Segmentation and Volume Estimation of the Habenula Using Deep Learning in Patients With Depression.

Background: The habenula is involved in the pathophysiology of depression. However, its small structure limits the accuracy of segmentation methods, and the findings regarding its volume have been inconsistent. This study aimed to create a highly accurate habenula segmentation model using deep learning, test its generalizability to clinical magnetic resonance imaging, and examine differences between healthy participants and patients with depression. Methods: This multicenter study included 382 participants (patients with depression: N = 234, women 47.0%; healthy participants: N = 148, women 37.8%). A 3-dimensional residual U-Net was used to create a habenula segmentation model on 3T magnetic resonance images. The reproducibility and generalizability of the predictive model were tested on various validation cohorts. Thereafter, differences between the habenula volume of healthy participants and that of patients with depression were examined. Results: A Dice coefficient of 86.6% was achieved in the derivation cohort. The test-retest dataset showed a mean absolute percentage error of 6.66, indicating sufficiently high reproducibility. A Dice coefficient of >80% was achieved for datasets with different imaging conditions, such as magnetic field strengths, spatial resolutions, and imaging sequences, by adjusting the threshold. A significant negative correlation with age was observed in the general population, and this correlation was more pronounced in patients with depression (p < 10-7, r = -0.59). Habenula volume decreased with depression severity in women even when the effects of age and scanner were excluded (p = .019, η2 = 0.099). Conclusions: Habenula volume could be a pathophysiologically relevant factor and diagnostic and therapeutic marker for depression, particularly in women.

Accurate segmentation of the habenula, a brain region implicated in depression, is challenging. In this study, we developed an automated human habenula segmentation model using deep learning techniques. The model was confirmed to be reproducible and generalizable at various spatial resolutions. Application of this model to a multicenter dataset confirmed that habenula volume decreased with age in healthy volunteers, an association that was more pronounced in individuals with depression. In addition, habenula volume decreased with the severity of depression in women. This novel model for habenula segmentation enables further study of the role of the habenula in depression.

Trends in patterns of treatment and survival of colorectal cancer patients using cancer registry data in Japan: 1995-2015.

Recent advances in treating colorectal cancer (CRC) have increased the importance of multidisciplinary treatment. This study aimed to clarify trends in the treatment and survival of CRC using population-based cancer registry data in Japan. We analyzed the survival of CRC cases diagnosed from 1995 through 2015 from a population-based cancer registry of six prefectures. The year of diagnosis was classified into five periods, and the trends in the detailed categorization of treatments and survival were identified. We calculated net survival and excess hazard of death from cancer using data on 256,590 CRC patients. The use of laparoscopic surgery has been increasing since 2005 and accounts for the largest proportion of treatment types in the most recent period. Net survival of CRC patients diagnosed after 2005 remained high for laparoscopic surgery and endoscopic surgery (endoscopic mucosal resection or endoscopic submucosal dissection). There was an upward trend in treatment with chemotherapy in addition to open and laparoscopic surgery. Using the excess hazard ratio at the regional stage since 2005, there has been a significant improvement in survival in the younger age group and the rectum cancer group. By type of treatment, there was a tendency toward significant improvement in the open surgery + chemotherapy group. We clarified the trends in treating CRC and the associated trends in survival. Continuous survey based on population-based data helps monitor the impact of developments in treatment.

[Current Status and Challenges of Cancer Survivorship Researchs in Japan].

Cancer patients have been able to live longer according to the development of early diagnosis and treatment. On the other hand, prolonged treatment period, increased cost burdens, and various late complications can occur as a result. In this article, I introduce research on cancer survivorship in Japan, about the statistics for cancer survivors, physical, mental, and social late complications. I also summarize the issues of survivorship research that should be conducted in Japan in the future. First, the 5-year survival has been used as a prognostic indicator for cancer survivors, however, the conditional survival, which is more useful information to predict the patients' future, was introduced. In addition, studies on late complications of cancer patients were summarized, including studies on the development of secondary cancer as a physical complication, suicide as a psychological complication, and continued employment and economic toxicity as social complications. Finally, we summarized the research and data bases that are needed to realize"cancer control that leaves no one behind".

Parental gender influences their intention to HPV vaccinate their children, and the association between HPV and COVID-19 vaccination intentions.

