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The evolution of cancer genomic medicine in Japan and the role of the National Cancer Center Japan

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Cancer Biology & Medicine 2024年第1期21卷 29-44页

作者： Teruhiko Yoshida Yasushi Yatabe Ken Kato Genichiro Ishii Akinobu Hamada Hiroyuki Mano Kuniko Sunami Noboru Yamamoto takashi Kohno Department of Genetic Medicine and Services National Cancer Center HospitalTokyo 104-0045Japan Department of Diagnostic Pathology National Cancer Center HospitalTokyo 104-0045Japan Clinical Research Support Offce Clinical Research Coordinating SectionBiobank Translational Research Support SectionNational Cancer Center HospitalTokyo 104-0045Japan Department of Pathology and Clinical Laboratories National Cancer Center Hospital EastChiba 277-8577Japan Division of Molecular Pharmacology National Cancer Center Research InstituteTokyo 104-0045Japan National Cancer Center Research Institute Tokyo 104-0045Japan Department of Laboratory Medicine National Cancer Center HospitalTokyo 104-0045Japan Department of Experimental Therapeutics National Cancer Center HospitalTokyo 104-0045Japan Division of Genome Biology National Cancer Center Research InstituteTokyo 104-0045Japan

The journey to implement cancer genomic medicine(CGM)in oncology practice began in the 1980s,which is considered the dawn of genetic and genomic cancer *** the time,a variety of activating oncogenic alterations and their functional significance were unveiled in cancer cells,which led to the development of molecular targeted therapies in the 2000s and *** CGM is still a relatively new discipline and it is difficult to predict to what extent CGM will benefit the diverse pool of cancer patients,the National Cancer Center(NCC)of Japan has already contributed considerably to CGM advancement for the conquest of *** back at these past achievements of the NCC,we predict that the future of CGM will involve the following:1)A biobank of paired cancerous and non-cancerous tissues and cells from various cancer types and stages will be *** quantity and quality of these samples will be compatible with omics *** biobank samples will be linked to longitudinal clinical information.2)New technologies,such as whole-genome sequencing and artificial intelligence,will be introduced and new bioresources for functional and pharmacologic analyses(e.g.,a patient-derived xenograft library)will be systematically deployed.3)Fast and bidirectional translational research(bench-to-bedside and bedside-to-bench)performed by basic researchers and clinical investigators,preferably working alongside each other at the same institution,will be implemented;4)Close collaborations between academia,industry,regulatory bodies,and funding agencies will be established.5)There will be an investment in the other branch of CGM,personalized preventive medicine,based on the individual's genetic predisposition to cancer.

关键词： Cancer genomic medicine biobank patient-derived xenograft multi-gene panel test whole genome sequencing

Inverse relationship between platelet Akt activity and hippocampal atrophy:A pilot case-control study in patients with diabetes mellitus

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World Journal of Clinical Cases 2024年第2期12卷 302-313页

作者： Haruhiko Tokuda Takamitsu Hori Daisuke Mizutani Tomoyuki Hioki Kumi Kojima takashi Onuma Yukiko Enomoto Tomoaki Doi Rie Matsushima-Nishiwaki Shinji Ogura Hiroki Iida Toru Iwama takashi Sakurai Osamu Kozawa Department of Metabolic Research Research InstituteNational Center for Geriatrics and GerontologyObu 474-8511Japan Department of Clinical Laboratory National Center for Geriatrics and GerontologyObu 474-8511Japan Department of Pharmacology Gifu University Graduate School of MedicineGifu 501-1194Japan Department of Neurosurgery Gifu University Graduate School of MedicineGifu 501-1194Japan Department of Dermatology Central Japan International Medical CenterMinokamo 505-8510Japan Department of Anesthesiology and Pain Medicine Gifu University Graduate School of MedicineGifu 501-1194Japan Department of Emergency Medicine Faculty of MedicineUniversity of ToyamaToyama 930-0194Japan Department of Emergency and Disaster Medicine Gifu University Graduate School of MedicineGifu 501-1194Japan Research Institute National Center for Geriatrics and GerontologyObu 474-8511Japan

