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Microsatellite instability (MSI) is a hallmark of mismatch repair (MMR) deficiency. High levels of MSI at mononucleotide and dinucleotide repeats in colorectal cancer (CRC) are attributed to inactivation of the MMR genes, hMLH1 and hMSH2. CRC with low levels of MSI (MSI-L) exists; however, its molecular basis is unclear. There is another type of MSI—elevated microsatellite alterations at selected tetranucleotide repeats (EMAST)—where loci containing [AAAG]n or [ATAG]n repeats are unstable. EMAST is frequent in non-CRCs; however, the incidence of EMAST and its cause in CRC is not known. Here, we report that MutS homologue 3 (MSH3) knockdown or MSH3-deficient cells exhibit the EMAST phenotype and low levels of mutations at dinucleotide repeats. About 60% of 117 sporadic CRC cases exhibit EMAST. All of the cases defined as MSI-H (16 cases) exhibited high levels of EMAST. Among 101 non–MSI-H cases, all 19 cases of MSI-L and 35 of 82 cases of MSS exhibited EMAST. Although non–MSI-H CRC tissues contained MSH3-negative tumor cells ranging from 2% to 50% of the total tumor cell population, the tissues exhibiting EMAST contained more MSH3-negative cells (average, 31.5%) than did the tissues not exhibiting EMAST (8.4%). Taken together, our results support the concept that MSH3 deficiency causes EMAST or EMAST with low levels of MSI at loci with dinucleotide repeats in CRC. [Cancer Res 2008;68(20):8465–72]

Supplementary Table 1 from Genetic Instability Caused by Loss of MutS Homologue 3 in Human Colorectal Cancer

Supplementary Figures 1-2 from Genetic Instability Caused by Loss of MutS Homologue 3 in Human Colorectal Cancer

Histopathological identification is usually required since the sensitivity of fungal culture is not sufficient for accurate diagnosis. On the other hand, pathological diagnosis, especially of molds, often is not accurate, even when performed by an experienced pathologist. This is particularly true in the differentiation between mucormycosis and aspergillosis, which have different drugs of choice and medical management. The diseases can easily become severe in a short period of time in accordance with the severity of the underlying disease or predisposing factors. Therefore, correct diagnosis is extremely important and should be entrusted to the pathologist.To develop an artificial intelligence (AI)-based automated histological diagnostic system for mold infection to support the diagnosis by general pathologists, especially for distinguishing between Aspergillus and Mucorales.We used two indicators for the diagnostic system; namely, the angle of independent hyphae and tortuosity of each hypha.We collected 147 and 67 image samples respectively from standard cases of aspergillosis and mucormycosis. All the images were successfully analyzed by automatic recognition of the two indicators. The independent areas divided by the threshold curve generated by two-dimensional plots of the data clearly include the test data obtained from the cases of Aspergillus and Mucorales. The present study demonstrates the usefulness of our newly developed AI-based diagnostic system. Further investigation is required for its practical use.

To elucidate tumor cell behavior associated with cancer stem cell (CSC) marker expression, the expression of CD133, CD44v9, and ALDH1A1, which are considered markers of CSCs, was examined in sporadic and ulcerative colitis (UC)-associated colorectal tumors.A total of 23 cases of sporadic colorectal cancer and 44 cases of adenoma were collected. Additionally, 22 cancer lesions and 38 dysplasia lesions were selected from 28 colectomy cases of UC with neoplastic lesions. Lesions were examined by immunohistochemistry using primary antibodies against CD133, CD44v9, ALDH1A1, Ki-67, cleaved-Caspase 3, and p53.CD133, CD44v9, and ALDH1A1 showed higher expression in both sporadic and UC-associated tumors than in the normal mucosa. ALDH1A1 expression in sporadic cancer was higher in the right colon than in the left colon (p=0.0089). ALDH1A1 expression in UC-associated cancer was higher in those with longer disease duration than in those with shorter disease duration (p=0.019). The CD44v9+/CD133- region had fewer cleaved-Caspase 3 positive cells in both sporadic and UC-associated cancers. In sporadic cancer, CD133+/ALDH1A1+ regions had fewer apoptotic cells than CD133+/ALDH1A1- regions, while CD133+/ALDH1A1- regions were less proliferative than CD133+/ALDH1A1+ regions in UC-associated cancer.CD44+/CD133- regions were commonly associated with low apoptosis in sporadic and UC-associated cancers; thus, these were considered target areas for CSCs. Additionally, the combination of markers comprising CSCs may differ between sporadic and UC-associated cancers.

