Feasibility and effectiveness of preconception check-ups at workplaces in Japan.

OBJECTIVES: Despite the recent increase in infertility and perinatal complications, preconception care is not commonly available in Japan. Working women are considered to have the greatest need for preconception care, as they increasingly marry and have children later in life. This study aimed to assess the feasibility and effectiveness of preconception check-ups in the workplace. METHODS: We provided 51 female employees aged 18-39 years with free preconception check-ups, including additional blood tests and an online medical questionnaire, during mandatory health check-ups at their workplace. A doctor provided online counselling based on the check-up results. We assessed fertility knowledge using the Cardiff Fertility Knowledge Scale (CFKS-J) and childbearing desire pre- and post-intervention. RESULTS: Preconception check-ups revealed various potential risk factors for future pregnancies, including underweight (12%), obesity (20%), Chlamydia trachomatis IgG antibody positivity (22%), low Rubella IgG antibody levels (47%), iron deficiency (12%), and 25-hydroxyvitamin D levels <30 ng/mL (98%). Post-intervention, the participants reported high satisfaction with the check-ups and significantly advanced their reproductive plans (P=0.008). Further, 95% of the participants indicated an intention to seek medical attention or make lifestyle changes. The post-intervention CFKS-J score (mean ± SD) was higher than the pre-intervention score (71.7 ± 19.3 versus 63.0 ± 22.0, P=0.006). CONCLUSIONS: We developed a preconception check-up package that can be integrated into workplace health examinations, complemented by tailored counselling. This novel check-up package is a feasible and effective approach for improving preconception health and fertility awareness.

A case of hereditary breast and ovarian cancer syndrome of initially presented as cancer of unknown primary with lymph node metastases unveiled by genetic analysis.

Cancer of unknown primary (CUP) is a heterogeneous disease concept involving various malignant tumors. Understanding its pathophysiology is often difficult, together with its treatment. Here, we present a case of CUP with abdominal lymph node enlargement and elevated carbohydrate antigen 125 levels. It initially resembled a favorable prognosis type similar to ovarian cancer, but metastases were observed in cervical lymph nodes, indicating a somewhat atypical CUP compared to the typical ovarian cancer-like CUP. We identified a germline Breast Cancer 1 (BRCA1) p.L63* variant through a family history inquiry and BRCA analysis, indicating hereditary breast and ovarian cancer syndrome. The patient achieved near-complete remission with platinum-based therapy followed by poly (ADP-ribose) polymerase (PARP) inhibitor. The variant has shown sensitivity in both clinical and pathogenic reports in the ClinVar database of the National Institutes of Health. No clinical studies reported on the efficacy of PARP inhibitors specific to this variant, but our case demonstrated the sensitivity of platinum-based therapy followed by PARP inhibitor. Reports of CUP in hereditary breast and ovarian cancer syndrome are very rare, with only a single report in the literature.

Intraoperative rapid diagnosis of pleural lavage cytology in non-small cell lung cancer.

OBJECTIVE: Positive pleural lavage cytology (PLC +) is a poor prognostic factor for non-small cell lung cancer (NSCLC). However, data on the impact of intraoperative rapid diagnosis of PLC (rPLC) are lacking. Therefore, we evaluated the efficacy of rPLC before resection during surgery. METHODS: A total of 1,838 patients who underwent rPLC for NSCLC between September 2002 and December 2014 were studied retrospectively. We assessed the clinicopathological factors between rPLC findings and the impact on survival of patients with curative resection. RESULTS: The rPLC + status was observed in 96 (5.3%) among 1,838 patients. The rPLC + group had more unsuspected N2 (30%) than the rPLC- group (p < 0.001). The 5-year overall survival (OS) of patients who underwent lobectomy or more extensive resection with rPLC + , negative rPLC (rPLC-), and microscopic pleural dissemination (PD) and/or malignant pleural effusion (PE) were 67.3, 81.3, and 11.0%, respectively. In the rPLC + group, the prognosis of patients with pN2 was equal to that of pN0-1 (5-year OS: 77.9% vs. 63.4%, p = 0.263). Undetectable dissemination in the first evaluation immediately after starting surgery was found in 9% of rPLC + patients by additional evaluation of the thoracic cavity. CONCLUSIONS: Patients with rPLC + have more favorable survival than those with microscopic PD/PE after surgery. Curative resection should be performed in patients with rPLC + , even if N2 is detected during surgery. However, the rPLC + group often has N2 upstaging; therefore, systematic nodal dissection should be performed in rPLC + patients for exact staging. rPLC may contribute to preventing oversight PD by re-evaluation during surgery.

