Health improvement framework for actionable treatment planning using a surrogate Bayesian model

効果的な健康改善プランを提案するAIを開発 --個別化医療における健康介入への活用に期待--. 京都大学プレスリリース. 2021-05-28.Clinical decision-making regarding treatments based on personal characteristics leads to effective health improvements. Machine learning (ML) has been the primary concern of diagnosis support according to comprehensive patient information. A prominent issue is the development of objective treatment processes in clinical situations. This study proposes a framework to plan treatment processes in a data-driven manner. A key point of the framework is the evaluation of the actionability for personal health improvements by using a surrogate Bayesian model in addition to a high-performance nonlinear ML model. We first evaluate the framework from the viewpoint of its methodology using a synthetic dataset. Subsequently, the framework is applied to an actual health checkup dataset comprising data from 3132 participants, to lower systolic blood pressure and risk of chronic kidney disease at the individual level. We confirm that the computed treatment processes are actionable and consistent with clinical knowledge for improving these values. We also show that the improvement processes presented by the framework can be clinically informative. These results demonstrate that our framework can contribute toward decision-making in the medical field, providing clinicians with deeper insights

Assessing impacts of coastal warming, acidification, and deoxygenation on Pacific oyster (Crassostrea gigas) farming: a case study in the Hinase area, Okayama Prefecture, and Shizugawa Bay, Miyagi Prefecture, Japan

Coastal warming, acidification, and deoxygenation are progressing primarily due to the increase in anthropogenic CO2. Coastal acidification has been reported to have effects that are anticipated to become more severe as acidification progresses, including inhibiting the formation of shells of calcifying organisms such as shellfish, which include Pacific oysters (Crassostrea gigas), one of the most important aquaculture resources in Japan. Moreover, there is concern regarding the combined impacts of coastal warming, acidification, and deoxygenation on Pacific oysters. However, spatiotemporal variations in acidification and deoxygenation indicators such as pH, the aragonite saturation state (Ωarag), and dissolved oxygen have not been observed and projected in oceanic Pacific oyster farms in Japan. To assess the present impacts and project future impacts of coastal warming, acidification, and deoxygenation on Pacific oysters, we performed continuous in situ monitoring, numerical modeling, and microscopic examination of Pacific oyster larvae in the Hinase area of Okayama Prefecture and Shizugawa Bay in Miyagi Prefecture, Japan, both of which are famous for their Pacific oyster farms. Our monitoring results first found Ωarag values lower than the critical level of acidification for Pacific oyster larvae in Hinase, although no impact of acidification on larvae was identified by microscopic examination. Our modeling results suggest that Pacific oyster larvae are anticipated to be affected more seriously by the combined impacts of coastal warming and acidification, with lower pH and Ωarag values and a prolonged spawning period, which may shorten the oyster shipping period and lower the quality of oysters.</p

Intranasal immunization with an RBD-hemagglutinin fusion protein harnesses preexisting immunity to enhance antigen-specific responses

Kawai A., Tokunoh N., Kawahara E., et al. Intranasal immunization with an RBD-hemagglutinin fusion protein harnesses preexisting immunity to enhance antigen-specific responses. Journal of Clinical Investigation 133, e166827 (2023); https://doi.org/10.1172/JCI166827.Intranasal vaccines are anticipated to be powerful tools for combating many infectious diseases, including SARS-CoV-2, because they induce not only systemic immunity but also mucosal immunity at the site of initial infection. However, they are generally inefficient in inducing an antigen-specific immune response without adjuvants. Here, we developed an adjuvant-free intranasal vaccine platform that utilizes the preexisting immunity induced by previous infection or vaccination to enhance vaccine effectiveness. We made RBD-HA, a fusion of the receptor-binding domain (RBD) of spike derived from SARS-CoV-2 as a vaccine target with HA derived from influenza A virus (IAV) as a carrier protein. Intranasal immunization of previously IAV-infected mice with RBD-HA without an adjuvant elicited robust production of RBD-specific systemic IgG and mucosal IgA by utilizing both HA-specific preexisting IgG and CD4+ T cells. Consequently, the mice were efficiently protected from SARS-CoV-2 infection. Additionally, we demonstrated the high versatility of this intranasal vaccine platform by assessing various vaccine antigens and preexisting immunity associated with a variety of infectious diseases. The results of this study suggest the promising potential of this intranasal vaccine platform to address problems associated with intranasal vaccines