Purpose: The coronavirus disease of 2019 (COVID-19) pandemic has increased public awareness of infectious diseases and interest in vaccines, including the human papilloma virus (HPV) vaccine. We investigated differences between parental gender and intentions to vaccinate their child for HPV and COVID-19. Methods: We analyzed data from Japan's COVID-19 and Society Internet Survey (JACSIS), a web-based cross-sectional survey of 2,444 respondents in 2021. Results: Females were more knowledgeable and more afraid of HPV and COVID-19 than males. The proportions of females in favor of, or against, HPV vaccination was higher than among males. The fathers' intention for HPV vaccination was significantly associated with the child's gender, knowledge regarding HPV, and intention to inoculate with the COVID-19 vaccine. The mothers' intention was also associated with her knowledge of HPV and her intention to seek the COVID-19 vaccine, but it included a greater fear of HPV infection. Both male and female parents favored the COVID-19 vaccine over the HPV vaccine. Parents approving of COVID-19 vaccination believed in the overall efficacy of vaccines and were more receptive to opinions from the administration and physicians, even if the parent was currently against HPV vaccination. Conclusions: Mothers were more knowledgeable about HPV and more favorable to vaccinate their child for HPV than fathers. The intention to have children COVID-19 vaccinated was also higher than for HPV vaccination. During this period of heightened public interest in vaccines due to the COVID-19 pandemic, this is a good time to educate and inform the public about HPV.

Do the general public get cancer statistics?-a questionnaire survey in Japan.

OBJECTIVES: The public does not always understand key information conveyed by epidemiologists and statisticians. The purpose of this study was to understand the level of public access to, trust in, and comprehension of, cancer statistics through a population-based survey in Japan. METHODS: We used an online research method, requesting online responses to a 15-question questionnaire. The survey was sent to males and females aged 20 years and older, selected by sex, age and prefecture to match the national population proportions shown in the latest census. The final number of valid responses was 10 477. The statistical analyses mainly used χ2 testing. RESULTS: Respondents were not frequently exposed to cancer statistics regardless of sex or age group, nor did they necessarily have confidence in the statistics. The increase of collected information and trust in cancer statistics was aligned with increasing age and cancer exposure. Respondents found Relative Risk and Relative Survival Rate easier to understand and more useful than the Standardized Incidence Ratio. In addition, those with cancer experience, higher income and were elderly gave more accurate responses when asked questions related to cancer incidence and probability of getting cancer. CONCLUSIONS: Our respondents showed limited familiarity with cancer statistical indicators. Enhanced awareness of indicators such as infographics and visual tools has the potential to enhance cancer visibility, thereby promoting public prevention and early detection efforts. Educating cancer patients about pertinent indicators can boost their confidence in managing their condition. Conversely, the introduction of indicators unrelated to the public should be discouraged.

The effect of center experience on allogeneic hematopoietic cell transplantation outcomes in acute myeloid leukemia.

This study aimed to address the prognostic impact of center experience based on the data of 7821 adults with acute myeloid leukemia who underwent allogeneic hematopoietic cell transplantation (HCT) from 2010 to 2019 in Japan, where medical care was provided within a uniform healthcare system. Center experience was defined based on the number of allogeneic HCTs performed for any indication during the study period, by which centers were divided into low-, intermediate-, and high-volume centers. After adjusting for known confounding factors, the risk of overall mortality was lowest for the high-volume centers and highest for the low-volume centers, with the difference between the center categories attributed primarily to the risk of relapse. Patients transplanted at high-volume centers had higher risks of acute and chronic graft-versus-host diseases but without an increased risk of non-relapse mortality (NRM). These findings reveal the presence of a center effect in allogeneic HCT conducted during the past decade in Japan, highlighting the difference in relapse based on center experience. The weaker effect on NRM compared with that on relapse suggests that the transplantation care quality is becoming equalized across the country.

Impact of Center Volume on Chronic Graft Versus Host Disease in Patients With Allogeneic Stem Cell Transplantation.

