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Background: With increasing awareness for radiation exposure, the study of diagnostic accuracy of coronary CT angiography (CCTA) with low radiation dose techniques is mandatory to both radiologist and clinician. Purpose: To compare diagnostic performance and effective radiation dose between step-and-shoot prospectively ECG-gated and retrospectively ECG-gated with tube current modulation (TCM) CCTA using 128-slice multidetector computed tomography (MDCT). Material and Methods: We retrospectively evaluated 60 patients who underwent CCTA with either of two different low-dose techniques using 128-slice MDCT (23 patients for step-and shoot-prospectively ECG-gated and 37 patients for retrospectively ECG-gated with TCM CCTA) followed by conventional coronary angiography. All coronary arteries and all segments thereof, except anatomical variants or small size (< 1.5 mm) ones, were included in analysis. Results: In per-segment analysis, sensitivity, specificity, positive predictive value, and negative predictive value were 91/96%, 95/94%, 75/73%, and 98/99% for step-and-shoot prospectively ECG-gated and retrospectively ECG gated with TCM CCTA, respectively, relative to conventional coronary angiography. Effective radiation dose were 1.75 ± 0.83 mSv, 4.91 ± 1.71 mSv in the step-and-shoot prospectively ECG-gated and retrospectively ECG-gated with TCM CCTA groups, respectively. Conclusion: The two low-radiation dose CCTA techniques using 128-slice MDCT yields comparable diagnostic performance for coronary artery disease in symptomatic patients with low heart rates. [ABSTRACT FROM AUTHOR]

A patient, a 62-year-old man, received endodontic treatment of the lower left canine complicated by apical overfilling of Calcipex II. At the second day after the root canal filling, the 14th day after placement of Calcipex II intracanal medication, he complained of a gingival swelling in the treated area. The incisional biopsy of the gingival swelling revealed a foreign body granuloma infiltrated with macrophages engulfing the fine Calcipex II granules but with polymorphonuclear leukocytes (PMNs). However, the gingival swelling was healed uneventfully, and the tooth was free of symptoms at 4 months' follow-up. This study first reports the Calcipex II-induced reaction in human periodontium. In the immunohistochemistry using antisera of lysozyme, CD31, CD68, interleukin-8 (IL-8), and poly(ADP-ribose) polymerase 1 (PARP-1), the granule-laden cells are positive for lysozyme, CD31, CD68, and PARP-1, but negative for IL-8. Thus, it is presumed that the granule-laden cells belong to the macrophages/monocytes rather than the PMNs, and that they gradually undergo the apoptotic processes. These data suggest that the canal dressing material, Calcipex II, is able to be widely dispersed into the periodontal tissues, primarily engulfed by macrophages, and resulted in the foreign body granuloma in the absence of acute inflammatory reaction. [ABSTRACT FROM AUTHOR]

The expression of PD-L1 on tumor cells (TC) is used as an immunotherapy biomarker in lung cancer, but heterogeneous intratumoral expression is often observed. To better understand heterogeneity in the lung cancer tumor microenvironment, we performed proteomic and whole-transcriptomic digital spatial profiling analyses of TCs and immune cells (IC) in spatially matched areas based on tumor PD-L1 expression and the status of the immune microenvironment. We validated our findings using IHC, data from The Cancer Genome Atlas, and immunotherapy cohorts. ICs in areas with high PD-L1 expression on TCs showed more features, indicative of immunosuppression and exhaustion, than ICs in areas with low PD-L1 expression on TCs. TCs highly expressing PD-L1 within immune-inflamed areas showed upregulation of proinflammatory processes, whereas TCs highly expressing PD-L1 within immune-deficient areas showed upregulation of various metabolic processes. Using differentially expressed genes of TCs between the immune-inflamed and immune-deficient areas, we identified a prognostic gene signature for lung cancer. In addition, we found that a high ratio of CD8+ cells to M2 macrophages predicted favorable outcomes in patients with PD-L1-expressing lung cancer after immune checkpoint inhibitor therapy. Overall, this study demonstrates that TCs and ICs have distinct spatial features within the lung tumor microenvironment that are related to tumor PD-L1 expression and IC infiltration., (©2024 American Association for Cancer Research.)

Rare pancreatic tumors and non-neoplastic tumor-like lesions present a diagnostic challenge due to their uncommon occurrence and overlapping imaging characteristics with more prevalent pancreatic neoplasms. Advances in imaging technologies and diagnostic criteria have contributed to increased detection of these rare entities in clinical practice. This pictorial review focuses on the radiologic-pathologic correlation of rare pancreatic tumors, including colloid carcinoma, acinar cell carcinoma, pancreatoblastoma, primary pancreatic lymphoma, and non-neoplastic tumor-like lesions such as hamartomas and inflammatory pseudotumors. Detailed imaging features, such as signal intensities on MRI and enhancement patterns on CT, are correlated with pathological findings to assist in the differential diagnosis. Familiarity with these characteristics is crucial for radiologists to ensure accurate diagnosis and guide appropriate treatment strategies, as management and prognosis significantly differ from common pancreatic neoplasms.

Recently, extracellular vesicles (EVs) have been developed as therapeutic targets for various diseases. Biodistribution is crucial for EVs intended for therapeutic purposes because it can determine the degree of on- and off-target effects. This study aimed to explore techniques to evaluate the biodistribution of unmodified EVs. We devised a novel quantitative polymerase chain reaction (qPCR)-based assay to detect unmodified EVs by targeting mitochondrial deoxyribonucleic acid (mtDNA), a constituent of EVs. We focused on specific mtDNA regions that exhibited homologous variations distinct from their rodent mtDNA counterparts to establish this analytical approach. Herein, we successfully designed primers and probes targeting human and rodent mtDNA sequences and developed a highly specific and sensitive qPCR method. Furthermore, the quantification range of EVs isolated from various cells differed based on the manufacturer and cell source. IRDye 800CW-labelled Expi293F EV mimetics were administered to the animals via the tail vein to compare the imaging test and mtDNA-qPCR results. The results obtained from imaging tests and mtDNA-qPCR to investigate EV biodistribution patterns revealed differences. The results revealed that our newly developed method effectively determined the biodistribution of unmodified EVs with high sensitivity and reproducibility., (© 2024 The Author(s). Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)

Background: We investigated the role of tumor cell-intrinsic PD-L1 signaling in the epithelial-mesenchymal transition (EMT) in non-small-cell lung cancer (NSCLC) and the role of EMT as a predictive biomarker for immune checkpoint inhibitor (ICI) therapy., Methods: PD-L1-overexpressing or PD-L1-knockdown NSCLC cells underwent RNA-seq and EMT phenotype assessment. Mouse lung cancer LLC cells were injected into nude mice. Two cohorts of patients with NSCLC undergoing ICI therapy were analyzed., Results: RNA-seq showed that EMT pathways were enriched in PD-L1-high NSCLC cells. EMT was enhanced by PD-L1 in NSCLC cells, which was mediated by transforming growth factor-β (TGFβ). PD-L1 promoted the activation of p38-MAPK by binding to and inhibiting the protein phosphatase PPM1B, thereby increasing the TGFβ production. Tumor growth and metastasis increased in nude mice injected with PD-L1-overexpressing LLC cells. In the ICI cohort, EMT signature was higher in patients with progressive disease than in those with responses, and EMT was significantly associated with poor survival in PD-L1-high NSCLC. In PD-L1-high NSCLC, EMT was associated with increased M2-macrophage and regulatory T-cell infiltrations and decreased cytotoxic T-cell infiltration., Conclusions: Tumor cell-intrinsic PD-L1 function contributes to NSCLC progression by promoting EMT. EMT may predict an unfavorable outcome after ICI therapy in PD-L1-high NSCLC., (© 2024. The Author(s).)

