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Spatial distributions of principal elements in a NFSa fibrosarcoma tumor treated with a vascular disruption agent, AVE8062 (a derivative of combretastatin A-4) at a single dose of 40 mg/kg were evaluated on the basis of particle-induced X-ray emission (PIXE) analysis using a submillimeter-sized proton beam. We found not only potassium and sulfur concentrations at the periphery of the treated tumor but also a ring-shaped calcium distribution in the area between the inner necrotic region and the periphery. These observations were supported by results for quantitative evaluation of elemental concentrations in the tumor samples obtained from conventional PIXE analysis based on the internal standard method. It is suggested that the potassium and sulfur concentrations are related to residual viable cells at the tumor periphery which are commonly observed in VDA treatments whereas the ring of calcium concentration just inside the tumor periphery is possibly derived from hypoxia-induced response. [ABSTRACT FROM AUTHOR]

Concentrations of the chemotherapeutic agent, cis-diamminedichloro-platinum(II) (CDDP) in NFSa fibrosarcoma tumors were investigated using a conventional PIXE analysis on the basis of an internal standard method to study enhancement of antitumor effects caused by proton therapy combined with CDDP treatment. Results of the PIXE analysis showed that platinum concentration of the tumors treated with CDDP at a single dose of 10 mg/kg was 2.0±0.1 µg/g and persisted at the level at least 6 hours after the administration. The present study demonstrated that the presence of CDDP in the tumor caused an enhanced therapeutic effect on tumor growth delay when CDDP treatment was combined with post proton-irradiation in comparison with CDDP treatment alone or proton therapy alone. [ABSTRACT FROM AUTHOR]

Every day for two weeks, participants at four sites (2 in the US, 1 in Canada, and 1 in Japan) described their self-esteem and affect and they described the events that occurred each day. Multilevel random coefficient modeling analyses found that the self_esteem of Japanese participants changed more in reaction to daily social events (both positive and negative) than it did for North American participants. For positive social events, the Japanese were more reactive in terms of positive affect than North Americans. For negative social events, the Japanese were more reactive in terms of depressed mood (ND) and deactive positive affect (PD) than North Americans. In contrast, the Japanese were less reactive to negative achievement events than North Americans in terms of PA and anxious mood. The Japanese were more reactive than North Americans to positive achievement events in terms of PA and ND. The results highlight the greater sensitivity of the Japanese to social concerns compared to North Americans, and the greater affective sensitivity of North Americans to failure in achievement domains. [ABSTRACT FROM AUTHOR]

Abstract: Ba complex oxides such as BaMO3 (BMO, M=Zr and Sn) were incorporated into ErBa2Cu3O7−δ (ErBCO) films on SrTiO3 (STO) substrates for realizing higher critical current densities (J c) in magnetic fields. Nanorods of BMO were formed in the ErBCO films with the rod diameter of about 10–20nm. Crystal grain alignment of both ErBCO films with BZO and BSO were found to be worse with increasing the doping concentration of BMO into the films, resulting in critical temperature (T c) degradation for the ErBCO films. J c of the ErBCO films were enhanced by the corporation of these BMO nanorods in the magnetic fields (B) applied particularly parallel to the c-axis (B//c). Additionally, it was observed that the J c values of the ErBCO films with BSO were higher than those of ErBCO films with BZO in the all measured magnetic fields (B//c), which indicated that the BSO nanorods acted as more effective pinning centers in ErBCO films. Extremely high J c of 0.41MA/cm2 was performed for the ErBCO film with BSO of 4.9mol% in the magnetic field (B//c) of 3T. We concluded that not only the decision of pinning materials, but also optimization of the three factors of crystallinity of the superconducting film, T c of the superconducting film, and doping concentration of the pinning materials into the superconducting film were important to realize higher J c in a magnetic field. [Copyright &y& Elsevier]