Chronic graft-versus-host disease (cGVHD) is a complication of allogeneic hematopoietic stem cell transplantation (HSCT), negatively impacting quality of life (QoL) and increasing the risk of death. Complexity in cGVHD diagnosis and treatment causes significant variations in cGVHD management strategies across medical centers and physicians despite the existence of published guidelines. Thus, we hypothesized that center volume is associated with cGVHD incidence and outcomes after cGVHD develops. This study aimed to evaluate the effect of center volume on the incidence of cGVHD in patients who underwent HSCT and outcomes in patients with cGVHD. Our retrospective study included 28,786 patients who underwent their first HSCT (overall cohort) and 7664 who developed cGVHD (cGVHD cohort). We categorized institutions into quartiles (very low, low, high, and very high) using the number of HSCTs performed during the study period. We assessed cGVHD incidence in overall cohort and overall survival (OS) in cGVHD cohort. The very high-volume group showed significantly higher cGVHD incidence (adjusted hazard ratio [HR], 1.38; 95% confidence interval [CI]: 1.30 to 1.46) compared to the very low-volume group. However, the cGVHD incidence was similar among very low-, low- and high-volume groups. Low, high, and very high-volume groups showed significantly higher OS with adjusted HRs of 0.83 (95% CI: 0.73 to 0.94), 0.69 (95% CI: 0.61 to 0.79), and 0.68 (95% CI: 0.60 to 0.76), respectively, compared with the very low-volume group. In conclusion, we revealed a higher incidence of cGVHD in the very high-volume group and a poor survival outcome in the very low-volume group in patients with cGVHD.

Parbendazole as a promising drug for inducing differentiation of acute myeloid leukemia cells with various subtypes.

Acute myeloid leukemia (AML) is a malignancy characterized by differentiation arrest of hematopoietic precursor cells. Differentiation therapy is effective for patients with acute promyelocytic leukemia; however, only a few effective differentiation therapies have been established for patients with other AML subtypes. In this study, seven benzimidazole anthelmintics were examined to determine the effects of differentiation on AML cells. The expression of monocyte markers (CD11b and CD14) was elevated after treatment with most benzimidazole anthelmintics. Among these drugs, parbendazole (PBZ) induced AML cell differentiation at low concentration. PBZ induced the monocyte marker expression, KLF4/DPYSL2A gene expression, and apoptosis for 21 AML cell lines with various subtypes and a primary AML sample. Finally, an in vivo analysis using an AML patient-derived xenograft mouse model showed a significant decrease in the chimerism level and prolonged survival in PBZ-treated mice. These findings could lead to a more effective differentiation therapy for AML.

Subsite-specific trends in mid- and long-term survival for head and neck cancer patients in Japan: A population-based study.

Advances in diagnostic techniques and treatment modalities have impacted head and neck cancer (HNC) prognosis, but their effects on subsite-specific prognosis remain unclear. This study aimed to assess subsite-specific trends in mid- and long-term survival for HNC patients diagnosed from 1993 to 2011 using data from population-based cancer registries in Japan. We estimated the net survival (NS) for HNC by subsite using data from 13 prefectural population-based cancer registries in Japan. Changes in survival over time were assessed by multivariate excess hazard model of mortality. In total, 68,312 HNC patients were included in this analysis. We observed an overall improvement in 5-year NS for HNC patients in Japan. However, survival varied among subsites of HNC, with some, such as naso-, oro- and hypopharyngeal cancers, showing significant improvement in both 5- and 10-year NS, whereas others such as laryngeal cancer showed only a slight improvement in 5-year NS and no significant change in 10-year NS after adjustment for age, sex and stage. In conclusion, the study provides insights into changing HNC survival by site at the population level in Japan. Although advances in diagnostic techniques and treatment modalities have improved survival, these improvements are not shared equally among subsites.

Effectiveness of catch-up and routine program of the 9-valent vaccine on cervical cancer risk reduction in Japan.