High strength and ultra low permeability concrete (HSULPC) is being considered as a material used to package transuranic (TRU) waste for disposal in geological repositories. Therefore, information on the permeability of HSULPC is essential. Permeability tests need to be highly accurate to determine the hydraulic conductivity of HSULPC because of its ultralow permeability. In our study, we measured the permeability of HSULPC samples using the transient pulse method. The temperature of the concrete was finely controlled and held constant. The hydraulic conductivities were determined from the measurements to be around 10(-13) to 10(-12) m/s for confining pressures between 2 and 10 MPa. The pore pressure was a constant 1 MPa. The results further showed that the permeability of HSULPC had a hysteretic dependence on the effective confining pressure. We found that the hydraulic conductivity of HSULPC is comparable to or less than that of intact Toki granite obtained from Gifu Prefecture in central Japan. It was also considered that the hydraulic conductivity of HSULPC stabilized at around 10(-13) m/s after being buried and stressed. The high density and impermeability of HSULPC would enable it to effectively confine C-14 radionuclides found in TRU waste.

Pancreatic leiomyosarcoma (PLMS) is an extremely rare tumor that accounts for 0.1% of pancreatic malignancies, and its chemotherapy has yet to be established. Generally, soft-tissue sarcoma chemotherapy is standard treatment with doxorubicin (DXR) alone. However, the effectiveness of gemcitabine (GEM) plus docetaxel (DOC) has been shown in uterine leiomyoma. In contrast, the GEM plus nab-paclitaxel (PTX) regimen has been established as first-line chemotherapy for unresectable pancreatic cancer. For this study, we selected the GEM plus nab-PTX regimen for patients with PLMS, achieving success in approximately 10 months. From a search on PubMed, we found only 12 cases of PLMS (including this case) that underwent chemotherapy. Our case is the first reported patient to have survived more than 2 years with chemotherapy alone. In a nude mouse model, the GEM plus DOC regimen was shown to significantly decrease tumor size when compared with DXR in leiomyosarcoma, and the GEM plus nab-PTX regimen was reported to significantly reduce necrosis when compared with DXR alone, GEM alone, DOC alone, nab-PTX alone and GEM plus DOC in soft-tissue sarcoma. GEM plus nab-PTX therapy might therefore be the first choice for soft-tissue sarcoma and leiomyosarcoma. This is the first reported case of PLMS treated with GEM plus nab-PTX.

AimsL-type amino acid transporter 1 (LAT1) is a major Na+-independent neutral amino acid transporter, forming a complex with CD98hc. The aim of this study is to investigate the significance of LAT1 and CD98hc in invasive breast cancer.MethodsLAT1 and CD98hc expression was immunohistochemically assessed in 280 invasive breast cancers and analysed for association with clinicopathological features.ResultsHigh levels of LAT1 and CD98hc were observed in triple-negative breast cancers (TNBCs) possessing negative immunoreactivity with oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, compared with non-TNBCs (NTNBCs), and were associated with lymph-node metastasis and higher nuclear grade. The high-LAT1-expression group showed a poor prognosis in NTNBC and TNBC, however, high-CD98hc-expression group showed a poor prognosis only in NTNBC. LAT1 and CD98hc expression could be the prognostic factors in univariate analyses, but not in multivariate analyses. Further, we found that invasive tumour components showed higher LAT1 and CD98hc expression than non-invasive tumour components.ConclusionsLAT1 and CD98hc may possess prognostic values in invasive breast cancer. LAT1 may be linked with cancer cell activities and disease progression in breast cancer.

