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Korean Journal of Radiology Jul 2024
Topics: Humans; Workload; Macau; Personnel Staffing and Scheduling; Radiology; Radiology Department, Hospital
PubMed: 38942453
DOI: 10.3348/kjr.2024.0296 -
Korean Journal of Radiology Jul 2024
Topics: Indonesia; Humans; Radiology; Internship and Residency
PubMed: 38942452
DOI: 10.3348/kjr.2024.0267 -
Korean Journal of Radiology Jul 2024
Topics: Hong Kong; Humans; Radiology
PubMed: 38942451
DOI: 10.3348/kjr.2024.0440 -
Drug Metabolism and Disposition: the... Jun 2024Recently, we have proposed simple methodology to derive clearance and rate constant equations, independent of differential equations, based on Kirchhoff's Laws, a common...
Recently, we have proposed simple methodology to derive clearance and rate constant equations, independent of differential equations, based on Kirchhoff's Laws, a common methodology from physics used to describe rate-defining processes either in series or parallel. Our approach has been challenged in three recent publications, two published in this journal, but notably what is lacking is that none evaluate experimental pharmacokinetic data. As reviewed here, manuscripts from our laboratory have evaluated published experimental data, demonstrating that the Kirchhoff's Laws approach explains (1) why all of the experimental perfused liver clearance data appear to fit the equation that was previously believed to be the well-stirred model, (2) why linear pharmacokinetic systemic bioavailability determinations can be greater than 1, (3) why renal clearance can be a function of drug input processes, and (4) why statistically different bioavailability measures may be found for urinary excretion versus systemic concentration measurements. Our most recent paper demonstrates (5) how the universally accepted steady-state clearance approach utilized by the field for the past 50 years leads to unrealistic outcomes concerning the relationship between liver-to-blood and hepatic availability , highlighting the potential for errors in pharmacokinetic evaluations based on differential equations. The Kirchhoff's Laws approach is applicable to all pharmacokinetic analyses of quality experimental data, those that were previously adequately explained with present pharmacokinetic theory, and those that were not The publications that have attempted to rebut our position do not address unexplained experimental data, and we show here why their analyses are not valid. The Kirchhoff's Laws approach to deriving clearance equations for linear systems in parallel or in series, independent of differential equations, successfully describes published pharmacokinetic data that has previously been unexplained. Three recent publications claim to refute our proposed methodology; these publications only make theoretical arguments, do not evaluate experimental data; never demonstrate that the Kirchhoff methodology provides incorrect interpretations of experimental pharmacokinetic data, including statistically significant data not explained by present pharmacokinetic theory. We demonstrate why these analyses are invalid.
PubMed: 38942444
DOI: 10.1124/dmd.124.001735 -
Indian Pacing and Electrophysiology... Jun 2024This paper presents a novel approach to gap mapping in pulmonary vein isolation (PVI) for atrial fibrillation (AF) treatment, utilizing the real-time Ripple (RR)...
This paper presents a novel approach to gap mapping in pulmonary vein isolation (PVI) for atrial fibrillation (AF) treatment, utilizing the real-time Ripple (RR) technique. Radiofrequency (RF) catheter ablation, particularly encircling PVI, is a common intervention for AF. Identifying left atrium-pulmonary vein conduction gaps is crucial for achieving PVI with minimal additional ablation if first-pass PVI is unsuccessful. However, identifying conduction gaps can be relatively challenging, often necessitating manual electrocardiogram reannotation due to the limitations of local activation time (LAT) maps. In the case of a 63-year-old patient with drug-resistant symptomatic persistent AF, the RR technique was utilized to identify conduction gaps during RF ablation. The technique involved pausing fast anatomical mapping (FAM), activating Ripple map (RM) feature on the CARTO 3 system and acquiring points with an ultrahigh-resolution mapping catheter. This approach revealed that the actual site of earliest activation differs from the LAT map indication, enabling successful PVI. The RM feature's capability to reflect actual excitation propagation without reliance on map annotations was crucial for precise conduction gap identification, overcoming inter-operator variability and inaccuracies of conventional methods. The RR technique not only facilitated real-time analysis during gap mapping but also significantly reduced the procedure time, minimizing potential complications. This case report highlights the efficacy of the RR technique in real-time gap mapping, demonstrating its value in cases where first-pass PVI is unsuccessful. The integration of this technique into PVI procedures can enhance both the accuracy and efficiency of catheter ablation for AF.
