A pilot study of game-based learning programs for childhood cancer survivors.

BACKGROUND: Childhood cancer survivors lacking awareness on their potential risks of late effects often fail to seek adequate follow-up care. Patient education matching their preference is of great importance to improve their adherence to survivorship care. In this study, we developed two age-dependent game-based learning programs, which enable continuous approaches for childhood cancer survivors along their intellectual maturation. Then, we assessed the effectiveness of the programs. METHODS: Childhood cancer survivors over 10 years of age who regularly visited a long-term follow-up clinic were enrolled in this study. They were requested to play either of two different types of game tools, one for school children and another for adolescents and young adults, for one month at home. To evaluate the educational effects of the programs, they were examined for health management awareness, self-esteem, and knowledge on cancer-related late effects before and after the intervention with age-based questionnaires and knowledge tests. RESULTS: Among 83 participants, 49 (59.0%) completed the assessments over the period of 12 months. The health management awareness and knowledge levels increased significantly at 1-month after the intervention as compared to the baseline in both school children and adolescents/young adults (for health management awareness, p = 0.011 in elementary school children; p = 0.007 in junior high school children; p < 0.001 in adolescents/young adults; for knowledge levels, p < 0.001 in school children; p < 0.001 in adolescents/young adults). The effect was maintained for 12 months in school children while it decreased in adolescents and young adults with time. Self-esteem significantly increased at 1-month (p = 0.002 in school children; p = 0.020 in adolescents/young adults) and was maintained for 12 months in both age groups. CONCLUSION: The game-based learning programs enhanced health locus of control and self-esteem in childhood cancer survivors. The game-based learning programs could be applied effectively to survivorship care as a new modality of patient education. TRIAL REGISTRATION: This study was retrospectively registered in UMIN-CTR ( UMIN000043603 ) on March 12, 2021.

Changes of cancer diagnosis disclosure to children in Japan in the last 20 years.

BACKGROUND: The practice of cancer diagnosis disclosure to children has been changed with the times. The regulations of clinical trials in the 2000s might change the practice in Japan. However, the perspective of this topic among children and adults has not been investigated in detail. METHODS: We studied changes in the practice of information sharing with children with cancer at pediatric cancer centers and the perspective of cancer diagnosis disclosure to children among school children, their parents and pediatric oncologists in the last 20 years by comparing the results of questionnaire surveys conducted in 1998, 2008 and 2018. RESULTS: This study revealed that the performing rate has increased with the times, but the institutions actively performing for children aged 7-9 years were 36.4% even in the 2018 survey. More than 70% of children wished diagnosis disclosure if they suffer from cancer in the series of surveys, while the ratio of parents who tell cancer diagnosis to their children hovered at 34.5 to 53.7% (p < 0.001 in all surveys). The ratio of pediatric oncologists having the policy to perform diagnosis disclosure proactively increased from 9.3 to 60.0%, while that of parents having the same policy stayed at 5.3% even in 2018. CONCLUSIONS: The performing rate of information sharing with children with cancer was significantly changed in the last 20 years. The opinion gaps were observed between parents and children and between parents and pediatric oncologists.

Change in children's perception of cancer in the last 10 years in Japan.

BACKGROUND: Social awareness of cancer can be changed with cancer education and proper distribution of cancer information. This study addressed the current situation and historical changes to children's perception of cancer. METHODS: Questionnaire surveys were conducted among healthy school children aged 10-15 years in 2008 and 2018. Knowledge of cancer was surveyed and compared with that of asthma, tuberculosis, and measles. The children were asked about their health information resources. RESULTS: The numbers of participants and collection rates were 438 and 63.9% in 2008, and 320 and 44.7% in 2018. Children's perception of cancer changed significantly in the last decade. The proportion of respondents answering "cancer affects children" changed from 78.3 to 89.5% (P = 0.0001), "cancer is preventable" from 42.0 to 49.7% (P = 0.0425), and "cancer is curable," from 52.4 to 66.0% (P = 0.0003). Significantly more junior high school students answered that cancer is preventable than elementary school children in 2018 (55.9 vs 42.7%, P = 0.0028). The major resources of information on health were television, parents, and books. The proportion of children choosing the Internet significantly increased from 15.3 to 47.8% (P < 0.0001). Significantly more junior high school students selected television and the Internet than elementary school children (94.5 vs 86.9%, P = 0.0202 for television; 57.1 vs 37.9%, P = 0.0007 for the Internet). CONCLUSIONS: The proportion of children correctly perceiving cancer information had increased in the last decade. Junior high school students better understood the information. The Internet is of increasing importance as an information resource for school children.

Understanding paleo-earthquakes in the Kuril Trench based on Late-Holocene tsunami deposits in the distal region from wave sources, northern Hidaka, Hokkaido, Japan.

