Intra-Abdominal Epithelioid Neoplasm With EWSR1::CREB Fusions Involving the Kidney: A Clinicopathologic and Molecular Characterization With an Emphasis on Differential Diagnosis.

Soft tissue neoplasms, harboring fusions between EWSR1 and FUS with genes encoding CREB transcription factors family (ATF1, CREB1, and CREM), are an emerging heterogeneous group of mesenchymal tumors that differ significantly in morphology, immunophenotypes, and behavior. Recently, EWSR1/FUS::CREB fusions have been recognized to define a group of aggressive neoplasms of epithelioid morphology with multiple growth patterns and a striking predilection for mesothelial-lined cavities. These neoplasms presenting as a primary neoplasm of intra-abdominal visceral organs are rare, which could elicit a wide range of differential diagnoses because of their diverse morphologies and immunohistochemical profiles. We report 3 cases of intra-abdominal epithelioid neoplasms with EWSR1::CREB fusions involving the kidney. This study included 2 female patients and 1 male patient, with age at presentation ranging from 17 to 61 years (mean: 32 years). All the patients underwent radical nephrectomy without adjunctive therapies. Grossly, the tumors were large, and all were solitary masses with sizes ranging from 5.6 to 30.0 cm (mean: 14.5 cm). Histologically, the neoplasms showed infiltrating and indistinct borders and were composed predominantly of monomorphic round-to-epithelioid cells with variable amounts of pale-to-clear cytoplasm, arranged in cords, nests, and sheets and embedded in a sclerotic hyalinized stroma with variable lymphoid cuffing either intermixed or at the periphery. Notably, a hemangiopericytomatous growth pattern was commonly seen. Nuclear atypia was mild, and mitotic activity was scarce. Immunohistochemically, all 3 cases were at least focally positive for epithelial membrane antigen and keratin AE1/AE3, with 2 tumors showing focal MUC4 expression and 1 case displaying diffuse CD34 and focal CAIX positivity. Targeted RNA sequencing identified EWSR1::CREM fusion in 2 cases and EWSR1::ATF1 fusion in 1 case. Subsequent fluorescence in situ hybridization analysis confirmed the RNA sequencing results. On follow-up, 1 patient developed multiple spinal bone metastases 5 months after the surgery while the other 2 patients were free of disease 9 and 120 months after diagnosis, respectively. Our findings demonstrate that intra-abdominal epithelioid neoplasms with EWSR1::CREB fusions may rarely occur primarily in the kidney and should be included in the differential diagnosis of primary renal epithelioid mesenchymal neoplasms.

ALK-Rearranged Renal Cell Carcinoma: A Multi-Institutional Study of 9 Cases With Expanding the Morphologic and Molecular Genetic Spectrum.

ALK-rearranged renal cell carcinoma (ALK-RCC) is rare, molecularly defined RCC subtype in the recently published fifth edition of World Health Organization classification of tumors. In this study, we described 9 ALK-RCCs from a clinicopathologic, immunohistochemical, and molecular genetic aspect, supporting and extending upon the observations by previous studies regarding this rare subgroup of RCC. There were 6 male and 3 female patients with ages ranging from 14 to 59 years (mean, 34.4 years). None of the patients had sickle cell trait. The diagnosis was based on radical or partial nephrectomy specimen for 8 patients and on biopsy specimen for 1. Tumor size ranged from 2.5 to 7.2 cm (mean, 2.8 cm). Follow-up was available for 6 of 9 patients (6-36 months); 5 had no tumor recurrence or metastasis and 1 developed lung metastasis at 24 months. The patient was subsequently treated with resection of the metastatic tumor followed by crizotinib-targeted therapy, and he was alive without tumor 12 months later. Histologically, the tumors showed a mixed growth of multiple patterns, including papillary, solid, tubular, tubulocystic, cribriform, and corded, often set in a mucinous background. The neoplastic cells had predominantly eosinophilic cytoplasm. Focally, clear cytoplasm with polarized nuclei and subnuclear vacuoles (n = 1), and pale foamy cytoplasm (n = 1) were observed on the tumor cells. The biopsied tumor showed solid growth of elongated tubules merging with bland spindle cells. Other common and uncommon features included psammomatous microcalcifications (n = 5), rhabdoid cells (n = 4), prominent intracytoplasmic vacuoles (n = 4), prominent chronic inflammatory infiltrate (n = 3), signet ring cell morphology (n = 2), and pleomorphic cells (n = 2). By immunohistochemistry, all 9 tumors were diffusely positive for ALK(5A4) and 4 of 8 tested cases showed reactivity for TFE3 protein. By fluorescence in situ hybridization analysis, ALK rearrangement was identified in all the 9 tumors; none of the tested tumors harbored TFE3 rearrangement (0/4) or gains of chromosomes 7 and 17 (0/3). ALK fusion partners were identified by RNA-sequencing in all 8 cases analyzed, including EML4 (n = 2), STRN (n = 1), TPM3 (n = 1), KIF5B (n = 1), HOOK1 (n = 1), SLIT1 (n = 1), and TPM1(3'UTR) (n = 1). Our study further expands the morphologic and molecular genetic spectrum of ALK-RCC.