The growing need for lithium-ion batteries, fueled by the widespread use of electric vehicles (EVs) and portable electronic devices, requires high energy density and safety. The cathode material Li 1-x (Ni y Co z Mn 1-y-z )O 2 (NCM) shows promise, but attaining high efficiency necessitates optimization of both composition and manufacturing methods. Polycrystalline LiNiCoMnO 2 powders were synthesized and assessed in this investigation using a polyvinyl alcohol (PVA) solution method. The study examined different synthesis conditions, such as the PVA to metal ions ratio and the molecular weight of PVA, to assess their influence on powder characteristics. Electrochemical analysis indicated that cathode materials synthesized with a relatively high quantity of PVA with a molecular weight of 98,000 exhibited the highest discharge capacity of 170.34 mAh/g and a high lithium-ion diffusion coefficient of 1.19 × 10 -9 cm 2 /s. Moreover, decreasing the PVA content, irrespective of its molecular weight, led to the production of powders with reduced surface areas and increased pore sizes. The adjustments of PVA during synthesis resulted in pre-sintering observed during the synthesis process, which had an impact on the long-term stability of batteries. The electrodes produced from the synthesized powders had a positive impact on the insertion and extraction of Li+ ions, thereby improving the electrochemical performance of the batteries. This study reveals that cathode materials synthesized with a high quantity of PVA with a molecular weight of 98,000 exhibited the highest discharge capacity of 170.34 mAh/g and a high lithium-ion diffusion coefficient of 1.19 × 10 -9 cm 2 /s. The findings underscore the significance of optimizing methods for synthesizing PVA-based materials to enhance the electrochemical properties of NCM cathode materials, contributing to the advancement of lithium-ion battery technology. The findings underscore the significance of optimizing methods for synthesizing PVA-based materials and their influence on the electrochemical properties of NCM cathode materials. This contributes to the continuous progress in lithium-ion battery technology., Competing Interests: Author Sung Geun Song was employed by the company IL SCIENCE Co., Ltd.. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The aim of this study was to evaluate the findings of CT scans in patients with pathologically confirmed primary colorectal squamous-cell carcinoma (SCC). The clinical presentation and CT findings in eight patients with pathologically confirmed primary colorectal squamous-cell carcinoma were retrospectively reviewed by two gastrointestinal radiologists. Hematochezia was the most common symptom (n = 5). The tumors were located in the rectum (n = 7) and sigmoid colon (n = 1). The tumors showed circumferential wall thickening (n = 4), bulky mass (n = 3), or eccentric wall thickening (n = 1). The mean maximal wall thickness of the involved segment was 29.1 mm ± 13.4 mm. The degree of tumoral enhancement observed via CT was well enhanced (n = 4) or moderately enhanced (n = 4). Necrosis within the tumor was found in five patients. The mean total number of metastatic lymph nodes was 3.1 ± 3.3, and the mean short diameter of the largest metastatic lymph node was 16.6 ± 5.7 mm. Necrosis within the metastatic node was observed in six patients. Invasions to adjacent organs were identified in five patients (62.5%). Distant metastasis was detected in only one patient. In summary, primary SCCs that arise from the colorectum commonly present as marked invasive wall thickening or a bulky mass with heterogeneous well-defined enhancement, internal necrosis, and large metastatic lymphadenopathies.

Biodistribution tests are crucial for evaluating the safety of cell therapy (CT) products in order to prevent unwanted organ homing of these products in patients. Quantitative polymerase chain reaction (qPCR) using intronic Alu is a popular method for biodistribution testing owing to its ability to detect donor cells without modifying CT products and low detection limit. However, Alu-qPCR may generate inaccurate information owing to background signals caused by the mixing of human genomic DNA with that of experimental animals. The aim of this study was to develop a test method that is more specific and sensitive than Alu-qPCR, targeting the mitochondrial DNA (mtDNA) sequence that varies substantially between humans and experimental animals. We designed primers for 12S, 16S, and cytochrome B in mtDNA regions, assessed their specificity and sensitivity, and selected primers and probes for the 12S region. Human adipose-derived stem cells, used as CT products, were injected into the tail vein of athymic NCr-nu/nu mice and detected, 7 d after administration, in their lungs at an average concentration of 2.22 ± 0.69 pg/μg mouse DNA, whereas Alu was not detected. Therefore, mtDNA is more specific and sensitive than Alu and is a useful target for evaluating CT product biodistribution., (© 2024. The Author(s).)

Recently identified human FOXP3 low CD45RA - inflammatory non-suppressive (INS) cells produce proinflammatory cytokines, exhibit reduced suppressiveness, and promote antitumor immunity unlike conventional regulatory T cells (T regs ). In spite of their implication in tumors, the mechanism for generation of FOXP3 low CD45RA - INS cells in vivo is unclear. We showed that the FOXP3 low CD45RA - cells in human tumors demonstrate attenuated expression of CRIF1, a vital mitochondrial regulator. Mice with CRIF1 deficiency in T regs bore Foxp3 low INS-T regs with mitochondrial dysfunction and metabolic reprograming. The enhanced glutaminolysis activated α-ketoglutarate-mTORC1 axis, which promoted proinflammatory cytokine expression by inducing EOMES and SATB1 expression. Moreover, chromatin openness of the regulatory regions of the Ifng and Il4 genes was increased, which facilitated EOMES/SATB1 binding. The increased α-ketoglutarate-derived 2-hydroxyglutarate down-regulated Foxp3 expression by methylating the Foxp3 gene regulatory regions. Furthermore, CRIF1 deficiency-induced Foxp3 low INS-T regs suppressed tumor growth in an IFN-γ-dependent manner. Thus, CRIF1 deficiency-mediated mitochondrial dysfunction results in the induction of Foxp3 low INS-T regs including FOXP3 low CD45RA - cells that promote antitumor immunity.

Chemical warfare agents (CWAs) pose a persistent threat to human safety, and bis(2-chloroethyl) sulfide, or sulfur mustard (SM) is one of the most dangerous substances and is able to cause serious harm. Detecting SM gas is vital, but current methods have high-temperature requirements and limited selectivity, mainly because of the lack of CWA receptor development, and this makes them challenging to use. To address this issue, we present a trisaryl phosphoric triamide-based resin receptor that preferentially interacts with a SM simulant 2-chloroethyl ethyl sulfide (2-CEES) through dipole interactions. The receptor was synthesized through a facile process using an amine and a triethyl phosphate and the properties of its coating were enhanced using epoxy chemistry. The receptor's superior triamide structure was evaluated using a quartz crystal microbalance and reactivity was confirmed by observing the variations in reactivity according to the number of phosphoramides. The receptor showed better reactivity to 2-CEES vapor than to the known poly(epichlorohydrin) and showed selectivity to other volatile organic compounds. Moreover, its durability was evident even 30 days post-coating. The applicability of this receptor extends to array sensors, sound acoustic wave sensors, and chemo-resistive and chemo-capacitive sensors, and it promises advances in chemical warfare agent detection., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Accurate classification of breast cancer molecular subtypes is crucial in determining treatment strategies and predicting clinical outcomes. This classification largely depends on the assessment of human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR) status. However, variability in interpretation among pathologists pose challenges to the accuracy of this classification. This study evaluates the role of artificial intelligence (AI) in enhancing the consistency of these evaluations., Methods: AI-powered HER2 and ER/PR analyzers, consisting of cell and tissue models, were developed using 1,259 HER2, 744 ER, and 466 PR-stained immunohistochemistry (IHC) whole-slide images of breast cancer. External validation cohort comprising HER2, ER, and PR IHCs of 201 breast cancer cases were analyzed with these AI-powered analyzers. Three board-certified pathologists independently assessed these cases without AI annotation. Then, cases with differing interpretations between pathologists and the AI analyzer were revisited with AI assistance, focusing on evaluating the influence of AI assistance on the concordance among pathologists during the revised evaluation compared to the initial assessment., Results: Reevaluation was required in 61 (30.3%), 42 (20.9%), and 80 (39.8%) of HER2, in 15 (7.5%), 17 (8.5%), and 11 (5.5%) of ER, and in 26 (12.9%), 24 (11.9%), and 28 (13.9%) of PR evaluations by the pathologists, respectively. Compared to initial interpretations, the assistance of AI led to a notable increase in the agreement among three pathologists on the status of HER2 (from 49.3 to 74.1%, p < 0.001), ER (from 93.0 to 96.5%, p = 0.096), and PR (from 84.6 to 91.5%, p = 0.006). This improvement was especially evident in cases of HER2 2+ and 1+, where the concordance significantly increased from 46.2 to 68.4% and from 26.5 to 70.7%, respectively. Consequently, a refinement in the classification of breast cancer molecular subtypes (from 58.2 to 78.6%, p < 0.001) was achieved with AI assistance., Conclusions: This study underscores the significant role of AI analyzers in improving pathologists' concordance in the classification of breast cancer molecular subtypes., (© 2024. The Author(s).)