In 2013, the national human papillomavirus (HPV) immunization program began. However, in June 2013, Japan's Ministry of Health, Labor and Welfare (MHLW) announced a "temporary" suspension of its recommendation for the human papillomavirus vaccine. Finally, in November 2021, the MHLW ended its suspension of the recommendation of the HPV vaccine. To address the 9-year gap in HPV vaccinations the suspension had caused, the MHLW conducted a program of catch-up vaccinations from April 2022 to March 2025. Finally, in April 2023, the 9-valent HPV vaccine was approved for both the routine and catch-up vaccination programs in Japan. In this study, we investigated the potential effects of the introduction of the 9-valent vaccine on the increased risk of cervical cancer in females born after fiscal year (FY) 2000. We estimated the lifetime relative risk of cervical cancer incidence and death using the improved routine and catch-up vaccination rates after the recent resumption of the governmental recommendation for women and girls to have the HPV vaccination. These relative risks were calculated using a lifetime risk of 1.000 for cervical cancer incidence and death for females born in FY 1993. We predicted that even if a 90% vaccination rate were to be achieved by FY 2024 with the 9-valent vaccine among women born between FY 2000 and FY 2005, the risk would remain higher than for the vaccination generation. Therefore, for women born between FY 2000 and FY 2005, it will be necessary to significantly improve the cervical cancer screening rate to compensate for this increased risk.

Trends in the stage distribution of colorectal cancer during the COVID-19 pandemic in Japan: a nationwide hospital-claims data analysis.

BACKGROUND: The COVID-19 pandemic has affected cancer care. The aim of this study was to clarify the trend of colorectal cancer (CRC) stage distribution in Japan during the COVID-19 pandemic. METHODS: In this retrospective study, we used an inpatient medical claims database established at approximately 400 acute care hospitals. From the database, we searched patients who were identified as having the main disease (using ICD-10codes [C18.0-C20]) between January 2018 and December 2020. A multivariate logistic regression analysis was used to determine the impact of the pandemic on CRC stage distribution each month, and the odds ratio (OR) for late-stage cancer was calculated. RESULTS: We analyzed 99,992 CRC patients. Logistic regression analysis, including the interaction term between increased late-stage CRC effect during the pandemic period and by each individual month, showed that the OR for late-stage CRC was highest in July during the pandemic, at 1.31 (95%CI: 1.13- 1.52) and also significantly higher in September at 1.16 (95%CI: 1.00- 1.35). CONCLUSION: We investigated the trend of CRC stage distribution during the COVID-19 pandemic using a nationwide hospital-claims database in Japan, and found that the proportion of early-stage cancers tended to decrease temporarily after the state of emergency declaration due to the COVID-19 pandemic, but the effect was only temporary.

Clinical Epidemiological Studies of Colorectal Cancer by Record Linkage of Cancer Registries and Biospecimen Data: A Systematic Review.

BACKGROUND: The incidence and prognosis of colorectal cancer are associated with lifestyle, family history, and genetic predisposition. Record linkage between cancer registries and biospecimen data would enable us to conduct clinical epidemiological studies on incidence or prognosis including genome information. In this study, we conducted a systematic review of clinical epidemiological studies of colorectal cancer using record linkage between cancer registries and biospecimen data and examined the possibilities for future use of this linkage. METHODS: We searched PubMed and Google Scholar for articles regarding cancer registries and biospecimen data use published before December 2021. Selected articles were summarized by cancer registry use, biospecimen use, exposure, outcome, informed consent, and participant numbers by study design and type of cancer registry. RESULTS: Of the 2,793 identified articles, 81 studies were included in this review. The most frequently used cancer registries and study design were site specific cancer registries and cohort studies. Most use of cancer registries was for patient selection in cohort studies and case selection in case-control studies. Most use of biospecimen data was for prognostic factors in cohort studies and risk factors in case-control studies. In site specific cancer registries for the examination of familial colorectal cancer, most use of biospecimen data is to examine genome mutation, expression, or deficiency. CONCLUSION: We suggest that record linkage between cancer registries and biospecimen data would enable the accurate capture of outcomes and detailed genome-environmental factors, and to conduct clinical epidemiological studies according to specific research questions and tailored study designs.

Improved Long-Term Net Survival after Allogeneic Hematopoietic Cell Transplantation in Patients with Hematologic Malignancies over Two Decades.

