Spatiotemporal Dipole Imaging of Brain Electrical Activity

Abstract. Cortical dipole imaging technique, which attempts to estimate the cortical dipole distribution from the scalp potentials, is one of the spatial enhancement techniques. In this approach, an equivalent dipole source layer is used to model brain electrical activity and has been shown to provide enhanced performance in imaging brain electrical sources as compared with the smeared scalp-recorded EEG. We explore suitable spatiotemporal filters for inverse estimation of an equivalent cortical dipole-layer distribution from the scalp potentials for imaging of brain electric sources. We have developed the parametric projection filter (PPF) based cortical imaging technique, which allows estimating cortical dipole layer inverse solutions in the presence of noise covariance. We have expanded the PPF to the time-varying filter in order to handle the spatiotemporally varying nature of brain electrical activity. Concretely, the noise covariance and the regularization parameter of the PPF are supposed to be timevariant in order to eliminate the influence of the background noise and eyes blink artifact. The present simulation results indicate that the estimation error is reduced substantially by taking the spatiotemporal properties of the noise into consideration, such as eyes blink artifacts and the proposed timevariant PPF method provides enhanced performance in rejecting time-varying noise

Nectin-2 is a potential target for antibody therapy of breast and ovarian cancers

BACKGROUND: Nectin-2 is a Ca(2+)-independent cell-cell adhesion molecule that is one of the plasma membrane components of adherens junctions. However, little has been reported about the involvement of Nectin-2 in cancer. METHODS: To determine the expression of Nectin-2 in cancer tissues and cancer cell lines, we performed gene expression profile analysis, immunohistochemistry studies, and flow cytometry analysis. We also investigated the potential of this molecule as a target for antibody therapeutics to treat cancers by generating and characterizing an anti-Nectin-2 rabbit polyclonal antibody (poAb) and 256 fully human anti-Nectin-2 monoclonal antibodies (mAbs). In addition, we tested anti-Nectin-2 mAbs in several in vivo tumor growth inhibition models to investigate the primary mechanisms of action of the mAbs. RESULTS: In the present study, we found that Nectin-2 was over-expressed in clinical breast and ovarian cancer tissues by using gene expression profile analysis and immunohistochemistry studies. Nectin-2 was over-expressed in various cancer cell lines as well. Furthermore, the polyclonal antibody specific to Nectin-2 suppressed the in vitro proliferation of OV-90 ovarian cancer cells, which express endogenous Nectin-2 on the cell surface. The anti-Nectin-2 mAbs we generated were classified into 7 epitope bins. The anti-Nectin-2 mAbs demonstrated antibody-dependent cellular cytotoxicity (ADCC) and epitope bin-dependent features such as the inhibition of Nectin-2-Nectin-2 interaction, Nectin-2-Nectin-3 interaction, and in vitro cancer cell proliferation. A representative anti-Nectin-2 mAb in epitope bin VII, Y-443, showed anti-tumor effects against OV-90 cells and MDA-MB-231 breast cancer cells in mouse therapeutic models, and its main mechanism of action appeared to be ADCC. CONCLUSIONS: We observed the over-expression of Nectin-2 in breast and ovarian cancers and anti-tumor activity of anti-Nectin-2 mAbs via strong ADCC. These findings suggest that Nectin-2 is a potential target for antibody therapy against breast and ovarian cancers

Living donor liver transplantation using sensitized lymphocytotoxic crossmatch positive graft

We describe a successful living donor liver transplantation (LDLT) using a lymphocytotoxic crossmatch highly positive graft. A 41-year-old woman with alcoholic liver cirrhosis was referred as a potential candidate for LDLT, and her husband was willing to donate his partial liver. As the T-lymphocytotoxic crossmatch titer was over 10,000×, the patient was first infused with rituximab for preoperative desensitization, and then five rounds of plasmapheresis were performed. After the third plasmapheresis, the lymphocytotoxic crossmatch test was negative. A left liver graft including the caudate lobe was implanted, and anti-CD25 antibody (basiliximab) was administered on postoperative days 1 and 4. The postoperative course was uneventful except for an episode of mild acute cellular rejection on postoperative day 27. Although the impact of a lymphocytotoxic crossmatch-positive liver graft on acute cellular rejection and graft survival in LDLT remains controversial, perioperative desensitization may provide benefits when using a highly sensitized liver graft

Risk-adjusted therapy for pediatric non-T cell ALL improves outcomes for standard risk patients: results of JACLS ALL-02