We propose a general green method coupled with a solid-state vibration ball milling strategy for the synthesis of various metal nanoparticles (MNPs), employing a polymeric carbohydrate dextran (Dx) as a reducing and stabilizing molecule. The synthesis of size-controlled Dx-based MNPs (Dx@MNPs), featuring comparatively narrow size distributions, was achieved by controlling the mass ratio of the reactants, reaction time, frequency of the vibration ball mill, and molecular weight of Dx. Notably, this process was conducted at ambient temperatures, without the aid of solvents and accelerating agents, such as NaOH, and conventional reductants as well as stabilizers. Thermal properties of the resulting Dx@MNPs nanocomposites were extensively investigated, highlighting the influence of metal precursors and reaction conditions. Furthermore, the catalytic activity of synthesized nanocomposites was evaluated through the reduction reaction of 4-nitrophenol, exhibiting great catalytic performance. In addition, we demonstrated the excellent biocompatibility of the as-prepared Dx@MNPs toward human embryonic kidney (HEK-293) cells, revealing their potential for anticancer activities. This novel green method for synthesizing biocompatible MNPs with Dx expands the horizons of carbohydrate-based materials as well as MNP nanocomposites for large-scale synthesis and controlled size distribution for various industrial and biomedical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

We present the first documented case of a fistula between the treated zone and the appendix after RFA in a patient with HCC. Contrast-enhanced CT and MRI revealed a subcapsular hepatic nodule with image findings of HCC located adjacent to the ascending colon and cecum. An ultrasound-guided core needle biopsy was subsequently performed to distinguish between hepatic metastasis and HCC. Post-RFA imaging identified a low-attenuating ablated area adjacent to an air-filled appendix. The patient later experienced complications, including increased liver enzymes and an abscess at the ablation site. Imaging revealed a fistulous tract between the RFA zone and the appendix. Over the following months, the patient underwent conservative treatment involving intravenous antibiotics and repeated percutaneous drainage, exhibiting eventual symptom relief and an absence of the fistulous tract upon subsequent imaging. This case highlights the rare complications that can arise during RFA due to peculiar anatomical variations, such as a subhepatic appendix, resulting from midgut malrotation and previous surgery. It is imperative for operators to be cognizant of potential anatomical variations when considering RFA treatment, ensuring comprehensive pre-procedural imaging and post-procedure monitoring. This case also emphasizes the potential viability of nonoperative management in complex scenarios in which surgical interventions pose significant risks.

Thymic epithelial cells (TECs) play a critical role in thymic development and thymopoiesis. As individuals age, TECs undergo various changes that impact their functions, leading to a reduction in cell numbers and impaired thymic selection. These age-related alterations have been observed in both mice and humans. However, the precise mechanisms underlying age-related TEC dysfunction remain unclear. Furthermore, there is a lack of a comprehensive study that connects mouse and human biological processes in this area. To address this gap, we conducted an extensive transcriptome analysis of young and old TECs in mice, complemented by further analysis of publicly available human TEC single-cell RNA sequencing data. Our analysis revealed alterations in both known and unknown pathways that potentially contribute to age-related TEC dysfunction. Specifically, we observed downregulation of pathways related to cell proliferation, T cell development, metabolism, and cytokine signaling in old age TECs. Conversely, TGF-β, BMP, and Wnt signaling pathways were upregulated, which have been known to be associated with age-related TEC dysfunctions or newly discovered in this study. Importantly, we found that these age-related changes in mouse TECs were consistently present in human TECs as well. This cross-species validation further strengthens the significance of our findings. In conclusion, our comprehensive analysis provides valuable insight into the biological and immunological characteristics of aged TECs in both mice and humans. These findings contribute to a better understanding of thymic involution and age-induced immune dysfunction., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interest., (Copyright © 2023. The Korean Association of Immunologists.)

Background: Postoperative opioid abuse following surgery is a major concern. This study sought to create an opioid reduction toolkit to reduce the number of narcotics prescribed and consumed while increasing awareness of safe disposal in pancreatectomy patients., Methods: Prescription, consumption, and refill request data for postoperative opioids were collected from patients receiving an open pancreatectomy before and after the implementation of an opioid reduction toolkit. Outcomes included safe disposal practice awareness for unused medication., Results: 159 patients were included in the study: 24 in the pre-intervention and 135 in the post-intervention group. No significant demographic or clinical differences existed between groups. Median morphine milliequivalents (MMEs) prescribed were significantly reduced from 225 (225-310) to 75 (75-113) in the post-intervention group (p < 0.0001). Median MMEs consumed were significantly reduced from 109 (111-207) to 15 (0-75), p < 0.0001), as well. Refill request rates remained equivalent during the study (Pre: 17% v Post: 13%, p = 0.9) while patient awareness of safe disposal increased (Pre: 25% v Post: 62%, p < 0.0001)., Discussion: An opioid reduction toolkit significantly reduced the number of postoperative opioids prescribed and consumed after open pancreatectomy, while refill request rates remained the same and patients' awareness of safe disposal increased., (Copyright © 2023 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Electrical stimulation such as transcranial direct current stimulation (tDCS) is widely used to treat neuropsychiatric diseases and neurological disorders. Computational modeling is an important approach to understand the mechanisms underlying tDCS and optimize treatment planning. When applying computational modeling to treatment planning, uncertainties exist due to insufficient conductivity information inside the brain. In this feasibility study, we performed in vivo MR-based conductivity tensor imaging (CTI) experiments on the entire brain to precisely estimate the tissue response to the electrical stimulation. A recent CTI method was applied to obtain low-frequency conductivity tensor images. Subject-specific three-dimensional finite element models (FEMs) of the head were implemented by segmenting anatomical MR images and integrating a conductivity tensor distribution. The electric field and current density of brain tissues following electrical stimulation were calculated using a conductivity tensor-based model and compared to results using an isotropic conductivity model from literature values. The current density by the conductivity tensor was different from the isotropic conductivity model, with an average relative difference | rD | of 52 to 73%, respectively, across two normal volunteers. When applied to two tDCS electrode montages of C3-FP2 and F4-F3, the current density showed a focused distribution with high signal intensity which is consistent with the current flowing from the anode to the cathode electrodes through the white matter. The gray matter tended to carry larger amounts of current densities regardless of directional information. We suggest this CTI-based subject-specific model can provide detailed information on tissue responses for personalized tDCS treatment planning., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Katoch, Kim, Choi, Ha, Kim, Yoon, Song, Kim and Kim.)

