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To determine the characteristics of pediatric patients 0-19 years of age who died after onset of SARS-CoV-2 infection in Japan during January 1-September 30, 2022, we reviewed multiple sources. We identified 62 cases, collected detailed information from medical records and death certificates, and conducted interviews, resulting in 53 patients with detailed information for our study. Among 46 patients with internal causes of death (i.e., not external causes such as trauma), 15% were <1 year of age, 59% had no underlying disease, and 88% eligible for vaccination were unvaccinated. Nonrespiratory symptoms were more common than respiratory symptoms. Out-of-hospital cardiac arrest affected 46% of patients, and time from symptom onset to death was <7 days for 77%. Main suspected causes of death were central nervous system abnormalities (35%) and cardiac abnormalities (20%). We recommend careful follow-up of pediatric patients after SARS-CoV-2 infection during the first week after symptom onset, regardless of underlying diseases. [ABSTRACT FROM AUTHOR]

Guangnanmycin A is a recently discovered congener of the well‐known antitumor drug lead leinamycin; its macrolactam ring, however, is even more strained than that of the parent compound. The first synthetic foray towards this challenging target is reported, which relies on molybdenum‐catalyzed macrocyclization by ring closing alkyne metathesis (RCAM) followed by ruthenium‐catalyzed redox isomerization of the propargyl alcohol thus formed; the resulting enone enabled the introduction of the yet missing exo‐methylene group by a modified Peterson olefination. The signature disulfide moiety of guangnanmycin A was installed by strain‐driven thia‐Michael addition followed by conversion of the thioether thus formed into an unsymmetric disulfide with the aid of (methylthio)dimethylsulfonium tetrafluoroborate and MeSSMe. While this sequence furnished racemic guangnanmycin A alcohol in good overall yield, the final oxidation to the corresponding acid failed, most likely because of the exceptional sensitivity of the strained scaffold. [ABSTRACT FROM AUTHOR]

Guangnanmycin A is a recently discovered congener of the well‐known antitumor drug lead leinamycin; its macrolactam ring, however, is even more strained than that of the parent compound. The first synthetic foray towards this challenging target is reported, which relies on molybdenum‐catalyzed macrocyclization by ring closing alkyne metathesis (RCAM) followed by ruthenium‐catalyzed redox isomerization of the propargyl alcohol thus formed; the resulting enone enabled the introduction of the yet missing exo‐methylene group by a modified Peterson olefination. The signature disulfide moiety of guangnanmycin A was installed by strain‐driven thia‐Michael addition followed by conversion of the thioether thus formed into an unsymmetric disulfide with the aid of (methylthio)dimethylsulfonium tetrafluoroborate and MeSSMe. While this sequence furnished racemic guangnanmycin A alcohol in good overall yield, the final oxidation to the corresponding acid failed, most likely because of the exceptional sensitivity of the strained scaffold. [ABSTRACT FROM AUTHOR]

Background: Adult spinal deformity has a substantially debilitating effect on older people's physical and mental health. However, the impact of sagittal malalignment on locomotive syndrome (LS), sarcopenia, and physical function in community-dwelling older women has not yet been clarified. This study aimed to investigate the association between these factors in community-dwelling middle aged and older women. Methods: A total of 361 women were recruited from participants performing aquatic exercises in a rural area of Japan. The body mass index, skeletal muscle mass index, trunk muscle mass, spinal inclination angle (SIA), grip strength, timed up-and-go test (TUG), maximum stride of the participants, and one-leg standing time were measured. Low back pain (LBP)- and health-related quality of life (HRQOL) were evaluated using the Oswestry Disability Index (ODI) and the Short-Form 8 questionnaire. Associations between the global sagittal alignment using SIA and investigating parameters were analyzed. Results: The prevalence of sarcopenia was 3.6%. The prevalence of LS (stages 1, 2, and 3) was 43.8% (158 of 361), and the number of participants in each LS stage was 203 (stage 0), 95 (stage 1), 28 (stage 2), and 35 (stage 3). The SIA was significantly correlated with the 25-question geriatric locomotive function scale (r′ = 0.292, p < 0.001), ODI (r′ = 0.267, p < 0.001), and TUG (r′ = 0.453, p < 0.001) after adjusting for age. In the receiver-operating characteristic curve analysis, the cutoff values of SIA for LS ≥ stage 2 and ODI ≥ 20% were 5°. Conclusions: LBP-related QOL and physical performance were significantly associated with global sagittal alignment. Global sagittal alignment was correlated with the three-stage category of LS. The spinal inclination of 5° was a cutoff value to predict exacerbation of mobility function and HRQOL status. [ABSTRACT FROM AUTHOR]

Objective: To apply the International Federation of Gynecology and Obstetrics (FIGO) 2018 staging system to all patients who underwent trachelectomy in our previous study and to update the oncologic and obstetric results. Methods: We retrospectively reviewed the medical records of patients in whom abdominal trachelectomy was attempted between June 2005 and September 2021. The FIGO 2018 staging system for cervical cancer was applied to all patients. Results: Abdominal trachelectomy was attempted for 265 patients. Trachelectomy was converted to hysterectomy in 35 patients, and trachelectomy was completed successfully in 230 (conversion rate: 13%). Applying the FIGO 2018 staging system, 40% of the patients who underwent radical trachelectomy had stage IA tumors. Among 71 patients who had tumors measuring =2 cm, 8 patients were classified as stage IA1 and 14 as stage IA2. Overall recurrence and mortality rates were 2.2% and 1.3%, respectively. One hundred twelve patients attempted to conceive after trachelectomy; 69 pregnancies were achieved in 46 patients (pregnancy rate: 41%). Twenty-three pregnancies ended in first-trimester miscarriage, and 41 infants were delivered between gestational weeks 23 and 37; 16 were deliveries at term (39%) and 25 were premature deliveries (61%). Conclusion: This study suggested that patients judged to be ineligible for trachelectomy and patients receiving overtreatment will continue to appear using the current standard eligibility criteria. With the revisions to the FIGO 2018 staging system, the preoperative eligibility criteria for trachelectomy, which were based on the FIGO 2009 staging system and tumor size, should be changed. [ABSTRACT FROM AUTHOR]

Objective: To analyze the effects of in‐person attendance at an academic conference held during the Covid‐19 pandemic on the health of the attendees, as assessed based on symptoms such as fever and cough attributed to infection with the Covid‐19 virus. Methods: A questionnaire was used to survey the members of the Japan Society of Obstetrics and Gynecology (JSOG) about their health during the period from August 7 to August 12, 2022, after the 74th Annual Congress of the JSOG, which was held August 5 to 7. Results: Our survey yielded responses from 3054 members (1566 of whom had attended the congress in person and 1488 of whom had not attended in person); 102 (6.5%) of the in‐person attendees and 93 (6.2%) of the people who did not attend in person reported problems with their health. No statistically significant difference was found between these two groups (p = 0.766). In a univariate analysis of factors affecting the presence of health problems, attendees with age ≥60 years had significantly fewer health problems than attendees who were in their 20s (odds ratio: 0.366 [0.167–0.802; p = 0.0120]). In a multivariate analysis, attendees who had received four vaccine shots had significantly fewer health problems than attendees who had received three shots (odds ratio: 0.397 [0.229–0.690, p = 0.0010]). Conclusion: Congress attendees who took precautions at the congress to avoid being infected and who had a high vaccination rate did not develop significantly more health problems associated with in‐person attendance at the congress. [ABSTRACT FROM AUTHOR]

Aim: Westernization of lifestyle has increased the numbers of patients with endometrial cancer and obesity. This study aimed to compare the clinical outcomes of robotic‐assisted surgery according to whether patients are obese, morbidly obese, or nonobese. Methods: Sixty‐three patients with endometrial cancer who underwent robotic‐assisted surgery between March 2014 and June 2022 were categorized according to whether they had a body mass index (BMI) <30 (group A, nonobese, n = 40), ≥30 and <35 (group B, obese, n = 13), or ≥35 (group C, morbidly obese, n = 10). Operation time, blood loss, perioperative complications, and recurrence rate were investigated. Results: Conversion to laparotomy was required in one case in group A and one in group C. There was no difference in total operation time, time for setting (including trocar installation and docking of the da Vinci robot), console time, or time for wound closure between the groups; however, there was a significant between‐group difference in the total time for setting and wound closure. There was no significant difference in blood loss or complications between the groups. Three patients in group A and two in group B received adjuvant treatment; none have shown evidence of recurrent disease during a mean observation time of 21 months (range, 2–29). Two cases in group A and one in group B had recurrence during a mean observation time of 38 months (range, 19–46). Conclusion: Patients with endometrial cancer who are obese can be treated safely by robotic‐assisted surgery with a low risk of complications and few relapses. [ABSTRACT FROM AUTHOR]