Abstract: We fabricated an ErBa2Cu3O7−δ (ErBCO) thin film with BaZrO3 (BZO) doping (BZO+ErBCO) on a SrTiO3 (STO) substrate by a pulsed laser deposition (PLD) method using a novel target which consists of two parts. One is ErBCO for a superconducting phase, the other is rectangular shaped BZO for pinning centers. From an X-ray diffraction (XRD) pattern, the ErBCO film was c-axis oriented and in-plane aligned on the STO substrate. Microstructures of the BZO+ErBCO film were observed by a transmission electron microscope (TEM). In the TEM image, nano-particles of BZO were observed in the film, not nano-rods. This result means that the novel target enables to dope BZO nano-particles into the film without any target changing. From the TEM image and thickness of the sample, a volume percentage of BZO nano-particles is calculated to be 7.3vol%. It is almost the same to the calculated value from the percentage of laser irradiating area. [Copyright &y& Elsevier]

Polymorphisms in the 5-flanking region of the tumor necrosis factor (TNF)-α gene were examined to study the genetic background of type 1 diabetes in Japanese. Five different biallelic polymorphisms were examined in 136 type 1 diabetic patients and 300 control subjects. The frequencies of individuals carrying TNF-α-857T allele (designated as TNFP-D allele) or -863A/-1,031C allele (designated as TNFP-B allele) were significantly increased in the patients as compared with the controls. Since these TNF-α alleles are in linkage disequilibria with certain DRB1 and HLA-B alleles, two-locus analyses were carried out. The TNFP-D allele did not increase the risk in either the presence or absence of the DRB1∗0405 or HLA-B54 allele, while the DRB1∗0405 and HLA-B54 alleles per se could confer susceptibility in both the TNFP-D allele-positive and -negative populations. Moreover, an odds ratio was remarkably elevated in the population carrying both DRB1∗0405 and HLA-B54. Similarly, the TNFP-B allele did not show significant association with the disease in either the HLA-B61-positive or -negative population, while the HLA-B61 allele could significantly increase the risk in the TNFP-B allele-positive population. These data suggest that the associations of TNFP-D and -B alleles may be secondary to their linkage disequilibria with the susceptible HLA class I and class II alleles. Because HLA-B and DRB1 genes were independently associated, both of these genes may be contributed primarily to the pathogenesis of type 1 diabetes in Japanese. [ABSTRACT FROM AUTHOR]

Abstract: BaSnO3 (BSO)-doped ErBa2Cu3O7−δ (ErBCO) films are grown by a pulsed laser deposition (PLD) method on SrTiO3 (STO) substrates for realizing high J C in a magnetic field. ErBCO ceramics with BSO-contents of 0–8.0wt% are used as targets. From XRD analyses of the obtained films, 00 l reflections of ErBCO are observed, indicating that the films are c-axis oriented. BSO grew in a shape of nanorod in all ErBCO films. The BSO-doped ErBCO films showed higher J C than non-doped ErBCO films in magnetic fields, suggesting that BSO nanorods plays a role of pinning centers. On the other hand, the J C properties depended strongly on the concentration of BSO-doped in ErBCO films; a 4wt% BSO-doped ErBCO film showed lower J C than that of a 2wt% BSO-doped film. These BSO-content dependences on J C for ErBCO films were understood as poor alignment of ErBCO crystal grains caused by BSO doping. We believe that the optimized BSO doping content into ErBCO films for high J C is around 2wt% among the obtained films. [Copyright &y& Elsevier]

Analysis of the detailed genomic structure of human N-cadherin revealed that the 16-exon gene is more than 72 kb in length and that it consists of a mosaic of exons. Five repeated cadherin domains, a transmembrane domain, and a cytoplasmic domain are encoded by exons 4 to 13, 13 and 14, and 14 to 16, respectively. A search for molecular variants in the entire coding region in 96 Japanese individuals resulted in the identification of eight sequence polymorphisms including three CCT- or GCC-type trinucleotide repeat polymorphisms adjacent to the initiation codon and five other novel single-nucleoticle polymorphisms (SNPs) in the coding region. Three of the five SNPs accompanied an amino acid substitution: Ala118Thr, Ala826Thr, and Asn845Ser. Knowlege of the fine gene structure and eight novel polymorphisms will be useful for the genetic study of the role of N-cadherin in diseases involving cell adhesion in the brain and in cardiomyocytes. [ABSTRACT FROM AUTHOR]

