Result 1 - 10 of total 94
Nature
| Keywords | covid19 |
|---|---|
| Publisher | WHO |
| Document type | Article |
| Note | WHO #Covidence: #637890 |
| Database | COVID19 |
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2023 Volume 13, Issue 1, Page(s) 4990
Abstract: Schistosomiasis is a major neglected tropical disease targeted for elimination as a public health issue by 2030, however there is an urgent need for more sensitive and specific diagnostic tests suitable to resource-limited settings. Here we developed ... ...
| Abstract | Schistosomiasis is a major neglected tropical disease targeted for elimination as a public health issue by 2030, however there is an urgent need for more sensitive and specific diagnostic tests suitable to resource-limited settings. Here we developed CATSH, a CRISPR-assisted diagnostic test for Schistosoma haematobium, utilising recombinase polymerase amplification, Cas12a-targeted cleavage and portable real-time fluorescence detection. CATSH showed high analytical sensitivity, consistent detection of a single parasitic egg and specificity for urogenital Schistosoma species. Thanks to a novel CRISPR-compatible sample preparation developed using simulated urine samples containing parasitic eggs, CATSH had a sample-to-result within 2 h. The components of CATSH can be lyophilised, reducing cold chain dependence and widening access to lower and middle-income countries. This work presents a new application of CRISPR diagnostics for highly sensitive and specific detection of parasitic pathogens in remote areas and could have a significant impact on the elimination of neglected tropical diseases. |
|---|---|
| MeSH term(s) | Animals ; Schistosoma haematobium/genetics ; Schistosomiasis haematobia/diagnosis ; Sensitivity and Specificity ; Neglected Diseases ; Eggs |
| Language | English |
| Publishing date | 2023-03-27 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2615211-3 |
| ISSN | 2045-2322 ; 2045-2322 |
| ISSN (online) | 2045-2322 |
| ISSN | 2045-2322 |
| DOI | 10.1038/s41598-023-31238-y |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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ACS sensors
2020 Volume 5, Issue 10, Page(s) 3133–3139
Abstract: Growing antimicrobial resistance (AMR) is a serious global threat to human health. Current methods to detect resistance include phenotypic antibiotic sensitivity testing (AST), which measures bacterial growth and is therefore hampered by a slow time to ... ...
| Abstract | Growing antimicrobial resistance (AMR) is a serious global threat to human health. Current methods to detect resistance include phenotypic antibiotic sensitivity testing (AST), which measures bacterial growth and is therefore hampered by a slow time to obtain results (∼12-24 h). Therefore, new rapid phenotypic methods for AST are urgently needed. Nanomechanical cantilever sensors have recently shown promise for rapid AST but challenges of bacterial immobilization can lead to variable results. Herein, a novel cantilever-based method is described for detecting phenotypic antibiotic resistance within ∼45 min, capable of detecting single bacteria. This method does not require complex, variable bacterial immobilization and instead uses a laser and detector system to detect single bacterial cells in media as they pass through the laser focus. This provides a simple readout of bacterial antibiotic resistance by detecting growth (resistant) or death (sensitive), much faster than the current methods. The potential of this technique is demonstrated by determining the resistance in both laboratory and clinical strains of |
|---|---|
| MeSH term(s) | Anti-Bacterial Agents/pharmacology ; Anti-Infective Agents/pharmacology ; Drug Resistance, Bacterial ; Escherichia coli ; Humans ; Microbial Sensitivity Tests |
| Chemical Substances | Anti-Bacterial Agents ; Anti-Infective Agents |
| Language | English |
| Publishing date | 2020-09-29 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ISSN | 2379-3694 |
| ISSN (online) | 2379-3694 |
| DOI | 10.1021/acssensors.0c01216 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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Scientific Reports, Vol 13, Iss 1, Pp 1-
2023 Volume 9
Abstract: Abstract Schistosomiasis is a major neglected tropical disease targeted for elimination as a public health issue by 2030, however there is an urgent need for more sensitive and specific diagnostic tests suitable to resource-limited settings. Here we ... ...