Dopamine ß-hydroxylase shapes intestinal inflammation through modulating T cell activation.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic and relapsing disease characterized by immune-mediated dysfunction of intestinal homeostasis. Alteration of the enteric nervous system and the subsequent neuro-immune interaction are thought to contribute to the initiation and progression of IBD. However, the role of dopamine beta-hydroxylase (DBH), an enzyme converting dopamine into norepinephrine, in modulating intestinal inflammation is not well defined. METHODS: CD4+CD45RBhighT cell adoptive transfer, and 2,4-dinitrobenzene sulfonic acid (DNBS) or dextran sodium sulfate (DSS)-induced colitis were collectively conducted to uncover the effects of DBH inhibition by nepicastat, a DBH inhibitor, in mucosal ulceration, disease severity, and T cell function. RESULTS: Inhibition of DBH by nepicastat triggered therapeutic effects on T cell adoptive transfer induced chronic mouse colitis model, which was consistent with the gene expression of DBH in multiple cell populations including T cells. Furthermore, DBH inhibition dramatically ameliorated the disease activity and colon shortening in chemically induced acute and chronic IBD models, as evidenced by morphological and histological examinations. The reshaped systemic inflammatory status was largely associated with decreased pro-inflammatory mediators, such as TNF-α, IL-6 and IFN-γ in plasma and re-balanced Th1, Th17 and Tregs in mesenteric lymph nodes (MLNs) upon colitis progression. Additionally, the conversion from dopamine (DA) to norepinephrine (NE) was inhibited resulting in increase in DA level and decrease in NE level and DA/NE showed immune-modulatory effects on the activation of immune cells. CONCLUSION: Modulation of neurotransmitter levels via inhibition of DBH exerted protective effects on progression of murine colitis by modulating the neuro-immune axis. These findings suggested a promising new therapeutic strategy for attenuating intestinal inflammation.

Identification of Gene-Allele System Conferring Alkali-Tolerance at Seedling Stage in Northeast China Soybean Germplasm.

Salinization of cultivated soils may result in either high salt levels or alkaline conditions, both of which stress crops and reduce performance. We sampled genotypes included in the Northeast China soybean germplasm population (NECSGP) to identify possible genes that affect tolerance to alkaline soil conditions. In this study, 361 soybean accessions collected in Northeast China were tested under 220 mM NaHCO3:Na2CO3 = 9:1 (pH = 9.8) to evaluate the alkali-tolerance (ATI) at the seedling stage in Mudanjiang, Heilongjiang, China. The restricted two-stage multi-locus model genome-wide association study (RTM-GWAS) with gene-allele sequences as markers (6503 GASMs) based on simplified genome resequencing (RAD-sequencing) was accomplished. From this analysis, 132 main effect candidate genes with 359 alleles and 35 Gene × Environment genes with 103 alleles were identified, explaining 90.93% and 2.80% of the seedling alkali-tolerance phenotypic variation, respectively. Genetic variability of ATI in NECSGP was observed primarily within subpopulations, especially in ecoregion B, from which 80% of ATI-tolerant accessions were screened out. The biological functions of 132 candidate genes were classified into eight functional categories (defense response, substance transport, regulation, metabolism-related, substance synthesis, biological process, plant development, and unknown function). From the ATI gene-allele system, six key genes-alleles were identified as starting points for further study on understanding the ATI gene network.

Ghost imaging lidar system for remote imaging.

