Identification Drug Targets for Oxaliplatin-Induced Cardiotoxicity without Affecting Cancer Treatment through Inter Variability Cross-Correlation Analysis (IVCCA).

The successful treatment of side effects of chemotherapy faces two major limitations: the need to avoid interfering with pathways essential for the cancer-destroying effects of the chemotherapy drug, and the need to avoid helping tumor progression through cancer promoting cellular pathways. To address these questions and identify new pathways and targets that satisfy these limitations, we have developed the bioinformatics tool Inter Variability Cross-Correlation Analysis (IVCCA). This tool calculates the cross-correlation of differentially expressed genes, analyzes their clusters, and compares them across a vast number of known pathways to identify the most relevant target(s). To demonstrate the utility of IVCCA, we applied this platform to RNA-seq data obtained from the hearts of the animal models with oxaliplatin-induced CTX. RNA-seq of the heart tissue from oxaliplatin treated mice identified 1744 differentially expressed genes with False Discovery Rate (FDR) less than 0.05 and fold change above 1.5 across nine samples. We compared the results against traditional gene enrichment analysis methods, revealing that IVCCA identified additional pathways potentially involved in CTX beyond those detected by conventional approaches. The newly identified pathways such as energy metabolism and several others represent promising target for therapeutic intervention against CTX, while preserving the efficacy of the chemotherapy treatment and avoiding tumor proliferation. Targeting these pathways is expected to mitigate the damaging effects of chemotherapy on cardiac tissues and improve patient outcomes by reducing the incidence of heart failure and other cardiovascular complications, ultimately enabling patients to complete their full course of chemotherapy with improved quality of life and survival rates.

Development and performance of SIAT bPET: a high-resolution and high-sensitivity MR-compatible brain PET scanner using dual-ended readout detectors.

PURPOSE: Positron emission tomography/magnetic resonance imaging (PET/MRI) is a powerful tool for brain imaging, but the spatial resolution of the PET scanners currently used for brain imaging can be further improved to enhance the quantitative accuracy of brain PET imaging. The purpose of this study is to develop an MR-compatible brain PET scanner that can simultaneously achieve a uniform high spatial resolution and high sensitivity by using dual-ended readout depth encoding detectors. METHODS: The MR-compatible brain PET scanner, named SIAT bPET, consists of 224 dual-ended readout detectors. Each detector contains a 26 × 26 lutetium yttrium oxyorthosilicate (LYSO) crystal array of 1.4 × 1.4 × 20 mm3 crystal size read out by two 10 × 10 silicon photomultiplier (SiPM) arrays from both ends. The scanner has a detector ring diameter of 376.8 mm and an axial field of view (FOV) of 329 mm. The performance of the scanner including spatial resolution, sensitivity, count rate, scatter fraction, and image quality was measured. Imaging studies of phantoms and the brain of a volunteer were performed. The mutual interferences of the PET insert and the uMR790 3 T MRI scanner were measured, and simultaneous PET/MRI imaging of the brain of a volunteer was performed. RESULTS: A spatial resolution of better than 1.5 mm with an average of 1.2 mm within the whole FOV was obtained. A sensitivity of 11.0% was achieved at the center FOV for an energy window of 350-750 keV. Except for the dedicated RF coil, which caused a ~ 30% reduction of the sensitivity of the PET scanner, the MRI sequences running had a negligible effect on the performance of the PET scanner. The reduction of the SNR and homogeneity of the MRI images was less than 2% as the PET scanner was inserted to the MRI scanner and powered-on. High quality PET and MRI images of a human brain were obtained from simultaneous PET/MRI scans. CONCLUSION: The SIAT bPET scanner achieved a spatial resolution and sensitivity better than all MR-compatible brain PET scanners developed up to date. It can be used either as a standalone brain PET scanner or a PET insert placed inside a commercial whole-body MRI scanner to perform simultaneous PET/MRI imaging.

DRG Explant Model: Elucidating Mechanisms of Oxaliplatin-Induced Peripheral Neuropathy and Identifying Potential Therapeutic Targets.