開腹術患者の体温変化が回復過程に与える影響(第二報) : 術後の体温推移と身体的・精神的諸問題について

開腹術患者の術後の体温変化とそれに関連した身体的・精神的問題を検討する目的で,20歳以上・全身麻酔・仰臥位で消化器系の開腹術を受けた74名を対象として,帰室時から約21時間後までの体温変化と手術関連情報,術後経過を解析した.また術前体温(BT_1)と帰室時体温(BT_2)を比較しΔBT(BT_2-BT_1)<0となった群を体温低下群(n=34),ΔBT≧0の群を体温非低下群(n=40)として検討し以下の結果を得た.1)低下群(34名中18名)は非低下群(40名中12名)に比べ有意に不眠の訴えが多く(p<0.05),シバリングなど術後の体温低下に伴う症状が多く出現しており,術中の体温低下が術後にも影響を及ぼす示唆が得られた.2)低下群・非低下群ともに帰室後37.8℃前後まで上昇するが,低下群では術後の体温変動も大きく,不眠やシバリングなどの症状発現を予測した対応および経過観察が必要である.To examine postoperative body temperature (BT) alterations and relevant physical and mental complications, postoperative records of BT and clinical courses until approximately 21 hours after surgery were retrospectively analyzed. Study subjects were 74 patients aged over 20 undergoing laparotomy under general anesthesia due to gastrointestinal disease in a spine position. Patients were divided into the following two groups according to the difference between preoperative BT (BT 1) and BT at the return to the ward (BT_2) : Group 1 ; BT decreased group (n=34) defined as ΔBT(BT_2-BT_1)<0, Group 2 ; BT not-decreased group (n=40) defined as ΔBT≧O. Results : 1) Insomnia was found more often in Group 1 (18 of 34 patients) than in Group 2 (12 of 40 patients) (p<0.05). Shivering was also recorded more often in Group I. These results suggest that intraoperative BT decrease may affect postoperative courses and BT alterations. 2) Most patients of both groups experienced rises in BT up to around 37.8 degree, but the range of postoperative BT changes was larger in Group 1. Postoperative courses in patients of Group 1 should be observed more carefully because these patients may often suffer from insomnia and shivering

開腹術患者の体温変化が回復過程に与える影響(第一報) : 術中の体温推移と帰室時体温の関連について

開腹術患者の術中・帰室時の体温変化と関連要因を明らかにする目的で,20歳以上・全身麻酔・仰臥位で消化器系の開腹術を受けた74名を対象として,術前・術中・帰室時の体温変化と基本属性,手術関連情報を解析した.また術前体温(BT_1)と帰室時体温(BT_2)を比較し,ΔBT(BT_2-BT_1)<0となった群を体温低下群(n=34),ΔBT≧0の群を体温非低下群(n=40)として検討し以下の結果を得た.1.体温非低下群で体表面積,肥満度,手術時間(234±82 vs 179±73分)が有意に高値であった(p<0.01).2.重回帰分析では体表面積借と手術時間がΔBT値に有意に影響する因子(p<0.01)であった.3.手術開始1時間の体温がBT_1より低値の場合,概ね術中,帰室時も体温が低く経過した.体表面積が小さく手術時間が短い患者は帰室時低体温の傾向が強く,手術開始1時間後の体温がその予測指標になると思われる.A retrospective analysis was made to determine clinical factors influencing perioperative body temperature alterations in patients undergoing laparotomy. Demographic data, body temperature (BT) before, during, and after surgery were collected from medical records of 74 patients aged over 20 undergoing laparotomy under general anesthesia due to gastrointestinal disease in a spine position. Patients were divided into the following two groups according to the difference between preoperative BT (BT_1) and BT at the return to the ward (BT_2) : Group 1 ; BT decreased group (n=34) defined as ΔBT(BT_2-BT_1)<0, Group 2 ; BT not-decreased group (n=40) defined as ΔBT≧0. Results : 1) Body Surface Area, Body Mass Index, operative time were significantly higher in Group 1 than those in Group 2. 2) Multi-regression analysis indicated Body Surface Area and operative time as significant factors influencingΔBT. When BT at 60 minutes after the start of surgery was decreased compared to BT 1, intraoperative and BT 2 were also decreased compared to BT 1 in most cases. Patients with low Body Surface Area and shorter operative time have tendency to suffer lower BT at the end of surgery, which may be predicted by the BT at 60 minutes after the start of surgery

