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Author(s):  
Kengo Shibuya ◽  
Haruo Saito ◽  
Hideaki Tashima ◽  
Taiga Yamaya

Abstract Positronium (Ps) lifetime imaging is gaining attention to bring out additional biomedical information from positron emission tomography (PET). The lifetime of Ps in vivo can change depending on the physical and chemical environments related to some diseases. Due to the limited sensitivity, Ps lifetime imaging may require merging some voxels for statistical accuracy. This paper presents a method for separating the lifetime components in the voxel to avoid information loss due to averaging. The mathematics for this separation is the inverse Laplace transform (ILT), and the authors examined an iterative numerical ILT algorithm using Tikhonov regularization, namely CONTIN, to discriminate a small lifetime difference due to oxygen saturation. The separability makes it possible to merge voxels without missing critical information on whether they contain abnormally long or short lifetime components. The authors conclude that ILT can compensate for the weaknesses of Ps lifetime imaging and extract the maximum amount of information.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Clovis H. T. Seumen ◽  
Urte Tomasiunaite ◽  
Daniel F. Legler ◽  
Christof R. Hauck

AbstractThe exquisite specificity of Toll-like receptors (TLRs) to sense microbial molecular signatures is used as a powerful tool to pinpoint microbial contaminants. Various cellular systems, from native human blood cells to transfected cell lines exploit TLRs as pyrogen detectors in biological preparations. However, slow cellular responses and limited sensitivity have hampered the replacement of animal-based tests such as the rabbit pyrogen test or lipopolysaccharide detection by Limulus amoebocyte lysate. Here, we report a novel human cell-based approach to boost detection of microbial contaminants by TLR-expressing cells. By genetic and pharmacologic elimination of negative control circuits, TLR-initiated cellular responses to bacterial molecular patterns were accelerated and significantly elevated. Combining depletion of protein phosphatase PP2ACA and pharmacological inhibition of PP1 in the optimized reporter cells further enhanced the sensitivity to allow detection of bacterial lipoprotein at 30 picogram/ml. Such next-generation cellular monitoring is poised to replace animal-based testing for microbial contaminants.


2021 ◽  
Author(s):  
Mahta Barekatain ◽  
Yameng Liu ◽  
Zhongying Wang ◽  
Vadim Cherezov ◽  
Scott E. Fraser ◽  
...  

ABSTRACTOrganelle heterogeneity and inter-organelle associations within a single cell contribute to the limited sensitivity of current organelle separation techniques, thus hindering organelle subpopulation characterization. Here we use direct current insulator-based dielectrophoresis (DC-iDEP) as an unbiased separation method and demonstrate its capability by identifying distinct distribution patterns of insulin vesicles from pancreatic β-cells. A multiple voltage DC-iDEP strategy with increased range and sensitivity has been applied, and a differentiation factor (ratio of electrokinetic to dielectrophoretic mobility) has been used to characterize features of insulin vesicle distribution patterns. We observed a significant difference in the distribution pattern of insulin vesicles isolated from glucose-stimulated cells relative to unstimulated cells, in accordance with functional maturation of vesicles upon glucose stimulation, and interpret this to be indicative of high-resolution separation of vesicle subpopulation. DC-iDEP provides a path for future characterization of subtle biochemical differences of organelle subpopulations within any biological system.


2021 ◽  
Vol 1 (2) ◽  
pp. 038-042
Author(s):  
Hebert Dedehouanou ◽  
Yazid Taïrou Toure ◽  
Laurence Yehouenou

The diagnosis of bacteriologically confirmed pulmonary tuberculosis in Benin and in other developing countries relies on the search for acid-fast bacilli through microscopy despite its limited sensitivity. The objective of this study is to evaluate the contribution of the Xpert test in the diagnosis of multidrug-resistant tuberculosis in all new suspects received at the Centre National Hospitalier Universitaire de Pneumo-Phtisiologie de Cotonou (CNHU-PPC) of Benin. The biological material consisted of sputum from new suspected TB patients received at CNHU-PPC during the third quarter of 2018. A total of two thousand three hundred and seventy-five (2375) suspected patients were included in the study, of which 52% were men and 48% were women. The most representative age range was 15-24 years, 28%. GeneXpert was able to diagnose pulmonary tuberculosis in 10.02% of patients, including 9.7% rifampicin-susceptible and 0.3% rifampicin-resistant patients who could not be detected by microscopy. This molecular diagnostic tool is of great value for the diagnosis of multidrug-resistant tuberculosis in new suspects.


