Baunknowles9396
Integrase strand transfer inhibitors (INSTIs) block the integration step of the retroviral lifecycle and are first-line drugs used for the treatment of HIV-1/AIDS. INSTIs have a polycyclic core with heteroatom triads, chelate the metal ions at the active site, and have a halobenzyl group that interacts with viral DNA attached to the core by a flexible linker. The most broadly effective INSTIs inhibit both wild-type (WT) integrase (IN) and a variety of well-known mutants. However, because there are mutations that reduce the potency of all of the available INSTIs, new and better compounds are needed. Models based on recent structures of HIV-1 and red-capped mangabey SIV INs suggest modifications in the INSTI structures that could enhance interactions with the 3'-terminal adenosine of the viral DNA, which could improve performance against INSTI resistant mutants. We designed and tested a series of INSTIs having modifications to their naphthyridine scaffold. One of the new compounds retained good potency against an expanded panel of HIV-1 IN mutants that we tested. Our results suggest the possibility of designing inhibitors that combine the best features of the existing compounds, which could provide additional efficacy against known HIV-1 IN mutants.
Omission errors in medical imaging can lead to missed diagnosis and harm to patients. The subject has been studied in conventional imaging, but no data is available for functional imaging in general and for PET/CT in particular. In this work, we evaluated the frequency and characteristics of perceptual omission errors in the PET component of oncologic PET/CT imaging and we analyze the hazardous scenarios prone to such modality-specific errors.
Perceptual omission errors were collected in one tertiary center PET/CT clinic during routine PET/CT reporting over a 26-month period. The omissions were detected either in reporting follow-up PET/CT studies of the same patient or during multidisciplinary meetings.
Significant omission errors were found in 1.2 % of the 2100 reports included in the study. The most common omissions were bone metastases and focal colon uptake. We identified six PET-specific causative factors contributing to the occurrence of omissions, and we propose solutions to minimize their influence.
The data presented here can help to promote the awareness of interpreting physicians to body areas that require higher attention and to implement reading strategies for improving the accuracy of PET/CT interpretation.
The data presented here can help to promote the awareness of interpreting physicians to body areas that require higher attention and to implement reading strategies for improving the accuracy of PET/CT interpretation.
The present study evaluates the relationship between PET/CT findings and survival in patients with locally advanced cervical cancer (LACC) with a squamous cell histology.
The study included 70 patients with LACC (FIGO stage IB2-IVA). The relationship between pretreatment PET/CT parameters, age, stage, lymph node metastasis and survival was evaluated using the univariate and multivariate Cox proportional hazards model.
The mean age of the 70 patients was 57.4 years and the mean duration of follow-up was 33.6 months. Disease progression occurred in 36 patients and 32 patients died during the follow-up period. In the univariate analysis, MTV-P and TLG-P were found to be related to progression-free survival (PFS), and stage, MTV-P, TLG-P and SUVmax-Ps were found to be related to overall survival (OS). However, only MTV-P and TLG-P were found to be independent prognostic factors for both PFS and OS.
The present findings suggest that volumetric PET parameters (MTV-P, TLG-P) predict the progression and survival of the patients with LACC.
The present findings suggest that volumetric PET parameters (MTV-P, TLG-P) predict the progression and survival of the patients with LACC.
Bioactive proteins represent the most important component class in biopharmaceutical products for therapeutic applications. Their production is most often biotechnologically realized by genetically engineered microorganisms. Selleckchem H-151 For the quality assurance of insulins as representatives of life-saving pharmaceuticals, analytical methods are required that allow more than total protein quantification in vials or batches. Chemical and physical factors such as unstable temperatures or shear rate exposure under storage can lead to misfolding, nucleation, and subsequent fibril forming of the insulins. The assumption is valid that these processes go parallel with a decrease in bioactivity.
Infrared (IR) spectroscopy has been successfully utilized for secondary structure analysis in cases of protein misfolding and fibril formation.
A reliable method for the quantification of the secondary structure changes has been developed using insulin dry-film Fourier-transform IR spectroscopy in combination with the attenuated t a fast and reliable analytical method for the determination of secondary structural changes within insulin molecules, as available in pharmaceutical insulin formulations and therefore challenges internationally established measurement techniques for quality control regarding time, costs, and effort of analysis.
Management of skin cancer worldwide is often a challenge of scale, in that the number of potential cases presented outweighs the resources available to detect and treat skin cancer.
This project aims to develop a polarimetry probe to create an accessible skin cancer detection tool.
An optical probe was developed to perform bulk tissue Stokes polarimetry, a technique in which a laser of known polarization illuminates a target, and the altered polarization state of the backscattered light is measured. Typically, measuring a polarization state requires four sequential measurements with different orientations of polarization filters; however, this probe contains four spatially separated detectors to take four measurements in one shot. The probe was designed to perform at a lower cost and higher speed than conventional polarimetry methods. The probe uses photodiodes and linear and circular film polarizing filters as detectors, and a low-coherence laser diode as its illumination source. The probe design takes advantage of the statistical uniformity of the polarization speckle field formed at the detection area.