Research towards practical applications of ghost imaging lidar system especially in longer sensing distance has been urgent in recent years. In this paper we develop a ghost imaging lidar system to boost an extension of remote imaging, where the transmission distance of the collimated pseudo-thermal beam can be improved hugely over long range and just shifting the adjustable lens assembly generates wide field of view suiting for short-range imaging. Based on the proposed lidar system, the changing tendency of illuminating field of view, energy density, and reconstructed images is analyzed and verified experimentally. Some considerations on the improvement of this lidar system are also discussed.

Fast focusing method in ghost imaging with a tracking trajectory.

The imaging environment is unstable for trembling disturbance, which is detrimental to object reconstruction. In this Letter, we experimentally investigated ghost imaging (GI) under a temporal trembling disturbance. The fast-focusing method based on imaging with small sampling measurements is proposed, and the theoretical model and algorithm are validated. It is demonstrated that the proposed method is effective to obtain a better-resolution image of the object under the strong trembling disturbance including a laboratory and a real trembling environment. The results provide a promising approach to deal with image degradation caused by an unstable environment and can find potential applications for ghost imaging in remote sensing.

Controlling beam dynamics with spectral quadratic phase modulation in the fractional Schrödinger equation.

The propagation dynamics of Gaussian beams and finite energy Airy beams with spectral quadratic phase modulation (QPM) modeled by the fractional Schrödinger equation (FSE) are numerically investigated. Compared with beam propagation in the standard Schrödinger equation, the focusing property of beams under FSE is influenced by the QPM coefficient and the Lévy index. For symmetric Gaussian beams, the focusing position increases and the focusing intensity decreases for the larger QPM coefficient or smaller Lévy index. For asymmetric Airy beams, multiple focusing positions occur, and the tendency of focusing intensity is opposite to that of Gaussian beams. Our results show the promising application of the FSE system for optical manipulation and optical splitting by controlling the QPM.

BER performance of an FSOC system over atmospheric turbulence channels based on computational temporal ghost imaging.

In a free space optical communication (FSOC) system, atmospheric turbulence will increase the bit error ratio (BER) and impair FSOC link reliability. Since computational temporal ghost imaging (CTGI) has anti-interference, we present an FSOC system over atmospheric turbulence based on CTGI. The simulation results show that the BER performance of CTGI is better than on-off keying under different atmospheric turbulence regimes. To improve the performance of the CTGI scheme, the influence of the number of transmission samples and code length is analyzed. It is shown that BER performance improves with the increment of the number of samples, while code length has no impact. This scheme provides an idea for reliable communication over atmospheric turbulence and an important reference for improving wireless optical communication in an extreme environment.

Highly accurate OAM mode detection network for ring Airy Gaussian vortex beams disturbed by atmospheric turbulence based on interferometry.

Atmospheric turbulence reduces the detection accuracy of orbital angular momentum (OAM) modes, which affects the performance of OAM optical communication. In this paper, we propose a method based on interferometry and a residual network (ResNet) to detect the OAM modes of ring Airy Gaussian vortex beams (RAGVBs) disturbed by atmospheric turbulence. The RAGVBs first interfere with spherical waves to obtain the sign features of the OAM modes, and then ResNet is employed to recognize OAM modes from the interferograms. The results demonstrate that the detection accuracy is higher than that of the OAM spectrum method under different turbulence strengths. The detection accuracy can even reach over 99% under strong fluctuations. Our research provides a reference for improving the performance of OAM optical communication through atmospheric turbulence.

Propagation dynamics and crosstalk of orbital angular momentum beams influenced by a supersonic wind-induced environmental disturbance.

Near field airflow induced by wind is an important factor influencing vortex beams propagation under airborne optical communication, and the cross-talk among different orbital angular momentum (OAM) modes occurs in OAM-based optical communication. In this paper, the propagation of vortex beams through a supersonic wind-induced random environment is investigated. The wind-induced phase model is firstly validated by wind tunnel experiment, with the phase model, vortex beams propagation under supersonic wind condition is analyzed, and the spiral spectrum distortion is discussed in detail. It is demonstrated that the larger wind velocity and boundary-layer thickness leads to the enhanced distortion and spiral spectrum expansion of OAM beams. The behavior of multiplexed vortex beams influenced by supersonic wind is also studied, and the effect of the topological charge interval is given. Our results may provide a powerful tool to estimate the effect of a random airflow environment on OAM-based communication performance under airborne condition.

Enhancing critical resolution of a ghost imaging system by using a vortex beam.

