 2013-01-11 DOI:...
1df329823dce9b206623e103e9542369_1
Text: Among the five hepatotropic hepatitis viruses, only hepatitis B virus (HBV) and its satellite hepatitis D virus (HDV) still wait for the development of an in vitro infection system in cell culture. One hepatocellular carcinoma (HCC) cell line, HepaRG, can be infected at a modest efficiency after weeks of culture ...
1df329823dce9b206623e103e9542369_2
The molecules on the cell membrane needed for HBV infection can be divided into two classes: low affinity and high affinity molecules. Among others, the heparan sulfates in the membrane proteins mediate the broad, but less specific, virus-cell interaction. However, the high affinity membrane partners for HBV remain elu...
1df329823dce9b206623e103e9542369_3
HBV envelope protein, namely the surface antigens, plays an essential role in the infection process. Both genetic and functional examination identified one domain in the Nterminus of HBV preS1 (amino acids 1-47) necessary for infection. This domain has been shown to function as a direct mediator for HBV by binding pres...
1df329823dce9b206623e103e9542369_4
Yan et al. have taken a reasonable approach to fish out possible HBV receptor(s) [6] . They engineered the first 2-47 amino acid peptide from PreS1 to increase its capacity to be cross-linked with proteins interacting with the cell membrane, without affecting its binding specificity. In order to obtain sufficient mater...
1df329823dce9b206623e103e9542369_5
Immunofluorescence staining clearly demonstrated the expression of HBV and HDV proteins in these cell lines, suggestive of a successful viral infection. In addition, they documented a 2-4-fold increase of viral RNA and DNA after infection in the cell line by real-time PCR. They also showed a Southern blot supporting th...
1df329823dce9b206623e103e9542369_6
NTCP is a transmembrane protein, usually located in the lateral surface (canalicular) of hepatocytes, which mediates bile acid transport [7] . Geographically, it is a good candidate for an HBV receptor. Moreover, the authors could convert the cell lines previously non-permissible to HBV infection to permissible by over...
1df329823dce9b206623e103e9542369_7
Looking forward, we need to understand how NTCP interacts with both HBV envelope proteins and with other cellular proteins, especially through the motif embedded in the cell membrane. NTCP itself is not sufficient to allow HBV infection, as the majority of HepaRG cells were found to express NPCT but not to be infected ...
1df329823dce9b206623e103e9542369_8
are expected to demonstrate the successful HBV infections in vitro.
1df329823dce9b206623e103e9542369_9
The HBV research community has searched for HBV receptors for decades. Many candidates have been discovered and then discarded. The current study, however, took advantage of a well-documented viral peptide required for HBV entry in combination with a state-of-the-art proteomics platform. As a Chinese proverb says "a th...
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Development of an ELISA-array for simultaneous detection of five encephalitis viruses https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3305475/ SHA: ef2b8f83d5a3ab8ae35e4b51fea6d3ed9eb49122 Authors: Kang, Xiaoping; Li, Yuchang; Fan, Li; Lin, Fang; Wei, Jingjing; Zhu, Xiaolei; Hu, Yi; Li, Jing; Chang, Guohui; Zhu, Qingyu...
34b5ce62689ba2bf860150408392d10a_1
Abstract: Japanese encephalitis virus(JEV), tick-borne encephalitis virus(TBEV), and eastern equine encephalitis virus (EEEV) can cause symptoms of encephalitis. Establishment of accurate and easy methods by which to detect these viruses is essential for the prevention and treatment of associated infectious diseases. C...
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have similar specificity and higher sensitivity compared with the conventional ELISAs. This method was validated by different viral cultures and three chicken eggs inoculated with infected patient serum. The results demonstrated that the developed ELISA-array is sensitive and easy to use, which would have potential for...
34b5ce62689ba2bf860150408392d10a_3
Text: Japanese encephalitis virus(JEV), tick-borne encephalitis virus(TBEV), eastern equine encephalitis virus (EEEV), sindbis virus(SV), and dengue virus(DV) are arboviruses and cause symptoms of encephalitis, with a wide range of severity and fatality rates [1] . Establishment of an accurate and easy method for detec...
34b5ce62689ba2bf860150408392d10a_4
Antibody arrays for simultaneous multiple antigen quantification are considered the most accurate methods [7] [8] [9] [10] . Liew [11] validated one multiplex ELISA for the detection of 9 antigens; Anderson [12] used microarray ELISA for multiplex detection of antibodies to tumor antigens in breast cancer, and demonstr...
34b5ce62689ba2bf860150408392d10a_5