Geological evidence, such as tsunami deposits, is crucial for studying the largest rupture zone of the Kuril Trench in Hokkaido, Japan, due to its poor historical record. Although 17th-century tsunami deposits are widely distributed across Hokkaido, the presence of multiple wave sources during that period, including the collapse of Mt. Komagatake, complicates the correlation with their wave sources. Understanding the regional distribution of these tsunami deposits can provide valuable data to estimate the magnitude of megathrust earthquakes in the Kuril Trench. The northern part of Hidaka, Hokkaido, where tsunamis from multiple wave sources are expected to overlap, is distant from the Kuril Trench. To clarify the depositional history of tsunami deposits in such distal areas, evaluating the influence of the depositional environments on the event layer preservation becomes even more critical. We conducted field surveys in Kabari, located in the northern Hidaka region, identifying three sand layers from the 10th to the 17th century and two layers dating beyond 2.3 thousand years ago. The depositional ages of most sand layers potentially correlate with tsunami deposits resulting from the Kuril Trench earthquakes. Utilizing reconstructed paleo-sea level data, we estimated that most sand layers reached approximately 2 m in height. However, it is noteworthy that the latest sand layer from the 17th century exhibited an unusual distribution, more than 3 m in height. This suggests a different wave source as the Mt. Komagatake collapse. The discovery of multiple sand layers and their distributions is crucial to constraining the maximum magnitude of giant earthquakes in the Kuril Trench and understanding the volcanic tsunami events related to Mt. Komagatake.

Creation of the first regional medical resource map for use in a disaster.

Background: Japan is located on the Pacific Ring of Fire and experiences frequent earthquakes. In addition, as the climate is changing due to global warming, heavy rains have caused frequent floods recently. Following the occurrence of disasters, citizens often experience confusion regarding access to healthcare services. Moreover, health professionals often face uncertainty regarding the availability of medical services in their local area. The Tokyo Kita city Pharmacist Association (KPA) independently developed the pharmacist safety confirmation (PSC) and pharmacy status confirmation (PSTC) systems to provide information regarding pharmaceutical resources during a disaster. These systems are very useful; however, they only provide information about pharmacies. Using this system as a base, a regional medical resource (RMR) map was created in cooperation with the Medical Association and Dental Association to provide useful medical resource information for clinicians and citizens during a disaster. Objectives: The study aimed to assess the effectiveness and reliability of the RMR map. Methods: The PSC and PSTC systems were originally invented by the KPA. The systems were employed in the event of actual earthquakes and flood damages and have produced positive results. An RMR map was created as a new resource map system by updating the software and platform of PSC and PSTC, and its reliability and efficacy were verified using drills. Drills were conducted seven times from 2018 to 2021. Results: Out of the 527 member facilities, 450 were registered. The response rate ranged from 49.4% to 73.8% and the system successfully created useful maps. Conclusion: This is the first report on the creation of an effective RMR map that can be used for helping people during disasters in Japan.

Students' perception of problem-based learning at a Japanese medical school: an exploratory sequential mixed method.

Objectives: This study aimed to assess the perception of PBL among Japanese medical students. Methods: Learning effects and challenges of PBL from the students' viewpoint were assessed with an exploratory sequential mixed method. Focus group discussions followed by thematic analysis were conducted with 27 students and residents. Then a questionnaire survey was carried out. A total of 119 out of 258 students (46.1%) responded. The results from 24 questions were analyzed with a residual analysis. Results: Thematic analysis extracted 14 themes from four discussion topics. The participants in focus group discussion regarded the PBL program as a better learning method than lectures. But some key phrases on the challenge of social interaction, including reluctance to actively discuss and collaborate with unfamiliar peers, were found. The questionnaire survey revealed a significantly lower adjusted standardized residual (ASR) for the positive response in five of six questions in the category of social interaction; improvement of communication skills (ASR = -3.303, n = 118, p < .001), enhancement of responsibility at group discussions (ASR = -2.078, n = 119, p = .038), building social networking (ASR = -3.006, n = 119, p = .003), becoming to sympathize with patients (ASR = -2.449, n = 119, p = .014) and understanding social aspects of clinical practice (ASR = -5.790, n = 119, p < .001). Conclusion: The Japanese medical students perceived PBL as an effective learning strategy. However, they had a problem with social interactions.

A dataset for distribution and characteristics of Holocene pyroclastic fall deposits along the Pacific coasts in western Hokkaido, Japan.

The tephra layers known with eruption ages play an important role in an investigation of tsunami history and archaeology in addition to volcanic history in Hokkaido, Japan. We investigated the event and tephra layers of the Late Holocene in the Pacific coast of western Hokkaido, where the stratigraphy of the Late Holocene has not been clarified. Surveys in coastal peatlands, mostly undisturbed deposits, have allowed for the discovery of thin tephra layers. The newly discovered tephra layers at the unexplored site were used to describe facies, observation under a polarization microscope, refractive index measurement of volcanic glasses, and chemical analysis, and correlated with the reported widespread tephras. We conducted wide-area field surveys and succeeded in revealing a wider distribution of tephra layers than previously known. The distribution of volcanic ash in the coastal area will contribute to the investigations of future volcanic and coastal hazards.

Close interaction with bone marrow mesenchymal stromal cells induces the development of cancer stem cell-like immunophenotype in B cell precursor acute lymphoblastic leukemia cells.