Background: Infection is a rare complication of percutaneous renal biopsy (RB). However, the questionnaire included in the Kidney Biopsy Guidebook 2020 in Japan revealed that antibiotic prophylaxis (AP) was administered at about 60% of hospitals. The objective of this study was to evaluate whether it is possible to omit AP for RB.Patients aged ≥ 15 years were eligible. Three hundred and sixty-four patients were recruited at 6 hospitals. The patients were randomly assigned to receive either a single dose of intravenous cefazolin or no antibiotic prophylaxis. The primary outcome was the percentage of patients that exhibited positive urine cultures 3 or 4 days after the RB. The secondary outcomes were the percentage of patients who were diagnosed with pyelonephritis, puncture site infections (PSI), or an infection other than pyelonephritis or PSI within 30 days, and cefazolin-induced side effects.With regard to the primary outcome, there was no statistically significant difference between the cefazolin group and the no AP group (2.9% versus 5.1%, p = 0.416). With regard to the secondary outcomes, only one patient (who belonged to no AP group) developed pyelonephritis. This patient underwent urinary catheterization. No PSI occurred. There were no significant intergroup differences in any secondary outcomes.This study revealed the incidence of post-percutaneous RB infections was minimal. Although the outcomes of this study did not lead to the conclusion that it is unnecessary to use AP for RB, the obtained data suggest that the effects of such AP may not be clinically significant.Methods: Infection is a rare complication of percutaneous renal biopsy (RB). However, the questionnaire included in the Kidney Biopsy Guidebook 2020 in Japan revealed that antibiotic prophylaxis (AP) was administered at about 60% of hospitals. The objective of this study was to evaluate whether it is possible to omit AP for RB.Patients aged ≥ 15 years were eligible. Three hundred and sixty-four patients were recruited at 6 hospitals. The patients were randomly assigned to receive either a single dose of intravenous cefazolin or no antibiotic prophylaxis. The primary outcome was the percentage of patients that exhibited positive urine cultures 3 or 4 days after the RB. The secondary outcomes were the percentage of patients who were diagnosed with pyelonephritis, puncture site infections (PSI), or an infection other than pyelonephritis or PSI within 30 days, and cefazolin-induced side effects.With regard to the primary outcome, there was no statistically significant difference between the cefazolin group and the no AP group (2.9% versus 5.1%, p = 0.416). With regard to the secondary outcomes, only one patient (who belonged to no AP group) developed pyelonephritis. This patient underwent urinary catheterization. No PSI occurred. There were no significant intergroup differences in any secondary outcomes.This study revealed the incidence of post-percutaneous RB infections was minimal. Although the outcomes of this study did not lead to the conclusion that it is unnecessary to use AP for RB, the obtained data suggest that the effects of such AP may not be clinically significant.Results: Infection is a rare complication of percutaneous renal biopsy (RB). However, the questionnaire included in the Kidney Biopsy Guidebook 2020 in Japan revealed that antibiotic prophylaxis (AP) was administered at about 60% of hospitals. The objective of this study was to evaluate whether it is possible to omit AP for RB.Patients aged ≥ 15 years were eligible. Three hundred and sixty-four patients were recruited at 6 hospitals. The patients were randomly assigned to receive either a single dose of intravenous cefazolin or no antibiotic prophylaxis. The primary outcome was the percentage of patients that exhibited positive urine cultures 3 or 4 days after the RB. The secondary outcomes were the percentage of patients who were diagnosed with pyelonephritis, puncture site infections (PSI), or an infection other than pyelonephritis or PSI within 30 days, and cefazolin-induced side effects.With regard to the primary outcome, there was no statistically significant difference between the cefazolin group and the no AP group (2.9% versus 5.1%, p = 0.416). With regard to the secondary outcomes, only one patient (who belonged to no AP group) developed pyelonephritis. This patient underwent urinary catheterization. No PSI occurred. There were no significant intergroup differences in any secondary outcomes.This study revealed the incidence of post-percutaneous RB infections was minimal. Although the outcomes of this study did not lead to the conclusion that it is unnecessary to use AP for RB, the obtained data suggest that the effects of such AP may not be clinically significant.Conclusion: Infection is a rare complication of percutaneous renal biopsy (RB). However, the questionnaire included in the Kidney Biopsy Guidebook 2020 in Japan revealed that antibiotic prophylaxis (AP) was administered at about 60% of hospitals. The objective of this study was to evaluate whether it is possible to omit AP for RB.Patients aged ≥ 15 years were eligible. Three hundred and sixty-four patients were recruited at 6 hospitals. The patients were randomly assigned to receive either a single dose of intravenous cefazolin or no antibiotic prophylaxis. The primary outcome was the percentage of patients that exhibited positive urine cultures 3 or 4 days after the RB. The secondary outcomes were the percentage of patients who were diagnosed with pyelonephritis, puncture site infections (PSI), or an infection other than pyelonephritis or PSI within 30 days, and cefazolin-induced side effects.With regard to the primary outcome, there was no statistically significant difference between the cefazolin group and the no AP group (2.9% versus 5.1%, p = 0.416). With regard to the secondary outcomes, only one patient (who belonged to no AP group) developed pyelonephritis. This patient underwent urinary catheterization. No PSI occurred. There were no significant intergroup differences in any secondary outcomes.This study revealed the incidence of post-percutaneous RB infections was minimal. Although the outcomes of this study did not lead to the conclusion that it is unnecessary to use AP for RB, the obtained data suggest that the effects of such AP may not be clinically significant. [ABSTRACT FROM AUTHOR]

Background: The major complication of renal biopsy is bleeding. Infection is an extremely rare complication of percutaneous renal biopsy, providing sterile techniques are used and bowel perforation does not occur. However, the questionnaire included in the Kidney Biopsy Guidebook 2020 in Japan reported that antibiotic prophylaxis was administered to patients undergoing percutaneous renal biopsy at 61% of 170 adult institutions and 57% of 54 pediatric institutions. The objective of this study is to show the non-inferiority of not administering antibiotic prophylaxis for percutaneous renal biopsy.Methods: Patients aged ≥15 years who are scheduled to undergo percutaneous renal biopsy are eligible for inclusion in the study. Three hundred and sixty-four patients will be recruited at 6 hospitals. The patients will be randomly assigned at a 1:1 ratio to receive either a single dose of intravenous cefazolin (1 g) or no antibiotic prophylaxis. The primary outcome is the number of patients that exhibit positive urine cultures (>105 colony-forming units/ml) 3 or 4 days after the renal biopsy, or at which point the patients are diagnosed with pyelonephritis until 3 or 4 days after the renal biopsy. The secondary outcomes are the number of patients who are diagnosed with pyelonephritis within 30 days after the renal biopsy, the number of patients who are diagnosed with puncture site infections within 30 days after the renal biopsy, the number of patients who are diagnosed with an infection other than pyelonephritis or a puncture site infection within 30 days after the renal biopsy, and the number of patients who experience cefazolin-induced side effects.Discussion: This randomized controlled trial aims to show the non-inferiority of not administering antibiotic prophylaxis for percutaneous renal biopsy. If this study shows that antibiotic prophylaxis is not needed, it would help to ensure patient safety and prevent the development of antibiotic-resistant bacteria.Trial Registration: UMIN Clinical Trials Registry (UMIN-CTR) UMIN000042378 . Registered on 7 Nov 2020. [ABSTRACT FROM AUTHOR]

Aim: Recently, a machine‐learning (ML) technique has been used to create generalizable classifiers for psychiatric disorders based on information of functional connections (FCs) between brain regions at resting state. These classifiers predict diagnostic labels by a weighted linear sum (WLS) of the correlation values of a small number of selected FCs. We aimed to develop a generalizable classifier for gambling disorder (GD) from the information of FCs using the ML technique and examine relationships between WLS and clinical data. Methods: As a training dataset for ML, data from 71 GD patients and 90 healthy controls (HCs) were obtained from two magnetic resonance imaging sites. We used an ML algorithm consisting of a cascade of an L1‐regularized sparse canonical correlation analysis and a sparse logistic regression to create the classifier. The generalizability of the classifier was verified using an external dataset. This external dataset consisted of six GD patients and 14 HCs, and was collected at a different site from the sites of the training dataset. Correlations between WLS and South Oaks Gambling Screen (SOGS) and duration of illness were examined. Results: The classifier distinguished between the GD patients and HCs with high accuracy in leave‐one‐out cross‐validation (area under curve (AUC = 0.89)). This performance was confirmed in the external dataset (AUC = 0.81). There was no correlation between WLS, and SOGS and duration of illness in the GD patients. Conclusion: We developed a generalizable classifier for GD based on information of functional connections between brain regions at resting state. [ABSTRACT FROM AUTHOR]