Oxaliplatin triggered chemotherapy induced peripheral neuropathy (CIPN) is a common and debilitating side effect of cancer treatment which limits the efficacy of chemotherapy and negatively impacts patients quality of life dramatically. For better understanding the mechanisms of CIPN and screen for potential therapeutic targets, it is critical to have reliable in vitro assays that effectively mirror the neuropathy in vivo . In this study, we established a dorsal root ganglia (DRG) explant model. This model displayed dose-dependent inhibition of neurite outgrowth in response to oxaliplatin, while oxalic acid exhibited no significant impact on the regrowth of DRG. The robustness of this assay was further demonstrated by the inhibition of OCT2 transporter, which facilitates oxaliplatin accumulation in neurons, fully restoring the neurite regrowth capacity. Using this model, we revealed that oxaliplatin triggered a substantial increase of oxidative stress in DRG. Notably, inhibition of TXNIP with verapamil significantly reduced oxidative stress level. Our results demonstrated the use of DRG explants as an efficient model to study the mechanisms of CIPN and screen for potential treatments.

Toward peripheral nerve mechanical characterization using Brillouin imaging spectroscopy.

Significance: Peripheral nerves are viscoelastic tissues with unique elastic characteristics. Imaging of peripheral nerve elasticity is important in medicine, particularly in the context of nerve injury and repair. Elasticity imaging techniques provide information about the mechanical properties of peripheral nerves, which can be useful in identifying areas of nerve damage or compression, as well as assessing the success of nerve repair procedures. Aim: We aim to assess the feasibility of Brillouin microspectroscopy for peripheral nerve imaging of elasticity, with the ultimate goal of developing a new diagnostic tool for peripheral nerve injury in vivo. Approach: Viscoelastic properties of the peripheral nerve were evaluated with Brillouin imaging spectroscopy. Results: An external stress exerted on the fixed nerve resulted in a Brillouin shift. Quantification of the shift enabled correlation of the Brillouin parameters with nerve elastic properties. Conclusions: Brillouin microscopy provides sufficient sensitivity to assess viscoelastic properties of peripheral nerves.

Influence of TPU/EVA Phase Morphology Evolution on Supercritical Carbon Dioxide Extrusion Foaming.

Ethylene-vinyl acetate copolymer (EVA) was added at different contents to the thermoplastic polyurethane (TPU) matrix to form a non-compatible blending system, and foaming materials with high pore density were prepared using the supercritical carbon dioxide extrusion method. The influence of the phase morphology and crystal morphology of the TPU/EVA blend on its foaming behavior was studied. The results show that EVA changed the phase morphology and crystal morphology of the blends, leading to the improved melt viscosity and crystallinity of the blend system. At the same time, interfacial nucleation increases the density of cells and decreases the cell thickness and size, which is beneficial for improving the foaming properties of the blends. For the EVA content of 10% (mass fraction), the cell size is small (105.29 µm) and the cell density is the highest (3.74 × 106 cells/cm3). Based on the TPU/EVA phase morphology and crystal morphology, it is found that the sea-island structure of the blend has better foaming properties than the bicontinuous structure.

Oxaliplatin-induced cardiotoxicity in mice is connected to the changes in energy metabolism in the heart tissue.

Oxaliplatin is a platinum-based alkylating chemotherapeutic agent used for cancer treatment. At high cumulative dosage, the negative effect of oxaliplatin on the heart becomes evident and is linked to a growing number of clinical reports. The aim of this study was to determine how chronic oxaliplatin treatment causes the changes in energy-related metabolic activity in the heart that leads to cardiotoxicity and heart damage in mice. C57BL/6 male mice were treated with a human equivalent dosage of intraperitoneal oxaliplatin (0 and 10 mg/kg) once a week for eight weeks. During the treatment, mice were followed for physiological parameters, ECG, histology and RNA sequencing of the heart. We identified that oxaliplatin induces strong changes in the heart and affects the heart's energy-related metabolic profile. Histological post-mortem evaluation identified focal myocardial necrosis infiltrated with a small number of associated neutrophils. Accumulated doses of oxaliplatin led to significant changes in gene expression related to energy related metabolic pathways including fatty acid (FA) oxidation, amino acid metabolism, glycolysis, electron transport chain, and NAD synthesis pathway. At high accumulative doses of oxaliplatin, the heart shifts its metabolism from FAs to glycolysis and increases lactate production. It also leads to strong overexpression of genes in NAD synthesis pathways such as Nmrk2. Changes in gene expression associated with energy metabolic pathways can be used to develop diagnostic methods to detect oxaliplatin-induced cardiotoxicity early on as well as therapy to compensate for the energy deficit in the heart to prevent heart damage.

