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Abstract: Differences in gender immune response have resulted in differences in immune protection and susceptibility to inflammatory diseases. Cultured peripheral blood mononuclear cells (PBMC) are widely used in immunomodulation studies, yet the influence of gender is usually not considered. We examined the effect of in vitro culture and phytohaemagglutinin (PHA) stimulation on PBMC lymphocyte subsets using flowcytometry. Full blood counts of whole blood showed higher levels of lymphocyte in male subjects. Lymphocyte subsets enumeration revealed higher NK cell counts in males and higher B cells in females. Cultured PBMC resulted in significant increases in B and total T cell percentages among females and NK cells among males. PHA stimulated significantly increased percentages of NK and total T cells in males and total activated T cells (CD69+) in females. Our results showed significant gender differences in lymphocyte subsets in cultured conditions. This may affect experimental outcome. [Copyright &y& Elsevier]

Background Purpose Methods Results Conclusions Long‐axis positron emission tomography (PET) has emerged as one of the recent research directions in PET due to its ability to significantly enhance sensitivity and counting performance for low‐dose imaging, rapid imaging, and whole‐body dynamic imaging.The PET system presented in this study is a long‐axis animal PET based on lutetium–yttrium orthosilicate and silicon photomultiplier, designed for whole‐body imaging in rats. It features a diameter of 143 mm and an axial length of 213.3 mm. This study evaluated the performance of this PET system in accordance with the National Electrical Manufacturers Association (NEMA) NU 4‐2008 standards.The performance evaluation was conducted according to the NEMA NU 4‐2008 standards in terms of spatial resolution, sensitivity, counting rate performance, scatter fraction (SF) and image quality. In addition, a rat imaging study was conducted to assess the imaging capability of this PET system.The average energy resolution of the PET system was 12.87%, the average coincidence timing resolution was 751 ps. The FWHM of spatial resolution reconstructed by filtered back projection and 3D‐OSEM‐PSF algorithm at 5 mm radial offset from the axial center were 1.65 and 0.88 mm. The peak absolute sensitivity measured by a point source at the center of the field of view was evaluated as 6.71% (361–661 keV) and 10.31% (250–750 keV). For the mouse‐like phantom, the SF was 11.0% and the peak noise equivalent counting rate (NECR) was 1193 kcps at 94.2 MBq (2.54 mCi). For the rat‐like phantom, the SF was 26.8% and the NECR was 682.5 kcps at 78.6 MBq (2.12 mCi).The performance measurement results demonstrate that this PET system exhibits high sensitivity and count rate performance, making it potential for high‐quality whole‐body dynamic imaging of rats. [ABSTRACT FROM AUTHOR]

Background: Patients with autoimmune diseases (AD) generally carry an increased risk of developing cancer. However, the effect of AD in hepatocellular carcinoma (HCC) patients receiving surgical treatment is uncertain. The present study aimed to investigate the potential influence of AD on the survival of HCC patients undergoing hepatectomies. Methods: Operated HCC patients were identified from the Chang Gung Research Database, and the survival outcomes of HCC patients with or without AD were analyzed ad compared. Cox regression model was performed to identify significant risk factors associated with disease recurrence and mortality. Results: From 2002 to 2018, a total of 5532 patients underwent hepatectomy for their HCC. Among them, 229 patients were identified to have AD and 5303 were not. After excluding cases who died within 30 days of surgery, the estimated median overall survival (OS) was 43.8 months in the AD (+) group and 47.4 months in the AD (–) group (P = 0.367). The median liver-specific survival and disease-free survival (DFS) were also comparable between the two groups. After Cox regression multivariate analysis, the presence of AD did not lead to a higher risk of all-cause mortality, liver-specific mortality, or disease recurrence. Conclusion: Our study demonstrated that autoimmune disease does not impair the OS and DFS of HCC patients undergoing liver resections. AD itself is not a risk factor for tumor recurrence after surgery. Patients eligible for liver resections, as a result, should be considered for surgery irrespective of the presence of AD. Further studies are mandatory to validate our findings. [ABSTRACT FROM AUTHOR]