2021 ◽  
Vol 9 (11) ◽  
pp. 2366
Author(s):  
Christopher G. Shield ◽  
Benjamin M. C. Swift ◽  
Timothy D. McHugh ◽  
Rebekah M. Dedrick ◽  
Graham F. Hatfull ◽  
...  

Mycobacterium tuberculosis and other non-tuberculous mycobacteria are responsible for a variety of different infections affecting millions of patients worldwide. Their diagnosis is often problematic and delayed until late in the course of disease, requiring a high index of suspicion and the combined efforts of clinical and laboratory colleagues. Molecular methods, such as PCR platforms, are available, but expensive, and with limited sensitivity in the case of paucibacillary disease. Treatment of mycobacterial infections is also challenging, typically requiring months of multiple and combined antibiotics, with associated side effects and toxicities. The presence of innate and acquired drug resistance further complicates the picture, with dramatic cases without effective treatment options. Bacteriophages (viruses that infect bacteria) have been used for decades in Eastern Europe for the treatment of common bacterial infections, but there is limited clinical experience of their use in mycobacterial infections. More recently, bacteriophages’ clinical utility has been re-visited and their use has been successfully demonstrated both as diagnostic and treatment options. This review will focus specifically on how mycobacteriophages have been used recently in the diagnosis and treatment of different mycobacterial infections, as potential emerging technologies, and as an alternative treatment option.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maxwell Abedi ◽  
Dan O. M. Bonsu ◽  
Isaac K. Badu ◽  
Richmond Afoakwah ◽  
Pooja Ahuja

Abstract Background The determination of the shooting distance using gunshot residue (GSR) analysis is crucial in the investigation and reconstruction of firearm-related crimes. However, the conventional chemographic method for GSR analysis is destructive and has limited sensitivity and selectivity. While the spectroscopic method has potential in GSR analysis for crime investigation, there is a current lack of consistency in the spectroscopic results obtained for shooting distance estimation via GSR analysis. Addressing such limitations will enhance the forensic capabilities of law enforcement and provide an added advantage to crime laboratories during an investigation. It will also reinforce the use of such spectroscopic data in a criminal investigation. Main text We obtained all peer-reviewed articles relevant to shooting distance estimation from searching Scopus, Web of Science, PubMed, and Google Scholar databases. We specifically searched the databases using the keywords “shooting distance,” “range of fire,” “gunshot residue,” “firearm discharge residue,” and “firearm-related crime” and obtained 3811 records. We further filtered these records using a combination of two basic keywords “gunshot residue” and “shooting distance estimations” yielding 108 papers. Following a careful evaluation of the titles, abstracts, and full texts, 40 original peer-reviewed articles on shooting distance estimation via GSR analysis were included in the study. The forgoing included additional sources (n = 5) we obtained from looking through the reference lists of the forensic articles we found. Short conclusion This paper discusses the current scope of research concerning the chemographic and spectroscopic analysis of GSR for shooting distance estimation. It also examines the challenges of these techniques and provides recommendations for future research.


Healthcare ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1558
Author(s):  
Jessica Pulvirenti ◽  
Maurizio Musso ◽  
Teresa Fasciana ◽  
Antonio Cascio ◽  
Maria Rita Tricoli ◽  
...  