However, the application of ELISA-based arrays is currently limited to detection of cancer markers or interleukins; no detection of pathogens has been reported. In this study, we developed an ELISA-based array for the simultaneous detection of five encephalitis viruses. Seven specific monoclonal antibodies were prepare...
34b5ce62689ba2bf860150408392d10a_6
Monoclonal antibodies were prepared from hybridoma cell lines constructed by Prof. Zhu et al. Purification was conducted by immunoaffinity chromatography on protein G affinity sepharose [13] . Specific monoclonal antibodies (4D5 against JEV, 2B5 against TBEV, 1F1 against SV, 2B8 against serotype 2 DV, 4F9 against serot...
34b5ce62689ba2bf860150408392d10a_7
JEV and DV were cultured in C6/36 cells; SV, TBEV, and EEEV were cultured in BHK-21 cells. The culture of TBEV and EEEV was conducted in biosafety level 3 facility, however, JEV, DV and SV were conducted in biosafety level 2 facility. Viral titers were determined by the 50% tissue culture infectious dose (TCID 50 ) met...
34b5ce62689ba2bf860150408392d10a_8
When spotting, different spotting buffers and concentrations of capture monoclonal antibodies were evaluated to optimize the ELISA-array assay. The optimization was evaluated by dot morphology and signal intensity. The tested spotting buffers included 1 × phosphate buffer saline (PBS), PBS +20% glycerol, and 1 × PBS + ...
34b5ce62689ba2bf860150408392d10a_9
Antigen binding was performed in PBS(containing 0.1% Tween-20 and 5% FCS) at 37°C for 2 h, followed by washing 3 times(1 × PBS containing 0.1% Tween-20). Incubation of ELISA plates with biotinylated detecting antibody cocktails was performed in PBS (containing 0.1% Tween-20 and 5% FCS) at 37°C for 2 h. After washing, s...
34b5ce62689ba2bf860150408392d10a_10
The identical antibodies used in the ELISA-array format were also tested in a conventional ELISA format to determine the difference in sensitivity and specificity of the two methods. The conventional ELISAs were performed at the same time as the ELISA-array assays to ensure similar reaction conditions. The conventional...
34b5ce62689ba2bf860150408392d10a_11
RNA was extracted from the inoculated chicken eggs using a RNeasy mini kit (Qiagen Inc., Valencia, CA, USA) according to the manufacturer's instructions. All RNA extraction procedures were conducted at BSL-3 facilities. The primers and probes were used as previously described [18] . The real-time RT-PCR was conducted w...
34b5ce62689ba2bf860150408392d10a_12
The spotting concentration of the capture antibodies varied from 0.2 to 0.0125 mg/ml (each was serially diluted 2-fold). The efficacy of the spotting concentration of the capture antibodies was evaluated by virus culture detection, the proper spotting concentration was determined by a combination of minimized cross rea...
34b5ce62689ba2bf860150408392d10a_13
Spot morphology observation (Figures 2a, b , and 2c) demonstrated that spotting buffer containing PBS with 20% glycerol produced tailed spot morphology; buffers containing PBS alone and PBS with 20% glycerol +0.004% Triton-X100 gave good spot morphology (round and full). Buffers containing PBS with 20% glycerol and PBS...
34b5ce62689ba2bf860150408392d10a_14
The optimized ELISA array layout is shown in Figure 3 , which was applied in the following experiments. Successful detection of viral pathogens requires a test with high sensitivity and specificity. To evaluate the performance of the designed antibody arrays, the specificity and sensitivity of the individual analyte...
34b5ce62689ba2bf860150408392d10a_15
Equal volumes of cultured TBEV, JEV, DV-2, DV-4, SV, and EEEV were prepared for single sample detection; two or three of the cultures were mixed for multiplex detection. A cocktail of biotin conjugated antibody (2A10, 4E11, and 1F1) was used in all tests. The results demonstrated that for all virus combinations, each v...
34b5ce62689ba2bf860150408392d10a_16
To be widely used in the clinical setting, the detection system should be easy to use and can be performed by untrained staff with little laboratory and experimental experience. Moreover, when the volume of the clinical samples is limited and an increasing number of pathogens per sample needs to be tested, the detectin...
34b5ce62689ba2bf860150408392d10a_17
It has been reported that an ELISA-array has been used in the diagnosis of cancer and auto-allergic disease [7, 12] ; however, No study has reported the detection of viral pathogens. In this study, we developed a multiplex ELISA-based method in a double-antibody sandwich format for the simultaneous detection of five en...
34b5ce62689ba2bf860150408392d10a_18
The production of a reliable antibody chip for identification of microorganisms requires careful screening of capture of antibodies [14] . Cross-reactivity must be minimized and the affinity of the antibody is as important as the specificity. First, we prepared and screened 23 monoclonal antibodies against eight viruse...
34b5ce62689ba2bf860150408392d10a_19