The Eplus-260 primate PET is an animal PET imaging system developed by the Institute of High Energy Physics, Chinese Academy of Sciences, which is designed to image non-human primates, especially the brain of large non-human primates. The system consists of 48 block detectors arranged in two 24-sided rings with a ring diameter of 263 mm and an axial extent of 64 mm. Each block detector is composed of a 16  ×  16 cerium-doped lutetium–yttrium orthosilicate crystal array with a pixel size of 1.9  ×  1.9  ×  10 mm3. This article presents a performance evaluation of the PET scanner according to the National Electrical Manufacturers Association NU-4 2008 standards. All measurements were made for an energy window of 360–660 keV and a coincidence timing window of 2 ns. In terms of the FWHM, the FBP reconstructed spatial resolution results in all three directions at the radial position of 5 mm were better than or approached to 2 mm, and remained below 3.0 mm within the central 5 cm diameter of the FOV. The peak absolute sensitivity of the scanner was measured 1.80%. For a monkey-sized phantom, the scatter fraction was 34.2% and the peak noise equivalent count rate (NECR) was 26.5 kcps at 64.3 kBq/cc. The overall imaging capabilities of the scanner were also assessed using in vivo imaging study of a rhesus macaque. The performance measurements demonstrate that the Eplus-260 primate PET scanner has the potential ability to obtain good quality and high-contrast images for non-human primates, especially the brain of large non-human primates and could be considered as one technologically advanced dedicated non-human primate PET scanner available today. [ABSTRACT FROM AUTHOR]

With the proposal of the road map of Time-of-Flight positron emission tomography (TOF-PET) with a Coincidence Time Resolution (CTR) of 10 ps by Paul Lecoq et al. in 2020, the technology based on TOF puts forward higher requirements on the performance of its core optical devices. In this manuscript, we developed a kind of Multi-Anode micro channel plate photomultiplier tube (MCP-PMT) based on Cherenkov radiator window. By using the Cherenkov radiator as the optical window of Multi-Anode MCP-PMT directly, the optical interface between the scintillator and the PMT window in conventional TOF-PET is eliminated, reducing light loss and further improve the time resolution of TOF-PET. The anode of this MCP-PMT can be split into a finely spaced array of collecting electrodes to achieve good positional sensitivity. In this paper, the single photon detection capability and time resolution of this kind of MCP-PMT are evaluated. The transit time spread (TTS) at single photon mode can reach 42.9 ps, and the TTS at multi photon mode is less than 10 ps. The CTR based on this kind of MCP-PMT is 156.7 ± 10.6 ps FWHM, which is equivalent to a position resolution of 23.5 ± 1.6 mm along a line of response (LOR). The performance uniformity of this kind MCP-PMT has also been calibrated. • A new Multi-anode MCP-PMT with Cherenkov Radiator Window. • The time resolution of this kind of MCP-PMT is less than 40 ps sigma. • The coincidence time resolution based on this kind of MCP-PMT is 156.7 ps FWHM. • This kind of multi-anode MCP-PMT shows great uniformity in gain and time resolution. [ABSTRACT FROM AUTHOR]

Background: Lenvatinib and atezolizumab plus bevacizumab(A + B) have been used for unresectable hepatocellular carcinoma (HCC) as first‐line therapy. Real‐world studies comparison of efficacy and safety in these two regimens are limited, we therefore conduct this study to investigate these issues. Methods: We retrospectively reviewed patients received lenvatinib (n = 46) and A + B (n = 46) as first‐line systemic therapy for unresectable HCC in a tertiary medical center. Objective response rate (ORR), progression free survival (PFS), and overall survival (OS) were evaluated according to modified Response Evaluation Criteria in Solid Tumors (mRECIST). Inverse probability weighting (IPW) was performed for baseline clinical features balance. Results: A total of 92 patients with median age of 63.8 year‐old, 78.3% male, 85.9% viral hepatitis infected, 67.4% BCLC stage C were enrolled. The median treatment and follow‐up duration were 4.7 months and 9.4 months, respectively. There was no significant difference in ORR (26.1% vs. 41.3%, p = 0.1226), PFS (5.9 vs. 5.3 months, p = 0.4066), and OS (not reached vs. not reached, p = 0.7128) between the lenvatinib and A + B groups. After IPW, the results of survival and response rate were also compared. Subgroup analysis suggested that using lenvatinib was not inferior to A + B in regards of PFS, including those with elder, Child‐Pugh class B, beyond up‐to‐seven, or portal vein invasion VP4 patients. Among the lenvatinib treated patients, multivariate analysis showed patients elder than 65‐year‐old was an independent predictor associated with shorter PFS (adjust HR: 2.085[0.914–4.753], p = 0.0213). The incidence rates of adverse events were similar between two groups (76 vs. 63%, p = 0.1740). Both of two regimens had similarly few impact on liver function by comparison of baseline, third month, and sixth month albumin‐bilirubin index and Child‐Pugh score. Conclusions: The efficacy and safety of lenvatinib are similar to A + B as a first‐line systemic therapy for unresectable HCC. [ABSTRACT FROM AUTHOR]