Introduction: The prognostic significance of lymphovascular space invasion (LVSI) in stage IA endometrial cancer remains unclear. The aim of this study was to evaluate the clinical significance of LVSI in stage IA endometrial cancer. Methods: Clinical data of patients with stage IA endometrial cancer who underwent initial surgery at our institution between January 2008 and December 2018 were reviewed retrospectively. Information of patients, surgery, and characteristics of cancer were obtained from medical records and pathological reports. Results: Two hundred ninety-seven patients were enrolled in this study. With a median follow-up of 60 months, 15 patients experienced recurrence (5.1%) and 4 patients died of endometrial cancer (1.3%). The recurrence and mortality rates did not differ significantly between the LVSI-positive and -negative groups (p = 0.07 and p = 0.41, respectively). Recurrence-free survival and endometrial cancer-specific survival also did not differ significantly between these groups (p = 0.11 and p = 0.49, respectively). The 5-year endometrial cancer-specific survival rates for tumors with and without LVSI were 97.0% and 98.9%, respectively. Among patients with low-grade tumors, recurrence-free survival and endometrial cancer-specific survival did not differ significantly between patients with tumors with and without LVSI (p = 0.92 and p = 0.72, respectively). The 5-year endometrial cancer-specific survival rates for low-grade tumors with and without LVSI were 100% and 99.3%, respectively. Conclusion: LVSI was not a prognostic factor of not only stage IA endometrial cancer but also stage IA low-grade cancer. [ABSTRACT FROM AUTHOR]

Sentinel node biopsy alone (SNB) reduces the postoperative complications of pelvic lymphadenectomy, such as lymphedema and lymphangitis; however, the long-term prognosis after SNB is unclear. The objective of this study was to evaluate the long-term outcome and complications of patients with early-stage cervical cancer who underwent SNB for hysterectomy or trachelectomy. We performed SNB for cervical cancer using a radioisotope method in 181 patients between 2009 and 2017. If the intraoperative sentinel lymph node evaluation was negative for metastasis, no further lymph nodes were removed. The median age of the patients was 34 years (range, 21–73 years). The International Federation of Gynecology and Obstetrics 2008 stage was IA1 in 6 patients, IA2 in 18, IB1 in 154, and IIA1 in 3. Of the 181 patients (44 with hysterectomy, 137 with trachelectomy), 8 did not undergo pelvic lymphadenectomy because of a false-negative intraoperative diagnosis, 20 received adjuvant therapy after surgery, and 4 (2.2%) experienced recurrence over a median follow-up period of 83.5 months (range, 25–145 months). In the four recurrent cases, recurrence occurred in the pelvis, lung, and bone in one patient each, while the remaining patient developed pelvic and para-aortic lymph node metastases. Of these four patients, one died, and the remaining three are alive without disease after multidisciplinary therapy. The 5-year progression-free and overall survival rates were 98.8% and 99.4%, respectively. Postoperative complications, such as lymphedema, were very low rate. SNB for early-stage cervical cancer might be safe and effective, with no increase in the recurrence and postoperative complications rate. • SNB for early-stage cervical cancer is safe and effective, with low rates of recurrence and postoperative complications. • The 5-year progression-free and overall survival rates of SNB were 98.8% and 99.4%, respectively. • Four (2.2%) of 181 patients experienced recurrence over a median follow-up period of 83.5 months. [ABSTRACT FROM AUTHOR]

Aim: The subterranean tissues of Panax ginseng, especially the root, have long been used in traditional Asian medicine. In traditional medicine, various formulas contain ginseng to relieve fatigue, improve splenic function, and strengthen immunity, while recent studies have reported many additional benefits, including improvement of Alzheimer's dementia. Multiple ginsenosides, polyacetylenes, and polysaccharides in ginseng root and rhizome contribute to these therapeutic activities. Most ginseng used today is cultivated and takes a long time to mature, so changes in the bioactive constituent profile with age could alter the potential health benefits. However, most studies on such age‐dependent changes in chemical composition have focused on ginsenosides. To examine the full spectrum of age‐dependent changes, the current study analyzed the contents of multiple secondary metabolites and primary metabolites in samples cultivated from one to five years. Methods: The contents of multiple secondary metabolites such as polyacetylenes and primary metabolites such as fatty acids, sugars, and phospholipids as well as ginsenosides were determined by liquid or gas chromatography–mass spectroscopy (LC/MS or GC/MS). Results: Ginsenoside Ro and 1,2‐dilinoleoyl‐sn‐glycero‐3‐phosphocholine increased substantially and progressively with number of years of cultivation. Other ginsenosides and sugars also increased with age, but with greater variability. Conversely, concentrations of falcarinol, fatty acids, and phosphatidic acid decreased with cultivation time. Conclusion: Cultivation years may influence the specific medicinal properties and other health benefits of ginseng preparations. [ABSTRACT FROM AUTHOR]

We investigated the biofilm removal effects of laser activated irrigation (LAI) using a pig model, focusing on the impact of the fiber tip position, and used a high-speed camera to observe the occurrence and positioning of the cavitation associated with laser irradiation. A total of 16 roots of deciduous mandibular second premolars from 4 pigs were used. After a pulpectomy, the canals were left open for 2 weeks and sealed for 4 weeks to induce intraradicular biofilm. Root canal irrigation was then performed with Er:YAG laser activation. The fiber tip was inserted at two different positions, i.e., into the root canal in the intracanal LAI group and into the pulp chamber in the coronal LAI group. Intracanal needle irrigation with saline or 5% NaOCl was utilized in the positive control and conventional needle irrigation (CNI) groups. SEM and qPCR were carried out to evaluate treatment efficacy. Statistical analysis was performed using ANOVA and a Tukey–Kramer post-hoc test for qPCR and with a Steel–Dwass test to compare the SEM scores, with α = 0.05. A high-speed camera was used to observe the generation of cavitation bubbles and the movement of the induced bubbles after laser irradiation. The intracanal and coronal LAI groups showed significantly lower amounts of bacteria than either the positive control or CNI groups. There was no significant difference found between the intracanal and coronal LAI groups. SEM images revealed opened dentinal tubules with the destruction of biofilm in both LAI groups. High-speed camera images demonstrated cavitation bubble production inside the root canal after a single pulse irradiation pulse. The generated bubbles moved throughout the entire internal multi-rooted tooth space. Coronal LAI can generate cavitation in the root canal with a simply placed fiber inside the pulp chamber, leading to effective biofilm removal. This method could thus contribute to the future development of endodontic treatments for refractory apical periodontitis caused by intraradicular biofilm. [ABSTRACT FROM AUTHOR]

The purpose of this study was to develop a one-dimensional (1-D) model for predicting the amount of unburned hydrocarbons (UHC) due to flame extinction by quenching close to the combustion chamber wall in a gasoline engine. The local Reynolds number was used to predict the thickness of the thermal boundary layer developed by in-cylinder flow caused by high speed charge passing through the intake valves. The effect of different intake port geometries, including moderate- and high-tumble types, on the thickness of the thermal boundary layer was examined. The flame extinction model was integrated into a 1-D gasoline engine model. The amount of UHC predicted by the model was compared with experimental results by using a single-cylinder gasoline engine under various engine operating conditions. The numerical values were found to be in reasonable agreement with the measured data. A methodology for controlling UHC was also proposed in the final section. [ABSTRACT FROM AUTHOR]

We devised and assessed open recruitment of host families for medical student homestays in a rural area of Hyogo Prefecture, Japan, so that program organizers would not have to depend on professional and personal connections. The duration of the homestays was one night and two days, and they were conducted in August 2016, 2017, and 2018. The purpose of this community-based medical education program was to promote interactions between medical students and residents of Tamba area. The study asked one family member from each host family to complete a questionnaire after the homestay, and their experiences were evaluated in the study. The questionnaire results were analyzed using a visual analog scale (VAS; 0–100 mm). Thirty-three host families participated in the homestay program over three years. Results showed that VAS scores were high for enjoyment of homestays (VAS; 92.4 ± 13.0), continuation of the homestay program (91.7 ± 12.7), continuation of participation in the homestay program (89.2 ± 16.2), and desire for the homestay students to work in the area in the future (95.4 ± 6.3). The recruitment of host families through advertising was an efficient method for this community-based medical education homestay program. The results indicate that it is possible to attract more host families through open recruitment, which will contribute to the sustainability of the homestay program. Further research, including a follow-up of the students who participated and whether they chose a rural area or Tamba to practice is needed in the future. Since this is an ongoing program, further research in a similar format can be conducted in the future. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to explore differences in the effects of online and in-person decentralized learning programs on students' satisfaction, attitudes toward community healthcare, and career intentions. Methods: This cross-sectional study used questionnaires administered before and after Kobe University's rural decentralized learning program (conducted in-person in 2018 and 2019 and online in 2020). Of the 208 medical students who participated in any of these three, 198 were included in this study. Questionnaires had ten items regarding program satisfaction, students' attitudes toward community healthcare, and career intention. Difference-in-differences analysis using linear regression was performed for the online and in-person programs' pre-post score differences. Results: Both programs showed improved scores for most outcomes. However, the difference-in-differences analysis indicated significant differences in the enjoyment of the program (F (5, 390) = 18.58, p < 0.01, R2 = 0.17) and recognition of whether local physicians looked happy (F (5, 390) = 12.82, p < 0.01, R2 = 0.16). The online program showed inferiority in the enjoyment of the program (β = -0.89, t (390) = -1.99, p = 0.05) and recognition of whether local physicians looked happy (β = -0.67, t (390) = -2.32, p = 0.02). Conclusions: The components of Kobe University's rural decentralized learning program could not be adequately replaced online. Further research should determine which components can be effectively replaced online and what results can be achieved when online programs consciously constructed to include such elements are compared to in-person programs. [ABSTRACT FROM AUTHOR]