Technical opportunities and challenges in developing total-body PET scanners for mice and rats.

Positron emission tomography (PET) is the most sensitive in vivo molecular imaging technique available. Small animal PET has been widely used in studying pharmaceutical biodistribution and disease progression over time by imaging a wide range of biological processes. However, it remains true that almost all small animal PET studies using mouse or rat as preclinical models are either limited by the spatial resolution or the sensitivity (especially for dynamic studies), or both, reducing the quantitative accuracy and quantitative precision of the results. Total-body small animal PET scanners, which have axial lengths longer than the nose-to-anus length of the mouse/rat and can provide high sensitivity across the entire body of mouse/rat, can realize new opportunities for small animal PET. This article aims to discuss the technical opportunities and challenges in developing total-body small animal PET scanners for mice and rats.

Performance of Dual-Ended Readout PET Detectors Based on BGO Arrays and BaSO4 Reflector.

In this paper, the performance of two dual-ended readout PET detectors based on 15 × 15 BGO arrays were compared. The crystal elements of one BGO array have polished lateral surfaces, while the crystal elements of the other BGO array have unpolished lateral surfaces. The two ends of the BGO elements are polished. The two BGO arrays both have a pitch size of 1.6 mm and thickness of 20 mm, and BaSO4 with a thickness of 80 µm was used as the reflector. Hamamatsu S14161-0305-08 SiPM arrays were used as photodetectors. All the measurements were performed at a bias voltage of 41.0 V and a temperature of 23.5 °C. The flood histograms show that all the crystal elements in the two BGO arrays were clearly resolved. The detector based on the BGO array with polished lateral surfaces provides an energy resolution of 16.9 ± 1.3%, timing resolution of 3.2 ± 0.2 ns, and DOI resolution of 18.4 ± 2.2 mm. In comparison, the detector based on the BGO array with unpolished lateral surfaces provides an energy resolution of 17.7 ± 2.0%, timing resolution of 3.5 ± 0.3 ns, and DOI resolution of 3.2 ± 0.2 mm.

Interaction of Interleukin 7 Receptor (IL7R) and IL6 Gene Polymorphisms with Smoking Associated with Susceptibility to Asthma in Chinese Han Adults.

BACKGROUND: the aim of this study was to investigate the relationship between the risk of asthma and multiple single nucleotide polymorphisms (SNPs) in interleukin 7 receptor (IL7R) and IL6 genes, as well as the gene- environment interactions. METHODS: This is a hospital- based case- control study. A total of 430 patients with asthma were continuously recruited. Four SNPs within IL7R and IL6 gene were genotyped by PCR based restriction fragment length polymorphism. The Hardy- Weinberg balance of all participants was tested by SNPstats. The best interaction combination of four SNPs in IL7R and IL6 genes and smoking was screened by generalized multifactor dimensionality reduction (GMDR). Logistic regression was used to test the association between four SNPs and asthma, and stratified analysis for rs1800795 gene-smoking interaction, synergy index (SI) was calculated. RESULTS: The rs1494558-G and rs1800795-C were associated with an increased risk of asthma, adjusted ORs (95% CI) was 1.81 (1.29-2.42) and 1.75 (1.20-2.28), respectively. GMDR indicated that the test accuracy for two-locus model involving rs1800795 and smoking was 0.5721, and the p = .011, the results providing evidence for rs1800795 gene-smoking interaction. The asthma risk was higher in smokers with GC or CC genotype than the sum of risks in subjects with smoking or GC or CC genotype alone, compared to the never smokers with GG genotype, the OR (95%CI) was 4.97 (3.01-7.24), and the synergy index (SI) was 1.68 (1.08-2.60). CONCLUSIONS: The rs1494558-G and rs1800795-C alleles, gene- environment interaction between rs1800795 and smoking were all associated with increased asthma risk.

A Privacy-Preserving Cross-Domain Healthcare Wearables Recommendation Algorithm Based on Domain-Dependent and Domain-Independent Feature Fusion.