Small extracellular vesicles (sEVs) provide major promise for advances in cancer diagnostics, prognostics, and therapeutics, ascribed to their distinctive cargo reflective of pathophysiological status, active involvement in intercellular communication, as well as their ubiquity and stability in bodily fluids. As a result, the field of sEV research has expanded exponentially. Nevertheless, there is a lack of standardisation in methods for sEV isolation from cells grown in serum‐containing media. The majority of researchers use serum‐containing media for sEV harvest and employ ultracentrifugation as the primary isolation method. Ultracentrifugation is inefficient as it is devoid of the capacity to isolate high sEV yields without contamination of non‐sEV materials or disruption of sEV integrity. We comprehensively evaluated a protocol using tangential flow filtration and size exclusion chromatography to isolate sEVs from a variety of human and murine cancer cell lines, including HeLa, MDA‐MB‐231, EO771 and B16F10. We directly compared the performance of traditional ultracentrifugation and tangential flow filtration methods, that had undergone further purification by size exclusion chromatography, in their capacity to separate sEVs, and rigorously characterised sEV properties using multiple quantification devices, protein analyses and both image and nano‐flow cytometry. Ultracentrifugation and tangential flow filtration both enrich consistent sEV populations, with similar size distributions of particles ranging up to 200 nm. However, tangential flow filtration exceeds ultracentrifugation in isolating significantly higher yields of sEVs, making it more suitable for large‐scale research applications. Our results demonstrate that tangential flow filtration is a reliable and robust sEV isolation approach that surpasses ultracentrifugation in yield, reproducibility, time, costs and scalability. These advantages allow for implementation in comprehensive research applications and downstream investigations. [ABSTRACT FROM AUTHOR]

Background and Aims: The Albumin-Bilirubin (ALBI) grade is a good index for liver function evaluation and is also associated with the outcomes of hepatocellular carcinoma patients receiving TACE. However, the correlation between the dynamic change to the ALBI score and clinical outcome is seldom discussed. Therefore, this study aimed to investigate the application of ALBI grade and dynamic change of ALBI grade (delta ALBI grade) after first TACE for prognosis prediction in HCC patients with chronic hepatitis C infection. Method: From January 2005 to December 2015, newly diagnosed naive chronic hepatitis C-hepatocellular carcinoma (CHC-HCC) patients who were treated with TACE as the initial treatment at the Chang Gung Memorial Hospital, Linkou Medical Center, were retrospectively recruited. The pre-treatment host factors, tumor status and noninvasive markers were collected. The Cox regression model was used to identify independent predictors of overall survival and tumor recurrence. Results: Among 613 treatment-naive CHC-HCC patients, 430 patients died after repeated TACE during a median follow-up of 26.9 months. Complete remission after repeated TACE occurred in 46.2% patients, and 208 patients (33.9%) had tumor recurrence, with a median recurrence-free interval of 8.5 months. In Cox regression analysis, ALBI grade II/III (aHR: 1.088, p = 0.035) and increased delta ALBI grade (aHR: 1.456, p = 0.029) were independent predictive factors for tumor recurrence. Furthermore, ALBI grade II/III (aHR: 1.451, p = 0.005) and increased delta ALBI grade during treatment (aHR: 1.436, p = 0.006) were predictive factors for mortality, while achieving complete response after repeated TACE (aHR: 0.373, p < 0.001) and anti-viral therapy (aHR: 0.580, p = 0.002) were protective factors for mortality. Conclusion: Both ALBI and delta ALBI grade are independent parameters to predict survival and tumor recurrence of CHC-HCC patients receiving TACE treatment. [ABSTRACT FROM AUTHOR]

Abstract: Structural brain abnormalities have been widely reported in major depressive disorder (MDD). However, many previous results cannot exclude the interferences of medication or multiple recurrent episodes. In this study, we examined structural brain abnormalities by comparing 68 drug-naïve first-episode adult-onset MDD and 68 healthy controls (HCs). Structural magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) methods were used. The mean values of grey matter volume/white matter volume (GMV/WMV) were calculated, then the differences between MDD and HCs were analyzed, and the associations of the differences with clinical characteristics of depression were discussed. The whole brain GMV/WMV did not differ between MDD patients and HCs; however, the regional GMV of the right pre-supplementary motor area (pre-SMA) was smaller in MDD patients. The GMV of both hippocampi was positively correlated with symptom severity and lower in patients with long durations. These results indicate the GMV reduction of the pre-SMA at an early stage of depression, whereas the GMV of the hippocampus is associated with depressive characteristics. Moreover, the whole brain GMV/WMV was negatively related to the duration of depression, supporting that volume loss could become progressive during the development of disease. These results may suggest the importance of identifying and intervening depression at an early stage, especially the first year after onset, to prevent volume loss in the brain. [Copyright &y& Elsevier]