Plasmodium malaria parasites are obligate intracellular protozoans that use a unique form of locomotion, termed gliding motility, to move through host tissues and invade cells. The process is substrate dependent and powered by an actomyosin motor that drives the posterior translocation of extracellular adhesins which, in turn, propel the parasite forward. Gliding motility is essential for tissue translocation in the sporozoite and ookinete stages; however, the short-lived erythrocyte-invading merozoite stage has never been observed to undergo gliding movement. Here we show Plasmodium merozoites possess the ability to undergo gliding motility in vitro and that this mechanism is likely an important precursor step for successful parasite invasion. We demonstrate that two human infective species, Plasmodium falciparum and Plasmodium knowlesi, have distinct merozoite motility profiles which may reflect distinct invasion strategies. Additionally, we develop and validate a higher throughput assay to evaluate the effects of genetic and pharmacological perturbations on both the molecular motor and the complex signaling cascade that regulates motility in merozoites. The discovery of merozoite motility provides a model to study the glideosome and adds a dimension for work aiming to develop treatments targeting the blood stage invasion pathways. [ABSTRACT FROM AUTHOR]

Background: The International Federation of Gynecology and Obstetrics (FIGO) staging system for Müllerian cancer was changed in 2014. Our objective was to evaluate the prognostic impact of stage IV subclassification in this new staging system, especially focusing on extra-abdominal lymph node metastasis. Methods: Eighty-two patients with stage IV Müllerian cancer treated between 2005 and 2016 at our hospital were retrospectively analyzed. Data for the following clinicopathological variables were analyzed: (1) FIGO stage; (2) tumor stage; (3) lymph node status; (4) histologic type; (5) neoadjuvant chemotherapy; (6) optimal surgery; and (7) bevacizumab use. Survival analysis was performed using Kaplan–Meier curves, log-rank tests, and Cox proportional hazards models. Results: In accordance with the new classification, 28 and 54 patients were classified as FIGO IVA and IVB, respectively. In the Cox proportional hazards model, early-stage tumors (T1b–3b) and optimal surgery were statistically significant favorable prognostic factors. However, the new FIGO system did not discriminate prognostically between stage IVA and IVB. Median overall survival of stage IVB patients diagnosed with extra-abdominal lymph node metastasis only was better than that of stage IVA and stage IVB patients diagnosed with solid organ metastasis. Conclusions: In this analysis of the revised FIGO system of patients reclassified as FIGO stage IVA or IVB, no new prognostic information was obtained. There is a possibility that stage IVB patients diagnosed with extra-abdominal lymph node metastasis only can be classified as an earlier stage. Further modification of the FIGO staging system may be needed to improve the prediction of patient prognosis. [ABSTRACT FROM AUTHOR]

Bone marrow adipocytes (BMAs) have recently been recognized as a niche component with a suppressive function. Obese individuals with abundant BMAs exhibit impaired hematopoietic regeneration after hematopoietic stem cell transplantation (HSCT). We hypothesized that plasminogen activator inhibitor type-1 (PAI-1), an adipokine that regulates the fibrinolytic system, contributes to impaired hematopoiesis in bone marrow (BM) microenvironment with abundant BMAs. We demonstrated that BMAs differentiated in vitro could secrete PAI-1 and were positive for PAI-1 in vivo. In addition, the abundance of BMAs was associated with high levels of PAI-1 expression. The BMA-rich microenvironment exhibited impaired hematopoietic regeneration after HSCT when compared with a BMA-less microenvironment. The impaired hematopoietic regeneration in BMA-rich microenvironment was significantly alleviated by PAI-1 knockout or PAI-1 inhibitor treatment. Obese mice with abundant BMAs, compared with normal-weight mice, exhibited higher bone marrow PAI-1 concentrations, increased fibrinolytic system suppression, and lower stem cell factor (SCF) concentrations after HSCT. PAI-1 inhibitor administration significantly activated the fibrinolytic system in obese mice, contributing to the higher SCF concentration. Moreover, PAI-1 inhibitor treatment significantly alleviated the impaired hematopoietic regeneration in obese mice both after 5-fluorouracil injection and HSCT. These results indicate that PAI-1 hinders hematopoietic regeneration in BMA-rich microenvironments. The blockade of PAI-1 activity could be a novel therapeutic means of facilitating hematopoietic reconstitution in BMA-rich patients. [Display omitted] • Bone marrow (BM) adipocytes produce plasminogen activator inhibitor type-1 (PAI-1). • PAI-1 inhibits the fibrinolytic system in the adipocyte-rich BM. • The blockade of PAI-1 facilitates hematopoietic recovery in the adipocyte-rich BM. [ABSTRACT FROM AUTHOR]

Elimination of measles and rubella has been achieved in several countries and some regions. After verified measles elimination, some countries have reported outbreaks among adults in occupational settings such as health care institution and school setting. Studies have reported that knowledge and attitude for measles and/or rubella are significantly associated with immunization uptake in adults, but few studies have been conducted in settings other than health care facilities and schools. We conducted a cross-sectional study among 134 office employees during a routine health checkup in June 17–20, 2014, to examine the association between willingness to receive immunization and knowledge and attitudes. Approximately 75% had a protective level of antibody for measles (PA≥1:256) and rubella (HI ≥ 32 IU/mL). After adjustment for sex, age and immune status, the attitudes that immunization prevents measles (adjusted odds ratio [aOR] = 7.8, 95% confidence interval [95%CI]: 2.5–24.7) and prevents infection and transmission to others (aOR = 4.0, 95%CI: 1.4–11.4). Knowing that males are the vulnerable group for rubella infection (aOR = 5.8, 95%CI: 2.4–13.9), attitude that immunization prevents rubella infection (aOR = 7.9, 95%CI: 2.4–26.5), and prevents infection and transmit to others (aOR = 6.7, 95%CI: 2.2–20.1) were significantly associated with willingness to receive immunization after adjustment for sex, age, and immune status. Studies have shown that physicians and other health care workers are important source of information for promotion of immunization. Thus, we recommend that physicians educate and promote immunization for measles and/or rubella to adults working in offices during routine health checks. [ABSTRACT FROM AUTHOR]

Aim: PEGylated liposomal doxorubicin (PLD) is a therapeutic agent for gynecological malignancy. Hypersensitivity reaction (HSR) is a major adverse effect that usually disappears after halting administration of PLD. Premedication is usually not necessary before administration of PLD to prevent HSR. Here, we evaluated the frequency of HSR during administration of PLD following premedication in Japanese women. Methods: We performed PLD administration in 78 patients (386 cycles) between 2013 and 2018. Granisetron hydrochloride and dexamethasone sodium phosphate were administered 30 min before PLD administration. Then, PLD (40 or 30 mg/m2 combined usage with carboplatin) was administered. We retrospectively reviewed the medical records of 78 patients and examined the frequency of HSR. Results: Seven of 78 (9%) patients showed HSR by PLD administration following premedication. One patient showed cardiopulmonary arrest in 13 min after PLD administration (grade 4). The other six patients showed grade 2 HSR. All patients developed HSR in the first course. The incidence of HSR was significantly higher in patients with allergic history than in patients without allergic history (p = 0.0151). Conclusions: Clinicians should be aware of the potential for HSR in patients administered PLD, particularly those with allergic history and those receiving the first cycle of PLD, even following premedication. [ABSTRACT FROM AUTHOR]

Purpose: Static stretching (SS) is performed in various settings, but there is no consensus about the effects of SS programmes on changes in muscle morphofunction. This study aimed to investigate the effects of a high-volume SS programme on muscle strength and architecture. Methods: Sixteen healthy young male adults participated, and the dominant leg was defined as the intervention side, with the non-dominant leg as the control side. Stretching exercises were performed two times per week (6 sets of 5 min, totally 30 min per session,) for 5-week using a stretching board under the supervision of the research team. Before and after SS intervention programme, plantar-flexor strength (maximum voluntary isometric contraction, MVC-ISO; maximum voluntary concentric contraction, MVC-CON) and architecture (muscle thickness, pennation angle, and fascicle length) were measured via dynamometer and ultrasound, respectively. Results: Following the SS-training programme, significant increases were observed for stretching side in MVIC-ISO at neutral ankle position (p = 0.02, d = 0.31, Δ = 6.4 ± 9.9%) and MVC-CON at 120°/s (p = 0.02, d = 0.30, Δ = 7.8 ± 9.1%), with no significant change on the control side. There was no significant change in any measure of muscle architecture for both intervention and control sides. Conclusion: Five-week high-volume SS induced positive changes on some measures of muscle strength but not hypertrophy of plantar-flexor muscles. Even with a volume much greater than already tested, the low strain offered by the SS per set seems be insufficient to induce architectural changes on skeletal muscle. [ABSTRACT FROM AUTHOR]