BACKGROUND Akt plays diverse roles in *** is involved in the pathogenesis of type 2 diabetes mellitus(T2DM),which is caused by insulin *** also plays a vital role in human platelet ***,the hippocampus is closely associated with memory and learning,and a decrease in hippocampal volume is reportedly associated with an insulin-resistant phenotype in T2DM patients without *** To investigate the relationship between Akt phosphorylation in unstimulated platelets and the hippocampal volume in T2DM *** Platelet-rich plasma(PRP)was prepared from the venous blood of patients with T2DM or age-matched *** pellet lysate of the centrifuged PRP was subjected to western blotting to analyse the phosphorylation of Akt,p38 mitogen-activated protein(MAP)kinase and glyceraldehyde 3-phosphate dehydrogenase(GAPDH).Phosphorylation levels were quantified by densitometric *** volume was analysed using a voxel-based specific regional analysis system for Alzheimer’s disease on magnetic resonance imaging,which proposes the Z-score as a parameter that reflects hippocampal *** The levels of phosphorylated Akt corrected with phosphorylated p38 MAP kinase were inversely correlated with the Z-scores in the T2DM subjects,whereas the levels of phosphorylated Akt corrected with GAPDH were ***,this relationship was not observed in the control *** These results suggest that an inverse relationship may exist between platelet Akt activation and hippocampal atrophy in T2DM *** findings provide insight into the molecular mechanisms underlying T2DM hippocampal atrophy.

关键词： Akt Platelet Hippocampal atrophy Magnetic resonance imaging Diabetes mellitus

Geomorphological evidence inconvenient for the antecedent rivers of the Arun and Tista across the Himalayan range

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Journal of Mountain Science 2024年第09期 3001-3017页

作者： NAKATA takashi KUMAHARA Yasuhiro NAIK Sambit Prasanajit SAKAI Harutaka Graduate School of Humanities and Social Sciences Hiroshima University Active Fault and Earthquake Hazard Mitigation Research Center Pukyong National University Department of Petroleum Engineering and Earth Sciences University of Petroleum and Energy Studies Graduate School of Science Kyoto University

The Arun and Tista Rivers, which flow across the Himalayas, are commonly known as antecedent valleys that overcame the rapid uplift of the Higher Himalayan ranges. To clarify whether the idea of antecedent rivers is acceptable, we investigated the geomorphology of the Himalayas between eastern Nepal and Bhutan Himalayas. The southern part of Tibetan Plateau, extending across the Himalayas as tectonically un-deformed glaciated terrain named as 'Tibetan Corridor,' does not suggest the regional uplift of the Higher Himalayas. The 8,000-m class mountains of Everest, Makalu, and Kanchenjunga are isolated residual peaks on the glaciated terrain composed of mountain peaks of 4,000–6,000 m high. The Tibetan glaciers commonly beheaded by Himalayan glaciers along the great watershed of the Himalayas suggest the expansion of Himalayan river drainage by glaciation. For the narrow upstream regions of the Arun and Tista Rivers with less precipitation behind the range, it is hard to collect enough water for the power of down-cutting their channels against the uplifting Himalayas. The fission track ages of the Higher Himalayan Crystalline Nappe suggest that the Himalayas attained their present altitude by 11–10 Ma, and the Arun and Tista Rivers formed deep gorges across the Himalayas by headward erosion.

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High-temperature corrosion of sintered RE_(2)Si_(2)O_(7)(RE=Yb and Ho)environmental barrier coating materials by volcanic ash

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International Journal of Minerals,Metallurgy and Materials 2024年第7期31卷 1628-1638页

作者： Ayahisa Okawa Son Thanh Nguyen Tadachika Nakayama Thi-Mai-Dung Do Hisayuki Suematsu Shu Yin Takuya Hasegawa Tsuneo Suzuki takashi Goto Koichi Niihara Institute of Multidisciplinary Research for Advanced Materials Tohoku UniversitySendai 980-8577Japan Department of Creative Engineering National Institute of TechnologyKushiro 084-0916Japan Extreme Energy-Density Research Institute Nagaoka University of TechnologyNagaoka 940-2188Japan Advanced Institute for Materials Research(WPI-AIMR) Tohoku UniversitySendai 980-8577Japan

Rare-earth silicates are promising environmental barrier coatings(EBCs)that can protect SiC_(f)/Si C_(m)substrates in next-genera tion gas turbine ***,RE_(2)Si_(2)O_(7)(RE=Yb and Ho)shows potential as an EBC due to its coefficient of thermal expansion(CTE)compatible with substrates and high resistance to water vapor *** target operating temperature for next-generation tur bine blades is 1400°*** is inevitable during adhesion to molten volcanic ash,and thus,understanding the corrosion behavior o the material is crucial to its *** study investigates the high-temperature corrosion behavior of sintered RE_(2)Si_(2)O_(7)(RE=Yb and Ho).Samples were prepared using a solid-state reaction and hot-press *** were then exposed to volcanic ash at 1400°C for 224,and 48 *** 48 h of exposure,volcanic ash did not react with Yb_(2)Si_(2)O_(7)but penetrated its interior,causing *** Ho_(2)Si_(2)O_(7)was partially dissolved in the molten volcanic ash,forming a reaction zone that prevented volcanic ash melts from penetrating the *** increasing heat treatment time,the reaction zone expanded,and the thickness of the acicular apatite grains increased The Ca:Si ratios in the residual volcanic ash were mostly unchanged for Yb_(2)Si_(2)O_(7)but decreased considerably over time for Ho_(2)Si_(2)O_(7).Th Ca in volcanic ash was consumed and formed apatite,indicating that RE^(3+)ions with large ionic radii(Ho>Yb)easily precipitated apatit from the volcanic ash.