An approach for live imaging of first cleavage in mouse embryos using fluorescent chemical probes for DNA, microtubules, and microfilaments.

Purpose: Dynamic morphological changes in the chromosome and cytoskeleton occur in mammals and humans during early embryonic development, and abnormalities such as embryonic chromosomal aneuploidy occur when development does not proceed normally. Visualization of the intracellular organelles and cytoskeleton allows elucidation of the development of early mammalian embryos. The behavior of the DNA and cytoskeleton in early mammalian embryos has conventionally been observed by injecting target molecule mRNAs, incorporating a fluorescent substance-expressing gene, into embryos. In this study, we visualized the chronological behavior of male and female chromosome condensation in mouse embryos, beginning in the two-pronuclear zygote, through the first division to the two-cell stage, using fluorescent chemical probes to visualize the behavior of DNA, microtubules, and microfilaments. Method: Mouse two-pronuclear stage embryo were immersed in medium containing fluorescent chemical probes to visualize DNA, microtubules, and microfilaments. Observation was performed with a confocal microscope. Results: This method allowed us to observe how chromosome segregation errors in first somatic cell divisions in mouse embryos and enabled dynamic analysis of a phenomenon called lagging chromosomes. Conclusions: By applying this method, we can observe any stage of embryonic development, which may provide new insights into embryonic development in other mammals.

Prognostic significance of tumor microenvironment assessed by machine learning algorithm in surgically resected non-small cell lung cancer.

BACKGROUND: A methodology to assess the immune microenvironment (IME) of non-small cell lung cancer (NSCLC) has not been established, and the prognostic impact of IME factors is not yet clear. AIMS: This study aimed to assess the IME factors and evaluate their prognostic values. METHODS AND RESULTS: We assessed CD8+ tumor-infiltrating lymphocyte (TIL) density, forkhead box protein P3+ (Foxp3+ ) TIL density, and programmed death receptor ligand-1 (PD-L1) tumor proportion score (TPS) using a machine-learning algorithm in whole-slide imaging (WSI). We dichotomized patients according to TIL density or TPS and compared their clinical outcomes. Between September 2014 and September 2015, 165 patients with NSCLC were enrolled in the study. We assessed IME factors in the epithelium, stroma, and their combination. An improvement in disease-free survival (DFS) was observed in the high CD8+ TIL density group in the epithelium, stroma, and the combination of both. Moreover, the group with high PD-L1 TPS in the epithelium showed better DFS than that with low PD-L1 TPS. In the multivariate analysis, the CD8+ TIL density in the combination of epithelium and stroma and PD-L1 TPS in the epithelium were independent prognostic factors (hazard ratio [HR] = 0.43; 95% confidence interval [CI] = 0.26-0.72; p = .001, HR = 0.49; 95% CI = 0.30-0.81; p = .005, respectively). CONCLUSION: Our approach demonstrated that the IME factors are related to survival in patients with NSCLC. The quantitative assessment of IME factors enables to discriminate patients with high risk of recurrence, who can be the candidates for adjuvant therapy. Assessing the CD8+ TIL density in the combination of epithelium and stroma might be more useful than their individual assessment because it is a simple and time-saving analysis of TILs in WSI.

The first nationwide website survey of the availability and costs of medical and non-medical oocyte cryopreservation in Japan.