Animal reservoirs of sarbecoviruses represent a significant risk of emergent pandemics, as evidenced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Vaccines remain successful at limiting severe disease and death, but the potential for further coronavirus zoonosis motivates the search for pan-coronavirus vaccines. This necessitates a better understanding of the glycan shields of coronaviruses, which can occlude potential antibody epitopes on spike glycoproteins. Here, we compare the structure of 12 sarbecovirus glycan shields. Of the 22 N-linked glycan attachment sites present on SARS-CoV-2, 15 are shared by all 12 sarbecoviruses. However, there are significant differences in the processing state at glycan sites in the N-terminal domain, such as N165. Conversely, glycosylation sites in the S2 domain are highly conserved and contain a low abundance of oligomannose-type glycans, suggesting a low glycan shield density. The S2 domain may therefore provide a more attractive target for immunogen design efforts aiming to generate a pan-coronavirus antibody response., Competing Interests: Declaration of interests R.A., G.S., W.-t.H., and D.R.B. are listed as inventors on pending patent applications describing the SARS-CoV-2 and HCoV-HKU1 S cross-reactive antibodies. G.S., D.R.B., and R.A. are listed as inventors on a pending patent application describing the S2 stem epitope immunogens., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Although epidermoid cysts are frequently seen as benign lesions, they are highly uncommon to develop into cancerous lesions. A 36-year-old man with a cystic mass present on his left flank since childhood presented to our department. Based on the patient's medical history and abdominal computed tomography scan, we excised the lesion under the suspicion of an epidermoid cyst. Histopathological evaluation revealed the presence of poorly differentiated carcinoma with squamoid and basaloid differentiation, which showed a strong possibility of carcinoma arising from an epidermal cyst. Next-generation sequencing using TruSight oncology 500 assay showed copy number variation of ATM and CHEK1 genes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Choi, Park, Song and Kim.)

The immune system plays a central role in the onset and progression of cancer. A better understanding of transcriptional changes in immune cell-related genes associated with cancer progression, and their significance in disease prognosis, is therefore needed. NanoString-based targeted gene expression profiling has advantages for deployment in a clinical setting over RNA-seq technologies. We analysed NanoString PanCancer Immune Profiling panel gene expression data encompassing 770 genes, and overall survival data, from multiple previous studies covering 10 different cancer types, including solid and blood malignancies, across 515 patients. This analysis revealed an immune gene signature comprising 39 genes that were upregulated in those patients with shorter overall survival; of these 39 genes, three (MAGEC2, SSX1 and ULBP2) were common to both solid and blood malignancies. Most of the genes identified have previously been reported as relevant in one or more cancer types. Using Cibersort, we investigated immune cell levels within individual cancer types and across groups of cancers, as well as in shorter and longer overall survival groups. Patients with shorter survival had a higher proportion of M2 macrophages and γδ T cells. Patients with longer overall survival had a higher proportion of CD8+ T cells, CD4+ T memory cells, NK cells and, unexpectedly, T regulatory cells. Using a transcriptomics platform with certain advantages for deployment in a clinical setting, our multi-cancer meta-analysis of immune gene expression and overall survival data has identified a specific transcriptional profile associated with poor overall survival., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: Relationship between cancer cell glycolysis and the landscape of tumor immune microenvironment in human cancers was investigated., Methods: Forty-one fresh lung adenocarcinoma (ADC) tissues were analyzed using flow cytometry for comprehensive immunoprofiling. Formalin-fixed tissues were immunostained for hexokinase-2 (HK2) to assess cancer cell glycolysis. For validation, formalin-fixed tissues from 375 lung ADC, 118 lung squamous cell carcinoma (SqCC), 338 colon ADC, and 78 lung cancer patients treated with anti-PD-1/PD-L1 immunotherapy were immunostained for HK2, CD8, and FOXP3., Results: Based on immunoprofiling of lung ADC, HK2 tumor expression was associated with the composition of lymphoid cells rather than myeloid cells. High HK2 tumor expression was associated with immunosuppressive/pro-tumorigenic features, especially decreased ratio of CD8 + T-cells to Tregs (rho = -0.415, P = 0.012). This correlation was also confirmed in four different cohorts including lung ADC and SqCC, colon ADC, and the immunotherapy cohort (rho = -0.175~-0.335, all P < 0.05). A low CD8 + T-cell to Treg ratio was associated with poor progression-free survival and overall survival in lung SqCC patients, and a shorter overall survival in the immunotherapy cohort (all, P < 0.05)., Conclusion: An increase in HK2 expression may contribute to shaping the immunosuppressive/pro-tumorigenic tumor microenvironment by modulating the CD8 + T-cell to Treg ratio. Targeting tumor HK2 expression might be a potential strategy for enhancing anti-tumor immunity., (© 2022. The Author(s).)

Background: T-cell factor 1 (TCF1) + Programmed cell death-1 (PD-1) + tumour-infiltrating lymphocytes (TILs) are a recently defined subset of exhausted T-cells (Texh-cells) that exhibit a progenitor phenotype. They have been associated with a response to immune checkpoint inhibitor (ICI) therapy in murine tumour models and in patients with malignant melanoma. We investigated the significance of TCF1 + PD-1 + TILs as a predictive biomarker for ICI therapy response in non-small-cell lung cancer (NSCLC)., Methods: Two different cohorts of NSCLC patients treated with ICI targeting the PD-1/PD-L1 pathway were included. RNA-seq was performed using NSCLC tissues obtained from 234 patients prior to immunotherapy (RNA-seq cohort). Double immunostaining of TCF1 and PD-1 and single immunostaining of other immunologic markers were performed in resected tumour tissues from another 116 patients (immunohistochemistry cohort)., Results: In the RNA-seq cohort, both Texh-cell and progenitor Texh-cell gene sets were enriched in responders compared with non-responders. Larger Texh-cell fractions and increased progenitor Texh-cell gene sets were significantly associated with better progression-free survival (PFS). In the immunohistochemistry cohort, the TCF1 + PD-1 + TIL number and PD-L1 tumour proportion score were significantly higher in responders than in non-responders. A high number of TCF1 + PD-1 + TILs was significantly associated with both PFS and overall survival (OS) after ICI therapy, and it independently predicted a better PFS and OS according to multivariate analysis., Conclusion: TCF1 + PD-1 + TILs, representing progenitor Texh-cells, predict both better response and survival in NSCLC patients after ICI therapy. Thus, they may be a useful predictive biomarker for ICI therapy in NSCLC., Competing Interests: Conflict of interest statement The authors declare no conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Primary central nervous system lymphoma (PCNSL) of peripheral T-cell lineage (T-PCNSL) is rare, and its genetic and clinicopathologic features remain unclear. Here, we present 11 cases of T-PCNSL in immunocompetent individuals from a single institute, focusing on their genetic alterations. Seven cases were subject to targeted panel sequencing covering 120 lymphoma-related genes. Nine of the eleven cases were classified as peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), of which one was of γδT-cell lineage. There was one case of anaplastic lymphoma kinase-positive anaplastic large cell lymphoma and another of extranodal natural killer (NK)/T-cell lymphoma (ENKTL) of αβT-cell lineage. The male to female ratio was 7 : 4 and the age ranged from 3 to 75 years (median, 61 y). Most patients presented with neurological deficits (n=10) and showed multifocal lesions (n=9) and deep brain structure involvement (n=9). Tumor cells were mostly small-to-medium, and T-cell monoclonality was detected in all nine evaluated cases. PTCL-NOS was CD4-positive (n=4), CD8-positive (n=3), mixed CD4-positive and CD8-positive (n=1), or CD4/CD8-double-negative (n=1, γδT-cell type). Cytotoxic molecule expression was observed in 4 (67%) of the 6 evaluated cases. Pathogenic alterations were found in 4 patients: one PTCL-NOS case had a frameshift mutation in KMT2C, another PTCL-NOS case harbored a truncating mutation in TET2, and another (γδT-cell-PTCL-NOS) harbored NRAS G12S and JAK3 M511I mutations, and homozygous deletions of CDKN2A and CDKN2B. The ENKTL (αβT-cell lineage) case harbored mutations in genes ARID1B, FAS, TP53, BCOR, KMT2C, POT1, and PRDM1. In conclusion, most of the T-PCNSL were PTCL-NOS, but sporadic cases of other subtypes including γδT-cell lymphoma, anaplastic lymphoma kinase-positive anaplastic large cell lymphoma, and ENKTL were also encountered. Immunophenotypic analysis, clonality test, and targeted gene sequencing along with clinicoradiologic evaluation, may be helpful for establishing the diagnosis of T-PCNSL. Moreover, this study demonstrates genetic alterations with potential diagnostic and therapeutic utility in T-PCNSL., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