This study was a second multicenter trial on childhood ALL by the Japan Childhood Leukemia Study Group (JACLS) to improve outcomes in non-T ALL. Between April 2002 and March 2008, 1138 children with non-T ALL were enrolled in the JACLS ALL-02 trial. Patients were stratified into three groups using age, white blood cell count, unfavorable genetic abnormalities, and treatment response: standard risk (SR), high risk (HR), and extremely high risk (ER). Prophylactic cranial radiation therapy (PCRT) was abolished except for CNS leukemia. Four-year event-free survival (4yr-EFS) and 4-year overall survival (4yr-OS) rates for all patients were 85.4% ± 1.1% and 91.2% ± 0.9%, respectively. Risk-adjusted therapy resulted in 4yr-EFS rates of 90.4% ± 1.4% for SR, 84.9% ± 1.6% for HR, and 66.5% ± 4.0% for ER. Based on NCI risk classification, 4yr-EFS rates were 88.2% in NCI-SR and 76.4% in NCI-HR patients, respectively. Compared to previous trial ALL-97, 4yr-EFS of NCI-SR patients was significantly improved (88.2% vs 81.2%, log rank p = 0.0004). The 4-year cumulative incidence of isolated (0.9%) and total (1.5%) CNS relapse were significantly lower than those reported previously. In conclusion, improved EFS in NCI-SR patients and abolish of PCRT was achieved in ALL-02

Generation of kidney tubular organoids from human pluripotent stem cells

Recent advances in stem cell research have resulted in methods to generate kidney organoids from human pluripotent stem cells (hPSCs), which contain cells of multiple lineages including nephron epithelial cells. Methods to purify specific types of cells from differentiated hPSCs, however, have not been established well. For bioengineering, cell transplantation, and disease modeling, it would be useful to establish those methods to obtain pure populations of specific types of kidney cells. Here, we report a simple two-step differentiation protocol to generate kidney tubular organoids from hPSCs with direct purification of KSP (kidney specific protein)-positive cells using anti-KSP antibody. We first differentiated hPSCs into mesoderm cells using a glycogen synthase kinase-3β inhibitor for 3 days, then cultured cells in renal epithelial growth medium to induce KSP+ cells. We purified KSP+ cells using flow cytometry with anti-KSP antibody, which exhibited characteristics of all segments of kidney tubular cells and cultured KSP+ cells in 3D Matrigel, which formed tubular organoids in vitro. The formation of tubular organoids by KSP+ cells induced the acquisition of functional kidney tubules. KSP+ cells also allowed for the generation of chimeric kidney cultures in which human cells self-assembled into 3D tubular structures in combination with mouse embryonic kidney cells

Enhancing evidence-informed policymaking in medicine and healthcare: stakeholder involvement in the Commons Project for rare diseases in Japan

Kogetsu A., Isono M., Aikyo T., et al. Enhancing evidence-informed policymaking in medicine and healthcare: stakeholder involvement in the Commons Project for rare diseases in Japan. Research Involvement and Engagement 9, 107 (2023); https://doi.org/10.1186/s40900-023-00515-5.Background: Although stakeholder involvement in policymaking is attracting attention in the fields of medicine and healthcare, a practical methodology has not yet been established. Rare-disease policy, specifically research priority setting for the allocation of limited research resources, is an area where evidence generation through stakeholder involvement is expected to be effective. We generated evidence for rare-disease policymaking through stakeholder involvement and explored effective collaboration among stakeholders. Methods: We constructed a space called ‘Evidence-generating Commons’, where patients, family members, researchers, and former policymakers can share their knowledge and experiences and engage in continual deliberations on evidence generation. Ten rare diseases were consequently represented. In the ‘Commons’, 25 consecutive workshops were held predominantly online, from 2019 to 2021. These workshops focused on (1) clarification of difficulties faced by rare-disease patients, (2) development and selection of criteria for priority setting, and (3) priority setting through the application of the criteria. For the first step, an on-site workshop using sticky notes was held. The data were analysed based on KJ method. For the second and third steps, workshops on specific themes were held to build consensus. The workshop agendas and methods were modified based on participants’ feedback. Results: The ‘Commons’ was established with 43 participants, resulting in positive effects such as capacity building, opportunities for interactions, mutual understanding, and empathy among the participants. The difficulties faced by patients with rare diseases were classified into 10 categories. Seven research topics were identified as priority issues to be addressed including ‘impediments to daily life’, ‘financial burden’, ‘anxiety’, and ‘burden of hospital visits’. This was performed by synthesising the results of the application of the two criteria that were particularly important to strengthen future research on rare diseases. We also clarified high-priority research topics by using criteria valued more by patients and family members than by researchers and former policymakers, and criteria with specific perspectives. Conclusion: We generated evidence for policymaking in the field of rare diseases. This study’s insights into stakeholder involvement can enhance evidence-informed policymaking. We engaged in comprehensive discussions with policymakers regarding policy implementation and planned analysis of the participants’ experiences in this project