Research question: How does the cost-related oocyte cryopreservation (OoC) vary by the facility in Japan, and what data is provided on the websites about OoC procedures? Design: Website survey. The websites of all 621 facilities that provide assistive reproductive technology registered in Japan were surveyed in 2021. Data included the rates of explicit statements regarding the provision of OoC for only medical reasons (medical only group) or non-medical reasons (non-medical group). Based on whether or not facilities that perform OoC clearly stated the cost on their websites, we compared the costs of OoC and annual storage cost between medical only and non-medical groups. Furthermore, we examined the stated number of OoC procedures performed and their clinical outcomes. Results: Of the 621 facilities, 146 (23.5%) clearly stated that they offer OoC on their websites. Of the 88 medical only groups and 58 non-medical groups, 24 (27.3%) and 42 (72.4%) clearly stated the OoC cost, and 27 (30.7%) and 44 (75.9%) clearly states the annual oocyte storage cost, respectively. The OoC costs were significantly higher for the non-medical group than in the medical group. In the medical only group, the annual storage cost remained almost the same regardless of the number of oocytes, while in the non-medical group, the annual storage cost was 2-3 times higher than in the medical only group. Only 16 facilities (16/146, 11.0%) had mentioned the number of OoC procedures, and five facilities (3.4%) provided information on the clinical outcomes after OoC. Conclusion: Costs related to OoC are higher for the non-medical group in Japan. In addition, the websites contain scant information on the costs and clinical outcomes of OoC.

Diagnostic sensitivity of solid volume measurement for pathological invasion in non-solid lung adenocarcinoma.

Background: In the current tumor-node-metastasis (TNM) classification, the clinical T descriptor is defined by solid size (SS) on a computed tomography (CT) slice and the pathological one is done by invasive size (IS) in microscopic evaluations. We sometimes experience discrepancies in diagnosis of both descriptors. A volume analyzing application enables semi-automatic measurement of three-dimensional (3D) parameters in cases where there are discrepancies in diagnosing tumors' solid size and IS. In this study, we aimed to evaluate the association between 3D parameters and pathological invasion in non-solid small-sized lung adenocarcinomas. Methods: We enrolled 246 consecutive patients who underwent pulmonary resection at Shizuoka Cancer Center. Patients with lung adenocarcinomas that were radiologically non-solid, node-negative and sized ≤3 cm were eligible. We used a volume analyzing application to retrospectively measure 3D parameters of max and mean Hounsfield units (HUs) and solid volume (SV). The cut-off value of these parameters for diagnosing invasive adenocarcinoma (IAD) was set by describing receiver operating characteristic (ROC) curves. The correlation of IAD with these parameters was compared to its correlation with the SS. This study was not registered. Results: Of 246 patients with adenocarcinoma, 183 (74.4%) had IADs. In multivariate analyses, the total size (TS) and SS were significantly associated with IAD (P=0.006, 0.001, respectively), whereas 3D parameters including SV were not (P=0.80). In radiological adenocarcinoma (2.1-3.0 cm), SV >300 mm3 diagnosed IAD with a higher sensitivity than that of the SS (0.93 and 0.83, respectively). Conclusions: TS >20 mm and SS >5 mm were well-correlated with IAD. SV measurement may complement the current computed tomographic diagnosis of IAD based on the SS (2.1-3.0 cm).

Anti-glutamic Acid Decarboxylase Antibody-Positive Gestational Diabetes Mellitus with Autoimmune Type 1 Diabetes Mellitus in the Early Postpartum Period: A Case Report and Literature Review.

Gestational diabetes mellitus (GDM) is a state of pre-diabetic impaired glucose tolerance initially occurring during pregnancy. Although abnormalities in glucose metabolism normally resolve rapidly after delivery, women with GDM have a higher lifetime risk of developing diabetes mellitus than those without GDM; thus, postpartum healthcare is essential. Of all GDM patients, 5%-10% test positive for diabetes-related autoantibodies, which increase the risk of developing type 1 diabetes mellitus (T1DM). Autoantibody measurement in GDM screening remains debatable; however, it may be useful for the postnatal follow-up of GDM patients at high risk of developing T1DM. We treated a 29-year-old woman who was GDM positive for anti-glutamic acid decarboxylase antibody (GADA) requiring high-dose insulin therapy during pregnancy. As the patient tested positive for GADA, she received judicious postpartum management, allowing for early diagnosis of T1DM and resumption of treatment. Her insulin secretory capacity was preserved at 1 year after parturition, suggesting either slowly progressive insulin-dependent T1DM or latent autoimmune diabetes in adults. This was a rare case of slowly progressive insulin-dependent T1DM or latent autoimmune diabetes in adults in the early postpartum period, but the fact that GADA was positive during pregnancy enabled early treatment without overlooking it. Measuring diabetes-related autoantibodies in patients considered to be at a high risk for T1DM, such as those who are of slim build, young, or suffering from autoimmune thyroid disorders, may be important for appropriate individualized follow-up.