G-, V-, and A-series nerve agents are extremely toxic organophosphorus chemical warfare agents (CWAs) that incorporate P═O functional groups. Their colorless, tasteless, and odorless nature makes rapid and efficient detection challenging. Here, we report an unprecedented N-triflyl phosphoric triamide ( N-TPT ) receptor, which is a new class of triple hydrogen bonding donor molecular sensors for CWA recognition via noncovalent host-guest-type interactions. The highly robust trifurcate structures were designed based on density functional theory (DFT) computations and synthesized from N -triflyl phosphorimidoyl trichloride by simple stepwise processes. Quartz crystal microbalance (QCM) analysis allowed robust detection of typical CWA simulants, such as dimethyl methylphosphonate. The concentration-dependent QCM profiles were fitted with the Sips isotherm model, revealing that the thermodynamic parameters of the binding behaviors are roughly correlated with the calculated results. Developed N-TPT receptors show higher binding abilities than previously reported receptors and reasonable selectivity over other volatile compounds.

Purpose: This study was performed to analyze the predictors that might contribute to urinary retention following semiclosed hemorrhoidectomy under spinal anesthesia., Methods: This retrospective study enrolled 2,176 consecutive patients with symptomatic grade III to IV hemorrhoids who underwent semiclosed hemorrhoidectomy between September 2018 and September 2019., Results: Among the 2,176 patients, 1,878 (86.3%) had no postoperative urinary retention, whereas 298 (13.7%) developed urinary retention after hemorrhoidectomy. The percentage of males was significantly higher in the retention group than in the non-retention group (60.4% vs. 48.1%; P=0.001). The risk of urinary retention was 1.52-fold higher in males than in females (95% confidence interval [CI], 1.13-2.04; P=0.005), 1.62-fold higher in old age (95% CI, 1.14-2.28; P=0.006), and 1.37-fold higher with high body mass index (BMI) (95% CI, 1.04-1.81; P=0.025). Patients with ≥4 resected hemorrhoids had a higher odds ratio (OR) of 1.46 (95% CI, 1.12-1.89; P=0.005) than patients with <4 resected hemorrhoids. Among the supplementary medication, patients who used analgesics had a higher OR of 2.06 (95% CI, 1.57-2.68; P=0.001) than those who did not., Conclusion: Male sex, age, high BMI, number of resected hemorrhoids, and supplementary analgesics are independent risk factors for urinary retention after semiclosed hemorrhoidectomy.

Radiation-induced injury is damage to normal tissues caused by unintentional exposure to ionizing radiation. Image-based evaluation of tissue damage by irradiation has an advantage for the early assessment of therapeutic effects by providing sensitive information on minute tissue responses in situ. Recent magnetic resonance (MR)-based electrical conductivity imaging has shown potential as an effective early imaging biomarker for treatment response and radiation-induced injury. However, to be a tool for evaluating therapeutic effects, validation of its reliability and sensitivity according to various irradiation conditions is required. We performed MR-based electrical conductivity imaging on designed phantoms to confirm the effect of ionizing radiation at different doses and on in vivo mouse brains to distinguish tissue response depending on different doses and the elapsed time after irradiation. To quantify the irradiation effects, we measured the absolute conductivity of brain tissues and calculated relative conductivity changes based on the value of pre-irradiation. The conductivity of the phantoms with the distilled water and saline solution increased linearly with the irradiation doses. The conductivity of in vivo mouse brains showed different time-course variations and residual contrast depending on the irradiation doses. Future studies will focus on validation at long-term time points, including early and late delayed response and evaluation of irradiation effects in various tissue types.

Background: To evaluate the characteristics of the tumor immune-microenvironment in brain metastases of non-small-cell lung cancer (NSCLC), we investigated the immunophenotype of primary NSCLC and its brain metastasis., Methods: Expression profiling of 770 immune-related genes in 28 tissues from primary and brain metastases of NSCLC was performed using the NanoString nCounter PanCancer Immune Profiling Panel. The immune cell profiles were validated by immunohistochemistry of 42 matched samples., Results: Based on unsupervised clustering and principal component analysis of the immune-related gene expression profile, tumors were primarily clustered according to the involved organ and further grouped according to the EGFR mutation status. Fifty-four genes were significantly differentially expressed between primary and brain metastatic tumors. Clustering using these genes showed that tumors harboring mutated EGFR tended to be grouped together in the brain. Pathway analysis revealed that various immune-related functions involving immune regulation, T cell activity, and chemokines were enriched in primary tumors compared to brain metastases. Diverse immune-related pathways were upregulated in brain metastases of EGFR-mutated compared to EGFR-wild-type adenocarcinoma, but not in primary tumors. The interferon-γ-related gene signature was significantly decreased in brain metastases. The anti-inflammatory markers TOLLIP and HLA-G were upregulated in brain metastases. The proportions of most immune cell subsets were decreased in brain metastases, but those of macrophages and CD56dim-NK-cells were increased, as was the ratios of CD163 + M2- to iNOS + M1-macrophages and NCR1 + NK-cells to CD3 + T cells., Conclusions: Our findings illustrate the immune landscape of brain metastases from NSCLC and reveal potential therapeutic strategies targeting cellular and non-cellular components of the tumor immune-microenvironment.

Leaf senescence is a developmental process induced by various molecular and environmental stimuli that may affect crop yield. The dark-induced leaf senescence-91 (DLS-91) plants displayed rapid leaf senescence, dramatically decreased chlorophyll contents, low photochemical efficiencies, and upregulation of the senescence-associated marker gene BrSAG12-1 . To understand DLS molecular mechanism, we examined transcriptomic changes in DLS-91 and control line DLS-42 following 0, 1, and 4 days of dark treatment (DDT) stages. We identified 501, 446, and 456 DEGs, of which 16.7%, 17.2%, and 14.4% encoded TFs, in samples from the three stages. qRT-PCR validation of 16 genes, namely, 7 MADS, 6 NAC, and 3 WRKY, suggested that BrAGL8-1 , BrAGL15-1 , and BrWRKY70-1 contribute to the rapid leaf senescence of DLS-91 before (0 DDT) and after (1 and 4 DDT) dark treatment, whereas BrNAC046-2 , BrNAC029-2/BrNAP , and BrNAC092-1/ORE1 TFs may regulate this process at a later stage (4 DDT). In-silico analysis of cis-acting regulatory elements of BrAGL8-1, BrAGL42-1, BrNAC029-2, BrNAC092-1, and BrWRKY70-3 of B. rapa provides insight into the regulation of these genes. Our study has uncovered several AGL-MADS, WRKY, and NAC TFs potentially worthy of further study to understand the underlying mechanism of rapid DLS in DLS-91.