EGUIDE project and treatment guidelines

Aim: Although treatment guidelines for pharmacological therapy for schizophrenia and major depressive disorder have been issued by the Japanese Societies of Neuropsychopharmacology and Mood Disorders, these guidelines have not been well applied by psychiatrists throughout the nation. To address this issue, we developed the ‘Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE)’ integrated education programs for psychiatrists to disseminate the clinical guidelines. Additionally, we conducted a systematic efficacy evaluation of the programs. Methods: Four hundred thirteen out of 461 psychiatrists attended two 1‐day educational programs based on the treatment guidelines for schizophrenia and major depressive disorder from October 2016 to March 2018. We measured the participants’ clinical knowledge of the treatment guidelines using self‐completed questionnaires administered before and after the program to assess the effectiveness of the programs for improving knowledge. We also examined the relation between the participants’ demographics and their clinical knowledge scores. Results: The clinical knowledge scores for both guidelines were significantly improved after the program. There was no correlation between clinical knowledge and participant demographics for the program on schizophrenia; however, a weak positive correlation was found between clinical knowledge and the years of professional experience for the program on major depressive disorder. Conclusion: Our results provide evidence that educational programs on the clinical practices recommended in guidelines for schizophrenia and major depressive disorder might effectively improve participants’ clinical knowledge of the guidelines. These data are encouraging to facilitate the standardization of clinical practices for psychiatric disorders

エイセイ ギジュツカ ダイ2ガクネン ニ オケル ビョウイン ジッシュウ ノ コウカ ニ カンスル ケントウ

衛生技術科では,2000年(平成12年度)より2年生の夏期休暇中および春期休暇中に,関連病院であるときわ病院で5日間の病院実習を行っている。3年目を迎えることを機に,平成14年春期実習,同年夏期実習において学生にアンケート調査を実施して,この実習の効果を検討した。また,学内実習について,病院実習開始以前と病院実習開始後で実習状況を比較検討した。実習内容は手術から組織診断まで一連の過程の見学,学生相互の超音波検査・採血実習,さらに医師による診察の見学などである。これらを通して,学生は医療職として患者に対する連切な態度やチーム医療の重要性を学びとっていること,成功体験が関連教科への興味に繋がっていること等が明らかになった。また,採血を含む学内での実習が円滑に行われるようになったという効果もあった。しかし,一方で明らかになった基礎知識の不足や医療に関する社会的問題への関心の薄さは,病院実習をより充実させていくためにこれから取り組まなくてはならない課題である。今回の調査から,早期の病院実習は学生の学習意欲を喚起し,高度化する医療を担う臨床検査技師を育成するために重要な役割を果たすことが確認された。今後も総合的な学習の場として,充実させていくべきであると考える。Since 2000, the Medical Technology department has used the spring and summer vacations of second-year students for five-day practical training sessions at Tokiwa Hospital, a hospital with ties to Tokiwa College. With the 2002 term marking the third year of the program, we distributed a questionnaire for both the spring and summer sessions, investigating the effectiveness of this program. Students learned the appropriate attitude to patients as a medical staff member, as well as the importance of team health care, through a series of observations ranging from an operation to pathologic diagnosis of tissues, inter-student abdominal ultrasound examinations, inter-student blood drawing, and the observation of a doctor\u27s physical examination. It was seen that successful experiences such as these among the students aroused interest in related subjects, and an additional effect of this training was to increase the smoothness of the subsequent courses containing blood-drawing practice held in the college. On the other hand, effort to improve the effectiveness of the practical training sessions is still required in order to deal with the students\u27 lack of basic knowledge, and lack of interest in medical issues that were revealed in the current sessions. This investigation confirmed that early practical training sessions in Tokiwa Hospital serve the important functions of both increasing the students\u27 will to study, and educating medical technologists who accomplish increasingly advanced medical examinations. This training should be continued as a opportunity for systematic study in the early stage of the Medical Technology department