Transfusion-transmitted malaria (TTM) is a rare occurrence with serious consequences for the recipient. In non-endemic areas, the incidence of transmission of malaria by transfusion is very low. We report a clinical case of transfusion-transmitted malaria due to Plasmodium malariae, which happened in a patient with acute hemorrhagic gastropathy. Case presentation: In April 2019, a 70-year-old Italian man with recurrent spiking fever for four days was diagnosed with a P. malariae infection, as confirmed using microscopy and real-time PCR. The patient had never been abroad, but about two months before, he had received a red blood cell transfusion for anemia. Regarding the donor, we revealed that they were a missionary priest who often went to tropical regions. Plasmodium spp PCR was also used on donor blood to confirm the causal link. Discussion and Conclusions: The donations of asymptomatic blood donors who are predominantly “semi-immune” with very low parasitic loads are an issue. The main problem is related to transfusion-transmitted malaria. Our case suggests that P. malariae infections in semi-immune asymptomatic donors are a threat to transfusion safety. Currently, microscopy is considered the gold standard for the diagnosis of malaria but has limited sensitivity to detect low levels of parasitemia. Screening using serological tests and molecular tests, combined with the donor’s questionnaire, should be used to reduce the cases of TTM.


2021 ◽  
Author(s):  
Yingying Jia ◽  
Jun Yang ◽  
Yangyang Zhu ◽  
Fang Nie ◽  
HaoAO Wu ◽  
...  

Ultrasound (US) imaging is part of conventional medical imaging in clinical practice that is low-cost, non-ionizing, portable and capable of real-time image acquisition and display. However, in certain cases, US has limited sensitivity and specificity in differentiating between malignant and benign lesions. Ultrasound-based radiomics, as a new branch of radiomics, can provide additional features such as heterogeneity of lesions that are invisible to the naked eye, alone or in combination with demographic, histological, genomic or proteomic data, thereby improving the accuracy of US in diagnosis of disease. This article provides an introduction to ultrasound-based radiomics, covering its workflow, the application of machine learning, and current research status. Current limitations of radiomics, such as consistency of image acquisition, parameter variations, and difficulty in calibrating quantitative methods in ultrasound, will also be covered.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1495-1495
Author(s):  
Gregor Hoermann ◽  
Manja Meggendorfer ◽  
Constance Baer ◽  
Heiko Müller ◽  
Wencke Walter ◽  
...  