Allogeneic (allo-) hematopoietic cell transplantation (HCT) has evolved as a curative therapy for hematologic malignancies and diseases, with practice changes over the past 2 decades. This study aimed to evaluate the change in 5-year net survival (NS) of allo-HCT recipients in a population-based cohort over the past 2 decades, which allows the estimation of a more HCT-specific long-term survival rate by considering background mortality changes. This study included 42,064 patients with hematologic malignancies who underwent their first allo-HCT in Japan between 2000 and 2018 and were reported to the Transplant Registry Unified Management Program. We compared the 5-year NS after allo-HCT in 4 consecutive HCT periods (2000 to 2004, 2005 to 2008, 2009 to 2012, and 2013 to 2018). The 5-year NS of the latest period was estimated using the period analysis method. Adjusted excess hazard ratios (EHRs) for 5-year NS over the HCT period were analyzed using an EHR model. In addition to the analysis of all hematologic malignancies, adjusted 5-year NS for each major hematologic malignancy, including acute myelogenous leukemia, acute lymphoblastic leukemia (ALL), myelodysplastic syndrome, adult T cell leukemia/lymphoma, chronic myeloid leukemia (CML), and malignant lymphoma, was analyzed. The probability of adjusted 5-year NS after HCT improved significantly over time: 35% in 2000 to 2004, 39% in 2005 to 2008, 45% in 2009 to 2012, and 49% in 2013 to 2018. The adjusted EHRs were .90 (95% confidence interval [CI], .86 to .93) in the 2005 to 2008 period, .77 (95% CI, .74 to .80) in the 2009 to 2012 period, and .65 (95% CI, .63 to .68) in the 2013 to 2018 period, with the 2000 to 2004 period as the reference. The 5-year NS improved among all hematologic malignancies, with a significant improvement in CML and ALL. The changes in 5-year NS from the 2000 to 2004 period to the 2013 to 2018 period ranged from 46% to 66% in CML and from 41% to 59% in ALL. In addition to the large improvement of 1-year NS, smaller but continued improvement in NS between 1 and 5 years after transplantation was observed. NS at 5 years conditional on being alive at 1 year increased from 64% in 2000 to 2004 to 73% in 2013 to 2018. Even after subtracting the background mortality in the general population, we found a significant improvement in long-term allo-HCT-specific survival rates for patients with hematologic malignancies over the past 2 decades in Japan.

Cost-effectiveness of preventive aspirin use and intensive downstaging polypectomy in patients with familial adenomatous polyposis: A microsimulation modeling study.

OBJECTIVE: Although there is increasing evidence to suggest the cost-effectiveness of aspirin use to prevent colorectal cancer (CRC) in the general population, no study has assessed cost-effectiveness in patients with familial adenomatous polyposis (FAP), who are at high risk of developing CRC. We examined the cost-effectiveness of preventive use of low-dose aspirin in FAP patients who had undergone polypectomy in comparison with current treatment practice. DESIGN: We developed a microsimulation model that simulates a hypothetical cohort of the Japanese population with FAP for 40 years. Three scenarios were created based on three intervention strategies for comparison with no intervention, namely intensive downstaging polypectomy (IDP) of colorectal polyps at least 5.0 mm in diameter, IDP combined with low-dose aspirin, and total proctocolectomy with ileal pouch-anal anastomosis (IPAA). Cost-effective strategies were identified using a willingness-to-pay threshold of USD 50,000 per QALY gained. RESULTS: Compared with no intervention, all strategies resulted in extended QALYs (21.01-21.43 QALYs per individual) and showed considerably reduced colorectal cancer mortality (23.35-53.62 CRC deaths per 1000 individuals). Based on the willingness-to-pay threshold, IDP with low-dose aspirin was more cost-effective than the other strategies, with an incremental cost-effectiveness ratio of $57 compared with no preventive intervention. These findings were confirmed in both one-way sensitivity analyses and probabilistic sensitivity analyses. CONCLUSION: This study suggests that the strategy of low-dose aspirin with IDP may be cost-effective compared with IDP-only or IPAA under the national fee schedule of Japan.

Morphological analysis of the impact of diabetes on gingival capillaries with non-invasive blood flow scope - A preliminary study.