Recently, recommender systems are applied to provide personalized recomendation for healthcare wearables. However, due to the sparsity problem, traditional recommendation algorithms are difficult to achieve desired performance. Considering that consumers often buy and rate other types of items on E-commerce platforms, we can leverage significant information in the auxiliary domains to improve the recommendation performance of healthcare wearables, which can be regarded as cross-domain recommendation. However, traditional cross-domain recommendation model cannot fully represent user's characteristics and fail to consider the leaks of original auxiliary domain ratings during the information transfer process. To overcome the two shortcomings, this paper proposes a Privacy-Preserving Cross-Domain Healthcare Wearables Recommendation algorithm (PPCDHWRec). Firstly, user's characteristics are divided into domain-dependent features and domain-independent features, which complement each other and fully depict the user's characteristics. Secondly, inspired by the latent factor model, we factorize the original rating information of each auxiliary domain by Funk-SVD and Orthogonal Nonnegative Matrix Tri-Factorization (ONMTF) model, to obtain user's domain-dependent and domain-independent features, respectively. Finally, the Factorization Machine algorithm is used to fuse the obtained user's features with the target domain information to provide the recommendation results. By hiding the item latent factors obtained in the factorization process, PPCDHWRec ensures that the original information cannot be inferred from the transferred user hidden vector. Hence, PPCDHWRec is a privacy-preserving recommendation model. Experiments on two groups of auxiliary domains, having high and low correlations with target domain, show the effectiveness of PPCDHWRec.

Performance evaluation of dual-ended readout PET detectors based on BGO arrays with different reflector arrangements.

OBJECTIVE: Dual-ended readout depth-encoding detectors based on bismuth germanate (BGO) scintillation crystal arrays are good candidates for high-sensitivity small animal positron emission tomography used for very-low-dose imaging. In this paper, the performance of three dual-ended readout detectors based on 15 × 15 BGO arrays with three different reflector arrangements and 8 × 8 silicon photomultiplier arrays were evaluated and compared. APPROACH: The three BGO arrays, denoted wo-ILG (without internal light guide), wp-ILG (with partial internal light guide), and wf-ILG (with full internal light guide), share a pitch size of 1.6 mm and thickness of 20 mm. Toray E60 with a thickness of 50µm was used as inter-crystal reflector. All reflector lengths in the wo-ILG and wf-ILG BGO arrays were 20 and 18 mm, respectively; the reflectors in the wp-ILG BGO array were 18 mm at the central region of the array and 20 mm at the edge. By using 18 mm reflectors, part of the crystals in the wp-ILG and wf-ILG BGO arrays worked as internal light guides. MAIN RESULTS: The results showed that the detector based on the wo-ILG BGO array provided the best flood histogram. The energy, timing and DOI resolutions of the three detectors were similar. The energy resolutions full width at half maximum (FWHM value) based on the wo-ILG, wp-ILG and wf-ILG BGO arrays were 27.2 ± 3.9%, 28.7 ± 4.6%, and 29.5 ± 4.7%, respectively. The timing resolutions (FWHM value) were 4.7 ± 0.5 ns, 4.9 ± 0.5 ns, and 5.0 ± 0.6 ns, respectively. The DOI resolution (FWHM value) were 3.0 ± 0.2 mm, 2.9 ± 0.2 mm, and 3.0 ± 0.2 mm, respectively. Over all, the wo-ILG detector provided the best performance.

Study of Cerenkov Light Emission in the Semiconductors TlBr and TlCl for TOF-PET.

Thallium bromide (TlBr) and thallium chloride (TlCl) are semiconductor materials with high transparency to visible light, high index of refraction, and high detection efficiency for gamma rays and annihilation photons. This manuscript reports on measurements of the light intensity and timing response of Cerenkov light emitted in one 3 mm × 3 mm × 5 mm slab of each of these materials operated in coincidence with a lutetium fine silicate (LFS) crystal with dimensions of 3 mm × 3 mm × 20 mm. A 22Na radioactive source was used. The measured average number of detected photons per event was 1.5 photons for TlBr and 2.8 photons for TlCl when these materials were coupled to a silicon photomultiplier. Simulation predicts these results with an overestimation of 12%. The best coincidence time resolution (CTR) for events in TlBr and TlCl were 329 ± 9 ps and 316 ± 9 ps, respectively, when events with 4 photons and >7 photons were selected. Simulation showed the CTR degraded from 120 ps to 405 ps in TlCl, and from 160 ps to 700 ps in TlBr when the first or second Cerenkov photon were selected. Results of this work show TlCl has a stronger Cerenkov light emission compared to TlBr and a greater potential to obtain the best timing measurements. Results also stress the importance of improving detection efficiency and transport of light to capture the first Cerenkov photon in timing measurements.

