REVIEW | doi:10.20944/preprints202307.0247.v1
Subject: Biology And Life Sciences, Life Sciences Keywords: antimicrobial resistance, antimicrobial peptides, aptamers, companion diagnostics, bacteriophages, companion diagnostics
Online: 4 July 2023 (14:08:46 CEST)
New antimicrobial approaches are essential to counter antimicrobial resistance. The drug development pipeline is exhausted with emergence of resistance resulting in unsuccessful trials. The lack of an effective drug developed from the conventional drug portfolio has mandated the introspection into the list of potentially effective unconventional alternate antimicrobial molecules. Alternate therapies, that are clinically explicable forms include monoclonal antibodies, antimicrobial peptides, aptamers and phages. Clinical diagnostics optimizes the drug delivery. In the era of diagnostic-based applications, it is logical to draw diagnostic based treatment for infectious diseases. Selection criteria of alternate therapeutics in infectious disease include detection, monitoring of response and resistance mechanism identification. Integrating these diagnostic applications is disruptive to the traditional therapeutic development. The challenges and mitigation methods need to be noted. Applying the goals of clinical pharmacokinetics that include enhancing efficacy and decreasing toxicity of drug therapy this review analyses the strong correlation of alternate antimicrobial therapeutics in infectious diseases. The relationship between drug concentration and the resulting effect defined by the pharmacodynamic parameters are also analyzed. This review analyzes the perspectives of aligning diagnostic initiatives into the use of alternate therapeutics with a particular focus on companion diagnostic applications in infectious diseases.
ARTICLE | doi:10.20944/preprints201811.0006.v1
Subject: Engineering, Civil Engineering Keywords: prestress monitoring; prestress loss; pre-tensioning; post-tensioning; long-gauge fiber Bragg grating; strain distribution
Online: 2 November 2018 (02:19:31 CET)
Prestress loss evaluation in prestressed strand is essential for prestressed structures. However, the sensors installed outside the duct can only measure the total prestress loss. The sensors attached on strand inside the duct also have several problems, such as inadequate durability in an aggressive environment, vulnerable damage at tensioning and so on. This paper proposes a new installation method for long-gauge fiber Bragg grating (LFBG) sensor to prevent accidental damage. Then the itemized prestress losses were determined in each stage of the pre-tensioning and post-tensioning according to the LFBG measurements. We verified the applicability of the LFBG sensors for prestress monitoring and the accuracy of the proposed prestress loss calculation method during pre-tensioning and post-tensioning. In the pre-tensioning case, the calculated prestress losses had less deviation from the true losses than those obtained from foil-strain gauges, and the durability of the LFBG sensors was better than foil-strain gauges, whereas in post-tensioning case, the calculated prestress losses were close to those derived from theoretical predictions. Finally, we monitored prestress variation in the strand for 90 days. The itemized prestress losses at each stages of post-tensioning were obtained by the proposed calculation method to show the prospect of the LFBG sensors in practical evaluation.
ARTICLE | doi:10.20944/preprints202101.0481.v1
Subject: Chemistry And Materials Science, Biomaterials Keywords: Antibacterial activity; Endodontic irrigant; Enterococcus faecalis; Quercetin; Root canal
Online: 25 January 2021 (10:54:58 CET)
(1) Background: Bacterial reinfection and root fracture are the main culprits related to root canal treatment failure. This study aimed to assess the utility of quercetin solution as an adjunctive endodontic irrigant that strengthen root canal dentin with commitment anti-biofilm activity and bio-safety. (2) Methods: Based on a noninvasive dentin infection model, dentin tubules infected with Enterococcus faecalis (E. faecalis) were irrigated with sterile water (control group), and 0, 1, 2, 4 wt% quercetin-containing ethanol solutions. The live and dead bacteria proportions within E. fae-calis biofilms were analyzed using confocal laser scanning microscopy (CLSM). Elastic modulus and hydroxyproline release and X-ray photoelectron spectroscopy (XPS) characterization was tested on irrigant-treated demineralized dentin to evaluate irrigants’ biostability. The cytotoxicity of irrigants was tested by CCK-8 assay. (3) Results: Quercetin increased the proportion of dead bacteria volumes within E. faecalis, and improved the flexural strength of dentin collagen com-pared to control group. The XPS characterization revealed an increase in C-O peak area under both C1s and O1s narrow-scan spectra. The CCK-8 assay confirmed no cytotoxicity of quercetin solutions. (4) Conclusions: Quercetin exhibited anti-biofilm activity, collagen-stabilizing effect as well as cytocompatibility, supporting quercetin as a potential candidate for endodontic irrigant.