Purpose: According to recent studies, magnetic resonance imaging (MRI) assessment of complex fistulas provides a significant benefit compared to fistulography, computed tomography, and ultrasonography. The aim of this study was to describe the accuracy of MRI and the importance of identifying puborectalis muscle involvement on MRI in patients with complex fistula., Methods: All patients who were clinically diagnosed with 'complex' or showed multiple fistula tracts underwent fistula MRI. Eligible patients were consecutive patients who underwent fistula MRI between September 2018 and September 2019 at our hospital., Results: A total of 83 patients (74 males, 9 females; 116 tracts) were included in this study. The sensitivity and specificity of MRI in diagnosing fistula tracts were 94.8% and 98.2%, respectively. The sensitivity and specificity in identifying internal opening were 93.9% and 97.3%, respectively. Of the 35 patients with puborectalis muscle involvement in the MRI, 31 images of suprasphincteric-type patients on the Park's classification were classified. The patients of puborectalis involvement were divided into 2 groups according to the surgical procedure that was performed. There were 12 sphincter-saving procedures and 19 sphincter division procedures performed. Recurrence was seen in 2 patients in the sphincter-saving procedure group, while no case was seen in the sphincter division procedure group. Five complications were found in the sphincter division procedure group, of which 2 reported incontinence., Conclusion: Fistula MRI is a highly accurate examination for evaluating complex fistulas, and the puborectalis muscle involvement findings are very important for diagnosis and treatment.

Invasive pulmonary aspergillosis (IPA) has been known to occur in immunocompromised patients, but has been rarely reported in immunocompetent patients. In immunocompetent patients, pulmonary fungal infections are not initially considered. This results in diagnosis and treatment delays, as well as poor prognosis. We report a case and serial CT findings of IPA in an immunocompetent 29-year-old male after congenital heart disease surgery., Competing Interests: Conflicts of Interest: The authors have no potential conflicts of interest to disclose., (Copyrights © 2020 The Korean Society of Radiology.)

Purpose: To retrospectively investigate incidence, clinical outcome, and risk factors of iatrogenic pleural effusion in patients with hepatic tumors undergoing radiofrequency (RF) ablation using artificial ascites (AA)., Materials and Methods: Patients (N = 163) who underwent RF ablation using AA were classified into pleural effusion and non-pleural effusion groups according to the presence of pleural effusion on immediate follow-up CT and chest radiograph after RF ablation. The pleural effusion group included asymptomatic and symptomatic subgroups. The incidence and subsequent clinical outcomes of patients developing pleural effusion after RF ablation were evaluated., Results: Overall, 96 patients (58.9%) developed pleural effusion, which resolved in 4.4 d ± 3.1. Hospital length of stay in the pleural effusion group was longer than the non-pleural effusion group (6.5 d ± 2.6 vs 5.7 d ± 2.8, P < .01). The pleural effusion group had longer AA infusion time (P = .01), larger infused AA volume (P < .01), and longer ablation time (P < .01) than the non-pleural effusion group. Eighteen patients (18.8%) developed symptomatic pleural effusion and had a larger infused AA volume than asymptomatic patients with pleural effusion (P < .01). Pleural effusion duration and hospital length stay were also longer in the symptomatic pleural effusion subgroup than in the asymptomatic subgroup (P < .01). Infused AA volume was the only independent prognostic factor of pleural effusion duration in multivariate analysis (P = .038)., Conclusions: Pleural effusion frequently occurs after RF ablation using AA. Although generally considered negligible, pleural effusion could be a clinical problem and prolong hospitalization. Therefore, operators should be careful not to infuse too much AA when performing RF ablation., (Copyright © 2020 SIR. Published by Elsevier Inc. All rights reserved.)

Purpose: B7-H3 has emerged as a promising target for cancer immunotherapy. We assessed the role of B7-H3 expression in tumour-infiltrating immune cells in non-small-cell lung cancer (NSCLC)., Methods: Tumour-infiltrating immune cell characterisation was performed by flow cytometry in a prospective cohort, whereas the relationship between B7-H3 expression and clinicopathological features was explored in a retrospective cohort., Results: B7-H3 expression was detected in tumour/epithelial cells and immune cells, including macrophages, monocytes, dendritic cells (DCs) and myeloid-derived suppressor cells. B7-H3 was expressed at higher levels in cells within the tumour than in cells within non-neoplastic tissues. B7-H3 expression score in tumour cells positively correlated with the amount of CD45 + immune cells (rho = 0.305, P = 0.010), CD8 + T-cells (rho = 0.330, P = 0.005), and the percentage of CD8 + /CD3 + T-cells (rho = 0.403, P < 0.001). Patients with high tumoural B7-H3 expression showed increased numbers of immune cells (P = 0.002), CD8 + T-cells (P = 0.011), natural killer cells (P = 0.073) and plasmacytoid DCs (P = 0.015). Tumoural B7-H3 expression was higher in males, smokers, squamous cell carcinomas, tumours with wild-type EGFR, poor differentiation, larger size and nodal metastasis (P < 0.05, all). Tumoural B7-H3 expression was associated with PD-L1 expression (P = 0.001), shorter 5-year overall survival (P = 0.012) and poor survival after anti-PD-1 blockade (P = 0.026)., Conclusions: Tumoural B7-H3 overexpression was associated with increased tumour-infiltrating cytotoxic lymphocytes and poor prognosis in NSCLC. Thus, B7-H3 is a promising prognostic biomarker and immunotherapeutic target in NSCLC., Competing Interests: Conflict of interest statement The authors declare no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: The aim of this study was to conduct a radiopathologic evaluation of right-angled traction bronchiectasis to differentiate idiopathic pulmonary fibrosis (IPF) without honeycombing from idiopathic nonspecific interstitial pneumonia (NSIP)., Materials and Methods: The derivation cohort included 78 consecutive patients with idiopathic NSIP (n = 39) or IPF (n = 39) without honeycombing who underwent preoperative thin-section computed tomography scans at a single tertiary hospital. The validation cohort comprised 22 patients (14 IPF and 8 NSIP) from another institution. We assessed conventional computed tomography findings, right-angled traction bronchiectasis on minimum intensity projection (MinIP) images, and pathologic features associated with right-angled bronchiectasis. Right-angled traction bronchiectasis was defined as abrupt kinking of a single bronchus by over 90 degrees or an abrupt angle close to 180 degrees of branching bronchi in the background of fibrosis. In the validation cohort, we evaluated the proportion of correct IPF diagnoses and interobserver agreement of 4 radiologists before and after reviewing MinIP images., Results: A probable usual interstitial pneumonia (UIP) pattern (odds ratio [OR], 6.948; 95% confidence interval [CI], 1.525-31.654; P = 0.012) and right-angled traction bronchiectasis (OR, 6.004; 95% CI, 1.980-18.209; P = 0.002) were independently associated with IPF. Patients with right-angled traction bronchiectasis were more likely to have extensive reticular opacity (OR, 1.149; 95% CI, 1.077-1.225; P < 0.001) and pathologically were more likely to have a broad extent of subpleural fibrosis (OR, 4.000; 95% CI, 1.457-10.987; P = 0.007) and relatively thick fibrosis (OR, 7.750; 95% CI, 2.504-23.991; P < 0.001). After reviewing MinIP images, the proportion of correct diagnoses increased from 40.9% to 54.5% to 50.0% to 77.3%. The mean kappa value for right-angled traction bronchiectasis was 0.489 ± 0.192., Conclusions: Right-angled traction bronchiectasis pathologically reflected a subpleural predominance of fibrosis and partly supported the radiologic differentiation of IPF without honeycombing from idiopathic NSIP.