Identification of prognostic biomarkers related to the tumor microenvironment in thyroid carcinoma.

Thyroid Carcinoma (THCA) is the most common endocrine tumor that is mainly treated using surgery and radiotherapy. In addition, immunotherapy is a recently developed treatment option that has played an essential role in the management of several types of tumors. However, few reports exist on the use of immunotherapy to treat THCA. The study downloaded the miRNA, mRNA and lncRNA data for THCA patients from the TCGA database ( https://portal.gdc.cancer.gov/ ). Thereafter, the tumor samples were divided into cold and hot tumors, based on the immune score of the tumor microenvironment. Moreover, the differentially expressed lncRNAs and miRNAs were obtained. Finally, the study jointly constructed a ceRNA network through differential analysis of the mRNA data for cold and hot tumors. The study first assessed the level of immune infiltration in the THCA tumor microenvironment then divided the samples into cold and hot tumors, based on the immune score. Additionally, a total of 568 up-regulated and 412 down-regulated DEGs were screened by analyzing the differences between hot and cold tumors. Thereafter, the study examined the differentially expressed genes for lncRNA and miRNA. The results revealed 629 differentially expressed genes related to lncRNA and 114 associated with miRNA. Finally, a ceRNA network of the differentially expressed genes was constructed. The results showed a five-miRNA hubnet, i.e., hsa-mir-204, hsa-mir-128, hsa-mir-214, hsa-mir-150 and hsa-mir-338. The present study identified the immune-related mRNA, lncRNA and miRNA in THCA then constructed a ceRNA network. These results are therefore important as they provide more insights on the immune mechanisms in THCA. The findings also provides additional information for possible THCA immunotherapy.

H2RSPET: a 0.5 mm resolution high-sensitivity small-animal PET scanner, a simulation study.

With the goal of developing a total-body small-animal PET system with a high spatial resolution of ∼0.5 mm and a high sensitivity >10% for mouse/rat studies, we simulated four scanners using the graphical processing unit-based Monte Carlo simulation package (gPET) and compared their performance in terms of spatial resolution and sensitivity. We also investigated the effect of depth-of-interaction (DOI) resolution on the spatial resolution. All the scanners are built upon 128 DOI encoding dual-ended readout detectors with lutetium yttrium oxyorthosilicate (LYSO) arrays arranged in 8 detector rings. The solid angle coverages of the four scanners are all ∼0.85 steradians. Each LYSO element has a cross-section of 0.44 × 0.44 mm2 and the pitch size of the LYSO arrays are all 0.5 mm. The four scanners can be divided into two groups: (1) H2RS110-C10 and H2RS110-C20 with 40 × 40 LYSO arrays, a ring diameter of 110 mm and axial length of 167 mm, and (2) H2RS160-C10 and H2RS160-C20 with 60 × 60 LYSO arrays, a diameter of 160 mm and axial length of 254 mm. C10 and C20 denote the crystal thickness of 10 and 20 mm, respectively. The simulation results show that all scanners have a spatial resolution better than 0.5 mm at the center of the field-of-view (FOV). The radial resolution strongly depends on the DOI resolution and radial offset, but not the axial resolution and tangential resolution. Comparing the C10 and C20 designs, the former provides better resolution, especially at positions away from the center of the FOV, whereas the latter has 2× higher sensitivity (∼10% versus ∼20%). This simulation study provides evidence that the 110 mm systems are a good choice for total-body mouse studies at a lower cost, whereas the 160 mm systems are suited for both total-body mouse and rat studies.

Energy and electron drift time measurements in a pixel CCI TlBr detector with 1.3 MeV prompt-gammas.