关键词： environmental barrier coating volcanic ash rare-earth disilicate corrosion

Biomass Control via UV Lamp Application and Nutrient Supply Restriction in the Biofiltration of Gaseous VOCs

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Journal of Environmental Science and Engineering(B) 2024年第3期13卷 97-104页

作者： takashi Higuchi Kokoro Hashizume School of Science and Engineering Ritsumeikan University1-1-1 Noji-higashiKusatsuShiga 525-8577Japan Graduate School of Science and Engineering Ritsumeikan University1-1-1 Noji-higashiKusatsuShiga 525-8577Japan

Biofiltration may have clogging problems owing to excess biomass growth during the treatment of gaseous *** this study,we employed an UV(Ultraviolet)lamp and controlled the nutrient supply to conduct a biofiltration process for treating 2-butanone(MEK:Methyl Ethyl Ketone)and toluene in a gas *** methods of UV lamp usage(direct and indirect irradiation)and several nutrient supply methods were ***,no clear effect was observed with either UV *** the optimal conditions,97%of the MEK and 69%of the toluene gases were removed after 29 s of EBRT(Empty Bed Retention Time).The inlet loads were 18 and 19 mg/(m^(3)·h)for MEK and toluene,*** these conditions,23 g-N/(m^(3)·day)of nitrate-nitrogen was *** biomass growth occurred during simultaneous excess nutrient supply and a persistent irrigation *** this study,we demonstrated the effective use of a dense nitrate solution to deliver an appropriate amount of nutrients and moisture,and the optimal irrigation frequency was four times per week.

关键词： Biofiltration gaseous VOCs(Volatile Organic Compounds) nutrient supply UV lamp ozone

Natural history of asymptomatic gallbladder stones in clinic without beds:A long-term prognosis over 10 years

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World Journal of Clinical Cases 2024年第1期12卷 42-50页

作者： Yuji Sakai Toshio Tsuyuguchi Hiroshi Ohyama Junichiro Kumagai takashi Kaiho Masayuki Ohtsuka Naoya Kato Tadao Sakai Department of Gastroenterology Sakai ClinicKimistu 299-1162Japan Department of Gastroenterology Graduate School of MedicineChiba UniversityChiba 260-8677Japan Department of Gastroenterology Chiba Prefectural Sawara HospitalChiba Prefectural Sawara HospitalSawara 287-0003Japan Department of Gastroenterology Kimitsu Central HospitalKisarazu 292-8535Japan Department of Surgery Kimitsu Central HospitalKisarazu 292-8535Japan Department of General Surgery Graduate School of MedicineChiba UniversityChiba 260-8677Japan

BACKGROUND Several studies have explored the long-term prognosis of patients with asymp-tomatic gallbladder *** reports were primarily conducted in facilities equipped with beds for addressing symptomatic *** To report the long-term prognosis of patients with asymptomatic gallbladder stones in clinics without bed *** We investigated the prognoses of 237 patients diagnosed with asymptomatic gallbladder stones in clinics without beds between March 2010 and October *** symptoms developed,patients were transferred to hospitals where appropriate treatment was *** investigated the asymptomatic and survival periods during the *** Among the 237 patients,214(90.3%)remained asymptomatic,with a mean asymptomatic period of 3898.9279±46.871 d(50-4111 d,10.7 years on average).Biliary complications developed in 23 patients(9.7%),with a mean survival period of 4010.0285±31.2788 d(53-4112 d,10.9 years on average).No patient died of biliary *** The long-term prognosis of asymptomatic gallbladder stones in clinics without beds was *** the condition became symptomatic,the patients were transferred to hospitals with beds that could address it;thus,no deaths related to biliary complications were *** finding suggests that follow-up care in clinics without beds is possible.