Background: The expression of programmed cell death ligand-1 (PD-L1) is a biomarker in patients with non-small-cell lung carcinoma (NSCLC). Patients with advanced-stage NSCLC receive a variety of molecular genetic tests, possibly resulting in insufficient tissue for immunoassay of PD-L1. Thus, to determine whether effusion fluid specimens are a reliable alternative to tissue specimens for PD-L1 testing, we compared the results of PD-L1 immunostaining using body-fluid cell blocks and tumor tissues., Methods: PD-L1 immunostaining was performed in 62 paired samples of cytology cell blocks (ie, immunocytochemistry) and tumor tissues (ie, immunohistochemistry) from 36 patients using the E1L3N, SP142, and SP263 anti PD-L1 antibody clones. Of the 62 cytology specimens, 50 were from malignant effusion fluid. PD-L1 expression was scored as the percentage of tumor cells with clear membranous staining., Results: A strong positive correlation was observed between the immunostains on cytology cell blocks and tumor tissue (Pearson's correlation coefficient, R = .804, P < .001). When the score was categorized as <1%, ≥1% and <10%, ≥10% and <50%, and ≥50%, the overall concordance rate was 74.2% (46/62, Cohen's k = 0.568). After dichotomizing the cases using cutoff values of 1%, 10%, and 50%, the concordance rates were 84% to 100% for both adenocarcinoma and squamous cell carcinoma. The concordance rate was higher in patients with NSCLC with an EGFR mutation and using the SP263 rather than the E1L3N clone., Conclusion: The results of PD-L1 immunostaining of cell blocks, particularly from effusion fluid, reflect the PD-L1 expression status of NSCLC tissue., (© 2020 Wiley Periodicals, Inc.)

Stresses and various infectious reagents caused multiple inflammatory diseases in swine in a livestock industrial environment. Therefore, there is a need for an effective therapeutic or preventive agent that could alleviate chronic and acute inflammation. We found that lysophosphatidic acid (LPA), a stress-induced potent endogenous inflammatory molecule, causes a broad range-regulation of inflammation related genes inflammation in swine macrophages. We further investigated the genome scaled transcriptional regulatory effect of a novel LPA-signaling antagonist, KA-1002 on swine macrophages, inducing the alleviated LPA-mediated inflammation related gene expression. Therefore, KA-1002 could potentially serve as a novel therapeutic or preventive agent to maintain physiologically healthy and balanced conditions of pigs.

We investigated the clinicopathological role of the PD-1/PD-L1 pathway in primary diffuse large B-cell lymphoma of the central nervous system (PCNS-DLBCL) arising in the immune-privileged site. PD-L1 immunostaining of ≥30% of tumor cells was defined as tPD-L1+, and PD-L1 immunostaining of ≥30% of total cellularity, including tumor and non-tumoral cells, as tmPD-L1+ . PD-1 + and CD8 + tumor-infiltrating lymphocytes (TILs) were enumerated. Thirty-five cases (35.7%) were tPD-L1+ and 47 cases (48%) were tmPD-L1+ . The number of TILs was greater in tmPD-L1+ cases than in tmPD-L1- cases (CD8 + , P = .050; PD-1 + , P = .019). tPD-L1+ and tmPD-L1+ cases tended to have a poor performance status. In contrast, the numbers of CD8 + and PD-1 + TILs tended to be higher in patients with a good performance status and MYC/BCL2 negativity. Patients with tPD-L1+ had a worse overall survival ( P = .026), and those with increased CD8 + or PD-1 + TILs tended to have a better overall survival ( P = .081 and 0.044, respectively). Tumoral PD-L1 expression and the number of PD-1 + TILs were independent prognostic factors. tPD-L1+ patients with a small number of CD8 + or PD-1 + TILs had the worst prognosis, and tPD-L1- patients with a large number of CD8 + or PD-1 + TILs had the best prognosis. In validation group, increased CD8 + or PD-1 + TILs were significantly associated with a prolonged survival, but PD-L1 had no prognostic significance. In conclusion, PD-L1 is frequently expressed in tumor cells and the immune microenvironment of PCNS-DLBCL and is correlated with increased TILs. PD-L1 and CD8 + and PD-1 + TILs have potential as prognostic biomarkers and therapeutic targets in PCNS-DLBCL.

Purpose: To identify prognostic factors influencing progression-free survival (PFS) of aggressive fibromatosis (AF) after postoperative radiotherapy (PORT) and assess correlations between immunohistochemistry (IHC) features of β-catenin/smooth muscle actin (SMA) and PFS., Materials and Methods: Records of 37 patients with AF treated by PORT from 1984 to 2015 were retrospectively reviewed. Fifteen patients underwent wide excision for AF and 22 patients received debulking operation. The median total dose of PORT was 59.4 Gy. IHC staining results of β-catenin and SMA were available for 11 and 12 patients, respectively., Results: The median follow-up duration was 105.9 months. Five-year PFS rate was 70.9%. Tumor size or margin status was not related to PFS in univariate analysis (p = 0.197 and p = 0.716, respectively). Multivariate analysis showed that increased interval from surgery to PORT (>5.7 weeks) was a marginal risk factor for PFS (p = 0.054). Administration of PORT at the initial diagnosis resulted in significantly improved PFS compared to deferring PORT after recurrence (p = 0.045). Patient with both risk factors of deferring PORT after recurrence and interval from surgery to PORT >5.7 weeks had significantly lower 5-year PFS than patients without risk factor (34.1% vs. 100.0%; p = 0.012). Nuclear β-catenin intensity tended to inversely correlate with 5-year PFS, although it did not reach statistical significance (62.5% at low vs. 100.0% at high; p = 0.260). SMA intensity was not related to PFS (p = 0.700)., Conclusion: PORT should be performed immediately after surgery irrespective of margin status or tumor size especially in recurrent case. Nuclear β-catenin staining intensity of IHC might correlate with local recurrence.

Primary central nervous system lymphoma of T-cell origin (T-PCNSL) is rare, and its clinicopathological features remain unclear. Peripheral T-cell lymphoma of γδ T-cell origin is an aggressive lymphoma mainly involving extranodal sites. Here, we report a case of γδ T-PCNSL involving the intramedullary spinal cord and presenting with paraplegia. A 75-year-old Korean woman visited the hospital complaining of back pain and lower extremity weakness. Magnetic resonance imaging revealed multifocal enhancing intramedullary nodular lesions in the thoracic and lumbar spinal cord. An enhancing nodular lesion was observed in the periventricular white matter of the lateral ventricle in the brain. There were no other abnormalities in systemic organs or skin. Laminectomy and tumor removal were performed. The tumor consisted of monomorphic, medium-to-large atypical lymphocytes with pale-to-eosinophilic cytoplasm. Immunohistochemically, the tumor cells were CD3(+), TCRβF1(-), TCRγ(+), CD30(-), CD4(-), CD8(-), CD56(+), TIA1(+), granzyme B(+), and CD103(+). Epstein-Barr virus in situ was negative. This case represents a unique T-PCNSL of γδ T-cell origin involving the spinal cord.

Objective: To evaluate pathological lesions in New Zealand white rabbits with acute kidney injury (AKI) of septic shock and to explore the potential role of poly (ADP-ribose) polymerase (PARP) in regulating AKI development., Materials and Methods: Endotoxic shock model in New Zealand white rabbits was first constructed. CVP (central venous pressure) was maintained at the baseline level by the saline administration. Rabbits were randomly assigned into sham group, LPS group, and LPS+3-AB group, respectively. Blood samples and kidney samples of rabbits were collected 4 h after LPS administration. Pathological kidney lesions were observed by HE (hematoxylin-eosin) staining and immunohistochemistry. Serum levels of renal damage markers (Scr, Cys-C, KIM-1, and NGAL) were detected by an automatic biochemical analyzer, immunoturbidimetry, and ELISA (enzyme-linked immunosorbent assay), respectively. Kidney energy metabolism changes (ATP, ADP, PCr, and NAD) were detected by HPLC (high performance liquid chromatography analysis). Western blot was conducted to detect protein expressions of NF-κB (nuclear factor-kappa B), TNF-α (tumor necrosis factor-α), ICAM-1 (intercellular cell adhesion molecule-1) and P-selectin in kidney tissues., Results: Significant pathological lesions in kidney tissues and higher pathological grade were seen in the LPS group. Multiple PARP-positive nuclei were found in renal tubular cells at the junction of renal cortex and renal cortex in the LPS group. Serum levels of Scr, KIM-1, NGAL, and Cys-C were remarkably higher in the LPS group than those of sham group. HPLC results showed decreased levels of ATP, ADP, PCr, and NAD in kidney cortex of LPS group compared with those of sham group. Western blot results suggested that protein expressions of NF-κB, TNF-α, ICAM-1, and P-selectin were remarkably upregulated in kidney tissues of LPS group. 3-AB pretreatment, the PARP inhibitor, remarkably alleviated pathological lesions and inflammation induced by AKI., Conclusions: Inhibition of PARP overactivation alleviated pathological kidney lesions, improved kidney energy metabolism and inhibited inflammatory response resulted from AKI.