Background: Cervical intraepithelial neoplasia (CIN) is a precancerous lesion that may progress to invasive cervical cancer without intervention. We aim to examine the prognostic outcomes and risk factors for recurrence after laser vaporization for CIN 3, CIN 2 with high-risk human papillomavirus (HPV) infection, and CIN 1 persisting for more than 2 years. Methods: Between 2008 and 2016, a total of 1070 patients underwent cervical laser vaporization using a carbon dioxide laser. We performed a retrospective review of their medical records to assess their clinical characteristics, pathologic factors, and prognostic outcomes. Results: The mean patient age was 34 years (range 18–64 years). The preoperative diagnosis was CIN 1 in 27 patients, CIN 2 in 485 patients, and CIN 3 in 558 patients. Over a median follow-up period of 15 months, the 2-year recurrence rate was 18.9%, and the 5-year recurrence rate was 46.5%. The 2-year retreatment rate was 12.6%, and the 5-year retreatment rate was 30.5%. We diagnosed 9 patients with invasive cancer after treatment; all patients underwent combined multidisciplinary treatment, and there were no deaths during follow-up. The recurrence-free interval was correlated with patient age (hazard ratio [HR], 1.028; 95% CI 1.005–1.051; P = 0.0167), body mass index (HR, 1.052; 95% CI 1.008–1.098; P = 0.0191), and glandular involvement (HR, 1.962; 95% CI 1.353–2.846; P = 0.0004). Conclusions: Cervical laser vaporization is effective and useful for patients with CIN who wish to preserve fertility. However, patients with glandular involvement, older age, and higher body weight require close follow-up for recurrence. [ABSTRACT FROM AUTHOR]

Vection has been reported to be enhanced by wind, as long as the wind is a normal temperature and not hot. However, here we report that a hot wind can facilitate vection, as long as it is natural and consistent with the visual stimulus. We created a fire-corridor stimulus that was consistent with a hot wind and a control stimulus composed of cubes, which were irrelevant to a hot wind. We compared the vection strength induced by a fire-corridor (fire condition) visual stimulus with that induced by geometric cubes (no-fire condition) visual stimulus. There were three wind type conditions: a normal temperature wind, hot wind, and no wind. The results showed that a normal temperature wind facilitated vection and that a hot wind (but not a normal wind) highly enhanced vection when a fire-corridor stimulus was presented. These results suggest that vection is highly affected and modulated by high-level cognitive processes. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to measure the predictive value of future scenarios prepared using horizon scanning. The future scenarios prepared at the initiative of the Japanese Government have had low predictive value. They have frequently failed to contribute to industrial development and caused social loss. Horizon scanning, which is a key methodology applied in foresight activities, has begun to be used in countries as part of their national innovation systems in lieu of conventional forecasting methods based on the assumption of technological innovation. Research was conducted to actually measure the predictive value of future scenarios prepared using horizon scanning. Design/methodology/approach: An online survey in Japan was conducted on ordinary people's attitudes. The questionnaires presented 20 scenarios regarding future society, which were created with the conventional method or horizon scanning method. Findings: Survey results verified that horizon scanning-based scenarios provided significantly higher predictive value than scenarios prepared using conventional methods. Practical implications: Implication 1: By eliminating bias in input data and perspectives adopted when considering scenarios, it may be expected that scenarios will be derived that have even higher "predictive value." Implication 2: By setting the layers of anticipated outputs high and the fields broad, it may be expected that scenarios will be derived that have even greater "change." Originality/value: The relatively high rate for the predictive value of the horizon scanning method, more than 40%, validated in this study was significant. [ABSTRACT FROM AUTHOR]

Background: To avoid the loss of fertility, chemotherapy should be chosen as an adjuvant treatment after trachelectomy. Our study evaluated the effectiveness and safety of adjuvant chemotherapy after abdominal trachelectomy for cervical cancer. Methods: Our institutional review board approved this clinical study, and informed consent was obtained from each patient. We began performing abdominal trachelectomy at our institution in 2005. Deep stromal invasion (more than two-thirds) with lymphovascular space invasion, diffuse cervical invasion, skip lesions in the vagina, and lymphovascular space invasion in the cardinal ligament and vagina were defined as intermediate-risk factors, and parametrial invasion and pelvic lymph node metastasis were defined as high-risk factors. Patients who had intermediate- or high-risk factors received post-trachelectomy adjuvant treatment. The medical records and information of the patients were reviewed retrospectively. Results: Through January 2020, we performed 212 trachelectomies. Among the included patients, 16 and 7 patients with intermediate- and high-risk cancer, respectively, received adjuvant chemotherapy after trachelectomy (2 and 21 patients underwent abdominal modified radical trachelectomy and radical trachelectomy, respectively). Among these patients, only one (4.3%) experienced relapse and subsequent death of the disease after a median postoperative follow-up of 80 months (range 12–146 months). The 5-year survival rate was 95.5%. Chemotherapy-related life-threatening acute adverse events were not observed. Persistent ovarian dysfunction and late adverse events did not occur. One woman achieved three pregnancies, and two infants were delivered. Conclusion: Adjuvant chemotherapy after abdominal trachelectomy could be an alternative treatment option from the aspects of effectiveness, safety, and fertility preservation. [ABSTRACT FROM AUTHOR]

Introduction: Adjuvant therapy is usually recommended for patients with intermediate-risk cervical cancer (deep stromal invasion [DSI], lymphovascular space invasion [LVSI], and bulky tumor) after radical hysterectomy. However, we previously reported that DSI, LVSI, and bulky squamous cell carcinoma (SCC) were not correlated with prognosis in multivariate analysis; therefore, the indications we use for adjuvant therapy include complete stromal invasion, not DSI or LVSI or bulky SCC. The objective of this study was to evaluate the adequacy of our therapeutic strategy for cervical cancer after radical hysterectomy. Methods: We performed 321 type III open radical hysterectomies for cervical cancer between 2001 and 2013. Eighty-two patients with DSI, LVSI, or bulky SCC did not receive adjuvant therapy after radical hysterectomy under informed consent. We retrospectively evaluated the prognosis of these 82 patients. Results: Forty-two patients had >2/3 DSI and 35 patients had 1/3–2/3 DSI. Five patients had LVSI alone. The mean patient age was 43 years (range, 27–72). Six patients (7%) experienced recurrence during a median follow-up period of 84 months (range, 1–206). Two of the 6 patients with recurrence suffered cervical cancer-related deaths, but the remaining 4 cases are alive without evidence of disease after treatment during a follow-up period of 87–165 months. The 5-year disease-free survival rate was 92.6%, and the 5-year overall survival rate was 96.3%. Conclusions: Adjuvant therapy for DSI, LVSI, or bulky SCC after open radical hysterectomy might not be necessary. Further data collection is warranted to determine the standard of care for patients with intermediate-risk cervical -cancer. [ABSTRACT FROM AUTHOR]

Shigellosis cases have decreased gradually in Japan in recent years, but indigenous shigellosis outbreaks sometimes occur in childcare facilities. From national surveillance data, we identified a shigellosis outbreak involving a kindergarten. After detecting Shigella sonnei in Kitakyushu City, we conducted active case finding and epidemiological investigation in Kindergarten Z, including stool specimen collection and interviews. The stool specimens were cultured, and isolated strains were subjected to pulsed-field gel electrophoresis (PFGE) and multiple-locus variable-number tandem-repeat analysis (MLVA). Between September 1 and December 31, 2014, we identified 19 cases: 14 confirmed, 2 suspected, and 3 asymptomatic. Of the 19 cases, 16 were epidemiologically associated with Kindergarten Z (10 pupils, 5 family members, and 1 teacher). On October 19, a pupil with gastrointestinal illness participated in the kindergarten's sports festival, in which the pupils were split into "red" and "white" teams; the pupil in question belonged to the red team. Attack rates of the red and white teams were 8% (7/82) and 0% (0/108), respectively (relative risk, 10.5; 95% confidence interval, 1.3–82.1). PFGE patterns were identical or similar for the isolates in all 17 cases; 7 isolates were identical, and the others had one locus difference on MLVA. We concluded that contact during the sports festival could have been responsible for spread of the shigellosis outbreak at the kindergarten, although the infection source was not determined. It is vital to inform guardians immediately after detection of shigellosis cases that symptomatic pupils should not participate in activities such as sports festivals. [ABSTRACT FROM AUTHOR]

Additive manufacturing (AM) is a new and promising production methodology adept at producing complex geometries, which can be optimized for lower weight and enhanced capabilities. The material properties of these additive components are dictated by the microstructures developed during processing, with a high sensitivity to grain structure and associated anisotropy. With this new processing modality comes the added difficulty of understanding the thermodynamics and kinetic mechanisms that dictate the evolution of microstructure. This research addresses the unique thermal conditions present in AM and the pathways for grain refinement in nanofunctionalized aluminum alloys. The Al-Ta system, in which Al 3 Ta intermetallic compounds are demonstrated to have substantial grain refining capacity, are the focus of this study. The grain size is shown to be reduced relative to pure aluminum by 1000X when tantalum is added at 1 vol%. The effectiveness of the Al 3 Ta intermetallic is dictated by the crystallography and availability of the inoculant phase under AM conditions. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Background: In community-based medical education, opportunities for medical students to interact with local residents are important. To facilitate such interaction, we aimed to evaluate acceptance of a homestay program and attitude toward community medicine among medical students. Methods: The participants (n = 39) were allowed to stay in the local homes of residents for one night in August 2016, 2017, and 2018. Before and after the homestays, the students responded to a self-reported questionnaire using the visual analog scale (VAS; 0–100 mm). The questionnaire included four questions on homestay/community medical training and community medicine and four questions about attitude toward community medicine in the local areas of medical students. Then, we compared the VAS scores before and after training. Results: The VAS scores for all questions about homestay/community medical training and community medicine significantly increased: "Is it worthwhile for you to have experience in the field of community medicine," "Did you find the homestay enjoyable," "Does the homestay add educational significance to the program," and "Is direct interaction with residents meaningful?" For the two questions about attitude toward community medicine, the VAS scores significantly increased: "Is there a challenge to practicing community medicine" and "In the future, do you want to work in Tamba area where you stayed?" Conclusions: The medical students were extremely enthusiastic about the educational program for community medicine involving residential homestays, which improved their attitudes toward practicing community medicine. Moreover, the students appreciated that their training sites could become their future workplaces. [ABSTRACT FROM AUTHOR]