| Abstract | Abstract Schistosomiasis is a major neglected tropical disease targeted for elimination as a public health issue by 2030, however there is an urgent need for more sensitive and specific diagnostic tests suitable to resource-limited settings. Here we developed CATSH, a CRISPR-assisted diagnostic test for Schistosoma haematobium, utilising recombinase polymerase amplification, Cas12a-targeted cleavage and portable real-time fluorescence detection. CATSH showed high analytical sensitivity, consistent detection of a single parasitic egg and specificity for urogenital Schistosoma species. Thanks to a novel CRISPR-compatible sample preparation developed using simulated urine samples containing parasitic eggs, CATSH had a sample-to-result within 2 h. The components of CATSH can be lyophilised, reducing cold chain dependence and widening access to lower and middle-income countries. This work presents a new application of CRISPR diagnostics for highly sensitive and specific detection of parasitic pathogens in remote areas and could have a significant impact on the elimination of neglected tropical diseases. |
|---|---|
| Keywords | Medicine ; R ; Science ; Q |
| Language | English |
| Publishing date | 2023-03-01T00:00:00Z |
| Publisher | Nature Portfolio |
| Document type | Article ; Online |
| Database | BASE - Bielefeld Academic Search Engine (life sciences selection) |
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2019 Volume 65, Issue 3, Page(s) 367–369
| MeSH term(s) | Anti-Bacterial Agents ; Drug Resistance, Bacterial ; Genotype ; Humans ; Semiconductors ; Tuberculosis |
|---|---|
| Chemical Substances | Anti-Bacterial Agents |
| Language | English |
| Publishing date | 2019-01-09 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't ; Comment |
| ZDB-ID | 80102-1 |
| ISSN | 1530-8561 ; 0009-9147 |
| ISSN (online) | 1530-8561 |
| ISSN | 0009-9147 |
| DOI | 10.1373/clinchem.2018.296715 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
| Ud II Zs.171: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG) |
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2021 Volume 189, Page(s) 113328
Abstract: The COVID-19 pandemic is challenging diagnostic testing capacity worldwide. The mass testing needed to limit the spread of the virus requires new molecular diagnostic tests to dramatically widen access at the point-of-care in resource-limited settings. ... ...
| Abstract | The COVID-19 pandemic is challenging diagnostic testing capacity worldwide. The mass testing needed to limit the spread of the virus requires new molecular diagnostic tests to dramatically widen access at the point-of-care in resource-limited settings. Isothermal molecular assays have emerged as a promising technology, given the faster turn-around time and minimal equipment compared to gold standard laboratory PCR methods. However, unlike PCR, they do not typically target multiple SARS-CoV-2 genes, risking sensitivity and specificity. Moreover, they often require multiple steps thus adding complexity and delays. Here we develop a multiplexed, 1-2 step, fast (20-30 min) SARS-CoV-2 molecular test using reverse transcription recombinase polymerase amplification to simultaneously detect two conserved targets - the E and RdRP genes. The agile multi-gene platform offers two complementary detection methods: real-time fluorescence or dipstick. The analytical sensitivity of the fluorescence test was 9.5 (95% CI: 7.0-18) RNA copies per reaction for the E gene and 17 (95% CI: 11-93) RNA copies per reaction for the RdRP gene. The analytical sensitivity for the dipstick method was 130 (95% CI: 82-500) RNA copies per reaction. High specificity was found against common seasonal coronaviruses, SARS-CoV and MERS-CoV model samples. The dipstick readout demonstrated potential for point-of-care testing in decentralised settings, with minimal or equipment-free incubation methods and a user-friendly prototype smartphone application. This rapid, simple, ultrasensitive and multiplexed molecular test offers valuable advantages over gold standard tests and in future could be configurated to detect emerging variants of concern. |
|---|---|
| MeSH term(s) | Biosensing Techniques ; COVID-19 ; Humans ; Molecular Diagnostic Techniques ; Nucleic Acid Amplification Techniques ; Pandemics ; RNA, Viral/genetics ; Real-Time Polymerase Chain Reaction ; Recombinases/genetics ; SARS-CoV-2 ; Sensitivity and Specificity |
| Chemical Substances | RNA, Viral ; Recombinases |
| Language | English |
| Publishing date | 2021-05-14 |
| Publishing country | England |
| Document type | Journal Article |
| ZDB-ID | 1011023-9 |
| ISSN | 1873-4235 ; 0956-5663 |
| ISSN (online) | 1873-4235 |
| ISSN | 0956-5663 |
| DOI | 10.1016/j.bios.2021.113328 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
| Zs.A 2275: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG) |
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2022 Volume 122, Issue 2, Page(s) 279–289
Abstract: Protein-protein interactions are fundamental to life processes. Complementary computational, structural, and biophysical studies of these interactions enable the forces behind their specificity and strength to be understood. Antibody fragments such as ... ...