X-ray Computed Tomography (CT) method is an integral part of hydraulic-fracture imaging, but its application to micro-fractures in cores is limited. This paper documents the visualization of fractured cores via an accessorial PET-CT approach to improve both spatial resolution and image contrast. PET-CT approach combines X-ray Computed Tomography (CT) and positron emission tomography (PET) method. CT technique provides information of core structure and accurate location of fractures based on density variations. PET is a nuclear imaging technique through inducing radionuclide into fractures, offering the potential to overcome CT limitations by providing information of micro-fractures. Combined PET-CT approach has been demonstrated as a technical advancement for imaging fractured cores better than simply CT or PET method. Comprehensive information of core structure, micro-fractures and connected fractures could be provided by PET-CT method. The applicability of each visualization technique was evaluated, the favorable implementation of combined PET-CT for laboratory core analysis was discussed. • Combined PET-CT technique was introduced to imaging hydraulic fractures in shale cores. • Improved image fusion method was proposed to fuse PET images and CT images. • Images with high resolution and contrast were obtained. • Combined PET-CT method shows superior to CT and PET method alone in providing comprehensive information of fractured cores. [ABSTRACT FROM AUTHOR]

The distribution, free concentration and metabolism of drugs can be significantly altered as a result of binding to albumin. At the same time, the conformational of serum albumin was also changed by interaction with low molecular weight drugs. In present work, we first equilibrated HSA in aqueous solution to obtain the solvated-HSA model. Further solvated-HSA was performed molecular docking with paclitaxel to find the binding sites. The two docking HSA-paclitaxel complexes were obtained and further equilibrated by a 12 ns MD simulation. Then, MMPBSA method was used to investigate the binding free energy of them. Finally, we correlated the fluctuations of residues with corresponding changes in the secondary structure by dssp method. Two binding sites of paclitaxel were found on HSA having considered the solvation effect. More hydrogen bonds were formed at site I respected to site II. A larger binding energy for primary binding also indicated that paclitaxel showed higher binding affinity mainly due to the stronger hydrogen bonding interactions. There was a significant difference between the two complexes on structure according to the dssp results. Moreover, structure of the binding sites exhibited more fluctuations after binding paclitaxel compared with other regions. Paclitaxel binding also induced distinct conformational changes in drug binding site even when it was empty and have contributed to a reduced binding capacity of HSA towards adriamycin. [ABSTRACT FROM PUBLISHER]

A new polygon positron emission mammography imaging system (PEMi) was developed in 2009 by the Institute of High Energy Physics, Chinese Academy of Sciences. PEMi is constructed in a polygon structure with lutetium yttrium orthosilicate crystal arrays mounted on a position-sensitive photomultiplier. The system consists of 64 blocks and each block is arranged in 16 \times 16 crystal arrays with a pixel size of 1.9~\times 1.9~ \times 15 mm. The diameter of the detector ring is 166 mm, and the axial length is 128 mm. The transaxial field of view of PEMi is 110 mm. The goal of the initial study was to test PEMi’s performance and the clinical imaging ability with a small group of selected subjects. The detectors have a measured intrinsic spatial resolution averaging 1.67 mm. The axial and tangential resolution remained under 2.5-mm full width at half maximum within the central 5-cm diameter of the field of view. The hot rods with a diameter of 1.7 mm can be clearly identified, and the structure of the region containing 1.35-mm diameter rods can also be observed. Using a 6-ns coincidence timing window and a \ 360 \sim \ 660-keV energy window, the peak sensitivity of the tomograph is 6.88%. The noise-equivalent count rate peak is 110\thinspace766 cps for a breast-like cylindrical phantom of 100 mm in diameter at an activity concentration of 0.03~\MBq/cc. The recovery coefficients ranged from 0.21 to 0.85 for rods between 1 mm and 5 mm in the image-quality phantom. The reconstructed image resolution achieved an improvement compared with whole-body positron emission tomography (PET), which might reduce the lower threshold on detectable lesion size. Example patient images demonstrate that PEMi is clinically feasible. And more detailed structure information was obtained with PEMi than with the whole-body PET imaging. [ABSTRACT FROM AUTHOR]