signals. The epitope was not defined; however, we suspect that the antibodies both target the surface of the virions. As one virion exits as, many with the same epitope appear, thus no interference occurred using the same antibody in the double-antibody sandwich format assay.
34b5ce62689ba2bf860150408392d10a_20
Currently, the availability of antibodies suitable for an array format diagnostic assay is a major problem. In the ELISA-array assay, this problem exists as well. Because of the limitation of available antibodies, this assay could only detect 5 pathogens. In the future, with increasing numbers of suitable antibodies, e...
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the virus-inactivation method. A conventional ELISA is a standard method in many diagnostic laboratories. We compared the ELISA-array with a conventional ELISA and confirmed that the advantage of the ELISA-array was evident with comparable specificity and higher sensitivity than ELISA. The time required for the ELISA-a...
1b5c75044775f5ecd17f750ba2e0f282_0
Changes in pulmonary tuberculosis prevalence: evidence from the 2010 population survey in a populous province of China https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3890533/ SHA: eef61bdfa49b8652fd660b5b8b7e74cf51922505 Authors: Wei, Xiaolin; Zhang, Xiulei; Yin, Jia; Walley, John; Beanland, Rachel; Zou, Guanyang; Zha...
1b5c75044775f5ecd17f750ba2e0f282_1
Abstract: BACKGROUND: This paper reports findings from the prevalence survey conducted in Shandong China in 2010, a province with a population of 94 million. This study aimed to estimate TB prevalence of the province in 2010 in comparison with the 2000 survey; and to compare yields of TB cases from different case findi...
1b5c75044775f5ecd17f750ba2e0f282_2
not present persistent cough. The yield of bacteriologically confirmed cases was 47% by symptom screening and 95% by CXRAY. Over 50% of TB cases were among over 65’s. CONCLUSIONS: The prevalence rate of bacteriologically confirmed cases was significantly reduced compared with 2000. The survey raised challenges to ident...
1b5c75044775f5ecd17f750ba2e0f282_3
Text: China, with an estimated prevalence of all TB cases of 108 per 100,000 in 2010, has the second highest TB burden in the world, accounting for 13% of all cases worldwide [1] . The World Health organization (WHO) estimated that China had reached the targets of 85% treatment success by 1993 and 70% case detection ra...
1b5c75044775f5ecd17f750ba2e0f282_4
Shandong province has a population of 94 million. It is a relatively developed province with a per capita GDP 1.6 times of the national average in 2010 [5] . The prevalence rate of TB in Shandong was lower compared with the average rate of China in 2000 [3] . Population representative samples were drawn in Shandong in ...
1b5c75044775f5ecd17f750ba2e0f282_5
The survey employed the same sampling methods as the China national survey in 2010, which was similar to the sampling methods used in 2000 [6] . The design of the surveys was in accordance with WHO recommendations [7] . The design effect factor due to cluster sampling was estimated at 1.28 [8] . A sample size of 52500 ...
1b5c75044775f5ecd17f750ba2e0f282_6
A stratified multi stage random sampling was used to select the 35 clusters within 17 prefectures in Shandong province. The number of clusters was randomly allocated in proportion to the provincial population at the prefectural, county/district and township levels. A cluster was defined as a community (a village in the...
1b5c75044775f5ecd17f750ba2e0f282_7
The survey was conducted from March to June 2010 by survey teams consisting of clinicians, public health doctors, radiologists, laboratory technicians and nurses. Local media was used to promote awareness of the survey. Community workers conducted a house-to-house census to update the database of residents, inform surv...
1b5c75044775f5ecd17f750ba2e0f282_8
Those who agreed to participate in the survey were invited to the county TB dispensary, where they completed a consultation with a trained clinical TB doctor regarding any symptoms suggestive of TB, such as persistent cough (lasting two weeks or longer), haemoptysis, weight loss and fever. All participants had a chest ...
1b5c75044775f5ecd17f750ba2e0f282_9
Sputum smears were conducted in local TB dispensaries. All sputum samples were cultured using the Löwenstein-Jensen medium in the provincial laboratory within 24 hours using cold chain transportation. Samples were excluded from TB when non-tuberculosis bacilli were identified from the culture. All sputum smear and cult...
1b5c75044775f5ecd17f750ba2e0f282_10
clinicians and radiologists were classified as CXRAY suggestive bacteriologically negative cases. Due to resource limitations the recommendation of broad-spectrum antimicrobial agents to confirm the diagnosis of negative TB cases was not applied in this survey [11] . Newly diagnosed cases were distinguished from previo...
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ConTEB - Covid-QA

