Olfactory Ensheathing Cell Tumor Arising from the Olfactory Mucosa

We report a rare case of olfactory ensheathing cell tumor. A female presented a large soft mass extending medially to the olfactory cleft and laterally to the middle meatus in the left nasal cavity. Imaging studies confirmed a cystic mass extending superiorly into the frontal lobe, indicating that the tumor arouse from the olfactory mucosa. A subtotal resection was achieved through an endoscopic endonasal approach without operative complications. Immunohistochemically constituent cells were diffusely positive for S-100 protein, but olfactory ensheathing cell tumor was diagnosed by negative staining for Leu7 (CD57). This case indicates that olfactory ensheathing cell tumor should be included in differential diagnoses for the olfactory cleft tumors

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Cancer stem cell markers CD44v9+/CD133- are associated with low apoptosis in both sporadic and ulcerative colitis-associated colorectal cancers

Objective. 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. Methods. 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. Results. 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. Conclusion. 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

Successful Treatment of Pulmonary Pleomorphic Carcinoma with Nivolumab: A Case Report

Pulmonary pleomorphic carcinoma (PPC) has a poor prognosis due to the poor results of treatment with systemic chemotherapy. We report the case of a 73-year-old woman with PPC who showed a favorable response to nivolumab. As first-line treatment for postoperative recurrence, she received carboplatin and nanoparticle albumin-bound paclitaxel. However, 12 months later, a new metastatic lymph node appeared. Nivolumab was administered as second-line treatment, and the patient showed a favorable prolonged response. The effects of treatment of PPC with nivolumab seem promising. The results of a future prospective study are expected to identify indicators for the treatment of PPC

Meta-analyses of individual versus group interventions for pre-school children with autism spectrum disorder (ASD)

<div><p>There is little evidence regarding the effects of individual and group intervention for children with autism spectrum disorder (ASD) on important outcomes. We performed meta-analyses using a random effects model to investigate the effectiveness of the individual and group intervention studies and to compare the effectiveness of these two types if possible. The main analysis which excluded studies at a high risk of bias (Analysis I) included 14 randomised controlled trials targeting children with ASD≤6 years of age (594 children). The results suggested that both individual and group interventions showed significant effects compared to the control condition on “reciprocity of social interaction towards others” (standard mean difference[SMD] [95%confidence interval{CI}] = 0.59[0.25, 0.93], p = 0.16; 0.45[0.02, 0.88], p = 0.39, respectively). Only individual interventions showed significant effects compared to the control condition on “parental synchrony” (SMD [95%CI] = 0.99 [0.70, 1.29], p<0.01). Our results showed no significant differences between individual and group interventions in effects on “autism general symptoms” (no study available for group intervention), “developmental quotient” (no study available for group intervention), “expressive language” (p = 0.56), “receptive language” (p = 0.29), “reciprocity of social interaction towards others” (p = 0.62), or “adaptive behaviour” (p = 0.43). We also performed sensitivity analyses including studies that had been excluded due to being at a high risk of potential bias (Analysis II). The results suggested that “reciprocity of social interactions towards others” showed significant effects for individual intervention compared to the control condition (0.50[0.31,0.69], p<0.001) but not for group intervention (0.23[-0.33, 0.78], p = 0.42). Individual intervention also showed significant effects on “parental synchrony” (0.98[0.30,1.66], p = 0.005) in the sensitivity analysis. The results also suggested no significant difference on all the outcomes between the individual and group interventions. We also reanalysed the data using cluster-robust standard errors as sensitivity analyses (Analysis III). Analysis III showed no significant effects in the intervention condition compared to the control condition on all the outcomes for both individual and group interventions. When Analysis II was reanalysed using cluster-robust standard errors (Analysis IV), individual interventions showed significant effects compared to the control condition on “reciprocity of social interaction towards others” and "parental synchrony" (mean estimate[95%CI], robust standard error, p = 0.50[0.20, 0.81], 0.13, 0.006; and 1.06[0.08, 2.05], 0.42, 0.04, respectively), and none of the outcomes showed significant effects under the intervention condition compared to the control condition for group interventions. The discrepancies in the results between the main analysis (Analysis I) and the sensitivity analyses (Analyses II, III, and IV) may be due to the small number of included studies. Since the outcome of “reciprocity of social interaction towards others” can be a dependent variable that is usually measured in a context-bound setting with the child's parent, we cannot conclude that individual interventions for pre-school children with ASD have significant effects on generalised skills for engaging in reciprocal interactions with others, even if the interventions have significant effects on the outcome. However, the outcomes of “reciprocity of social interaction towards others” may be promising targets for both individual and group interventions involving pre-school children with ASD. “Parental synchrony” may also be a promising target for individual interventions.</p><p><b>Trial registration:</b> (<a href="https://www.ncbi.nlm.nih.gov/pubmed/22396224" target="_blank">CRD42011001349</a>).</p></div

The results of sensitivity analyses for Analysis I with cluster-robust variance estimation (Analysis III).

<p>The results of sensitivity analyses for Analysis I with cluster-robust variance estimation (Analysis III).</p

Forest plot of “qualitative impairment in social interaction” (Analysis I).

<p>Forest plot of “qualitative impairment in social interaction” (Analysis I).</p

Forest plot of “initiating joint attention” (Analysis I).

<p>Forest plot of “initiating joint attention” (Analysis I).</p