Invasive fungal rhinosinusitis (FRS) is a rare but intractable infectious disease of the sinonasal region with destructive direct infiltration into surrounding tissues, such as the bone, orbit and brain, and potential dissemination to systemic organs. Symptomatic assessments and imaging are frequently not sufficiently diagnostic, and histopathological examination is essential for definite diagnosis of FRS. We herein report a case of chronic invasive FRS (CIFRS) in a 58-year-old Japanese male with end-stage diabetic nephropathy that required maintenance dialysis after graft rejection of living kidney transplantation. His initial main clinical presentation was sinus gangrene, which gradually progressed from the paranasal sinus to the nasal septum and oral palate, but not towards the intracranial or orbital region, for two months. The patient was first strongly suspected to have extranodal natural killer/T cell lymphoma (ENKTL), nasal type, a subtype of malignant lymphoma, based on the macroscopic appearance of the gangrene, expansion pattern and high serum soluble interleukin-2 level; however, repeated biopsies and eventual resection led to diagnosis of CIFRS due to Aspergillus niger and Mucor. The disease was improved by surgical resection in combination with antifungal pharmacologic treatment with liposomal amphotericin B and voriconazole. CIFRS typically occurs in immunocompetent patients and shows intracranial progression, but this case shows that atypical CIFRS with an uncommon expansion pattern can occur in an immunodeficient patient.

Gastrointestinal colonization has been considered as the primary source of candidaemia; however, few established mouse models are available that mimic this infection route. We therefore developed a reproducible mouse model of invasive candidiasis initiated by fungal translocation and compared the virulence of six major pathogenic Candida species. The mice were fed a low-protein diet and then inoculated intragastrically with Candida cells. Oral antibiotics and cyclophosphamide were then administered to facilitate colonization and subsequent dissemination of Candida cells. Mice infected with Candida albicans and Candida tropicalis exhibited higher mortality than mice infected with the other four species. Among the less virulent species, stool titres of Candida glabrata and Candida parapsilosis were higher than those of Candida krusei and Candida guilliermondii. The fungal burdens of C. parapsilosis and C. krusei in the livers and kidneys were significantly greater than those of C. guilliermondii. Histopathologically, C. albicans demonstrated the highest pathogenicity to invade into gut mucosa and liver tissues causing marked necrosis. Overall, this model allowed analysis of the virulence traits of Candida strains in individual mice including colonization in the gut, penetration into intestinal mucosa, invasion into blood vessels, and the subsequent dissemination leading to lethal infections., Scientific Reports, 10(1), art.no.3814; 2020

Onychomycosis is a common and intractable superficial mycosis that occurs worldwide. Treatment with both oral and topical drugs is recommended, but the objective evaluation procedure to determine the efficacy of and the appropriate delivery system for the drugs remains controversial. This may be attributed to the lack of a reliable animal model that not only mirrors the pathophysiology of human onychomycosis but is also feasible. Therefore, we attempted to establish an animal model of onychomycosis using immunosuppressed guinea pigs and elucidate the pathophysiology of human onychomycosis. In the present study, we applied Trichophyton mentagrophytes TIMM2789 to the hind limb nails of corticosteroid-treated guinea pigs. The nails were examined macroscopically and histopathologically at 0, 14, and 42 days after a 2-week exposure period to the fungus. A large portion of the experimentally infected nails showed discoloration, which is an important clinical sign, and most infections were confirmed histopathologically in the deep layer of the nail plate at all time points. The infection rates at 0, 14, and 42 days after exposure were 39%, 61%, and 78%, respectively. Thus, we established an animal model of onychomycosis with good reproducibility and that might be appropriate for extrapolation to the pathophysiology of the human disease.

Background Plaque hardness in carotid artery stenosis correlates with cerebral infarction. This study aimed to quantitatively compare plaque hardness with histopathological findings and identify the pathological factors involved in plaque hardness. Methods This study included 84 patients (89 lesions) undergoing carotid endarterectomy (CEA) at our institution. Plaque hardness was quantitatively measured immediately after excision using a hardness meter. Collagen and calcification were evaluated as the pathological factors. Collagen was stained with Elastica van Gieson stain, converted to a gray-scale image, and displayed in a 256-step histogram. The median gray-scale median (GSM) was used as the collagen content. The degree of calcification was defined by the hematoxylin–eosin stain as follows: "0:" no calcification, "1:" scattered microcalcification, or "2:" calcification greater than 1 mm or more than 2% of the total calcification. Carotid echocardiographic findings, specifically echoluminance or the brightness of the narrowest lesion of the plaque, classified as hypo-, iso-, or hyper-echoic by comparison with the intima-media complex surrounding the plaque, and clinical data were reviewed. Results Plaque hardness was significantly negatively correlated with GSM [Spearman's correlation coefficient: -0.7137 (p p = 0.0206). For plaque hardness and echoluminance (hypo-iso-hyper), significant differences were found between hypo-iso (p = 0.0220), hypo-hyper (p = 0.0006), and iso-hyper (p = 0.0015): the harder the plaque, the higher the luminance. In single regression analysis, GSM, sex, and diabetes mellitus were significant variables, and in multiple regression analysis, only GSM was extracted as a significant variable. Conclusions Plaque hardness was associated with a higher amount of collagen, which is the main component of the fibrous cap. Greater plaque hardness was associated with increased plaque stability. The degree of calcification may also be associated with plaque hardness.

