神経芽腫におけるPD-L1発現と腫瘍組織浸潤リンパ球の潜在的役割について

Purpose: The programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway has garnered much attention for its roles in clinical oncology. The aim of this study was to examine the clinical impact of the PD-L1 expression and tumor-infiltrating lymphocytes (TILs) on neuroblastoma. Methods: We evaluated the PD-L1 expression and TIL status in 31 patients with neuroblastoma who underwent a biopsy or resection by an immunohistochemical analysis. Furthermore, we performed the serial analysis of the PD-L1 status before and after chemotherapy in 15 patients. Results: Among the 31 cases, 11 (35%) showed a positive PD-L1 expression. The survival analysis showed a trend toward an association between PD-L1 positivity and a decreased overall survival. PD-L1 positivity tended to be associated with higher levels of tumor markers. In the serial analysis of the PD-L1 status, positivity was noted in 8 of 15 patients before chemotherapy and 6 after chemotherapy. Notably, all four patients with a positive PD-L1 status both before and after chemotherapy had recurrence, and 3 of them died during the follow-up period. Conclusion: Our findings suggest that the PD-L1 tumor expression might be a good biomarker for the treatment of neuroblastoma patients, especially for advanced neuroblastoma.博士（医学）・乙第1458号・令和2年6月30日© Springer-Verlag GmbH Germany, part of Springer Nature 2020This is a post-peer-review, pre-copyedit version of an article published in Pediatric surgery international. The final authenticated version is available online at: http://doi.org/10.1007/s00383-019-04616-9

Cost Performance and Efficacy of Off-pump Coronary Artery Bypass Grafting

Off-pump coronary artery bypass grafting (Off-Pump CABG) may provide an alternative form of surgical revascularization by avoiding the unwanted complications of cardiopulmonary bypass, particularly in high-risk patients. To clarify the efficacy and cost performance of Off- Pump CABG, we studied the postoperative course of Off-Pump CABG and compared it to On- pump coronary artery bypass grafting (On-Pump CABG). From Aug. 1998 to Feb. 2002, twenty-eight patients who had preoperative complications such as cerebral vascular disease (11), chronic renal failure (4), atheromatous aorta (4), one lung (1), severely impaired left ventricular function (6), re-do CABG (1), and cancer (1) underwent Off- Pump CABG. Another thirty-six patients who underwent On-Pump CABG served as a control. The Off-Pump CABG patients were almost the same age as the On-Pump CABG patients (68 ± 8 vs 64 ± 8 years, ns). The Number of grafts was similar in both groups (2.6 ± 1.0 vs 2.9 ± 1.0, ns). Peak CK, peak CKMB, peak LDH, and peak GOT release were significantly lower in the Off-Pump CABG group compared with the On-Pump CABG group. Graft patency rates were similar in both groups (98 0n Off-Pump CABG vs 98 0n On-Pump CABG). The total cost for surgery and patient care was significantly lower (p<0.0001) in the Off-Pump CABG group ($21000 ± 7000) compared with the On-Pump CABG group ($ 33000 ± 4200). Off-Pump CABG is less invasive to the myocardium, is less expensive, and has a similar efficacy in comparison with On-Pump CABG

Application of First-Principles-Based Artificial Neural Network Potentials to Multiscale-Shock Dynamics Simulations on Solid Materials

The use of artificial neural network (ANN) potentials trained with first-principles calculations has emerged as a promising approach for molecular dynamics (MD) simulations encompassing large space and time scales while retaining first-principles accuracy. To date, however, the application of ANN-MD has been limited to near-equilibrium processes. Here we combine first-principles-trained ANN-MD with multiscale shock theory (MSST) to successfully describe far-from-equilibrium shock phenomena. Our ANN-MSST-MD approach describes shock-wave propagation in solids with first-principles accuracy but a 5000 times shorter computing time. Accordingly, ANN-MD-MSST was able to resolve fine, long-time elastic deformation at low shock speed, which was impossible with first-principles MD because of the high computational cost. This work thus lays a foundation of ANN-MD simulation to study a wide range of far-from-equilibrium processes

ネパール デタールムラ ジュウミン ノ ケンコウ チョウサ ト シシュウ シッカン リカン ジョウキョウ ナラビニ シシュウビョウゲンサイキン ニ カンスル チョウサ