Assessing the position of the Bragg peak (BP) in hadron radiotherapy utilizing prompt-gamma imaging (PGI) presents many challenges in terms of detector physics. Gamma detectors with the capability of extracting the best energy, timing, and spatial information from each gamma interaction, as well as with high detection efficiency and count rate performance, are needed for this application. In this work we present the characterization of a pixel Cerenkov charge induction (CCI) thallium bromide (TlBr) detector in terms of energy and and electron drift time for its potential use in PGI. The CCI TlBr detector had dimensions of 4 × 4 × 5 mm3 and one of its electrodes was segmented in pixels with 1.7 mm pitch. A silicon photomultiplier (SiPM) was optically coupled to one of the faces of the TlBr slab to read out the Cerenkov light promptly emitted after the interaction of a gamma ray. The detector was operated stand-alone and the 1.275 prompt gammas from a 22Na radioactive source were used for the study. The electron drift time was obtained by combining the Cerenkov and charge induction signals and then used as a measure of the depth of interaction. The electron mobility in TlBr was estimated as ∼27 cm2 V-1 s-1. Energy resolutions between 3.4% and 4.0% at 1.275 MeV were obtained after depth-correction. These values improved to 3.0%-3.3% when events with drift times of 3-6 µs were selected. These results show the potential of pixel CCI TlBr detectors to resolve gamma interactions in the detector with mm-like accuracy in 3D and with excellent energy resolution. Previous studies with CCI TlBr devices have shown a timing resolution of <400 ps full width at half maximum when detecting 511 keV gamma rays, therefore, the timing accuracy is expected to improve with the increased energy of the gamma rays in PGI. While other important detector characteristics such as count rate capability remain to be studied, results from this work combined with other preliminary data show pixel CCI detectors can simultaneously provide excellent energy, timing, and spatial resolution performance and are a very promising option for PGI in hadron therapy.

Performance comparison of dual-ended readout depth-encoding PET detectors based on BGO and LYSO crystals.

The performance of dual-ended readout depth-encoding positron emission tomography (PET) detectors based on bismuth germanate (BGO) coupled to silicon photomultipliers (SiPM) arrays was measured for the first time and compared to lutetium-yttrium oxyorthosilicate (LYSO)-based detectors using the same readout. The BGO and LYSO crystal arrays all had a crystal pitch of 2.2 mm and were coupled to 8 × 8 SiPM arrays with a matching pitch of 2.2 mm, using a one-to-one coupling configuration. Three types of crystals with Toray reflector were used: polished LYSO, polished BGO, and unpolished BGO, and for two different crystal thicknesses of 20 mm and 30 mm. All the crystal elements in the BGO arrays were clearly resolved in the flood histogram. Better flood histograms were obtained using the LYSO arrays for a selected crystal thickness, and better flood histograms were obtained using the 20 mm thick crystal arrays for a selected crystal type. The average crystal level energy resolution and timing resolution for 20 mm polished LYSO, polished BGO and unpolished BGO crystals at their optimal SiPM bias voltage were 18.6 ± 1.3% and 1.19 ± 0.20 ns, 17.8 ± 0.8% and 4.43 ± 0.47 ns, and 18.0 ± 1.0% and 4.68 ± 1.0 ns, respectively. Depth-of-interaction (DOI) resolution of the 20 mm polished LYSO array was 2.31 ± 0.17 mm and for the 20 mm unpolished BGO array was 3.53 ± 0.25 mm. However, polished BGO arrays with Toray reflector did not provide DOI information. Our key conclusion is that dual-ended readout depth-encoding 20 mm thick unpolished BGO detectors are good candidates for low-activity PET systems with small field-of-view and low timing performance requirements, such as preclinical or compact organ-dedicated PET systems, with the advantage over LYSO of having no background radiation and significantly lower cost.

Design and performance of SIAT aPET: a uniform high-resolution small animal PET scanner using dual-ended readout detectors.