Strain TUM18999T was isolated from the skin of a patient with burn wounds in Japan. The strain was successfully cultured at 20–42 °C (optimum, 30–35 °C) in 1.0–4.0% NaCl (w/v) and at pH 5.5–9.5, optimum pH 5.5–8.5. The phylogenetic tree reconstructed using 16S rRNA, gyrB, rpoB and rpoD gene sequences indicated that strain TUM18999T is closely related to Pseudomonas otitidis MCC10330T. Although the partial 16S rRNA gene sequence (1412 bp) of TUM18999T exhibits high similarity to those of Pseudomonas alcaligenes NBRC 14159T (99.08 %) and Pseudomonas otitidis MCC10330T (98.51 %), multi-locus sequence analysis using 16S rRNA, gyrB, rpoB and rpoD genes reveals a clear distinction between TUM18999T and other Pseudomonas species. In addition, an average nucleotide identity >90 % was not observed in the P. aeruginosa group. Moreover, TUM18999T and P. otitidis can be distinguished based on the minimum inhibitory concentration for carbapenem. Meanwhile, the cellular fatty acids are enriched with C18 : 1 ω7c/C18 : 1 ω6c (34.35 %), C16 : 1 ω7c/C16 : 1 ω6c (24.22 %), C16 : 0 (19.79 %) and C12 : 0 (8.25 %). Based on this evidence, strain TUM18999T can be defined as representing a novel Pseudomonas species, with the proposed name Pseudomonas tohonis sp. nov. The type strain is TUM18999T (GTC 22698T=NCTC 14580T).

Background A combination of positron emission tomography and computed tomography (PET/CT) is an important modality for the diagnosis of carcinoma. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) have been reported as metabolic parameters in PET/CT since the late 1990s, and they are expected to be useful in diagnosing diverse cancers and as prognostic biomarkers. We evaluated the potential of these parameters in the prognosis of colorectal cancer (CRC) by comparing them with conventional parameters, including the maximum standardized uptake value (SUVmax). We enrolled 84 patients who underwent surgery for CRC without distal metastasis between April 2015 and April 2019. SUVmax, MTV, and TLG were measured by 18F-fluorodeoxyglucose (FDG)-PET/CT. To find an optimal threshold value related to prognosis, the volume of interest in the primary carcinoma was measured at fixed relative and absolute thresholds based on SUVmax (30%, 40%, and 50%; 2.5, 3.0, and 3.5, respectively), tumor-to-liver standardized uptake ratios, TLR (1.0, 1.5, and 2.0), and SUV normalized to lean body mass, SUL (2.0, 2.5, and 3.0). After classifying the patients into two groups according to pathological N stage, the optimal threshold values of all metabolic parameters were compared between groups using a non-parametric comparison test. Result The most suitable thresholds for MTV were a SUVmax of 3.5 and a TLR 2.0. TLG with a SUVmax value of 40% showed the most significant difference. The MTV standard uptake ratio of 2.0 was significantly associated with pathological N stage. Conclusion Our results suggest that an MTV TLR 2.0 on PET/CT reflects pathological N stage in local patients with CRC.