Objective: For oncologic safety, vaginal radical trachelectomy is generally performed only in patients with cervical cancers smaller than 2 cm. However, because inclusion criteria for abdominal trachelectomy are controversial, we evaluated the safety of abdominal trachelectomy for cervical cancers ≥2 cm. Methods: We began performing abdominal trachelectomies at our institution in 2005, primarily for squamous cell carcinoma ≤3 cm or adenocarcinoma/adenosquamous carcinoma ≤2 cm. If a positive sentinel lymph node or cervical margin was diagnosed intraoperatively by frozen section, the trachelectomy was converted to a hysterectomy. Medical records of these patients were reviewed retrospectively. Patients who had undergone simple abdominal trachelectomy were excluded from this study. Results: We attempted trachelectomy in 212 patients. Among the 135 patients with tumors <2 cm, trachelectomy was successful in 120, one of whom developed recurrence and none of whom died of their disease. Among 77 patients with tumors ≥2 cm, trachelectomy was successful in 62, 2 of whom developed recurrence and 1 of whom died of her disease. The overall relapse rate after trachelectomy was 1.6% (0.8% in <2 cm group and 3.2% in ≥2 cm group), and the mortality rate was 0.5% (0% in <2 cm group and 1.6% in ≥2 cm group). Recurrence-free survival (p=0.303) and overall survival (p=0.193) did not differ significantly between the <2 cm and ≥2 cm groups. Conclusions: Abdominal trachelectomy with intraoperative frozen sections of sentinel lymph nodes and cervical margins is oncologically safe, even in patients with tumors ≥2 cm. [ABSTRACT FROM AUTHOR]

Background/Aims: Intestinal fibrosis is a major complication of Crohn's disease (CD). The profibrotic protein transforming growth factor-ß (TGF-ß) has been considered to be critical for the induction of the fibrotic program. TGF-ß has the ability to induce not only the expression of extracellular matrix (ECM) including collagen, but also the production of plasminogen activator inhibitor-1 (PAI-1) that prevents enzymatic degradation of the ECM during the onset of fibrotic diseases. However, the significance of PAI-1 in the developing intestinal fibrosis has not been fully understood. In the present study, we examined the actual expression of PAI-1 in fibrotic legion of intestinal inflammation and its correlation with the abnormal ECM deposition. Methods: Chronic intestinal inflammation was induced in BALB/c mice using 8 repeated intrarectal injections of 2,4,6-trinitrobenzene sulfonic acid (TNBS). TM5275, a PAI-1 inhibitor, was orally administered as a carboxymethyl cellulose suspension each day for 2 weeks after the sixth TNBS injection. Results: Using a publicly available dataset (accession number, GSE75214) and TNBS-treated mice, we observed increases in PAI-1 transcripts at active fibrotic lesions in both patients with CD and mice with chronic intestinal inflammation. Oral administration of TM5275 immediately after the onset of intestinal fibrosis upregulated MMP-9 (matrix metalloproteinase 9) and decreased collagen accumulation, resulting in attenuation of the fibrogenesis in TNBS-treated mice. Conclusions: PAI-1-mediated fibrinolytic system facilitates collagen degradation suppression. Hence, PAI-1 inhibitor could be applied as an anti-fibrotic drug in CD treatment. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the applicability of the Øie‐Tozer model to predict human distribution volume (Vd) in the central compartment (V1), Vd at steady state (Vdss), and Vd at beta phase (Vdβ) based on animal Vd. Twenty compounds that have a human V1/Vdss of 0.053–0.66 were selected from the literature. After intravenous administration of the compounds at 0.1 mg/kg to rats, dogs, and monkeys, plasma concentrations were determined, and pharmacokinetic parameters were obtained by one/two‐compartmental analyses. The human V1, Vdss, and Vdβ were predicted from animal Vd using the Øie‐Tozer model, and the predictability was compared with that using proportionality and simple allometry. The Øie‐Tozer model was the most reliable method for the overall prediction of Vd and applicable for accurately predicting human V1, Vdss, and Vdβ (89%, 85%, and 68% of the compounds within a 3‐fold error, respectively) when data of monkey for V1 and data of three animal species for Vdss and Vdβ were used. Additionally, the predicted human Vd with the two‐compartment model was applicable for predicting pharmacokinetic profiles/parameters in humans after intravenous administration of 18 compounds [except for valproic acid (monophasic elimination profile) and chlorpromazine (deviation: Vdss < V1)]. The prediction was more accurate than that using the predicted Vdss with the one‐compartment model (e.g., underestimation of maximum plasma concentrations: 2 vs 8 compounds within a 3‐fold error, respectively). In summary, the Øie‐Tozer model was applicable for predicting human V1, Vdss, and Vdβ, and their predicted Vd with the two‐compartment model can lead to accurate pharmacokinetic prediction of compounds that show biphasic elimination. [ABSTRACT FROM AUTHOR]

• Co-assembly of gold nanoparticles and polymer nanoparticles on glass substrate. • Gold nanoparticle clusters incorporated into the interstice of polymer nanoparticles. • Raman signals enhanced by multi-layering of the co-assembly of nanoparticles. Regularly ordered polymer nanoparticle (PNP) assemblies incorporating gold nanoparticle (Au NP) clusters into the PNP interstices were fabricated by a simultaneous deposition of PNPs and Au NPs on a glass substrate. Monodisperse PNPs with an average size of 66 nm were employed as a template in the co-assembly to create the sub-100 nm periodic Au nanostructures on the substrate. First, mono-layering of PNP array with incorporation of 14 nm Au NPs was performed by a drop-casting to examine the number ratio of Au NPs to PNPs for multi-layering. Absorption spectra of the mono-layered co-assemblies of PNPs and Au NPs were employed to characterize the clustered state of Au NPs in the interstices of mono-layered PNPs. The number ratio suitable for homogeneous incorporation of Au NPs clustered in the interstice was found to be ranged from 6 to 8 in the characterization. Then, multi-layered co-assemblies of PNPs and clustered Au NPs were fabricated by a vertical deposition method with the Au NP number ratio of 8 to PNPs. Lifting rate of the substrate on which the PNPs were deposited was varied in the vertical deposition method to tune the film thickness of NP co-assembly. A decrease in the lifting rate to 1 μm/s could thicken the film to 0.71 μm corresponding to 13 layers of PNPs, resulting in the fabrication of periodic structures of Au NP clusters with a high packing density. Signal-to-noise ratio in the Raman measurement using p -mercaptobenzoic acid as a target molecule was successfully enhanced by multi-layering of the co-assembly, indicating that Au NP clusters were homogeneously incorporated into the interstices of PNPs in the co-assemblies. [ABSTRACT FROM AUTHOR]

Metals and metal alloys are widely used in medical devices that contact blood and/or tissue, and various coating materials for the metal parts have been proposed to improve surface properties such as biocompatibility. This study aims to understand the performance of new coating materials, copolymers of methyl acrylate and acrylic acid, in terms of their biocompatibility and adhesive strength to a metal surface. Blood compatibility was investigated through platelet and coagulation system responses. Cytocompatibility was studied in three cell-line types (endothelium, smooth muscle, and fibroblasts) in terms of cell viability and morphology; these tests showed that compatibility depended on the cell types and acrylic acid content of the copolymers. Because of their blood compatibility and adhesion strength, the methyl acrylate and acrylic acid copolymers containing 10–24 mol% acrylic acid were found to be excellent candidates as potential coating materials for devices contacting blood. [ABSTRACT FROM AUTHOR]

Aim: To evaluate how the desire to have children and engage in sexual activity change after trachelectomy in Japanese women with early‐stage cervical cancer who strongly desired to have children before surgery. Methods: Desire to have children, coital pain, fear of sexual intercourse, sexual activity frequency and libido were assessed in cervical cancer patients who received follow‐up after trachelectomy. An anonymous questionnaire survey was conducted via informed consent. Results: Of the 151 patients who underwent trachelectomy at Kyushu University Hospital between 2005 and 2015, 46 patients were evaluated; the response rate was 30%. The desire to have children disappeared in 13 of 46 (28%) patients, and 14 (30%) patients experienced increased coital pain. Moreover, 19 (41%) patients experienced fear of sexual intercourse, and sexual frequency decreased in 24 (52%) patients. Conclusion: Trachelectomy is an important fertility‐sparing surgical method; however, this study revealed loss of the desire to have children and/or to engage in sexual activity in some patients after surgery. Counseling about these issues is important and should be addressed. [ABSTRACT FROM AUTHOR]