Abstract Background: Systemic mastocytosis (SM) is a hematologic neoplasm characterized by the infiltration of clonal mast cells in the bone marrow or other extra-cutaneous organs. The clinical course varies between advanced and non-advanced (indolent and smoldering SM) forms of SM. The vast majority of patients harbor the activating D816V mutation in the KIT tyrosine kinase. Additional somatic mutations in other genes have been recognized as risk factors in SM. Cytogenetic aberrations are rarely found in SM but have been associated with advanced disease. Whole genome sequencing (WGS) and whole transcriptome sequencing (WTS) have been described as an alternative to cytogenetics and targeted molecular genetic analysis in myeloid cancers. Aim: To assess the ability of WGS/WTS to detect cytogenetic aberrations and recurrent somatic mutations in SM. Methods: 120 patients (51 female, 69 male) diagnosed with SM were analyzed with WGS/WTS and results were compared with orthogonal data of KIT D816V PCR, targeted sequencing, and cytogenetics. 47 patients (39%) were diagnosed with advanced SM (1 mast cell leukemia, 3 aggressive SM, 43 SM with associated hematologic neoplasm). For WGS, 2x151bp paired-end reads were generated on NovaSeq 6000 and HiSeqX machines (Illumina, San Diego, CA). BaseSpace's Tumor/Normal app v3 was used to call variants with Strelka Somatic Variant Caller v2.4.7 and structural variants (aberrations with >50bp in size) with Manta (v0.28.0). Genomic DNA from a mixture of multiple anonymous donors (Promega, Fitchburg, WI, USA) was used as normal. For WTS, 2x101 bp paired-end reads were produced with a median of 50 mio. reads per sample, aligned with STAR v2.5.0, and variants were called using Isaac Variant Caller v2.3.13. Results: WGS/WTS detected cytogenetic aberrations in 21% of patients: 2 patients displayed a complex aberrant karyotype, 3 balanced structural aberrations, 16 copy number alterations, and 6 copy number neutral losses of heterozygosity. Aberrations detected by chromosome banding analysis were also found by WGS in all but three patients (small clones with aberrations present in ≤20% of metaphases and <10% of interphase nuclei as determined by FISH). In contrast, WGS/WTS detected additional aberrations in 16 patients. The frequency of chromosomal aberrations detected by WGS/WTS was higher in advanced compared to non-advanced SM (34% vs. 12%, p<0.05). KIT D816V was detected by PCR in 98%, by WGS in 21% and by WTS in 46% of patients. The detection rate by WGS was significantly higher in advanced (36%) compared to non-advanced SM (12%, p<0.05) while no difference was observed for WTS (45% vs. 47%). Somatic mutations outside of KIT were analyzed within a subset of 121 genes recurrently mutated in hematologic neoplasms. 46% of patients showed non-KIT mutations with a median of 2 mutations per patient. Both frequency of non-KIT mutations as well as the median number of mutations per patient was higher in advanced (83%; n=3) compared to non-advanced SM (22%, n=1, p<0.05). Finally, we analyzed the impact of genetic aberrations on survival in our SM cohort. Patients were grouped according to the presence of chromosomal aberrations and gene mutations (non-KIT) as assessed by WGS/WTS. SM patients with both types of aberrations (n=16), one type of aberration (n=47; gene mutations only n=38; chromosomal aberrations only n=8), or no aberration but KIT D816V (n=57) showed significant differences in overall survival (p<0.05, Figure 1). Con clusions: WGS/WTS has limited sensitivity for detection of KIT D816V in SM. This finding can be explained by the low KIT D816V mutation burden typically found in bone marrow aspirates of SM patients. In line, we observed a slightly higher detection rate in advanced SM and in RNA-based WTS analysis. As WGS/WTS will be applied for the diagnostic workup of myeloid malignancies in the future and SM associated with other hematologic neoplasms may be overlooked if not specifically investigated, additional PCR-based techniques are still mandatory to rule out KIT D816V as a diagnostic criterion for SM. In contrast, WGS/WTS detects both chromosomal aberrations and additional gene mutations in patients with SM and can be used as an alternative to cytogenetics and targeted sequencing for risk assessment. In particular, the absence of genetic aberrations in WGS/WTS identifies SM patients with indolent course of the disease and favorable prognosis. Figure 1 Figure 1. Disclosures Hoermann: Novartis: Honoraria. Kern: MLL Munich Leukemia Laboratory: Other: Part ownership. Haferlach: MLL Munich Leukemia Laboratory: Other: Part ownership. Haferlach: MLL Munich Leukemia Laboratory: Other: Part ownership.


2021 ◽  
Vol 22 (18) ◽  
pp. 9928
Author(s):  
Olga V. Morozova

Nanosilver with sizes 1–100 nm at least in one dimension is widely used due to physicochemical, anti-inflammatory, anti-angiogenesis, antiplatelet, antifungal, anticancer, antibacterial, and antiviral properties. Three modes of the nanosilver action were suggested: “Trojan horse”, inductive, and quantum mechanical. The Ag+ cations have an affinity to thiol, amino, phosphate, and carboxyl groups. Multiple mechanisms of action towards proteins, DNA, and membranes reduce a risk of pathogen resistance but inevitably cause toxicity for cells and organisms. Silver nanoparticles (AgNP) are known to generate two reactive oxygen species (ROS)-superoxide (•O2−) and hydroxyl (•OH) radicals, which inhibit the cellular antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) and cause mechanical damage of membranes. Ag+ release and replacement by electrolyte ions with potential formation of insoluble AgCl result in NP instability and interactions of heavy metals with nucleic acids and proteins. Protein shells protect AgNP core from oxidation, dissolution, and aggregation, and provide specific interactions with ligands. These nanoconjugates can be used for immunoassays and diagnostics, but the sensitivity is limited at 10 pg and specificity is restricted by binding with protective proteins (immunoglobulins, fibrinogen, albumin, and others). Thus, broad implementation of Ag nanostructures revealed limitations such as instability; binding with major blood proteins; damage of proteins, nucleic acids, and membranes; and immunosuppression of the majority of cytokines.


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