Tests of each probe component, and the complete system put together, were performed to evaluate error and confirm the probe's performance despite its low-cost components. This probe's potential is demonstrated in a pilot clinical study on 71 skin lesions. The degree of polarization was found to be a factor by which malignant melanoma could be separated from other types of skin lesions.
Tests of each probe component, and the complete system put together, were performed to evaluate error and confirm the probe's performance despite its low-cost components. This probe's potential is demonstrated in a pilot clinical study on 71 skin lesions. The degree of polarization was found to be a factor by which malignant melanoma could be separated from other types of skin lesions.
Digital holographic microscopy (DHM) is a promising technique for the study of semitransparent biological specimen such as red blood cells (RBCs). It is important and meaningful to detect and count biological cells at the single cell level in biomedical images for biomarker discovery and disease diagnostics. However, the biological cell analysis based on phase information of images is inefficient due to the complexity of numerical phase reconstruction algorithm applied to raw hologram images. New cell study methods based on diffraction pattern directly are desirable.
Deep fully convolutional networks (FCNs) were developed on raw hologram images directly for high-throughput label-free cell detection and counting to assist the biological cell analysis in the future.
The raw diffraction patterns of RBCs were recorded by use of DHM. Ground-truth mask images were labeled based on phase images reconstructed from RBC holograms using numerical reconstruction algorithm. A deep FCN, which is UNet, was trained on the diffraction pattern images to achieve the label-free cell detection and counting.
The implemented deep FCNs provide a promising way to high-throughput and label-free counting of RBCs with a counting accuracy of 99% at a throughput rate of greater than 288 cells per second and 200 μm × 200 μm field of view at the single cell level. Compared to convolutional neural networks, the FCNs can get much better results in terms of accuracy and throughput rate.
High-throughput label-free cell detection and counting were successfully achieved from diffraction patterns with deep FCNs. It is a promising approach for biological specimen analysis based on raw hologram directly.
High-throughput label-free cell detection and counting were successfully achieved from diffraction patterns with deep FCNs. It is a promising approach for biological specimen analysis based on raw hologram directly.
One of the modern trends in medical diagnostics is based on metabolomics, an approach allowing determination of metabolites which can be the specific features of disease. High-resolution gas spectroscopy allows investigation of the gas metabolite content of samples of biological origin. We present the elaboration of a method of studying diabetic and non-diabetic biological samples, prepared as pellets, by terahertz (THz) high-resolution spectroscopy.
The main idea of the work is studying the content of thermal decomposition gas products of diabetic and non-diabetic dried blood plasma and kidney tissues for revealing the set of gas-markers that characterized the diabetes by the THz high-resolution spectroscopy method.
We present an approach to study the diabetic and non-diabetic blood plasma (human and rats) and kidney tissues (rats), using high-resolution spectroscopy based on the non-stationary effect of THz frequency range. The methods of preparing the blood and kidney tissue samples as pellets and of vaporizing the samples were developed.
The measurements of rotational absorption spectra of vapors at heating the pellets prepared from blood and kidney tissue were carried out in 118 to 178GHz frequency range. The absorption lines appearing in spectra of the sample vapors were detected and identified. The molecular contents of thermal decomposition products differed for non-diabetic and diabetic samples; e.g., main marker is acetone appearing in the diabetic blood (human and rats) and in the diabetic kidney tissue.
Our paper illustrates the potential ability for determining the metabolite content of biological samples for diagnostics and prognosis of diseases for clinical medicine.
Our paper illustrates the potential ability for determining the metabolite content of biological samples for diagnostics and prognosis of diseases for clinical medicine.
19p13.3 microduplication syndrome is a newly defined intrauterine onset growth retardation syndrome characterized by microcephaly, moderate intellectual disability, speech delay, and mild dysmorphic features. The PIAS4 gene located in this region plays a crucial role as a transcriptional co-regulator in various cellular pathways including STAT, p53/TP53 and growth hormone (GH) signaling and mutations in this gene are thought to be responsible for clinical features.
We present a 10 year-old girl with intrauterine onset growth retardation, microcephaly, and mild facial dysmorphic features. Treatment with GH was started at 4 years and 9 months of age targeting the severe short stature (-3.65 standard deviation score, SDS) since she had significant IGF-1 response to exogenous GH. Microarray study demonstrated a 19p13.3 microduplication of 4.4 Mb. FISH analyses revealed mosaic extra signals (27.5% on blood lymphocytes, and 47% on buccal epithelium) of 19p13.3 region. At the age of 10, her height was at -2.37 SDS, and she had mild intellectual disability which has been described in 19p13.