ARTICLE | doi:10.20944/preprints202201.0131.v1
Subject: Medicine And Pharmacology, Other Keywords: methicillin-resistant Staphylococcus aureus; Matrix-Assisted Laser Desorption/Ionization Time-of-Flight; antibiotic susceptibility test; artificial intelligence
Online: 10 January 2022 (19:01:57 CET)
Combining Matrix-Assisted Laser Desorption/Ionization Time-of-Flight (MALDI-TOF) spectra data and artificial intelligence (AI) has been introduced for rapid prediction on antibiotic susceptibility test (AST) of S. aureus. Based on the AI predictive probability, the cases with probabilities between low and high cut-offs are defined as “grey zone”. We aimed to investigate the underlying reasons of unconfident (grey zone) or wrong predictive AST. A total 479 S. aureus isolates were collected, analyzed by MALDI-TOF, and AST prediction, standard AST were obtained in a tertiary medical center. The predictions were categorized into the correct prediction group, wrong prediction group, and grey zone group. We analyzed the association between the predictive results and the demographic data, spectral data, and strain types. For MRSA, larger cefoxitin zone size was found in the wrong prediction group. MLST of the MRSA isolates in the grey zone group revealed that uncommon strain types composed 80%. Amid MSSA isolates in the grey zone group, the majority (60%) was composed of over 10 different strain types. In predicting AST based on MALDI-TOF AI, uncommon strains and high diversity would contribute to suboptimal predictive performance.
ARTICLE | doi:10.20944/preprints202304.0773.v1
Subject: Biology And Life Sciences, Animal Science, Veterinary Science And Zoology Keywords: Key words: transcriptome profiles; long non-coding RNAs; single-nucleotide polymorphisms; alternative splicing; sheep; preimplantation; Single-cell RNA sequencing
Online: 23 April 2023 (04:57:02 CEST)
Numerous dynamic and complicated processes characterize development from the oocyte to the embryo. However, given the importance of functional transcriptome profiles, long non-coding RNAs, single-nucleotide polymorphisms, and alternative splicing during embryonic development, the effect that these features have on the blastomeres of 2-, 4-, 8-, 16-cell, and morula stages of development have not been studied. Here, we conducted a scRNA-seq survey of cells from sheep from the oocyte to the blastocyst developmental stages. We then carried out experiments to identify and functionally analyze the transcriptome profiles, long non-coding RNAs, single-nucleotide polymorphisms (SNPs), and alternative splicing (AS). We founded that between the oocyte and zygote groups significantly down-regulated genes and the second-largest change in gene expression occurred between the 8- and 16-cell stages. We used various methods to construct a profile to characterize cellular and molecular features and systematically analyze the related GO and KEGG profile of cells of all stages from the oocyte to the blastocyst. This large-scale, single-cell atlas provides key cellular information and will likely assist clinical studies in improving preimplantation genetic diagnosis.
Subject: Biology And Life Sciences, Virology Keywords: COVID-19; coronavirus; fulminant myocarditis; infection; echocardiography.
Online: 7 April 2020 (01:03:22 CEST)
Background: Coronavirus Disease 2019 (COVID-19) has been demonstrated to be the cause of pneumonia. Nevertheless, it has not been reported as the cause of acute myocarditis or fulminant myocarditis. Case presentation: A 63-year-old male was admitted with pneumonia and cardiac symptoms. He was genetically confirmed as having COVID-19 according to sputum testing on the day of admission. He also had elevated troponin I (Trop I) level (up to 11.37 g/L) and diffuse myocardial dyskinesia along with a decreased left ventricular ejection fraction (LVEF) on echocardiography. The highest level of interleukin-6 was 272.40 pg/ml. Bedside chest radiographs showed typical ground-glass changes indicative of viral pneumonia. Laboratory test results for viruses that cause myocarditis were all negative. The patient conformed to the diagnostic criteria of the Chinese expert consensus statement for fulminant myocarditis. After receiving antiviral therapy and mechanical life support, Trop I was reduced to 0.10 g/L, and interleukin-6 was reduced to 7.63 pg/ml. Moreover, the LVEF of the patient gradually recovered to 68%. The patient died of aggravation of secondary infection on the 33rd day of hospitalization. Conclusion: COVID-19 patients may develop severe cardiac complications such as myocarditis and heart failure. This is the first report of COVID-19 complicated with fulminant myocarditis. The mechanism of cardiac pathology caused by COVID-19 needs further study.
ARTICLE | doi:10.20944/preprints202312.0036.v1
Subject: Medicine And Pharmacology, Surgery Keywords: Spinal fusion; Interbody cage; Sagittal balance; Artificial intelligence; Machine learning; Spinal parameters
Online: 1 December 2023 (08:12:03 CET)
Transforaminal lumbar interbody fusion (TLIF) is a commonly used technique for treating lumbar degenerative diseases. Here, we developed a fully computer-supported pipeline to predict the cage height and the degree of lumbar lordosis subtraction from the pelvic incidence (PI-LL) after TLIF surgery through preoperative X-ray images. The automated pipeline included two primary stages. First, a deep learning model was used to extract essential features from X-ray images. Second, five machine learning algorithms were trained to identify the optimal models to predict the interbody cage height and postoperative PI-LL. Lasso regression and support vector regression exhibited superior performance for predicting the interbody cage height and postoperative PI-LL, respectively. For cage height prediction, the root mean square error (RMSE) was calculated as 1.01, and the model achieved the highest accuracy at a height of 12 mm, with exact prediction achieved in 54.43% (43/79) of cases. In most of the remaining cases, the prediction error of the model was within 1 mm. In addition, the model demonstrated adequate performance for predicting PI-LL, with an RMSE of 5.19 and an accuracy of 0.81 for PI-LL stratification. In conclusion, the interbody cage height and postoperative PI-LL can be reliably predicted using artificial intelligence and ML models.