Background/purpose: Diabetes mellitus (DM) induces microangiopathy in various tissues, leading to several complications. However, limited studies have reported the impact of diabetes on gingival capillaries. The aim of this study was to investigate the morphological evaluation and to analyze the influence of diabetes on gingival capillaries. Materials and methods: Medical interviews and periodontal examinations were performed on 29 patients with periodontitis. The subjects were divided into two groups: those with or without type 2 diabetes (DM or non-DM group). Gingival capillary density and morphology in the buccal marginal gingiva were evaluated using a capillary blood flow scope (magnification: × 560). Results: Probing pocket depth, plaque index, and gingival index were not significantly different between the DM and non-DM groups. The mean HbA1c was 7.9 ± 1.5% in the DM group (n = 14). Using an oral moisturizing gel as immersion agent, gingival capillaries can be observed under high magnification. The gingival capillary density was 10.5 ± 3.9/mm2 and 9.1 ± 2.7/mm2 in the non-DM group and DM group, respectively. There were no significant differences between the groups. Gingival capillary density was not significantly associated with probing pocket depth, plaque index, or gingival index. The proportion of capillary morphological abnormalities was significantly higher in the DM group than non-DM group. However, capillary morphological abnormalities were not significantly associated with the HbA1c. Conclusion: The present study first documented the morphological abnormalities of gingival capillaries in patients with type 2 diabetes using the capillary blood flow scope. Gingival capillary density might not be affected by diabetes.

Impact of cancer and other causes of death on mortality of cancer patients: A study based on Japanese population-based registry data.

Cancer registry data provide a very important source of information for improving our understanding of the epidemiology of various cancers. In this work, we estimated the 5-year crude probabilities of death from cancer and from other causes for five common cancers, namely stomach, lung, colon-rectum, prostate and breast, in Japan, using population-based registry data. Based on data on 344 676 patients diagnosed with one of these cancers between 2006 and 2008 in 21 prefectures participating in the Monitoring of Cancer Incidence in Japan (MCIJ) and followed-up for at least 5 years, we used a flexible excess hazard model to compute the crude probabilities of death for different combinations of sex, age and stage at diagnosis. For tumours diagnosed at the distant stage, as well as for regional lung tumours, the vast majority of deaths at 5 years in cancer patients were attributable to the disease itself (although this proportion was only around 60% in older prostate cancer patients). For localised and most regional tumours, the impact of other causes of death on the total mortality increased with age at diagnosis, especially for localised breast, colorectal and gastric cancer. By allowing the partition of the mortality experience of cancer patients into a cancer- and an other-cause-specific component, crude probability of death estimates provide insight into how the impact of cancer on mortality might differ among populations with different background mortality risks. This might be useful for informing discussions between clinicians and patients about treatment options.

Fragment imaging in the infrared photodissociation of the Ar-tagged protonated water clusters H3O+-Ar and H+(H2O)2-Ar.

Infrared photodissociation of protonated water clusters with an Ar atom, namely H3O+-Ar and H+(H2O)2-Ar, was investigated by an imaging technique for mass-selected ions, to reveal the intra- and intermolecular vibrational dynamics. The presented system has the advantage of achieving fragment ion images with the cluster size- and mode-selective photoexcitation of each OH stretching vibration. Translational energy distributions of photofragments were obtained from the images upon the excitation of the bound (νb) and free (νf) OH stretching vibrations. The energy fractions in the translational motion were compared between νbI and νfI in H3O+-Ar or between νbII and νfII in H+(H2O)2-Ar, where the labels "I" and "II" represent H3O+-Ar and H+(H2O)2-Ar, respectively. In H3O+-Ar, the νfI excitation exhibited a smaller translational energy than νbI. This result can be explained by the higher vibrational energy of νfI, which enabled it to produce bending (ν4) excited H3O+ fragments that should be favored according to the energy-gap model. In contrast to H3O+-Ar, the νbII excitation of an Ar-tagged H2O subunit and the νfII excitation of an untagged H2O subunit resulted in very similar translational energy distributions in H+(H2O)2-Ar. The similar energy fractions independent of the excited H2O subunits suggested that the νbII and νfII excited states relaxed into a common intermediate state, in which the vibrational energy was delocalized within the H2O-H+-H2O moiety. However, the translational energy distributions for H+(H2O)2-Ar did not agree with a statistical dissociation model, which implied another aspect of the process, that is, Ar dissociation via incomplete energy randomization in the whole H+(H2O)2-Ar cluster.

[Geographic information in National Cancer Registry data: Overseas examples and challenges in Japan].

