Lymphopenia at diagnosis predicts survival of patients with immunodeficiency-associated lymphoproliferative disorders

The number of patients who are administered immunosuppressive agents has been increasing. Accordingly, more patients face higher risks for developing immunodeficiency-associated lymphoproliferative disorders (LPD). Although immunodeficiency-associated LPD are distinct from other lymphoid neoplasms in terms of their immunocompromised backgrounds, little is known about the impact of lymphopenia at diagnosis on survival in patients with these LPD. Seventy-one immunodeficiency-associated LPD in Kyoto University Hospital (post-transplant LPD (PTLD), n = 26; other iatrogenic immunodeficiency-associated LPD, n = 45) were reviewed and analyzed. The median age at diagnosis was 63 years (range, 3–83). Diffuse large B cell lymphoma was the most common subtype (n = 33), followed by Hodgkin lymphoma (n = 12), B cell monomorphic LPD not specified (n = 11), and polymorphic LPD or early-phase diseases (n = 15). The median follow-up period for survivors was 2.5 years and overall survival (OS) and progression-free survival (PFS) at 2.5 years were 75% and 67%, respectively. Multivariate analysis showed that lymphopenia (≤ 800/μL) at diagnosis predicted inferior OS (HR, 3.72; P = 0.043) and PFS (HR, 3.82; P = 0.012). Serum albumin values also strongly affected OS (> 3.18 g/dL vs. ≤ 3.18 g/dL; HR, 0.21; P = 0.010) and PFS (HR, 0.26; P = 0.013). Lymphopenia at diagnosis is suggested to predict inferior OS and PFS in patients with immunodeficiency-associated LPDs. Immunocompromised status might affect disease progression in these distinct lymphoid neoplasms growing under immunocompromised backgrounds

Mapping the Ethical Issues of Brain Organoid Research and Application

脳オルガノイドの研究と臨床応用での倫理問題を体系化. 京都大学プレスリリース. 2021-04-07.Society is not ready to make human brains. 京都大学プレスリリース. 2021-03-26.In 2008, researchers created human three-dimensional neural tissue – known as the pioneering work of “brain organoids.” In recent years, some researchers have transplanted human brain organoids into animal brains for applicational purposes. With these experiments have come many ethical concerns. It is thus an urgent task to clarify what is ethically permissible and impermissible in brain organoid research. This paper seeks (1) to sort out the ethical issues related to brain organoid research and application and (2) to propose future directions for additional ethical consideration and policy debates in the field. Toward (1), this paper first outlines the current state of brain organoid research, and then briefly responds to previously raised related ethical concerns. Looking next at anticipated scientific developments in brain organoid research, we will discuss (i) ethical issues related to in vitro brain organoids, (ii) ethical issues raised when brain organoids form complexes or have relationships with other entities, and (iii) ethical issues of research ethics and governance. Finally, in pursuit of (2), we propose research policies that are mindful of the ethics of brain organoid research and application and also suggest the need for an international framework for research and application of brain organoids

Oxaliplatin-Associated Amaurosis Fugax

Oxaliplatin-associated amaurosis fugax has not been reported, and its clinical course and treatment remain largely unclear. A 70-year-old man with advanced gastric cancer was treated with the SOX regimen. After cycle 1 of oxaliplatin infusion, the patient realized that his right eye had visual field impairment, which he described as darkening of the right half of his visual field and loss of vision lasting about 1 min and occurring about 7 times a day. The daily frequency of this occurrence gradually decreased, and his visual field impairment improved in 1 week. However, as the same symptoms recurred from cycle 2 to cycle 5 of treatment, oxaliplatin was discontinued from cycle 6 and switched to S-1 monotherapy. Subsequently, the patient’s amaurosis fugax improved. To our knowledge, this is the first report describing clinical course and treatment of oxaliplatin-associated amaurosis fugax

Wounding triggers callus formation via dynamic hormonal and transcriptional changes