In an imaging system, resolution and signal-to-noise ratio (SNR) are two important indexes to characterize imaging quality. Ghost imaging is a novel imaging method whose imaging resolution and SNR are affected by the speckle size. In this paper, the relation between speckle size and resolution as well as that between speckle size and SNR in the GI system is analyzed in detail. It is shown that the critical resolution, resolvable minimum-separation between two adjacent objects, is approximately equal to the speckle size (speckle diameter). There exists an optimum SNR when the speckle size is larger than the object size. Based on our conclusion, we propose a scheme to enhance the critical resolution of the GI system by using a vortex beam, and the enhancement ability under different topological charges is clearly presented, which can be quantized by a simple formula.

Propagation dynamics of Laguerre-Gaussian beams in the fractional Schrödinger equation with noise disturbance.

The evolution of Laguerre-Gaussian (LG) beams in the fractional Schrödinger equation (FSE) with Gaussian noise disturbance is numerically investigated. Without noise disturbance, the peak intensity of LG beams increases with the increment of radial or azimuthal indices, and the turning point of the peak intensity between different radial indices exists. As propagation distance gets longer, the intensity of the outermost sub-lobe exceeds that of the main lobe. When Gaussian noise is added, for a given noise level, the stability of peak intensity is enhanced as the Lévy index increases, while the center of gravity shows the opposite phenomenon. Moreover, the increment of the radial index can weaken the stability of the center of gravity. We also investigate the stability of the peak intensity of Airy beams in the FSE, and generally, the stability of LG beams is better than that of Airy beams. All these properties show that LG beams modeled by the FSE have potential applications in optical manipulation and communications.

Analysis of the allowable maximum amplitude of random jitter in computational ghost imaging.

The imaging blur caused by the relative motion between an imaging system and an imaging target can be eliminated by a compensation operation based on the motion law, although it is invalid when the movement is random. In this paper, the influence of the random jitter on imaging resolution is investigated quantitatively in a computational ghost imaging system, and the maximum of random-jitter amplitude that the system can allow is analyzed. The numerical and experimental results verify our conclusion, and the error between the experiment and simulation is less than 12%. The main reason for the error is the disturbance of experimental noise. By using ghost imaging algorithms to reduce the corresponding impact, this error can be further reduced to 6%.

Improving the signal-to-noise ratio of computational ghost imaging of a reflective object with a rough surface by Hadamard modulated light field.

We propose an optimization scheme to improve the reconstruction quality of computational ghost imaging (GI) of a reflective target with a rough surface by using the Hadamard modulation light field (HCGI). By comparison with computational GI with a traditional Gaussian light field (GCGI), the signal-to-noise ratio of GCGI is quite bad, and it is difficult to distinguish the imaging signal from the background when the surface roughness of the object is higher, while a ghost image with better quality can be obtained by HCGI. The difference is explained by comparing the distribution of the correlation coefficient. Additionally, it is found that HCGI has better noise robustness in comparison with GI with other random coded patterns.

Comparison of PD-L1 detection methods, platforms and reagents in bladder cancer.

In this retrospective study, we collected 282 bladder cancer patients diagnosed from 2011 to 2018. Two mechanisms, fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC), were used to detect programmed death molecule ligand 1 (PD-L1) expression, and these analyses were performed on different platforms using different antibodies (22C3, 28-8, and SP263). The results were compared, and related clinical parameters were analysed to explore the consistencies and correlations between different detection methods, clonal antibodies and platforms for the detection of PD-L1 in bladder cancer patients to more effectively identify patients who are suitable for immunotherapy. The rate of PD-L1 positivity with 28-8 (42.3 %) was higher than that with 22C3 (22.1 %) or SP263 (22.1 %). The rate of PD-L1 positivity with SP263 was consistent with that of 22C3, and patients with positive PD-L1 expression detected by SP263 had longer overall survival in clinical parameter analysis. However, the rate of PD-L1 positivity with FISH was only 2.10 %, and the rate of agreement between FISH and IHC was only 1.06 %. In conclusion, the detection of PD-L1 with SP263 and IHC was more consistent and had a higher prognostic value, providing guidance for clinical diagnosis and treatment. The clinical application of FISH for PD-L1 detection needs to be further explored.

Effect of temperature on synthesis of clavulanic acid and impurity substance G during fermentation by Streptomyces clavuligerus.