This dataset is part of ConTEB (Context-aware Text Embedding Benchmark), designed for evaluating contextual embedding model capabilities. It focuses on the theme of Healthcare, particularly stemming from articles about the COVID-19 pandemic.

Dataset Summary

This dataset was designed to elicit contextual information. It is built upon the COVID-QA dataset. To build the corpus, we start from the pre-existing collection documents, extract the text, and chunk them (using LangChain's RecursiveCharacterSplitter with a threshold of 1000 characters). We use GPT-4o to annotate which chunk, among the gold document, best contains information needed to answer the query. Since chunking is done a posteriori without considering the questions, chunks are not always self-contained and eliciting document-wide context can help build meaningful representations.

This dataset provides a focused benchmark for contextualized embeddings. It includes a curated set of original documents, chunks stemming from them, and queries.

  • Number of Documents: 115
  • Number of Chunks: 3351
  • Number of Queries: 1111
  • Average Number of Tokens per Doc: 153.9

Dataset Structure (Hugging Face Datasets)

The dataset is structured into the following columns:

  • documents: Contains chunk information:
    • "chunk_id": The ID of the chunk, of the form doc-id_chunk-id, where doc-id is the ID of the original document and chunk-id is the position of the chunk within that document.
    • "chunk": The text of the chunk
  • queries: Contains query information:
    • "query": The text of the query.
    • "answer": The answer relevant to the query, from the original dataset.
    • "chunk_id": The ID of the chunk that the query is related to, of the form doc-id_chunk-id, where doc-id is the ID of the original document and chunk-id is the position of the chunk within that document.

Usage

We will upload a Quickstart evaluation snippet soon.

Citation

We will add the corresponding citation soon.

Acknowledgments

This work is partially supported by ILLUIN Technology, and by a grant from ANRT France.

Copyright

All rights are reserved to the original authors of the documents.

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