Propionibacterium acnes is implicated in the pathogenesis of sarcoidosis. We investigated the usefulness of immunohistochemistry (IHC) with a commercially available P. acnes-specific monoclonal antibody (PAB antibody) for differentiating sarcoidosis from other granulomatous diseases. Formalin-fixed paraffin-embedded tissue samples from 94 sarcoidosis patients and 30 control patients with other granulomatous diseases were examined by the original manual IHC method. We also compared the detection frequency of P. acnes in sarcoid granulomas between manual and automated IHC methods. P. acnes was detected in sarcoid granulomas of samples obtained by transbronchial lung biopsy (64%), video-associated thoracic surgery (67%), endobronchial-ultrasound-guided transbronchial-needle aspiration (32%), lymph node biopsy (80%), and skin biopsy (80%) from sarcoidosis patients, but not in any non-sarcoid granulomas of the samples obtained from control patients. P. acnes outside granulomas, however, was frequently detected in both groups. The detection status of P. acnes in granulomas did not correlate with the clinical characteristics of sarcoidosis patients. The automated Leica system exhibited the best detection sensitivity (72%) and almost an identical localization for P. acnes in sarcoid granulomas compared with the manual method. IHC with a PAB antibody is useful for differentiating sarcoidosis from other granulomatous diseases by detecting P. acnes in granulomas. An automated method by the Leica system can be used in pathology laboratories for differential diagnosis of granulomas by IHC with the PAB antibody.

Trichosporon species are some of the most common pathogenic yeasts in Asia, and many are resistant to echinocandin antifungal drugs. Effective treatment of fungal infections requires the selection of appropriate antifungals and the accurate identification of the causal organism. However, in histopathological specimens Trichosporon spp. are often misidentified as Candida species due to morphological similarities. In situ hybridization (ISH) is a useful technique for identifying fungal species in formalin-fixed and paraffin-embedded (FFPE) tissue sections. Although many novel probes for ISH are available, the practical use of ISH for identification of fungi remains limited, in part due to the lack of adequate verifications. We conducted a two-center retrospective observational study in which the ISH technique was used to differentiate Trichosporon spp. and C. albicans in FFPE tissue from autopsy specimens. The study included 88 cases with blood stream yeast infection without Cryptococci extracted from 459 autopsy files of cases with proven invasive fungal infection (IFI). Positive signals for the Trichosporon spp. protein nucleic acid (PNA) probe and C. albicans PNA probe were seen for 7 and 35 cases, respectively, whereas the remaining 46 were negative for both. For the Trichosporon spp.- positive specimens, 5/7 were reported as candidiasis in autopsy records. Our results suggested that accurate histological identification of fungal infections remains challenging, but ISH may be a suitable approach to support histological findings. In addition, this retrospective study suggested that trichosporonosis may have high prevalence among cases of bloodstream yeast infections in Japan.

Aim Current approaches for hepatic steatosis assess only a small point within the liver and might cause inaccuracy for longitudinal observation. We aimed to establish a reliable non-invasive method for whole hepatic lipid content evaluation. Methods A total of 52 patients with hepatic steatosis underwent liver biopsy. Hepatic lipid content was assessed by Dixon in-phase/out-of-phase magnetic resonance imaging and proton magnetic resonance spectroscopy. Using multi-slice and multi-point magnetic resonance imaging, we calculated the lipid intensity of every voxel throughout the liver and showed the color-mapped lipid distributions. This new analysis could also quantify the whole hepatic lipid and whole liver volumes absolutely. The diagnostic performance of hepatic lipid content between the new analysis and proton magnetic resonance spectroscopy methods was compared by receiver operating characteristic curve analysis referring to the steatosis scores of the liver biopsy. Results Areas under the receiver operating characteristic for the diagnosis of steatosis scores ≥1, ≥2, and ≥3 using magnetic resonance imaging and proton magnetic resonance spectroscopy were 0.86 (95% confidence interval [CI] 0.70-1.00) and 0.98 (95% CI 0.93-1.00), 0.94 (95% CI 0.87-1.00) and 0.93 (95% CI 0.86-1.00), and 0.95 (95% CI 0.89-1.00) and 0.97 (95% CI 0.93-1.00), respectively, showing comparable diagnostic accuracies. However, color mapping showed some inconsistencies between the methods. Conclusions We described a non-invasive and repeatable evaluation method of whole hepatic lipid accumulation with absolute quantification and color mapping. Hepatic steatosis was accurately evaluated regardless of heterogeneous lipid accumulation. The whole hepatic lean volume, reflecting the hepatic parenchymal condition, can also be determined by this method.