Minimal residual disease of leukemia may reside in the bone marrow (BM) microenvironment and escape the effects of chemotherapeutic agents. This study investigated interactions between B cell precursor (BCP)-acute lymphoblastic leukemia (ALL) cells and BM mesenchymal stromal cells (BM-MSCs) in vitro. Five BCP-ALL cell lines established from pediatric patients and primary samples from a BCP-ALL patient were examined by flow cytometry and immunocytochemistry for expression of specific cell surface markers and cell adhesion proteins. The cell lines developed chemoresistance to commonly used anti-leukemic agents through adhesion to MSC-TERT cells in long-term culture. The change in chemosensitivity after adhering to BM-MSCs was associated with the expression of CD34, CD133, P-glycoprotein and BCRP/ABCG2, and downregulation of CD38. Similar phenotypic changes were observed in primary samples obtained by marrow aspiration or biopsy from a BCP-ALL patient. BM-MSC-adhering leukemia cells also showed deceleration of cell proliferation and expressed proteins in the Cadherin and Integrin pathways. These results suggest that BCP-ALL cells residing in the BM microenvironment may acquire chemoresistance by altering their phenotype to resemble that of cancer stem cells. Our results indicate that cell adhesion could be potentially targeted to improve the chemosensitivity of residual BCP-ALL cells in the BM microenvironment.

Social defeat stress induces phosphorylation of extracellular signal-regulated kinase in the leptomeninges in mice.

AIMS: Animal studies using various stress models have shown that excessive environmental stress induces depression? and anxiety?like behaviors through inflammatory responses in the brain and periphery. Although the leptomeningeal cells have multiple functions related to inflammatory responses in the brain, whether environmental stress influences the leptomeninges remains unknown. In this study, we aimed to examine phosphorylation of the extracellular signal-regulated kinase (ERK) in the leptomeninges. METHODS: We subjected C57BL/6 male mice to a single episode of social defeat stress and analyzed the expression of phosphorylated ERK in the leptomeninges by immunohistochemistry. RESULTS: Social defeat stress in mice induced phosphorylation of ERK in the leptomeninges, adjacent to vascular endothelial cells and the glia limitans. This ERK phosphorylation was maintained for at least one hour after the stress. CONCLUSIONS: This study shows the effect of environmental stress on the leptomeninges for the first time and paves the way for elucidating its functional role in stress-induced changes in neural functions.

Functional characterization of hematopoietic stem cells in the spleen.

OBJECTIVE: Hematopoietic stem cells (HSCs) reside in both bone marrow (BM) and spleen in adult mice. However, whether BM and spleen HSCs are functionally similar is not known. Spleen HSCs were compared with BM HSCs by various assays. MATERIALS AND METHODS: Whole BM and spleen cells were quantitatively analyzed by competitive repopulation. Single-cell transplantation was performed with HSCs purified from BM and spleen. A parabiosis model was used to distinguish organ-specific HSCs from circulating HSCs. The cell cycle was analyzed with pyronin Y staining and bromodeoxyuridine uptake. RESULTS: Repopulating and self-renewal potentials were similar on a clonal basis between BM and spleen HSCs, whereas the HSC frequency in the spleen was significantly lower than that in the BM. Analysis of parabiotic mice suggested that most HSCs are long-term residents in each organ. Cell-cycle analysis revealed that spleen HSCs cycle twice as frequently as do BM HSCs, suggesting that G(0) phase length is longer in BM HSCs than in spleen HSCs. The cycling difference between BM and spleen HSCs was also observed in mice that had been reconstituted with BM or spleen cells, suggesting that HSC quiescence is regulated in an organ-specific manner. CONCLUSIONS: Spleen HSCs and BM HSCs are functionally similar, but their cycling behaviors differ.

Lnk regulates integrin alphaIIbbeta3 outside-in signaling in mouse platelets, leading to stabilization of thrombus development in vivo.

The nature of the in vivo cellular events underlying thrombus formation mediated by platelet activation remains unclear because of the absence of a modality for analysis. Lymphocyte adaptor protein (Lnk; also known as Sh2b3) is an adaptor protein that inhibits thrombopoietin-mediated signaling, and as a result, megakaryocyte and platelet counts are elevated in Lnk-/- mice. Here we describe an unanticipated role for Lnk in stabilizing thrombus formation and clarify the activities of Lnk in platelets transduced through integrin alphaIIbbeta3-mediated outside-in signaling. We equalized platelet counts in wild-type and Lnk-/- mice by using genetic depletion of Lnk and BM transplantation. Using FeCl3- or laser-induced injury and in vivo imaging that enabled observation of single platelet behavior and the multiple steps in thrombus formation, we determined that Lnk is an essential contributor to the stabilization of developing thrombi within vessels. Lnk-/- platelets exhibited a reduced ability to fully spread on fibrinogen and mediate clot retraction, reduced tyrosine phosphorylation of the beta3 integrin subunit, and reduced binding of Fyn to integrin alphaIIbbeta3. These results provide new insight into the mechanism of alphaIIbbeta3-based outside-in signaling, which appears to be coordinated in platelets by Lnk, Fyn, and integrins. Outside-in signaling modulators could represent new therapeutic targets for the prevention of cardiovascular events.