Effect of temperature on synthesis of Clavulanic acid (CA) and impurity substance G during fermentation by Streptomyces clavuligerus were investigated. Results show that fermentation at 24 °C is the most favorable for CA synthesis though the fermentation duration was 20-30 hours longer than fermentation at 26 and 28 °C. Meanwhile, the impurity substance G was only 110 mg/L in the end broth of fermentation at 24 °C, which was significantly lower than 148 and 180 mg/L of fermentation at 26 and 28 °C, respectively. Correlation of specific growth rate and CA synthesis was statistically analyzed based on data of 10 batches of industrial fermentation. Two temperature-shift strategies were investigated in 50 L fermenter. Fermentation with 26-24 °C temperature strategy achieved 5097 mg/L CA titer, meanwhile the fermentation duration was shortened 24 hours comparing with fermentation at constant 24 °C. Fermentation with 26-24 °C control strategy was validated in a 60 m3 industrial fermenter, in which 4960 mg/L of CA was achieved while impurity G substance was decreased to titer 65 mg/L from 200 to 300 mg/L of normal production.

Ghost imaging influenced by a supersonic wind-induced random environment.

Near field airflow induced by wind is an important factor influencing imaging quality when the imaging system is placed on a moving platform with high speed, such as airborne imaging. In this Letter, ghost imaging through an airflow environment is experimentally and numerically investigated. The experiment is performed with a wind tunnel, and imaging quality decreases with wind velocity. The simulation model of ghost imaging through this kind of environment is proposed, and simulation results match well with experiments. With the model, imaging results are extended into the supersonic wind region with the effects of airflow factors discussed in detail, and a comparison between airflow and atmosphere turbulence is presented. The results can find potential applications in optical imaging and may be a powerful tool to estimate the effect of airflow on performance of the imaging system.

Upregulation of OATP1A2 in human oesophageal squamous cell carcinoma cells via the HDAC6-GCN5/PCAF-H3K9Ac axis.

1. OATP1A2 overexpressed is involved in chemotherapy disposition, indicating its role in tumour development and progression.2. CHIP and siRNA were used to evaluate the status of histone acetylation at the OATP1A2 promoter. The role of OATP1A2 was analysed by gene-set enrichment and overall survival analysis.3. OATP1A2 expression levels in ESCC was notably higher than that in para-cancer tissues. OATP1A2 high expression are associated with bile salt metabolic pathway and poor prognosis. Furthermore, HDAC6 was repressed in ESCC, increasing the levels of H3K9Ac catalysed by GCN5/PCAF at the OATP1A2 promoter region.4. Abnormal histone hyperacetylation mediated by the HDAC6-GCN5/PCAF-H3K9Ac axis resulted in increased OATP1A2 expression in ESCC, and OATP1A2 may serve as a promising prognostic biomarker for ESCC.5. In conclusion, this study indicated that suppression of OATP1A2 would inhibit the progression and prognosis in ESCC.

Added value of contrast-enhanced ultrasound (CEUS) in the diagnosis of primary retroperitoneal serous adenocarcinoma: a case report.

BACKGROUND: Primary retroperitoneal serous adenocarcinoma (PRSA) is a rare malignant disease. Given the rarity of the disease, the imaging features of PRSA are unclear. Contrast-enhanced ultrasound (CEUS) also plays an important role in the evaluation of the differential diagnosis of retroperitoneal lesions. CASE PRESENTATION: We report the case of a 62-year-old woman of with increased CA125 levels for 1 year who was referred to our hospital. After conducting contrast-enhanced computed tomography and magnetic resonance imaging, the mass was misdiagnosed as a chocolate cyst. After transvaginal ultrasound (TUS) combined with CEUS, cystadenocarcinoma was considered as the initial diagnosis. Pathology results confirmed PRSA as the final diagnosis. CONCLUSIONS: CEUS features of PRSA are reported for the first time based on this case, potentially aiding in the differential diagnosis of this rare entity before surgery.

Ghost imaging for detecting trembling with random temporal changing.

The imaging environment can be destabilized for moving objects and imaging platforms, thus leading the detection to be random trembling, which is detrimental to object reconstruction. In this Letter, we experimentally investigate ghost imaging for detecting trembling with random temporal changing, and an improvement method based on the temporal property of the imaging process is proposed. It is demonstrated that this method is effective in addressing image degradation due to the trembling disturbance and obtaining a higher-quality image of the object. The results provide a promising approach to deal with image degradation caused by an unstable environment and can find potential applications for ghost imaging in remote sensing.