The efficacy of a machine learning algorithm for assessing tumour components as a prognostic marker of surgically resected stage IA lung adenocarcinoma.

BACKGROUND: The importance of the stromal components in tumour progression has been discussed widely, but their prognostic role in small size tumours with lepidic components is not fully understood. Applying digital tissue image analysis to whole-slide imaging may enhance the accuracy and reproducibility of pathological assessment. This study aimed to evaluate the prognostic value of tumour components of lung adenocarcinoma by measuring the dimensions of the tumour consisting elements separately, using a machine learning algorithm. METHODS: Between September 2002 and December 2016, 317 patients with surgically resected, pathological stage IA adenocarcinoma with lepidic components were analysed. We assessed the whole tumour area, including the lepidic components, and measured the epithelium, collagen, elastin areas and alveolar air space. We analysed the prognostic impact of each tumour component. RESULTS: The dimensions of the epithelium and collagen areas were independent significant risk factors for recurrence-free survival (hazard ratio, 8.38; 95% confidence interval, 1.14-61.88; P = 0.037, and hazard ratio, 2.58; 95% confidence interval, 1.14-5.83; P = 0.022, respectively). According to the subgroup analysis when combining the epithelium and collagen areas as risk factors, patients with tumours consisting of both large epithelium and collagen areas showed significantly poor prognoses (P = 0.002). CONCLUSIONS: We assessed tumour components using a machine learning algorithm to stratify the post-operative prognosis of surgically resected stage IA adenocarcinomas. This method might guide the selection of patients with a high risk of recurrence.

Influence of LINE-Assisted Provision of Information about Human Papillomavirus and Cervical Cancer Prevention on HPV Vaccine Intention: A Randomized Controlled Trial.

We conducted a prospective, randomized two-arm, parallel group, and open label trial to investigate whether the use of LINE would increase HPV vaccine intention among not completely vaccinated university students. In June 2020, we recruited students aged between 18 and 35 years from four universities in Japan. Among the 357 enrollees (female, 53%), 178 and 179 participants were randomized into the LINE and Mail groups, respectively. At baseline, within three years, vaccine intention was observed in 40% vs. 42% of participants, respectively. At the first intervention, which provided similar PDF leaflets about HPV vaccine and cervical cancer prevention, there was no significant difference in vaccine intention between the two groups. However, at the second intervention of LINE-assisted knowledge intervention for 5 days per week for 7 weeks, the LINE group had a higher proportion of vaccine intention than the no intervention group (66% vs. 44%, OR: 2.62, 95% confidence interval (CI): 1.59-4.35) in per-protocol analysis. The significance remained in the intention-to-treat analysis of multiply imputed datasets. Although LINE did not directly increase HPV vaccine intention compared to conventional posts, the LINE-assisted provision of information was effective in improving HPV vaccine intention among Japanese university and college students.

Comparison of treatment outcomes between first-line chemotherapy with or without bevacizumab for advanced ovarian, fallopian tube, and primary peritoneal cancer (Tohoku gynecologic cancer unit: TGCU-RS001 study).