| Abstract | Protein-protein interactions are fundamental to life processes. Complementary computational, structural, and biophysical studies of these interactions enable the forces behind their specificity and strength to be understood. Antibody fragments such as single-chain antibodies have the specificity and affinity of full antibodies but a fraction of their size, expediting whole molecule studies and distal effects without exceeding the computational capacity of modeling systems. We previously reported the crystal structure of a high-affinity nanobody 59H10 bound to HIV-1 capsid protein p24 and deduced key interactions using all-atom molecular dynamics simulations. We studied the properties of closely related medium (37E7) and low (48G11) affinity nanobodies, to understand how changes of three (37E7) or one (48G11) amino acids impacted these interactions; however, the contributions of enthalpy and entropy were not quantified. Here, we report the use of qualitative and quantitative experimental and in silico approaches to separate the contributions of enthalpy and entropy. We used complementary circular dichroism spectroscopy and molecular dynamics simulations to qualitatively delineate changes between nanobodies in isolation and complexed with p24. Using quantitative techniques such as isothermal titration calorimetry alongside WaterMap and Free Energy Perturbation protocols, we found the difference between high (59H10) and medium (37E7) affinity nanobodies on binding to HIV-1 p24 is entropically driven, accounted for by the release of unstable waters from the hydrophobic surface of 59H10. Our results provide an exemplar of the utility of parallel in vitro and in silico studies and highlight that differences in entropic interactions between amino acids and water molecules are sufficient to drive orders of magnitude differences in affinity. |
|---|---|
| MeSH term(s) | Humans ; Single-Domain Antibodies ; Thermodynamics ; Entropy ; Amino Acids/metabolism ; HIV Infections ; Protein Binding ; Calorimetry |
| Chemical Substances | Single-Domain Antibodies ; Amino Acids |
| Language | English |
| Publishing date | 2022-12-16 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 218078-9 |
| ISSN | 1542-0086 ; 0006-3495 |
| ISSN (online) | 1542-0086 |
| ISSN | 0006-3495 |
| DOI | 10.1016/j.bpj.2022.12.019 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
| Zs.A 235: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG) |
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| Zs.MO 2: Show issues |
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Diagnostics (Basel, Switzerland)
2022 Volume 12, Issue 5
Abstract: The COVID-19 pandemic has unveiled a pressing need to expand the diagnostic landscape to permit high-volume testing in peak demand. Rapid nucleic acid testing based on isothermal amplification is a viable alternative to real-time reverse transcription ... ...
| Abstract | The COVID-19 pandemic has unveiled a pressing need to expand the diagnostic landscape to permit high-volume testing in peak demand. Rapid nucleic acid testing based on isothermal amplification is a viable alternative to real-time reverse transcription polymerase chain reaction (RT-PCR) and can help close this gap. With the emergence of SARS-CoV-2 variants of concern, clinical validation of rapid molecular tests needs to demonstrate their ability to detect known variants, an essential requirement for a robust pan-SARS-CoV-2 assay. To date, there has been no clinical validation of reverse transcription recombinase polymerase amplification (RT-RPA) assays for SARS-CoV-2 variants. We performed a clinical validation of a one-pot multi-gene RT-RPA assay with the E and RdRP genes of SARS-CoV-2 as targets. The assay was validated with 91 nasopharyngeal samples, with a full range of viral loads, collected at University College London Hospitals. Moreover, the assay was tested with previously sequenced clinical samples, including eleven lineages of SARS-CoV-2. The rapid (20 min) RT-RPA assay showed high sensitivity and specificity, equal to 96% and 97%, respectively, compared to gold standard real-time RT-PCR. The assay did not show cross-reactivity with the panel of respiratory pathogens tested. We also report on a semi-quantitative analysis of the RT-RPA results with correlation to viral load equivalents. Furthermore, the assay could detect all eleven SARS-CoV-2 lineages tested, including four variants of concern (Alpha, Beta, Delta, and Omicron). This variant-proof SARS-CoV-2 assay offers a significantly faster and simpler alternative to RT-PCR, delivering sensitive and specific results with clinical samples. |
|---|---|
| Language | English |
| Publishing date | 2022-05-19 |
| Publishing country | Switzerland |
| Document type | Journal Article |
| ZDB-ID | 2662336-5 |
| ISSN | 2075-4418 |
| ISSN | 2075-4418 |
| DOI | 10.3390/diagnostics12051263 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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Biochemical Society transactions
2012 Volume 40, Issue 4, Page(s) 603–608
Abstract: The alarming rise in drug-resistant hospital 'superbugs' and the associated increase in fatalities is driving the development of technologies to search for new antibiotics and improve disease diagnostics. One of the most successful drug targets is the ... ...