Background: The baseline data obtained in the CKD-JAC demonstrated that insufficient treatment was being provided for renal anemia by institutions specializing in renal disease. The objective of this study was to investigate the status of treatment for renal anemia, including renal/cardiovascular outcomes and mortality, at regional medical facilities since the development of long-acting erythropoiesis-stimulating agents (LA-ESA). Methods: Non-dialysis outpatients with chronic kidney disease and renal anemia were eligible. Anemia was treated based on the clinical condition of each patient and targeted hemoglobin (Hb) levels. Results: A total of 283 patients from 21 institutions were enrolled and followed up for a maximum of 3 years. A doubling of the serum creatinine level was observed in 89 patients, and renal replacement therapy was initiated in 57 patients. Multivariate Cox regression analysis revealed that a lower mean Hb level (mHb) and receiving fewer frequency of ESA during the follow-up period were independent determinants of the composite renal outcome and overall mortality. During the follow-up period, the percentages of patients with mHb of 10–10.9 g/dL and ≥ 11 g/dL were increased. Similar trends were seen regardless of whether the patients were treated by nephrologists or non-nephrologists. The frequency of ESA treatment was increased among the patients treated by non-nephrologists; however, it was much lower than nephrologists. Conclusion: This study demonstrated that, in the era of LA-ESA treatment, higher Hb levels are associated with reduced composite renal outcomes at regional medical facilities. The importance of renal anemia management should be highlighted, even among non-nephrologists. [ABSTRACT FROM AUTHOR]

Upon hematopoietic stem cell transplantation (HSCT), the availability of recipients' niches in the bone marrow (BM) is one of the factors that influence donor HSC engraftment and hematopoietic reconstitution. Therefore, myeloablative conditioning, such as irradiation and/or chemotherapy, which creates empty niches in the recipients' BM, is required for the success of HSCT. However, the conventional myeloablation causes extensive damages to the patients' BM, which results in the treatment-induced severe complications and even mortality. Thus, alternative and mild conditioning could fulfill the need for safer HSCT-based therapies for hematological and nonhematological disorders. Recently, we have demonstrated that pharmacological inhibition of plasminogen activator inhibitor-1 (PAI-1) activity increases cellular motility and cause detachment of HSCs from the niches. In this study, we performed HSCT using a PAI-1 inhibitor without any myeloablative conditioning. Donor HSCs were transplanted to recipient mice that were pretreated with saline or a PAI-1 inhibitor. Saline pretreated nonmyeloablative recipients showed no engraftment. In contrast, donor cell engraftment was detected in the PAI-1 inhibitor pretreated recipients. Multilineage differentiation, including lymphoid and myeloid cells, was observed in the PAI-1 inhibitor pretreated recipients. Donor-derived cells that exhibited multilineage reconstitution as well as the existence of stem/progenitor cells were detected in the secondary recipients, confirming the maintenance of donor HSCs in the BM of PAI-1 inhibitor pretreated primary recipients. The results indicate that the PAI-1 blockade vacates functional niches in the recipients' BM, which allows the engraftment of long-term multilineage HSCs without myeloablative conditioning. • PAI-1 blockade can vacate functional niches that allows donor HSC engraftment without any myeloablative conditioning. • Donor HSCs exhibit multilineage differentiation and long-term reconstitution in the PAI-1 inhibitor pretreated recipients. • PAI-1 inhibitor-based treatment may replace the conventional pretreatments in HSCT. [ABSTRACT FROM AUTHOR]

The metabolism and pharmacokinetics of DSP‐0565 [2‐(2′‐fluoro[1,1′‐biphenyl]‐2‐yl)acetamide], an antiepileptic drug candidate, was investigated in rats, dogs, and humans. In human hepatocytes, [14C]DSP‐0565 was primarily metabolized via amide bond hydrolysis to (2′‐fluoro[1,1′‐biphenyl]‐2‐yl)acetic acid (M8), while in rat and dog hepatocytes, it was primarily metabolized via both hydrolysis to M8 and hydroxylation at the benzene ring or the benzyl site to oxidized metabolites. After single oral administration of [14C]DSP‐0565 to rats and dogs, the major radioactivity fraction was recovered in the urine (71–72% of dose) with a much smaller fraction recovered in feces (23–25% of dose). As primary metabolites in their excreta, M8, oxidized metabolites, and glucuronide of DSP‐0565 were detected. The contribution of metabolic pathways was estimated from metabolite profiles in their excreta: the major metabolic pathway was oxidation (57–62%) and the next highest was the hydrolysis pathway (23–33%). These results suggest that there are marked species differences in the metabolic pathways of DSP‐0565 between humans and animals. Finally, DSP‐0565 human oral clearance (CL/F) was predicted using in vitro–in vivo extrapolation (IVIVE) with/without animal scaling factors (SF, in vivo intrinsic clearance/in vitro intrinsic clearance). The SF improved the underestimation of IVIVE (fold error = 0.22), but the prediction was overestimated (fold error = 2.4–3.3). In contrast, the use of SF for hydrolysis pathway was the most accurate for the prediction (fold error = 1.0–1.4). Our findings suggest that understanding of species differences in metabolic pathways between humans and animals is important for predicting human metabolic clearance when using animal SF. [ABSTRACT FROM AUTHOR]

When collecting large amounts of neuroimaging data associated with psychiatric disorders, images must be acquired from multiple sites because of the limited capacity of a single site. However, site differences represent a barrier when acquiring multisite neuroimaging data. We utilized a traveling-subject dataset in conjunction with a multisite, multidisorder dataset to demonstrate that site differences are composed of biological sampling bias and engineering measurement bias. The effects on resting-state functional MRI connectivity based on pairwise correlations because of both bias types were greater than or equal to psychiatric disorder differences. Furthermore, our findings indicated that each site can sample only from a subpopulation of participants. This result suggests that it is essential to collect large amounts of neuroimaging data from as many sites as possible to appropriately estimate the distribution of the grand population. Finally, we developed a novel harmonization method that removed only the measurement bias by using a traveling-subject dataset and achieved the reduction of the measurement bias by 29% and improvement of the signal-to-noise ratios by 40%. Our results provide fundamental knowledge regarding site effects, which is important for future research using multisite, multidisorder resting-state functional MRI data. [ABSTRACT FROM AUTHOR]

Monodisperse silica particles (SiPs) were surface‐modified with a newly designed silane coupling agent comprising a triethoxysilane and an alkyl halide, namely, 6‐(triethoxysilyl)hexyl 2‐bromopropionate, which was further treated with potassium O‐ethyl dithiocarbonate (PEX) to immobilize xanthate molecules on the particle surfaces. Surface‐initiated macromolecular design via interchange of xanthates (MADIX) polymerization of vinyl acetate (VAc) was conducted with the xanthate‐functionalized SiPs. The polymerization was well controlled and produced SiPs coated with poly(vinyl acetate) (PVAc) with a well‐defined target molar mass and a graft density of about 0.2 chains nm−2. Dynamic light scattering and TEM measurements revealed that the hybrid particles were highly dispersible in good solvents without any aggregation. The PVAc brushes were hydrolyzed with hydrochloric acid to produce poly(vinyl alcohol) brushes on the SiP surfaces. In addition, the number of xanthate molecules introduced on the SiP surfaces could be successfully controlled by adjusting the concentration of PEX. Thus, the SiPs have two functionalities: xanthates able to act as a MADIX chain‐transfer agent and alkyl bromide initiation sites for atom transfer radical polymerization (ATRP). By using these unique bifunctional particles, mixed polymer brushes were constructed on the SiPs by MADIX of VAc followed by ATRP of styrene or methyl methacrylate. Well brushed: Surface‐initiated polymerization of vinyl acetate from xanthate‐modified silica particles resulted in hybrid particles grafted with well‐defined poly(vinyl acetate) brushes (see scheme). Hydrolysis of the poly(vinyl acetate) brushes generated the first well‐defined, concentrated poly(vinyl alcohol) brushes. A strategy for fabricating mixed polymer brushes was also developed. [ABSTRACT FROM AUTHOR]

An ensemble of nitrogen-vacancy (NV) centers in diamond is a fascinating candidate for realizing a sensitive magnetic field sensor. In particular, since the axes of the NV centers are distributed along four directions, a collection of measurement data from NV centers with different axes provides information on the vector components of a magnetic field. However, in the conventional approach, the low measurement contrast of NV centers limits the sensitivity of vector magnetic field sensing. Recently, to overcome this problem, multi-frequency control of the NV centers has been proposed. The key idea is that four types of NV centers with different axes are simultaneously controlled by multi-frequency microwave pulses. Here, we demonstrate vector magnetic field sensing with an ensemble of NV centers in diamond via such multi-frequency control with pulsed-type measurements. We use Hahn echo pulses and extract information on the vector components of an applied AC magnetic field. We find that the sensitivity of the vector field sensing with multi-frequency control is better than that with single-frequency control for every vector component of a magnetic field. [ABSTRACT FROM AUTHOR]