Background Lipofuscin is an indicator of aging. We examined the clinicopathologic significance of lipofuscin deposition in the renal tubules of renal allografts. Method We analyzed allograft biopsy specimens from living kidney transplantations from January to December 2015. For controls, we analyzed native kidney biopsy specimens obtained from January 2015 to December 2016. We identified granules with a yellow-to-tan shade in renal tubules as lipofuscin. Results The donor age at transplantation was significantly older in lipofuscin deposition biopsy specimens than in those without, whereas the time after transplantation age was not different between the 2 groups with renal allografts. In native kidney biopsies, age at biopsy was significantly older in lipofuscin deposition biopsy specimens than in those without. We compared “massive lipofuscin deposition,” defined as lipofuscin deposition on both sides of 3 or more renal tubules, and donor-age matched control allograft biopsies without lipofuscin deposition. Comparing these 2 groups, recipient age at transplantation was significantly older in the massive lipofuscin deposition group. Conclusion Lipofuscin deposition on tubular epithelium is not a surrogate marker of aging of kidneys allografts, although lipofuscin deposition was significantly greater in older tissues from native kidneys. The older age of recipients may be associated with massive lipofuscin deposition in renal allografts.

Although numerous recent studies have reported the development of sarcoidosis in patients treated with tumor necrosis factor alpha (TNF-α) inhibitors, it is unclear whether the pathogenesis of drug-induced sarcoidosis is identical to that of spontaneous sarcoidosis. We herein present the case of a patient who developed sarcoidosis 6 months after the introduction of etanercept as treatment for rheumatoid arthritis. Typical clinical symptoms with noncaseating epithelioid granulomas detected in a mediastinal lymph node specimen were consistent with the diagnosis of sarcoidosis. Immunohistochemistry revealed Propionibacterium acnes in the noncaseating granulomas. The present findings suggest that Propionibacterium acnes is a cause of sarcoidosis, even when the disease is induced by TNF-α inhibitors.

Background The rate of aspergillosis has decreased due to improvements in therapy. The rate of mucormycosis, however, has gradually increased in recent years. Both aspergillosis and mucormycosis produce histologically similar hyphae, pointing to the need for an objective tool to distinguish between them. Methods Three aspergillosis cases and three mucormycosis cases were selected from autopsy cases in our hospital. Representative histological images were captured and hyphal angles in extravascular and intravascular lesions were calculated. Results For both extravascular and intravascular lesions, the average hyphal angle of aspergillosis was acute, and the standard deviation was less than that of mucormycosis. In aspergillosis, the average hyphal angle for extravascular lesions was acute, and the standard deviation was less than that for intravascular lesions. However, for mucormycosis, there was no significant difference in both the average and standard deviation of the hyphal angles. Conclusion Surgical pathologists should carefully examine the histological characteristics of the fungus to correctly identify specimens and be able to administer proper therapies.

Tissue-resident memory T cells (TRMs) are a novel nonvascular memory T cell subset. Although CD8+ TRMs are well-characterized, CD4+ TRMs-especially lung-resident memory Th17 cells-are still being defined. In this study, we characterized lung-resident memory Th17 cells (lung TRM17) and their role in protection against the highly virulent fungus Cryptococcus gattii. We found that intravenously transferred DCs preferentially migrated to lungs and attracted recipient DCs and led to the induction of long-lived Th17 cells expressing characteristic markers. This population could be clearly discriminated from circulating T cells by intravascular staining and was not depleted by the immunosuppressive agent FTY720. The C. gattii antigen re-stimulation assay revealed that vaccine-induced lung Th17 cells produced IL-17A but not IFNγ. The DC vaccine significantly increased IL-17A production and suppressed fungal burden in the lungs and improved the survival of mice infected with C. gattii. This protective effect was significantly reduced in the IL-17A knockout (KO) mice, but not in the FTY720-treated mice. The protective effect also coincided with the activation of neutrophils and multinucleated giant cells, and these inflammatory responses were suppressed in the vaccinated IL-17A KO mice. Overall, these data demonstrated that the systemic DC vaccine induced lung TRM17, which played a substantial role in anti-fungal immunity.