关键词： Gallbladder stone Acute cholangitis Acute cholecystitis Asymptomatic gallbladder stone Symptomatic gallbladder stone

Radical radiotherapy without surgical tumor resection for rectal cancer

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World Journal of Clinical Oncology 2024年第11期15卷 1390-1393页

作者： takashi Ono Masashi Koto Department of Radiation Oncology Faculty of MedicineYamagata UniversityYamagata 990-9585Japan

In this editorial,I would like to comment on the article,recently published in the World Journal of Clinical *** article focuses on non-surgical treatments for locally recurrent rectal cancer,including the watch-and-wait(WW)strategy after total neoadjuvant therapy(TNT)and particle beam *** treatment options for rectal cancer continue to evolve,the high complete response rate achieved with TNT has led to the development of a new non-surgical approach:*** followed by consolidation chemotherapy,in particular,has a low rate of tumor growth and is a treatment aimed at achieving a cure without ***,the risk of recurrence within two years is significant,necessitating careful *** standardized follow-up methods that can be implemented by many physicians is *** ion radiotherapy has demonstrated high local control with a low incidence of severe late toxicities,even after previous pelvic *** these new non-surgical curative treatments for rectal cancer require further investigation,future advancements in this field are anticipated.

关键词： Rectal cancer Locally recurrent rectal cancer Total neoadjuvant therapy Watch-and-wait Carbon ion radiotherapy Proton beam therapy

Evaluation of bacterial contamination and medium-term oncological outcomes of intracorporeal anastomosis for colon cancer:A propensity score matching analysis

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World Journal of Gastrointestinal Surgery 2024年第3期16卷 670-680页

作者： Hajime Kayano Nana Mamuro Yutaro Kamei takashi Ogimi Hiroshi Miyakita Toshio Nakagohri Kazuo Koyanagi Masaki Mori Seiichiro Yamamoto Department of Gastroenterological Surgery Tokai University School of MedicineIsehara 259-1193KanagawaJapan

BACKGROUND Although intracorporeal anastomosis(IA)for colon cancer requires longer operative time than extracorporeal anastomosis(EA),its short-term postoperative results,such as early recovery of bowel movement,have been reported to be equal or *** IA requires opening the intestinal tract in the abdominal cavity under pneumoperitoneum,there are concerns about intraperitoneal bacterial infection and recurrence of peritoneal dissemination due to the spread of bacteria and tumor ***,intraperitoneal bacterial contamination and medium-term oncological outcomes have not been *** cavity in *** Of 127 patients who underwent laparoscopic colon resection for colon cancer from April 2015 to December 2020,75 underwent EA(EA group),and 52 underwent IA(IA group).After propensity score matching,the primary endpoint was 3-year disease-free survival rates,and secondary endpoints were 3-year overall survival rates,type of recurrence,surgical site infection(SSI)incidence,number of days on antibiotics,and postoperative biological *** Three-year disease-free survival rates did not significantly differ between the IA and EA groups(87.2%and 82.7%,respectively,P=0.4473).The 3-year overall survival rates also did not significantly differ between the IA and EA groups(94.7%and 94.7%,respectively;P=0.9891).There was no difference in the type of recurrence between the two *** addition,there were no significant differences in SSI incidence or the number of days on antibiotics;however,postoperative biological responses,such as the white blood cell count(10200 vs 8650/mm^(3),P=0.0068),C-reactive protein(6.8 vs 4.5 mg/dL,P=0.0011),and body temperature(37.7 vs 37.5℃,P=0.0079),were significantly higher in the IA *** IA is an anastomotic technique that should be widely performed because its risk of intraperitoneal bacterial contamination and medium-term oncological outcomes are comparable to those of EA.

关键词： Colon cancer Intracorporeal anastomosis 3-year disease-free survival Recurrence Surgical site infection Postoperative biological response

Proposal of a Method to Easily Understand Rainfall Infiltration in Railway Embankments

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Journal of Civil Engineering and Architecture 2024年第6期18卷 261-268页

作者： takashi Nakayama Tadashi Hara Keigo Koizumi C.S.Inspector Co. Ltd.2-7-2 Nambanaka Naniwa-Ku Osaka-ShiOsaka-Fu 556-0011Japan Research and Education Faculty Kochi University2-5-1 Akebonocho Kochi-ShiKochi-Ken 780-8072Japan Earth Watch Institute Inc.8-10 Toyotsucho Suita-ShiOsaka-Fu 564-0051Japan

Slope failures due to heavy or prolonged rain have been occurring frequently in Japan in recent *** railway embankments,even small-scale surface collapse can result in track ***,train operation during rainy periods is regulated according to empirical rules based on rainfall and disaster ***,the validity of operation regulations is lacking because the rainfall infiltration circumstances inside the slope are *** have been attempting to understand rainfall infiltration in railway embankments by applying a method of predicting surface collapse from observations of volumetric water content in the *** used previous field monitoring and model experiments to propose a method for easily understanding the state of rainfall infiltration in the surface layer of an embankment using the relative history of volumetric water content at different *** this study,we applied this simple determination method to railway embankments with different topography and geological environments to demonstrate the versatility of the method.

关键词： Railway embankments field monitoring volumetric water content