Background: To evaluate the prognostic outcome and surgical complications in patients with early-stage cervical cancer who underwent sentinel node navigation surgery (SNNS) for hysterectomy or trachelectomy.Methods: A total of 139 patients who underwent SNNS using 99mTc phytate between 2009 and 2015 were evaluated. No further lymph node dissection was performed when intraoperative analysis of the sentinel lymph nodes (SLNs) was negative for metastasis. We compared the surgical complications between the SNNS group and 67 matched patients who underwent pelvic lymph node dissection (PLND) after SLN mapping between 2003 and 2008. We also examined the clinical outcomes in the SNNS group.Results: The mean number of detected SLNs was 2.5 per patient. Fourteen of the 139 patients in the SNNS group underwent PLND based on the intraoperative SLN results. The amount of blood loss, the operative time, and the number of perioperative complications were significantly less in the SNNS group than in the matched PLND group. There was no recurrence during a follow-up period ranging from 2 to 88 months (median 40 months) in the SNNS group.Conclusions: Using SNNS for early-stage cervical cancer is safe and effective and does not increase the recurrence rate. A future multicenter trial is warranted. [ABSTRACT FROM AUTHOR]

It has been reported that phytoextracts that contain alkylresorcinols (ARs) protect against severe myofibrillar degeneration found in isoproterenol-induced myocardial infarction. In this study, we examined the effect of dietary ARs derived from wheat bran extracts on muscle atrophy in denervated mice. The mice were divided into the following four groups: (1) sham-operated (control) mice fed with normal diet (S-ND), (2) denervated mice fed with normal diet (D-ND), (3) control mice fed with ARs-supplemented diet (S-AR) and (4) denervated mice fed with ARs-supplemented diet (D-AR). The intake of ARs prevented the denervation-induced reduction of the weight of the hind limb muscles and the myofiber size. However, the expression of ubiquitin ligases and autophagy-related genes, which is associated with muscle proteolysis, was slightly higher in D-AR than in D-ND. Moreover, the abundance of the autophagy marker p62 was significantly higher in D-AR than in D-ND. Muscle atrophy has been known to be associated with a disturbed energy metabolism. The expression of pyruvate dehydrogenase kinase 4 (PDK4), which is related to fatty acid metabolism, was decreased in D-ND as compared with that in S-ND. In contrast, dietary supplementation with ARs inhibited the decrease of PDK4 expression caused by denervation. Furthermore, the abnormal expression pattern of genes related to the abundance of lipid droplets-coated proteins that was induced by denervation was improved by ARs. These results raise the possibility that dietary supplementation with ARs modifies the disruption of fatty acid metabolism induced by lipid autophagy, resulting in the prevention of muscle atrophy. [ABSTRACT FROM AUTHOR]

Abstract In Arthropoda, the ovary is classified into Chelicerata-type and Mandibulata-type, based on the oocyte-growth position within the ovary. By contrast, oocytes of Diplopoda and Chilopoda grow within the hemocoelic space. However, as the position of oocyte-growth in Symphyla and Pauropoda has not been confirmed, whether the hemocoelic nature of oocyte-growth is common among myriapods remains ambiguous. This study described the ovarian structure of Hanseniella caldaria to reveal the oocyte-growth position in Symphyla. The oocyte is surrounded by the follicle epithelium, and the inner surface of the follicle epithelium, i.e., the space between follicle cells and oocytes, is lined with a basement membrane. The follicle epithelial layer continues to the ovarian epithelium via the follicle extension with a continuous layer of basement membrane. Data on the architecture of the follicle suggest that the follicle pouch opens to the hemocoel. Hence, the oocyte of H. caldaria grows within the hemocoelic space. Based on our findings in H. caldaria and previous studies in a millipede and in centipedes, the hemocoelic nature of oocyte-growth is considered as a common feature among myriapods and a synapomorphy of the Myriapoda for which morphological synapomorphies have been ambiguous. Highlights • The ovarian structure of Hanseniella caldaria is described. • The follicle epithelium continues to the ovarian epithelium with a basement membrane. • The follicle pouch of H. caldaria is considered to open to the hemocoel. • The hemocoelic oocyte-growth is regarded as a synapomorphy of Myriapoda. [ABSTRACT FROM AUTHOR]

Poly(2-methoxyethyl acrylate) is known to exhibit good blood compatibility. This study was designed to understand the effect of methoxyethyl ester groups on the platelet compatibility of polymers. Polymers bearing either methoxyethyl ester or methyl ester groups, such as poly(acrylate)s, poly(methacrylate)s, and poly(vinyl benzoate)s, were prepared and a comparative study of the ester groups was performed. Polymers bearing methoxyethyl ester groups and poly(methyl acrylate) exhibited good and approximately equal platelet compatibility, regardless of their chemical structure, as estimated using flow cytometry and scanning electron microscopy. To understand these results, the static properties (namely, surface wettability by contact angle and water structure by differential scanning calorimetry) and a dynamic property (13C-NMR relaxation time of the functional groups) were analyzed. The results showed that platelet compatibility could be interpreted from the water structure and dynamic property. [ABSTRACT FROM AUTHOR]

Background. Influenza-associated encephalopathy (IAE) can result in severe neurologic disease with high mortality. Most IAE cases are reported among children worldwide. Understanding of IAE among adults is limited. Methods. Data were collected on IAE cases reported through the National Epidemiological Surveillance of Infectious Diseases database in Japan from 2010 through 2015. IAE cases were stratified by age category and analyzed using descriptive statistics to assess differences in characteristics and outcomes. Results. Among 385 IAE cases, median age at diagnosis was 7 years (range, 0-90), and 283 (74%) were aged <18 years. Mean seasonal incidence of IAE cases among children and adults (aged ≥18 years) was 2.83 and 0.19 cases per 1 000 000 population, respectively. IAE incidence did not vary by predominant influenza A virus subtype. IAE frequency was highest in school-aged (5-12 years) children (38%), followed by children aged 2-4 years (21%) and adults aged 18-49 years (11%). The proportion of cases with seizures was more common in children. There were more cases with cerebrospinal fluid pleocytosis among adults than in children (P < .01), especially among those aged 18-49 (17%) and 50-64 (19%) years. Case fatality proportion was highest in those aged 40-64 (17%) and ≥65 (20%) years. Conclusions. We found differences in the clinical features of IAE between adults and children in Japan. Although IAE incidence was higher in children, mortality was higher in adults. Efforts are needed to prevent and improve survival of patients with IAE, especially in adults. [ABSTRACT FROM AUTHOR]

Objective To analyze patient characteristics of cancer rehabilitation and outcomes at our hospital. Methods This retrospective study analyzed 580 patients, who underwent cancer rehabilitation at our hospital and rehabilitation outcome after therapy were investigated. The relationship between the initial Barthel index and discharge outcomes was investigated, with a special focus on cancer patients with bone metastasis. The Barthel index and performance status (Eastern Cooperative Oncology Group) before and after rehabilitation were analyzed, and threshold value of home discharge was calculated from a receiver operating characteristic curve (ROC). General criteria for home discharge from our hospital included independence in performing basic activities of daily living such as bathing, feeding, and toileting or availability of home support from a family member/caregiver. Results The outcomes after rehabilitation among all the patients were as follows: discharge home 59%, death 13%, and others 27%. Statistical differences were observed between the initial and final values of the Barthel index in patients with bone metastasis, who could be discharged home (p=0.012). ROC analysis of the initial Barthel index for predicting home discharge revealed a threshold value of 60, sensitivity of 0.76, and specificity of 0.72. Conclusion The patients with bone metastasis had a lower rate of home discharge and a higher rate of mortality than all the study patients who underwent cancer rehabilitation at our hospital. It is proposed that at the time of initiation of rehabilitation for patients with bone metastasis, an initial Barthel index lower than 60 might predict a worse outcome than home discharge. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To investigate the surgical outcome of FIGO stage IA1 cervical adenocarcinoma. Methods: Between 2005 and 2011, 12 patients from Kyushu University Hospital had cervical adenocarcinoma, with a tumor depth of less than 3 mm and a horizontal width of less than 7 mm (FIGO stage IA1), diagnosed by cervical conization. All patients underwent simple hysterectomy or simple trachelectomy with pelvic lymphadenectomy. Results: The mean patient age was 34 years (range, 26–70 years). The median follow‐up period was 70.5 months (range, 26–99 months). No pelvic lymph‐node metastasis was seen, and no patient experienced disease recurrence. Conclusion: Early invasive cervical adenocarcinoma with a depth of invasion of 3 mm or less and a horizontal spread of 7 mm or less has little potential for nodal metastasis or recurrence. Therefore, simple hysterectomy or trachelectomy, without lymphadenectomy, might be an alternative treatment option for stage IA1 cervical adenocarcinoma. [ABSTRACT FROM AUTHOR]