Wounding is a primary trigger of organ regeneration, but how wound stress reactivates cell proliferation and promotes cellular reprogramming remains elusive. In this study, we combined transcriptome analysis with quantitative hormonal analysis to investigate how wounding induces callus formation in Arabidopsis (Arabidopsis thaliana). Our time course RNA-seq analysis revealed that wounding induces dynamic transcriptional changes, starting from rapid stress responses followed by the activation of metabolic processes and protein synthesis and subsequent activation of cell cycle regulators. Gene ontology analyses further uncovered that wounding modifies the expression of hormone biosynthesis and response genes, and quantitative analysis of endogenous plant hormones revealed accumulation of cytokinin prior to callus formation. Mutants defective in cytokinin synthesis and signaling display reduced efficiency in callus formation, indicating that de novo synthesis of cytokinin is critical for wound-induced callus formation. We further demonstrate that type-B ARABIDOPSIS RESPONSE REGULATOR-mediated cytokinin signaling regulates the expression of CYCLIN D3;1 (CYCD3;1) and that mutations in CYCD3;1 and its homologs CYCD3;2 and 3 cause defects in callus formation. In addition to these hormone-mediated changes, our transcriptome data uncovered that wounding activates multiple developmental regulators, and we found novel roles of ETHYLENE RESPONSE FACTOR 115 and PLETHORA3 (PLT3), PLT5, and PLT7 in callus generation. All together, these results provide novel mechanistic insights into how wounding reactivates cell proliferation during callus formation

BMP4 Sufficiency to Induce Choroid Plexus Epithelial Fate from Embryonic Stem Cell-Derived Neuroepithelial Progenitors

Choroid plexus epithelial cells (CPECs) have essential developmental and homeostatic roles related to the cerebrospinal fluid (CSF) and blood-CSF barrier they produce. Accordingly, CPEC dysfunction has been implicated in many neurological disorders, such as Alzheimer’s disease, and transplant studies have provided proof-of-concept for CPEC-based therapies. However, such therapies have been hindered by the inability to expand or generate CPECs in culture. During development, CPECs differentiate from preneurogenic neuroepithelial cells and require Bone Morphogenetic Protein (BMP) signaling, but whether BMPs suffice for CPEC induction is unknown. Here we provide evidence for BMP4 sufficiency to induce CPEC fate from neural progenitors derived from mouse embryonic stem cells (ESCs). CPEC specification by BMP4 was restricted to an early time period after neural induction in culture, with peak CPEC competency correlating to neuroepithelial cells rather than radial glia. In addition to molecular, cellular, and ultrastructural criteria, derived CPECs (dCPECs) had functions that were indistinguishable from primary CPECs, including self-assembly into secretory vesicles and integration into endogenous choroid plexus epithelium following intraventricular injection. We then used BMP4 to generate dCPECs from human ESC-derived neuroepithelial cells. These findings demonstrate BMP4 sufficiency to instruct CPEC fate, expand the repertoire of stem cell-derived neural derivatives in culture, and herald dCPEC-based therapeutic applications aimed at the unique interface between blood, CSF, and brain governed by CPECs

Identification of neural oscillations and epileptiform changes in human brain organoids

Brain organoids represent a powerful tool for studying human neurological diseases, particularly those that affect brain growth and structure. However, many diseases manifest with clear evidence of physiological and network abnormality in the absence of anatomical changes, raising the question of whether organoids possess sufficient neural network complexity to model these conditions. Here, we explore the network-level functions of brain organoids using calcium sensor imaging and extracellular recording approaches that together reveal the existence of complex network dynamics reminiscent of intact brain preparations. We demonstrate highly abnormal and epileptiform-like activity in organoids derived from induced pluripotent stem cells from individuals with Rett syndrome, accompanied by transcriptomic differences revealed by single-cell analyses. We also rescue key physiological activities with an unconventional neuroregulatory drug, pifithrin-α. Together, these findings provide an essential foundation for the utilization of brain organoids to study intact and disordered human brain network formation and illustrate their utility in therapeutic discovery

看護基礎教育におけるラベルワーク技法を用いた看護研究計画書作成の取り組み

3年課程の看護基礎教育で3年前期に履修する「看護研究の基礎（演習）」において、看護研究計画書の作成をラベルワーク技法を用いて展開した。履修学生に質問紙による演習方法の評価を求め、16名から回答を得た。この演習方法全体に対して「演習の楽しさ」や「演習の満足感」の評価が高かった。細部においては、「研究課題の絞り込み」、「先行研究の整理」、「図考・図解による思考の整理」などの頂目において高い評価を得た。初めて研究計画書作成に取り組む学生の演習方法として、この方法は有効な教育方法となる可能性を確認した。課題は、最初に具体的な事象を捉えて疑問ラベルを出す段階や文献検索ならびにその読み込みをする段階における学習支援を強化することである