PubMed: 38942383
DOI: 10.1016/j.ipej.2024.06.008 -
Journal of Advanced Research Jun 2024The Prime Editing (PE) system is a precise and versatile genome editing tool with great potential in plant breeding and plant synthetic biology. However, low PE...
INTRODUCTION
The Prime Editing (PE) system is a precise and versatile genome editing tool with great potential in plant breeding and plant synthetic biology. However, low PE efficiency severely restricts its application, especially in dicots. PE can introduce small tags to trace target protein or cis-element to regulate gene transcription which is an expertise superior to other gene editing tools. Owing to low efficiency, PE adaption in stably transformed Arabidopsis is lacking.
OBJECTIVES
This study aimed to investigate the issue of low PE efficiency in dicots and develop systematic solutions to improve it. Currently, PE in dicots is undetectable and inconsistent, and this study seeks to address it. Split PE into several parts showed better performance in some target sites in mammal cells. We plan to discover the optimal split PE combination in dicot.
METHODS
We conducted large-scale transformation experiments in dicot model plants Arabidopsis thaliana (At) and Nicotiana benthamiana (Nb) by Agrobacterium-mediated transformation with deep amplicon sequencing (0.2-0.5 million clean total reads).
RESULTS
The editing efficiency decreased upon using a fused reverse transcriptase (RT) or an extended pegRNA separately and further decreased dramatically when these were used together. With the help of the pol II strategy to express PE gRNA (pegRNA), we named the most effective split PE combination as a multi-modular assembled prime editing system (mPE). mPE exhibited improved precise editing efficiency on most gene sites with various editing types, ranging from 1.3-fold to 1288.5-fold and achieved PE on some sites that could not be edited by original PE2. Especially, mPE showed superiority for multi-base insertion with an average improvement of 197.9-fold.
CONCLUSION
The original PE architecture strongly inhibited the cleavage activity of Cas9. Split PE improved PE efficiency extensively and was in favor of introducing small insertions in dicot plants, indicating that different PE variants might have their own expertise.
PubMed: 38942381
DOI: 10.1016/j.jare.2024.06.021 -
American Journal of Veterinary Research Jun 2024To improve the current recommendations for the diagnosis of canine heartworm (Dirofilaria immitis) disease.
Loop-mediated isothermal amplification polymerase chain reaction in place of a modified Knott test in screening dogs for heartworm (Dirofilaria immitis) infection combined with antigen detection test.
OBJECTIVE
To improve the current recommendations for the diagnosis of canine heartworm (Dirofilaria immitis) disease.
ANIMALS
Blood samples collected from 35 shelter dogs in the Republic of Korea.
METHODS
Samples were tested for the presence of microfilaria using the modified Knott (MK) test and D immitis DNA using species-specific loop-mediated isothermal amplification (LAMP) PCR. The blood samples were additionally assessed for the presence of heartworm antigens using the Antigen Rapid Canine Heartworm AG Test Kit 2.0 (Bionote Co). The performance of the MK test and LAMP PCR was assessed through statistical analysis, with a paired McNemar test utilized for comparison.
RESULTS
The heartworm antigen was detected in 28.5% of the subjects. Of the 10 positive animals, the MK test detected microfilaria in 4 of 35 (11.4%) animals, and LAMP PCR detected D immitis DNA in 6 of 35 (17.1%). The results of this study indicate that the LAMP PCR showed more positive results in samples compared to the conventional MK test.
CLINICAL RELEVANCE
The D immitis-specific LAMP PCR assay has the potential to function as an alternative to current detection methods. It could complement the existing antigen detection tests in diagnosing canine heartworm infections.