ネパール中央部カスキ郡・デタール村住民の生活習慣を含めた健康調査、歯科検診、歯周病原細菌に関して 調査し、以下の結果を得た。 １．う蝕罹患状況・未処置かつ重症化したう蝕歯をもつ者が多い。一人平均う蝕本数が加齢とともに増加していた。う蝕処置 をしている者が少なく、抜去している歯が多かった。 ２．歯周疾患罹患状況・歯周組織検査ではCPI：0（健全）の者はどの年代でも少なく、加齢に伴い重症化していた。・喫煙者と非喫煙者の比較では、CPI値が喫煙者の方が高く、喫煙と歯周病の関連性が示唆された。・ブラッシングの回数は2回者が最も多く、回数が多い者ほどCPI値は低値を示した。 ３．唾液潜血反応検査と歯周病原細菌検査・唾液潜血反応陽性者は95％だった。また、ブラッシング時出血自覚症状の有無と唾液潜血反応の結果は、ほぼ一致した。・歯肉に炎症ある者にPorphyromonas gingivalis （ Pg 菌）に対する血漿抗体価陽性の傾向が認められ、唾液潜血反応結果では潜血反応陽性者の Pg 菌に対する血漿抗体価は陰性の傾向が認められた。このことから、この地域の歯周病罹患率ならびにう蝕罹患率は高く、重症化していることが示唆された。A health check including an interview about life habits, dental checkup and investigation of periodontopathic bacteria of periodontal disease among the residents of Dhital village, Kaski District,Nepal was conducted. The results are as follows: １．Prevalence of dental caries・There were many residents who had serious tooth decay resulting from lerving it untreated.The average number of tooth decay has increased with aging.There were not many people who treated their tooth decay,and many of their teeth were extracted. ２．Prevalence of periodontal disease・The survey of periodontal tissue showed that there were only a few people with CPI:0（healthy periodontal tissue）in every generation,and prevalence rate was rising with aging.・The comparison between smokers and non-smokers showed that the average CPI values of　smokers were higher than that of non-smokers, and it suggested a correlation between smoking and progression of periodontal disease.・There were a large number of people who brushed their teeth twice a day. The more examination they brushed their teeth, the lower the value of average CPI became. ３．Salivary occult blood test and periodontopathic bacteria test・Positive persons of occdlt blood examination were 95%. The presence of the subjective symptom with respect to bleeding during brushing teeth almost agreed with the result of the salivary occult blood test.・A positive trend for plasma antibody value against Porphyromonas gingivalis was found among the people with gingival inflammation. As a result of reaction against salivary occult blood, there was a negative trend for the plasma antibody value against Porphyromonas gingivalis . From there results,it was suggested that among people living in thie district, prevalence of both periodontal disease and tooth decay were high,and their conditions were serious

Clinical Significance of Propionibacterium acnes in the Formation of Noncaseating Epithelioid-Cell Granulomas of the Mediastinal Lymph Nodes and Lung in Patients with Lung Cancer:Differential Diagnosis Between Sarcoid Reactions and Sarcoidosis

Objectives:Sarcoidosis is a systemic noncaseating epithelioid-cell granulomatous disease of unknown origin.Granulomas occurring around malignant tumors and regional lymph nodes can be caused by sarcoid reactions.The mechanisms underlying sarcoidosis and sarcoid reactions remain unclear. Whether increaseduptake of fluorodeoxyglucose( FDG) in lymph nodes on positron emission tomography( PET) is caused bytumor metastasis, the concurrent presence of sarcoidosis, or sarcoid reactions must be determined to ensureproper disease staging and selection of treatment policy. We studied patients who underwent surgery forlung cancer and had no histopathological evidence of lymph-node metastasis in whom concurrent sarcoidosisor sarcoid reactions were diagnosed.Methods:In six patients who underwent surgery for primary lung cancer, granulomatous lesions werehistopathologically studied in dissected lymph nodes and lung. Tissue sections were stained with monoclonalantibodies against Propionibacterium acnes( PAB antibodies).Results:The six patients had noncaseating epithelioid-cell granulomas in mediastinal lymph nodes andlung. Clinically, concurrent sarcoidosis was suspected, but the results of staining the tissue specimens withPAB antibodies( in granulomas, alveolar macrophages, Hamazaki-Wesenberg bodies, and lymphatic sinuses)suggested sarcoid reactions in 5 patients. In one patient in whom granulomas stained positive with PAB antibodies,concurrent sarcoidosis was diagnosed.Conclusions:In patients with lung cancer who have no distinct systemic evidence of sarcoidosis, thepresence of noncaseating epithelioid-cell granulomas in the lung hilum or mediastinum is usually caused bysarcoid reactions

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Biases in Understanding Attention Deficit Hyperactivity Disorder and Autism Spectrum Disorder in Japan

Recent research has shown high rates of comorbidity between attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) and difficulties regarding differential diagnosis. Unlike those in Western countries, the Japanese ADHD prevalence rate is lower relative to that of ASD. This inconsistency could have occurred because of cultural diversities among professionals such as physicians. However, little is known about attitudes toward ADHD and ASD in non-Western cultural contexts. We conducted two experiments to identify biases in ASD and ADHD assessment. In Study 1, we examined attitudes toward these disorders in medical doctors and mental health professionals, using a web-based questionnaire. In Study 2, medical doctors and clinical psychologists assessed four fictional cases based on criteria for ADHD, ASD, oppositional defiant disorder, and disinhibited social engagement disorder (DSED). Diagnosis of ASD was considered more difficult relative to that of ADHD. Most participants assessed the fictional DSED case as ASD, rather than DSED or ADHD. The results provide evidence that Japanese professionals are more likely to attribute children’s behavioral problems to ASD, relative to other disorders. Therefore, Japanese therapists could be more sensitive to and likely to diagnose ASD, relative to therapists in other countries. These findings suggest that cultural biases could influence clinicians’ diagnosis of ADHD and ASD