ORIGINAL ARTICLE, Introduction: Positron emission tomography (PET)/computed tomography (CT) plays an important role in cancer diagnosis. Recently, novel metabolic parameters obtained on PET/CT, such as metabolic tumor volume (MV) and total lesion glycolysis (TLG), have been reported to be diagnostic and prognostic biomarkers of various cancers. We evaluated the potential of these glucose metabolic parameters for the prognostic diagnosis of colorectal cancer (CRC), comparing them with conventional parameters such as the maximum standardized uptake value (SUV max) and maximum average SUV within a 1-cm3 spherical volume (SUV peak). Methods: This study included 82 patients who underwent surgical resection of CRC without distal metastasis between April 2015 and December 2017. They underwent [18F]-fluorodeoxyglucose-PET/CT and measurement of MV, TLG, SUV max, SUV mean, and SUV peak. After classifying the patients into four groups by pathological T stage, the metabolic parameters of each group were compared between the left- and right-sided large intestine using nonparametric multiple comparison test, and their prognosis was analyzed using Cox proportional hazards regression analysis. Results: The TLG value had a significant relation with the pathological T stage of the left-sided large intestine. Multivariate analysis of the clinicopathologic parameters (TLG, location, histological type, and T stage), revealed only the TLG of the primary tumor as an independent prognostic factor for recurrence within a year after surgery without distant metastasis. Conclusions: Our study results may suggest that TLG in PET/CT reflects a pathological T stage and plays a role in the prognosis of patients with local CRC.

Japan Nuclear Energy Safety Organization (JNES) has published an aggregate test method so-called as JNES flow (the method mainly composed of international methods RILEM AAR 3 and RILEM AAR 4) and alkali-silica reaction (ASR) diagnosis method.In this research, we conducted the RILEM methods using Japanese aggregates, which were international aggregate test methods that were considered to be highly reliable. Especially, we evaluated the suitability of various RILEM aggregate testing methods for Japanese aggregates with regard to methods for detecting reactivity of late expansive aggregates, which have been reported in recent years.Furthermore, for the ASR diagnostic method that emphasizes the petrological evaluation test after collecting concrete cores samples, various test specimens with different stages of deterioration were produced, and the core appearance observation and polarization microscope observation were performed on the collected core samples. We also conducted observations using a film scanner and evaluated the applicability of the proposed ASR diagnostic method to Japanese aggregates.Based on the above, an example of the alkali aggregate reaction test flow of concrete structures effective for reactive aggregates were proposed through comparison among various domestic and international aggregate test methods. Furthermore, an example of the alkali aggregate reaction diagnosis flow of concrete structures was proposed by conducting tests with several methods using cores which were sampled from the concrete specimens and the concrete structures.

Interleukin (IL)-11 is a member of the IL-6 family of cytokines and is involved in multiple cellular responses, including tumor development. However, the origin and functions of IL-11-producing (IL-11+) cells are not fully understood. To characterize IL-11+ cells in vivo, we generate Il11 reporter mice. IL-11+ cells appear in the colon in murine tumor and acute colitis models. Il11ra1 or Il11 deletion attenuates the development of colitis-associated colorectal cancer. IL-11+ cells express fibroblast markers and genes associated with cell proliferation and tissue repair. IL-11 induces the activation of colonic fibroblasts and epithelial cells through phosphorylation of STAT3. Human cancer database analysis reveals that the expression of genes enriched in IL-11+ fibroblasts is elevated in human colorectal cancer and correlated with reduced recurrence-free survival. IL-11+ fibroblasts activate both tumor cells and fibroblasts via secretion of IL-11, thereby constituting a feed-forward loop between tumor cells and fibroblasts in the tumor microenvironment., The stromal fibroblast population in the colon is composed of heterogeneous and distinct cell subtypes that play a crucial role in the development of colitis and colon cancer. Here the authors generate IL-11 reporter mice and characterize the origin and phenotype of inflammatory IL-11+ fibroblasts in colitis and colon cancer preclinical models.

We herein report a 73-year-old man who experienced cerebral infarction caused by infection with a Mucromycocetes species. A delay in anti-fungal treatment might result in a lethal clinical outcome. We were unable to establish an accurate diagnosis based on histological findings and cerebrospinal fluid culture. Therefore, we performed polymerase chain reaction (PCR) using paraffin-embedded specimens, and based on the findings, successfully started administering anti-fungal treatment. We suggest that PCR using sinus specimens be applied when mucormycosis is suspected as an etiology of cerebral infarction and a confirmative diagnosis cannot be established based on the results of pathological examinations or cerebrospinal fluid culture.