PubMed: 38942062
DOI: 10.2460/ajvr.24.02.0027 -
Cell Genomics Jun 2024Sexual dimorphism, differences between males and females of the same species, is widespread in mammals. However, good animal models to study human sexually dimorphic...
Sexual dimorphism, differences between males and females of the same species, is widespread in mammals. However, good animal models to study human sexually dimorphic phenotypes are currently lacking. In this issue, DeCasien et al. explore the potential of rhesus macaque as a model for investigating sexually dimorphic traits in the human brain.
PubMed: 38942022
DOI: 10.1016/j.xgen.2024.100585 -
Cell Reports. Medicine Jun 2024Prior studies indicate no correlation between the gut microbes of healthy first-degree relatives (HFDRs) of patients with Crohn's disease (CD) and the development of CD....
Prior studies indicate no correlation between the gut microbes of healthy first-degree relatives (HFDRs) of patients with Crohn's disease (CD) and the development of CD. Here, we utilize HFDRs as controls to examine the microbiota and metabolome in individuals with active (CD-A) and quiescent (CD-R) CD, thereby minimizing the influence of genetic and environmental factors. When compared to non-relative controls, the use of HFDR controls identifies fewer differential taxa. Faecalibacterium, Dorea, and Fusicatenibacter are decreased in CD-R, independent of inflammation, and correlated with fecal short-chain fatty acids (SCFAs). Validation with a large multi-center cohort confirms decreased Faecalibacterium and other SCFA-producing genera in CD-R. Classification models based on these genera distinguish CD from healthy individuals and demonstrate superior diagnostic power than models constructed with markers identified using unrelated controls. Furthermore, these markers exhibited limited discriminatory capabilities for other diseases. Finally, our results are validated across multiple cohorts, underscoring their robustness and potential for diagnostic and therapeutic applications.
PubMed: 38942021
DOI: 10.1016/j.xcrm.2024.101624 -
EBioMedicine Jun 2024Drug development for atrial fibrillation (AF) has failed to yield new approved compounds. We sought to identify and prioritise potential druggable targets with support...
BACKGROUND
Drug development for atrial fibrillation (AF) has failed to yield new approved compounds. We sought to identify and prioritise potential druggable targets with support from human genetics, by integrating the available evidence with bioinformatics sources relevant for AF drug development.
METHODS
Genetic hits for AF and related traits were identified through structured search of MEDLINE. Genes derived from each paper were cross-referenced with the OpenTargets platform for drug interactions. Confirmation/validation was demonstrated through structured searches and review of evidence on MEDLINE and ClinialTrials.gov for each drug and its association with AF.
FINDINGS
613 unique drugs were identified, with 21 already included in AF Guidelines. Cardiovascular drugs from classes not currently used for AF (e.g. ranolazine and carperitide) and anti-inflammatory drugs (e.g. dexamethasone and mehylprednisolone) had evidence of potential benefit. Further targets were considered druggable but remain open for drug development.
INTERPRETATION
Our systematic approach, combining evidence from different bioinformatics platforms, identified drug repurposing opportunities and druggable targets for AF.
FUNDING
KK is supported by Barts Charity grant G-002089 and is mentored on the AFGen 2023-24 Fellowship funded by the AFGen NIH/NHLBI grant R01HL092577. RP is supported by the UCL BHF Research Accelerator AA/18/6/34223 and NIHR grant NIHR129463. AFS is supported by the BHF grants PG/18/5033837, PG/22/10989 and UCL BHF Accelerator AA/18/6/34223 as well as the UK Research and Innovation (UKRI) under the UK government's Horizon Europe funding guarantee EP/Z000211/1 and by the UKRI-NIHR grant MR/V033867/1 for the Multimorbidity Mechanism and Therapeutics Research Collaboration. AF is supported by UCL BHF Accelerator AA/18/6/34223. CF is supported by UCL BHF Accelerator AA/18/6/34223.
PubMed: 38941956
DOI: 10.1016/j.ebiom.2024.105194