For radiation detection, the imaging system should have a large field of view (FOV) and high detection efficiency because it has to be used in a radiation environment where the quantity and direction of radioactive sources are unknown. A panorama coded-aperture gamma camera optimized for use in complex nuclear environment has been developed and evaluated with an angular resolution of 3.5°. Typical gamma cameras have the limited field of view ranging from 10° to 60° in both horizontal and vertical direction. The system presented in this paper extends the field of view to 360° in the horizontal direction and 60° in the vertical direction. The partial encoding of coded aperture imaging is mitigated by convolving the data of diverse adjacent modules with a partial transmission function. The experimental feasibility of measuring multiple sources in the 360° horizontal field of view was demonstrated with a panoramic image. The results showed that the system could clearly identify the direction of multiple radiation sources in an unknown extended radiation environment. The system can help to simplify the clean up and decommissioning of nuclear sites. [ABSTRACT FROM AUTHOR]

Abstract: A depth discrimination method is devised based on a multirow linear array detector for push-broom Compton scatter imaging. Two or more rows of detector modules are placed at different positions towards a sample. An improved parallel-hole collimator is fixed in front of the modules to restrict their fields of view. The depth information could be indicated by comparing the signal differences. In addition, an available detector and several related simulations using GEANT4 are given to support the method well. [Copyright &y& Elsevier]

Abstract: A PET module that comprises a pair of compact, high-resolution and large-area detectors based on silicon photomultipliers (SiPM) was developed and evaluated. The detector''s effective area was 24mm×24mm. LYSO crystals measuring 1.9mm×1.9mm×10mm and charge division circuit were employed to obtain high spatial resolution with relatively concise Front-end electronics (FEE). Initial results showed the detector to be compatible with 1.5T magnetic fields. The system''s intrinsic FWHM spatial resolution is 1.50mm. The average energy resolution is 18.5% and the coincidence timing resolution is 2.6ns. [Copyright &y& Elsevier]

Positron emission tomography (PET) is a non-invasive imaging tool for the evaluation of brain function and neuronal activity in normal and diseased conditions with high sensitivity. The macaque monkey serves as a valuable model system in the field of translational medicine, for its phylogenetic proximity to man. To translation of non-human primate neuro-PET studies, an effective and objective data analysis platform for neuro-PET studies is needed. A set of stereotaxic templates of macaque brain, namely the Institute of High Energy Physics & Jinan University Macaque Template (HJT), was constructed by iteratively registration and averaging, based on 30 healthy rhesus monkeys. A brain atlas image was created in HJT space by combining sub-anatomical regions and defining new 88 bilateral functional regions, in which a unique integer was assigned for each sub-anatomical region. The HJT comprised a structural MRI T1 weighted image (T1WI) template image, a functional FDG-PET template image, intracranial tissue segmentations accompanied with a digital macaque brain atlas image. It is compatible with various commercially available software tools, such as SPM and PMOD. Data analysis was performed on a stroke model compared with a group of healthy controls to demonstrate the usage of HJT. We have constructed a stereotaxic template set of macaque brain named HJT, which standardizes macaque neuroimaging data analysis, supports novel radiotracer development and facilitates translational neuro-disorders research. • Developing a population stereotaxic PET template, named HJT, for the macaque brain. • Identifying 88 bilateral functional regions in HJT. • Performance of HJT on the platform of commercially available software such as SPM and PMOD. • Application of HJT in voxel-wised analysis of stroke macaque model. [ABSTRACT FROM AUTHOR]

A point spread function (PSF) for the blurring component in positron emission tomography (PET) is studied. The PSF matrix is derived from the single photon incidence response function. A statistical iterative reconstruction (IR) method based on the system matrix containing the PSF is developed. More specifically, the gamma photon incidence upon a crystal array is simulated by Monte Carlo (MC) simulation, and then the single photon incidence response functions are calculated. Subsequently, the single photon incidence response functions are used to compute the coincidence blurring factor according to the physical process of PET coincidence detection. Through weighting the ordinary system matrix response by the coincidence blurring factors, the IR system matrix containing the PSF is finally established. By using this system matrix, the image is reconstructed by an ordered subset expectation maximization (OSEM) algorithm. The experimental results show that the proposed system matrix can substantially improve the image radial resolution, contrast, and noise property. Furthermore, the simulated single gamma-ray incidence response function depends only on the crystal configuration, so the method could be extended to any PET scanner with the same detector crystal configuration. [ABSTRACT FROM AUTHOR]