Proton beam therapy for bone sarcomas of the skull base and spine: A retrospective nationwide multicenter study in Japan

We conducted a retrospective, nationwide multicenter study to evaluate the clinical outcomes of proton beam therapy for bone sarcomas of the skull base and spine in Japan. Eligibility criteria included: (i) histologically proven bone sarcomas of the skull base or spine; (ii) no metastases; (iii) ≥20 years of age; and (iv) no prior treatment with radiotherapy. Of the 103 patients treated between January 2004 and January 2012, we retrospectively analyzed data from 96 patients who were followed-up for >6 months or had died within 6 months. Seventy-two patients (75.0%) had chordoma, 20 patients (20.8%) had chondrosarcoma, and four patients (7.2%) had osteosarcoma. The most frequent tumor locations included the skull base in 68 patients (70.8%) and the sacral spine in 13 patients (13.5%). Patients received a median total dose of 70.0 Gy (relative biological effectiveness). The median follow-up was 52.6 (range, 6.3–131.9) months. The 5-year overall survival, progression-free survival, and local control rates were 75.3%, 49.6%, and 71.1%, respectively. Performance status was a significant factor for overall survival and progression-free survival, whilst sex was a significant factor for local control. Acute Grade 3 and late toxicities of ≥Grade 3 were observed in nine patients (9.4%) each (late Grade 4 toxicities [n = 3 patients; 3.1%]). No treatment-related deaths occurred. Proton beam therapy is safe and effective for the treatment of bone sarcomas of the skull base and spine in Japan. However, larger prospective studies with a longer follow-up are warranted

SARS-CoV-2 disrupts respiratory vascular barriers by suppressing Claudin-5 expression

臓器チップ技術を用いて新型コロナウイルスが血管へ侵入するメカニズムを解明 --Claudin-5発現抑制による呼吸器の血管内皮バリア破壊--. 京都大学プレスリリース. 2022-09-22.A study using an organ-on-a-chip reveals a mechanism of SARS-CoV-2 invasion into blood vessels --Disruption of vascular endothelial barrier in respiratory organs by decreasing Claudin-5 expression--. 京都大学プレスリリース. 2022-09-27.In the initial process of coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects respiratory epithelial cells and then transfers to other organs the blood vessels. It is believed that SARS-CoV-2 can pass the vascular wall by altering the endothelial barrier using an unknown mechanism. In this study, we investigated the effect of SARS-CoV-2 on the endothelial barrier using an airway-on-a-chip that mimics respiratory organs and found that SARS-CoV-2 produced from infected epithelial cells disrupts the barrier by decreasing Claudin-5 (CLDN5), a tight junction protein, and disrupting vascular endothelial cadherin–mediated adherens junctions. Consistently, the gene and protein expression levels of CLDN5 in the lungs of a patient with COVID-19 were decreased. CLDN5 overexpression or Fluvastatin treatment rescued the SARS-CoV-2–induced respiratory endothelial barrier disruption. We concluded that the down-regulation of CLDN5 expression is a pivotal mechanism for SARS-CoV-2–induced endothelial barrier disruption in respiratory organs and that inducing CLDN5 expression is a therapeutic strategy against COVID-19