BACKGROUND: Outcomes with and without bevacizumab as first-line chemotherapy in Japanese-only ovarian cancer patients have not been reported. In this study, we report a retrospective study conducted at the Tohoku Gynecologic Cancer Unit. PATIENTS AND METHODS: The study included 453 patients with stage III/IV ovarian, fallopian tube, and primary peritoneal cancer who received first-line platinum-based chemotherapy. The patients were divided into two groups: bevacizumab (168 patients) and without bevacizumab (285 patients). The primary endpoint was the rate of platinum-resistant recurrence and the secondary endpoints were the antitumor response, progression-free survival, overall survival, and adverse events. RESULTS: The objective response rates for patients with measurable diseases treated with and without bevacizumab were 84.5% and 73.0%, respectively (P = 0.0066). Platinum-resistant recurrence in the groups treated with and without bevacizumab was noted in 31 (18.4%) and 111 (38.6%) patients, respectively (P < 0.0001). The median progression-free survival for the bevacizumab and without bevacizumab groups was 23 and 15 months, respectively (P = 0.0002), and the median overall survival was not reached and 49 months, respectively (P = 0.0005). Hypertension of grade 3 or higher was observed in 21 patients (12.5%) in the bevacizumab group (P < 0.001), and proteinuria was observed in 18 patients (10.7%) and 1 patient (0.3%) in the bevacizumab and without bevacizumab groups, respectively (P < 0.001). Intestinal perforation was observed in only one patient (0.6%) in the bevacizumab group. CONCLUSION: Combination and maintenance with bevacizumab in primary chemotherapy for advanced ovarian, fallopian tube, and primary peritoneal cancer was effective in reducing platinum-resistant recurrence rates and prolonging progression-free and overall survival.

Quantitative severity of emphysema is related to the prognostic outcome of early-stage lung cancer.

OBJECTIVES: Although pulmonary emphysema is a component of chronic obstructive pulmonary disease, the prognostic significance of the quantitative severity of emphysema in patients with primary lung cancer is unclear. This study aimed to identify the association between the quantitative severity of emphysema detected by the low-attenuation area on computed tomography and the prognostic outcome of early non-small-cell lung cancer. METHODS: A consecutive series of 1062 patients who underwent lobectomy for clinical stage I and II non-small-cell lung cancer were enrolled in this study. The clinicopathological features and long-term outcomes of patients with primary lung cancer in emphysema were investigated. The extent of emphysema in the lobe where the tumour was present was measured by preoperative computed tomography as a percentage of the low-attenuation area (LAA%). RESULTS: LAA% ≥ 1.0% was detected in 145 (13.7%) patients. LAA% was associated with pleural invasion (P < 0.0001), vascular invasion (P < 0.0001) and a larger tumour size (P = 0.001). The overall survival and recurrence-free survival in patients with LAA% ≥ 1.0% and with LAA% < 1.0% at 5 years were 78.6% and 92.1% (P < 0.0001) and 68.7% and 85.2% (P < 0.0001), respectively. According to the Cox proportional hazards model, LAA% was an independent prognostic factor for overall survival and recurrence-free survival (P = 0.0004 and P = 0.003, respectively). CONCLUSIONS: The quantitative severity of pulmonary emphysema was found to be associated with poor prognosis and clinicopathological aggression in early non-small-cell lung cancer.

HPV vaccine intention among university students during suspension of active recommendation in Japan.

In Japan, active recommendation of the human papillomavirus vaccine was withheld between 2013 and 2021 due to adverse reaction reports. This resulted in low vaccine coverage with reports from less than 1%. This study aimed to investigate if knowledge and health-belief related factors associated with vaccine intention among young adolescents with the hope that our findings may be helpful in promotion campaigns. We recruited students in four colleges and universities in Akita Prefecture from 2020 to 2021 who had never been vaccinated. A total of 318 students (male 54%, mean age 21 years) responded to a self-administered questionnaire; only 6% reported immediate vaccine intention, and 61% reported no such intention or "do not know." The correct percentages of 20-item knowledge about HPV vaccine-related morbidity, mortality, and prevention were very low regardless of gender (average males 41.4% vs. females 39.6%). Multivariable logistic regression models demonstrated that in males, higher levels of literacy, perceived susceptibility, and place for vaccination (logistical barrier) were associated with HPV vaccine intention, whereas "no need now" was associated with less intention. In females, a higher level of knowledge was significantly associated with vaccine intention, whereas "concerns of adverse effects" were associated with less intention.