| Abstract | The alarming rise in drug-resistant hospital 'superbugs' and the associated increase in fatalities is driving the development of technologies to search for new antibiotics and improve disease diagnostics. One of the most successful drug targets is the bacterial cell wall, an evolutionary feature of virtually all prokaryotes and vital for their survival by providing mechanical strength. The recent discovery of bacterial cytoskeletal proteins analogous to the key force-bearing machinery in eukaryotes also provides new opportunities for drug discovery, but little is known about their mechanical role in bacteria. In the present short article, I review recent developments in the field of nanotechnology to investigate the mechanical mechanisms of action of potent antibiotics on cell wall and cytoskeletal targets with unprecedented spatial, temporal and force resolution and the development of a new generation of nanomechanical devices to detect pathogens for point-of-care diagnostics. |
|---|---|
| MeSH term(s) | Animals ; Anti-Bacterial Agents ; Cell Wall/drug effects ; Cytoskeleton/drug effects ; Humans ; Nanomedicine/methods ; Nanotechnology/methods |
| Chemical Substances | Anti-Bacterial Agents |
| Language | English |
| Publishing date | 2012-08 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't ; Review |
| ZDB-ID | 184237-7 |
| ISSN | 1470-8752 ; 0300-5127 |
| ISSN (online) | 1470-8752 |
| ISSN | 0300-5127 |
| DOI | 10.1042/BST20120082 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
| Zs.A 944: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG) |
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medRxiv
Abstract: The COVID-19 pandemic has challenged testing capacity worldwide. The mass testing needed to stop the spread of the virus requires new molecular diagnostic tests that are faster and with reduced equipment requirement, but as sensitive as the current gold ... ...
| Abstract | The COVID-19 pandemic has challenged testing capacity worldwide. The mass testing needed to stop the spread of the virus requires new molecular diagnostic tests that are faster and with reduced equipment requirement, but as sensitive as the current gold standard protocols based on polymerase chain reaction. We developed a fast (25-35 minutes) molecular test using reverse transcription recombinase polymerase amplification for simultaneous detection of two conserved regions of the virus, targeting the E and RdRP genes. The diagnostic platform offers two complementary detection methods: real-time fluorescence or visual dipstick. The analytical sensitivity of the test by real-time fluorescence was 9.5 (95% CI: 7.0-18) RNA copies per reaction for the E gene and 17 (95% CI: 11-93) RNA copies per reaction for the RdRP gene. The analytical sensitivity for the dipstick readout was 130 (95% CI: 82-500) RNA copies per reaction. The assay showed high specificity with both detection methods when tested against common seasonal coronaviruses, SARS-CoV and MERS-CoV model samples. The dipstick readout demonstrated potential for point-of-care testing, with simple or equipment-free incubation methods and a user-friendly prototype smartphone application was proposed with data capture and connectivity. This ultrasensitive molecular test offers valuable advantages with a swift time-to-result and it requires minimal laboratory equipment compared to current gold standard assays. These features render this diagnostic platform more suitable for decentralised molecular testing. |
|---|---|
| Keywords | covid19 |
| Language | English |
| Publishing date | 2021-02-19 |
| Publisher | Cold Spring Harbor Laboratory Press |
| Document type | Article ; Online |
| DOI | 10.1101/2021.02.17.21251732 |
| Database | COVID19 |
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