In this work, a small animal PET scanner named SIAT aPET was developed using dual-ended readout depth encoding detectors to simultaneously achieve high spatial resolution and high sensitivity. The scanner consists of four detector rings with 12 detector modules per ring; the ring diameter is 111 mm and the axial field of view (FOV) is 105.6 mm. The images are reconstructed using an ordered subset expectation maximization (OSEM) algorithm. The spatial resolution of the scanner was measured by using a 22Na point source at the center axial FOV with different radial offsets. The sensitivity of the scanner was measured at center axis of the scanner with different axial positions. The count rate performance of the system was evaluated by scanning mouse-sized and rat-sized phantoms. An ultra-micro hot-rods phantom and two mice injected with 18F-NaF and 18F-FDG were scanned on the scanner. An average depth of interaction (DOI) resolution of 1.96 mm, energy resolution of 19.1% and timing resolution of 1.20 ns were obtained for the detector. Average spatial resolutions of 0.82 mm and 1.16 mm were obtained up to a distance of 30 mm radially from the center of the FOV when reconstructing a point source in 1% and 10% warm backgrounds, respectively, using OSEM reconstruction with 16 subsets and 10 iterations. Sensitivities of 16.0% and 11.9% were achieved at center of the scanner for energy windows of 250-750 keV and 350-750 keV respectively. Peak noise equivalent count rates (NECRs) of 324 kcps and 144 kcps were obtained at an activity of 26.4 MBq for the mouse-sized and rat-sized phantoms. Rods of 1.0 mm diameter can be visually resolved from the image of the ultra-micro hot-rods phantom. The capability of the scanner was demonstrated by high quality in-vivo mouse images.

FosB recruits KAT5 to potentiate the growth and metastasis of papillary thyroid cancer in a DPP4-dependent manner.

OBJECTIVE: Dipeptidyl peptidase IV (DPP4) has been indicated as a possible prognostic biomarker in papillary thyroid cancer (PTC). However, the mechanism of DPP4 during metastasis of PTC remains unclear. In this study, we investigated whether lysine acetyltransferase 5 (KAT5) and FBJ murine osteosarcoma viral oncogene homolog B (FosB) synergistically regulate high DPP4 expression in PTC. METHODS: PTC tissues and matched paracancerous tissues were harvested, followed by the establishment of IHH-4 and TPC-1 cells with downregulation of DPP4. The relevance of DPP4 on the metastasis of PTC cells was assessed. Subsequently, the effect of KAT5 on the transcription of DPP4 was verified. The binding relationship between FosB and DPP4 was predicted by a bioinformatics website. Functional rescue experiments were performed to evaluate cell activities after overexpression of KAT5 or FosB in cells with DPP4 knockdown. RESULTS: DPP4 was overexpressed in PTC tissues and cell lines, which was correlated with higher risks for metastases and poorer survival. DPP4 downregulation curtailed cell growth and metastasis. Moreover, KAT5 acetylated DPP4 promoter histone, which promoted transcription activation of DPP4. Subsequently, FosB recruited KAT5 at the DPP4 promoter, thereby enhancing DPP4 transcriptional activation. Further overexpression of KAT5 or FosB in cells with low expression of DPP4 promoted cell activity. Finally, DPP4 expedited p62 nuclear translocation to elevate Keap1/Nrf2 expression, thus facilitating the growth and metastasis of PTC cells. CONCLUSION: FosB enhanced the growth and metastasis of PTC cells by recruiting histone acetyltransferases KAT5 to increase DPP4 transcription and activate the p62/Keap1/Nrf2 signaling.

A Method to Extract Causality for Safety Events in Chemical Accidents from Fault Trees and Accident Reports.

Chemical event evolutionary graph (CEEG) is an effective tool to perform safety analysis, early warning, and emergency disposal for chemical accidents. However, it is a complicated work to find causality among events in a CEEG. This paper presents a method to accurately extract event causality by using a neural network and structural analysis. First, we identify the events and their component elements from fault trees by natural language processing technology. Then, causality in accident events is divided into explicit causality and implicit causality. Explicit causality is obtained by analyzing the hierarchical structure relations of event nodes and the semantics of component logic gates in fault trees. By integrating internal structural features of events and semantic features of event sentences, we extract implicit causality by utilizing a bidirectional gated recurrent unit (BiGRU) neural network. An algorithm, named CEFTAR, is presented to extract causality for safety events in chemical accidents from fault trees and accident reports. Compared with the existing methods, experimental results show that our method has a higher accuracy and recall rate in extracting causality.