Low-energy ion bombardment during film growth can significantly modify film properties. The practical advantages of using an ionized cluster beam (ICB) include reduced damages and high deposition rates at low temperature. The design and the characteristics of the ICB source are described. The ionized cluster trajectories and the potential profiles were numerically calculated in order to optimize the design. The ionization chamber has restrictive electrodes to enhance the ionization probability in the low cluster density region near the anode. With these electrodes, the source provides uniform ion current densities up to 30 µA/cm² at voltages ranging from 200 to 8000 V over a 127 mm diam substrate at a distance of 300 mm from the source. The ICB source can operate over a wide temperature range up to 2000°C. Deposition rates up to 120 nm/min are obtained for Ti, Si, and Cu. The source has successfully operated for more than 100 h in several industrial applications. [ABSTRACT FROM AUTHOR]

Background: Owing to the risk of atypical femoral fractures, total hip arthroplasty presents unique challenges for patients with ipsilateral osteoarthritis and localized periosteal thickening in the femoral subtrochanteric region. Stem length selection is critical for minimizing stress concentration in the thickened cortex to avoid such fractures. Herein, we report the case of a 78-year-old woman with ipsilateral hip osteoarthritis and localized subtrochanteric periosteal thickening. Methods: Preoperative planning included a finite element analysis to assess the stress distribution across various stem lengths. A simulation was conducted to determine the optimal stem length to span the cortical thickening and reduce the risk of postoperative complications. Results : The finite element analysis indicated that a stem length of >150 mm was required to effectively reduce the stress at the site of cortical thickening. A 175 mm stem was selected for total hip arthroplasty, which provided a favorable stress distribution and avoided the risk of stress concentration. Conclusions: In cases of ipsilateral osteoarthritis with localized subtrochanteric periosteal thickening, finite element analysis can be valuable for preoperative planning to determine the optimal stem length, thereby reducing the risk of atypical femoral fractures. Further studies with multiple cases are recommended to validate these findings and improve surgical outcomes.

Background/aim: Age-related decline in the number of ovulations and ovum quality are major causes of female infertility, and stem cells have been reported to be effective in tissue regeneration. However, current therapeutic modalities are inadequate. This study investigated the effects of adipose-derived mesenchymal stem cells (ASCs) on ovarian functions in aged mice., Materials and Methods: Following the characterization of ASCs using flow cytometry, the effects of ASCs on the number of ovulations, fertilization rate, and blastocyst-formation rate were investigated. In addition, the number of ovarian follicles and serum anti-Müllerian hormone (AMH) levels were examined. ASCs marked with Kusabira Orange were used to examine the location after cell administration. The quality of ovulated oocytes was analyzed using next-generation RNA sequencing., Results: ASCs showed characteristics of mesenchymal stem cells and were distributed to various organs, including the ovarian stroma. The transplantation resulted in increased number of oocytes and ovulation in the ovaries and increased AMH values. Genetic analysis revealed improved oocyte quality and increased fertilization and blastocyst-formation rates., Conclusion: ASC therapy may be effective in improving fertility in older women., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Many countries, including Japan, are experiencing declining birth rates. Assisted reproductive technologies have consistently demonstrated good results in resolving infertility. Although the development of fertilized eggs into blastocysts has been recognized as a crucial step in assisted reproductive technologies, the involved mechanisms are currently unclear. Here, we established a new culture system for the in vitro development of fertilized eggs into blastocysts. In the Transwell culture system, the rate of blastocysts hatching from fertilized eggs cultured with adipose-derived stem cells (ASCs) was significantly higher than that of blastocysts cultured only with fertilized eggs. Gene ontology analysis revealed that the developed blastocysts displayed essential gene expression patterns in mature blastocysts. Additionally, when cultured with 3rd-passage ASCs, the developed blastocysts expressed the core genes for blastocyst maturation and antioxidant properties compared to those cultured only with fertilized eggs or cultured with 20th-passage ASCs. These results suggest that the Transwell culture system may imitate the in vivo tubal culture state for fertilized eggs. Exosomes derived from stem cells with stemness potential play a powerful role in the development of blastocysts from fertilized eggs. Additionally, the exosomes expressed specific microRNAs; therefore, the Transwell culture system resulted in a higher rate of pregnancy. In future, the extraction of their own extracellular vesicles from the culture medium might contribute to the development of novel assisted reproductive technologies.