Artificial Intelligence-Powered Prediction of ALK Gene Rearrangement in Patients With Non-Small-Cell Lung Cancer.

PURPOSE: Several studies reported the possibility of predicting genetic abnormalities in non-small-cell lung cancer by deep learning (DL). However, there are no data of predicting ALK gene rearrangement (ALKr) using DL. We evaluated the ALKr predictability using the DL platform. MATERIALS AND METHODS: We selected 66 ALKr-positive cases and 142 ALKr-negative cases, which were diagnosed by ALKr immunohistochemical staining in our institution from January 2009 to March 2019. We generated virtual slide of 300 slides (150 ALKr-positive slides and 150 ALKr-negative slides) using NanoZoomer. HALO-AI was used to analyze the whole-slide imaging data, and the DenseNet network was used to build the learning model. Of the 300 slides, we randomly assigned 172 slides to the training cohort and 128 slides to the test cohort to ensure no duplication of cases. In four resolutions (16.0/4.0/1.0/0.25 µm/pix), ALKr prediction models were built in the training cohort and ALKr prediction performance was evaluated in the test cohort. We evaluated the diagnostic probability of ALKr by receiver operating characteristic analysis in each ALKr probability threshold (50%, 60%, 70%, 80%, 90%, and 95%). We expected the area under the curve to be 0.64-0.85 in the model of a previous study. Furthermore, in the test cohort data, an expert pathologist also evaluated the presence of ALKr by hematoxylin and eosin staining on whole-slide imaging. RESULTS: The maximum area under the curve was 0.73 (50% threshold: 95% CI, 0.65 to 0.82) in the resolution of 1.0 µm/pix. In this resolution, with an ALKr probability of 50% threshold, the sensitivity and specificity were 73% and 73%, respectively. The expert pathologist's sensitivity and specificity in the same test cohort were 13% and 94%. CONCLUSION: The ALKr prediction by DL was feasible. Further study should be addressed to improve accuracy of ALKr prediction.

A Survey of Genetic Counseling for Non-invasive Prenatal Testing Examinees in Akita.

Introduction: In recent years, there has been an increase in noninvasive prenatal testing (NIPT), where maternal blood samples are used to extract fetal cell-free DNA. Despite this being offered in several facilities in urban areas, NIPT remains to be scarcely unavailable in rural areas. Moreover, there is lacking information with regard to how pregnant women in rural areas perceive NIPT. Thus, in this study, we conducted a survey among pregnant women who came to our clinic for NIPT and examined their views on NIPT and genetic counseling. Methods: A questionnaire survey was administered to pregnant women who requested NIPT and underwent genetic counseling at our hospital between November 2016 and February 2020. The questionnaire was administered twice, once after completing the genetic counseling and once after explaining the NIPT results. The number of genetic counseling and NIPT sessions and positive test results, as well as anxiety about the test and evaluation of genetic counseling and NIPT, were assessed. Results: In total, 115 patients received genetic counseling, of which 109 underwent NIPT. The test results were found to be positive in six patients. As per our findings, 103 patients (93%) indicated they needed genetic counseling for NIPT, whereas 99 (93%) were satisfied with the counseling they received from a genetic medicine specialist. On the other hand, 82 patients (77%) requested for more testing facilities. Conclusions: The enhancement of genetic counseling systems is essential to expand the environment in which NIPT is performed. Therefore, we need to consider the need to make the NIPT testing environment more conducive and inform clients of the importance of genetic counseling in NIPT.

Out-of-pocket payment and patients' treatment choice for assisted reproductive technology by household income: a conjoint analysis using an online social research panel in Japan.