The ability to rapidly detect, identify, and monitor chemical warfare agents (CWAs) is imperative for both military and civilian defense. Since most CWAs and their simulants have an organophosphonate group, which is a hydrogen (H)-bond acceptor, many H-bond donors have been developed to effectively bind to the organophosphonate group. Although thioureas have been actively studied as an organocatalyst, they are relatively less investigated in CWA detection. In addition, there is a lack of studies on the structure-property relationship for gas phase detection. In this study, we synthesized various thioureas of different chemical structures, and tested them for sensing dimethylmethylphosphonate (DMMP), a CWA simulant. Molecular interaction between DMMP and thiourea was measured by 1 H NMR titration and supported by density functional theory (DFT) calculations. Strong H-bond donor ability of thiourea may cause self-aggregation, and CH-π interaction can play an important role in the DMMP detection. Gas-phase adsorption of DMMP was also measured using a quartz crystal microbalance (QCM) and analyzed using the simple Langmuir isotherm, showing the importance of structure-induced morphology of thioureas on the surface.

Retinal ganglion cell (RGC) injury is one of the important pathological features of diabetes-induced retinal neurodegeneration. Increasing attention has been paid to find strategies for protecting against RGC injury. Long noncoding RNAs (lncRNAs) have emerged as the key regulators of many cell functions. Here, we show that Sox2OT expression is significantly down-regulated in the retinas of STZ-induced diabetic mice and in the RGCs upon high glucose or oxidative stress. SOX2OT knockdown protects RGCs against high glucose-induced injury in vitro. Moreover, Sox2OT knockdown plays a neuroprotective role in diabetes-related retinal neurodegeneration in vivo. Sox2OT knockdown could regulate oxidative stress response in RGCs and diabetic mouse retinas. Sox2OT knockdown plays an anti-oxidative role via regulating NRF2/HO-1 signaling activity. Taken together, Sox2OT knockdown may be a therapeutic strategy for the prevention and treatment of diabetes-induced retinal neurodegeneration.

The objective of the study is to investigate the effects of the Numb/Notch signal pathway on the radiosensitivity of lung cancer cell line H358. MTT assay and colony forming assay were used to detect the effects of different doses of X-rays and MW167 on the in vitro proliferation of the lung cancer cell line H358. Flow cytometry was applied to evaluate the effects of X rays on the apoptosis of H358. Scratch assay and Transwell invasion assay were used to examine the effects of X-rays on the migration and invasion abilities of H358. The mRNA and protein expressions in the signal pathway were detected by real-time PCR and western blot. Assays in vitro confirmed the effects of the Numb/Notch pathway inhibitor on the radiosensitivity to lung cancer. MW167 enhanced the inhibiting effects of X-ray on the proliferation of H358 cell line. After the addition of MW167, the apoptosis rates significantly increased, but the invasion and migration abilities decreased significantly. Meanwhile, MW167 could dose-dependently promote the increase of expression of Numb, which is the upstream gene of the Numb/Notch signaling pathway, but inhibit the expression of and HES1. In vivo experiments revealed that cell proliferation was suppressed in the radiation, pathway inhibitor, and pathway inhibitor + radiation groups, and the pathway inhibitor + radiation group exhibited more active anti-tumor ability when compared with the blank group (all P < 0.05); Numb expression was up-regulated, but Notch1 and HES1 expressions were down-regulated in those three groups, and also, the pathway inhibitor + radiation group exhibited more significant alternation when compared with the blank group (all P < 0.05); cell apoptosis was promoted in those three groups, and the pathway inhibitor + radiation group showed more active apoptosis when compared with the blank group (all P < 0.05). Repression of the Numb/Notch pathway enhances the effects of radiotherapy on the radiosensitivity of the lung cancer cell line H358, and thus the Numb/Notch pathway may be a new target of radiotherapy for lung cancer.

Background/aims: Advanced glycation end products (AGEs) could elicit oxidative stress, trigger and aggravate endothelium damage in several ischemic retinopathies including diabetic retinopathy (DR). The leaves of Eucommia ulmoides O., also referred to as Tu-chung or Du-zhong, have been used for the treatment of hypertension and diabetes, showing great antioxidant activity and anti-glycation activity. Lignans is one of the main bioactive components of Eucommia ulmoides. This study mainly investigated the effect of lignans treatment on AGEs-induced endothelium damage., Methods: MTT assay, Hoechst staining, and calcein-AM/ propidium iodide (PI) staining was conducted to determine the effect of lignans treatment on endothelial cell function in vitro. Retinal trypsin digestion, Evans blue assay, isolectin staining, and western blots were conducted to determine the effect of lignans treatment on retinal microvascular function in vivo. Western blot, protein immunoprecipitation (IP), MTT assays, and enzyme activity assay was conducted to detect the effect of ligans treatment on oxidative stress response., Results: Lignans protected retinal endothelial cell against AGEs-induced injury in vitro and diabetes-induced vascular dysfunction in vivo. Lignans treatment could regulate oxidative stress response in retinal endothelial cell line, retina, and liver. Moreover, we showed that NRF2/HO-1 signaling was critical for lignans-mediated oxidative stress regulation., Conclusion: Lignans treatment could protect against endothelial dysfunction in vivo and in vitro via regulating Nrf2/HO-1 signaling. Lignans might be developed as a promising drug for the treatment of diabetes-induced microvascular dysfunction., (© 2016 The Author(s) Published by S. Karger AG, Basel.)

This study aimed to investigate the inhibition of vascular endothelial growth factor (VEGF) by small hairpin RNA (shRNA) interference combined with radiotherapy on the growth of cervical cancer SiHa cell xenografts in nude mice. The effective pVEGF-shRNA plasmid was screened by reverse transcription-polymerase chain reaction (RT-PCR), and the cell apoptosis rate was estimated by flow cytometry. A nude mouse cervical xenograft model was established and all models were divided into four groups: blank control, VEGF shRNA, radiotherapy, and combined treatment. We calculated the tumor growth curve and the inhibitory rate. The histopathological changes of the microvascular density and VEGF protein expression were observed by immunohistochemistry. The expressions of VEGF and hypoxia inducible factor-1α (HIF-1α) proteins in the tumor tissue were analyzed via Western blot. VEGF shRNA interference inhibited the expression of radiation-induced VEGF (P < 0.05), induced apoptosis (P < 0.05), downregulated the HIF-1α protein, and reduced angiogenesis. Compared with the other three groups, the combined treatment group showed the most significant effects (P < 0.01). VEGF shRNA interference combined with radiotherapy promotes the radiosensitivity of tumors via improvement of the hypoxic microenvironment.

A-disintegrin and metalloproteinase 10 (ADAM10) is involved in the generation of amyloid-β (Aβ) during amyloid precursor protein (APP) processing, and has a protective effect against Aβ neurotoxicity. We explored how metallothionein-III (MT-III) is regulated in the non-amyloidogenic pathway to generate soluble APPα (sAPPα). MT-ІІІ increased sAPPα levels and reduced Aβ peptide levels, but did not affect ADAM10 expression. However, MT-III increased the activity of ADAM10. MT-ІІІ-induced sAPPα secretion, and Aβ peptide formation was blocked by specific inhibitors of furin, proprotein convertase7 (PC7), and PKCα. These results demonstrate that MT-ІІІ increases the amount of active ADAM10 in association with furin, PC7 and PKCα., (Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)