Worldwide, research based on geographic information of official statistical data, including cancer registries, is utilized for cancer control and public health policies. The National Cancer Registry of Japan was launched in 2016, making it possible to use data on cancer incidence systematically. Given the nature of this comprehensive survey, the usefulness of the National Cancer Registry would be further enhanced when it is utilized at small-regional levels, such as in municipalities or even smaller geographical units. It is essential to maintain a balance between privacy protection and data usability. Currently, the national and prefectural councils determine the availability of the data from the National Cancer Registry at the small-regional level on an individual application basis. Under this framework, use of the data is often restricted or declined. This paper showcases three model countries where geographic information obtained from cancer registry data are widely utilized: the United States, Canada, and the United Kingdom. It further discusses measures to ensure that data are effectively used, without compromising data privacy. In the three countries, data-providing systems have been established to compile the necessary data from the cancer registry and other linked databases, in accordance with the purpose of use. The relationships between healthcare access and various outcomes are elaborately examined at the small-regional level. In Japan, similar utilization of data has not been fully implemented, and there remain many hurdles to the application of the data use. For the National Cancer Registry to promote research and further enhance cancer control, it is necessary to establish a system that enables effective and safe utilization of the data from the National Cancer Registry, including linkage with other data and on-site use.

Human transthyretin gene expression is markedly increased in repair Schwann cells in an in vitro model of hereditary transthyretin amyloidosis.

Hereditary transthyretin (TTR) amyloidosis (ATTRv) is characterized by TTR amyloid deposition in the peripheral nervous system. It remains unknown why variant TTR preferentially deposits in the peripheral nerves and dorsal root ganglia. We previously detected low levels of TTR expression in Schwann cells and established an immortalized Schwann cell line, TgS1, derived from a mouse model of ATTRv amyloidosis expressing the variant TTR gene. In the present study, the expression of TTR and Schwann cell marker genes was investigated in TgS1 cells by quantitative RT-PCR. TTR gene expression was markedly upregulated in TgS1 cells incubated in non-growth medium-Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum. The expression levels of c-Jun, Gdnf and Sox2 were increased, while Mpz was downregulated, suggesting that TgS1 cells exhibit a repair Schwann cell-like phenotype in the non-growth medium. Western blot analysis revealed that TTR protein was produced and secreted by the TgS1 cells. Furthermore, downregulation of Hsf1 with siRNA induced TTR aggregates in the TgS1 cells. These findings indicate that TTR expression is markedly increased in repair Schwann cells, likely to promote axonal regeneration. Therefore, aged dysfunctional repair Schwann cells may cause the deposition of variant TTR aggregates in the nerves of patients with ATTRv.

Isolation of OXA-48-like carbapenemase-producing Escherichia coli susceptible to piperacillin/tazobactam in a Japanese patient without a history of travel abroad.

Oxacillinase (OXA)-48-like ß-lactamases are the most common carbapenemases in Enterobacterales in certain regions of the world and are being introduced on a regular basis into regions of non-endemicity. Japan has been characterized by low rates of carbapenemase-producing Enterobacterales, and among them, OXA-48-like carbapenemase-producing isolates are extremely rare. Here we describe a Japanese medical worker, without a history of travel abroad, who was diagnosed as having a community-acquired urinary tract infection, and whose urine sample was found to be positive for OXA-48-like carbapenemase-producing Escherichia coli. None of her close contacts had a history of foreign travel, and the same drug-resistant organism was not observed in other patients who had been hospitalized and undergone environmental culture tests in the same medical institution. This isolate was resistant to penicillins, narrow-spectrum cephalosporins, fluoroquinolones, and cefmetazole, but was susceptible to broad-spectrum cephalosporins, piperacillin/tazobactam, and meropenem and displayed reduced susceptibility to imipenem. The modified carbapenem inactivation test supported carbapenemase production, but inhibitor-based synergistic tests yielded negative results of carbapenemase production. Multiplex polymerase chain reaction revealed the presence of the carbapenemase gene (blaOXA-48) blaTEM and AmpC ß-lactamase gene (blaDHA). Singleplex polymerase chain reaction targeting the blaOXA-48 region amplified a product sequencing to nearly the full length (722 bp) and matching 100% with OXA-48. The present case highlights a new concern regarding OXA-48-like carbapenemase-producing Enterobacterales, which remain challenging to detect for clinical laboratories in regions of non-endemicity, and may already be latent in Japan.