BACKGROUND: Economic disparities affect access to assisted reproductive technology (ART) treatment in many countries. At the time of this survey, Japan provided partial reimbursement for ART treatment only for those in low- or middle-income classes due to limited governmental budgets. However, the optimal level of financial support by income class remains unclear. METHODS: We conducted a conjoint analysis of ART in Japan in January 2020. We recruited 824 women with fertility problems aged 25 to 44 years via an online social research panel. They completed a questionnaire of 16 hypothetical scenarios measuring six relevant ART attributes (i.e., out-of-pocket payment, pregnancy rate, risk of adverse effects, number of visits to outpatient clinics, consultation hours and kindness of staff) and their relations to treatment choice. RESULTS: Mixed-effect logistic regression models showed that all six attributes significantly influenced treatment preferences, with participants valuing out-of-pocket payment the most, followed by pregnancy rates and kindness of staff. Significant interactions occurred between high household income (≥ 8 million JPY) and high out-of-pocket payment (≥ 500,000 JPY). However, the average marginal probability of the highest-income patients (i.e., ≥ 10 million JPY, ineligible for the subsidy) receiving ART treatment at the average cost of 400,000 JPY was 47%, compared to 56 - 61% of other income participants, who opted to receive ART at an average cost of 100,000 JPY after a 300,000 JPY subsidy. CONCLUSION: Our results suggest that out-of-pocket payment is the primary determinant in patients' decision to opt for ART treatment. High-income patients were more likely to choose treatment, even at a high cost, but their income-based ineligibility for government financial support might discourage some from receiving treatment.

Creation, effects on embryo quality, and clinical outcomes of a new embryo culture medium with 31 optimized components derived from human oviduct fluid: A prospective multicenter randomized trial.

Purpose: Our aim is to make an ideal embryo culture medium close to human oviduct fluid (HOF) components, and to evaluate the quality of this medium with embryo quality and clinical outcomes in assisted reproductive technology (ART) by a prospective randomized controlled trial (RCT). Methods: Study I: HOF was collected laparoscopically from patients (n = 28) with normal pelvic findings. According to HOF analysis results, the new medium "HiGROW OVIT®" (OVIT) was designed. Study II: Embryos (2 pronuclei (2PN) = 9633) were assigned from 1435 patients. The blastulation rate (BR), good BR (gBR), utilized (transferred/cryo-preserved) BR (uBR), pregnancy rate (PR), and miscarriage rate (MR) were compared between the OVIT and control groups by RCT. Results: The novel medium 'OVIT' was produced according to 31 HOF components. The concentrations of essential amino acids (e-AAs) were lower in OVIT than in current media, yet the opposite was true for ne-AA concentrations. gBR and uBR were higher in the OVIT group than in the control group. In the older female group, gBT and uBR were significantly higher in the OVIT group. Conclusions: The novel medium 'OVIT' was produced according to HOF data. The OVIT had significantly better embryo quality and clinical outcomes than the current media.

Adult-onset Still's Disease during Pregnancy Treated with Tocilizumab.

A 28-year-old woman exhibited a spiking fever, arthritis, and liver disfunction when she was 22 weeks pregnant. She was diagnosed with adult-onset Still's disease (AOSD). As her condition was resistant to corticosteroid therapy, tocilizumab (TCZ) was selected. The TCZ treatment was effective, and she delivered a healthy child while receiving TCZ treatment. Cases in which AOSD first arises during pregnancy are rare, and there have been no reports of TCZ treatment for AOSD being initiated during pregnancy. Although the safety of TCZ treatment during pregnancy has not been established, it may be effective against severe AOSD that develops during pregnancy.

Developments of GNSS buoy for a synthetic geohazard monitoring system.

A global navigation satellite system (GNSS) buoy system for early tsunami warnings has been developed for more than 20 years. The first GNSS buoy system using a real-time kinematic algorithm (RTK) was implemented in the Nationwide Ocean Wave information network for Ports and HArbourS (NOWPHAS) wave monitoring system in Japan in 2008. The records of NOWPHAS were used to update the tsunami alert by the Japan Meteorological Agency (JMA), owing to the tsunami generated by the 2011 Tohoku-oki earthquake (Mw9.0). However, considering that the distance limit is less than 20 km for the RTK algorithm, a new system was designed by introducing a new positioning algorithm and satellite data transmission to place the buoy much farther from the coast. A new technique for the continuous monitoring of ocean-bottom crustal movements was also implemented in the new system. The new buoy system can be used for weather forecasting and ionospheric monitoring as well.