Hypothesis: While conventional in silico immunogenicity risk assessments focus on measuring immunogenicity based on the potential of therapeutic proteins to be processed and presented by a global population-wide set of human leukocyte antigen (HLA) alleles to T cells, future refinements might adjust for HLA allele frequencies in different geographic regions or populations, as well for as individuals in those populations. Adjustment by HLA allele distribution may reveal risk patterns that are specific to population groups or individuals, which current methods that rely on global-population HLA prevalence may obscure., Key Findings: This analysis uses HLA frequency-weighted binding predictions to define immunogenicity risk for global and sub-global populations. A comparison of assessments tuned for North American/European versus Japanese/Asian populations suggests that the potential for anti-therapeutic responses (anti-therapeutic antibodies or ATA) for several commonly prescribed Rheumatoid Arthritis (RA) therapeutic biologics may differ, significantly, between the Caucasian and Japanese populations. This appears to align with reports of differing product-related immunogenicity that is observed in different populations., Relevance to Clinical Practice: Further definition of population-level (regional) and individual patient-specific immunogenic risk profiles may enable prescription of the RA therapeutic with the highest probability of success to each patient, depending on their population of origin and/or their individual HLA background. Furthermore, HLA-specific immunogenicity outcomes data are limited, thus there is a need to expand HLA-association studies that examine the relationship between HLA haplotype and ATA in the clinic., Competing Interests: ADG and WM are senior officers and majority shareholders of EpiVax, Inc, a privately owned immunoinformatics and vaccine design company. ADG, WM and AHG are employees of EpiVax, Inc. Due to this relationship with EpiVax, these authors acknowledge that there is a potential conflict of interest inherent in the publication of this manuscript, and attest that the work contained in this research report is free of any bias that might be associated with the commercial goals of the company. NS, TH, MH, YM are employed by Pfizer Japan. These authors acknowledge that there is a potential conflict of interest inherent in the publication of this manuscript, and attest that the work contained in this research report is free of any bias that might be associated with the commercial goals of the company. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author ADG declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Sugiyama, Terry, Gutierrez, Hirano, Hoshi, Mizuno, Martin, Yasunaga, Niiro, Fujio and De Groot.)

Background: Implantation failure due to thin endometrium has emerged as a major cause of infertility. In this study, we aimed to assess the safety and preliminary efficacy of adipose tissue-derived regenerative cells (ADRCs), a source of adipose-derived stem cells, in infertility patients with implantation failure., Methods: Five infertile women with implantation failure despite artificial reproductive technology were enrolled in this study and treated with ADRCs via the intrauterine route. The primary outcome was the incidence of adverse events. Additional outcomes were endometrial thickness after ADRC treatment and pregnancy success after embryo transfer., Results: There were no adverse events in any patient. There was no elevation of white blood cell count, C-reactive protein, or D-dimer levels. There was a significant difference in endometrial thickness in the secretory phase before versus after intrauterine transplantation of ADRCs (3.8 ± 1.3 mm versus 8.8 ± 2.8 mm, respectively; p<0.05). A gestational sac and fetal heartbeat were detected on transvaginal ultrasound in two of five patients., Conclusion: Intrauterine infusion of autologous ADRCs is a simple and safe procedure that may ameliorate the endometrial microenvironment in infertile women with implantation failure., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Yotsumoto et al.)

Here, we propose a laboratory exercise to quickly determine single nucleotide polymorphisms (SNPs) in human alcohol dehydrogenase 1B (ADH1B) and aldehyde dehydrogenase 2 (ALDH2) genes involved in alcohol metabolism. In this exercise, two different genotyping methods based on polymerase chain reaction (PCR), namely allele-specific (AS) PCR and a PCR-restriction fragment polymorphism (RFLP) analysis, can be performed under the same PCR program (2-step × 35 cycles, 35 min total) in parallel using a hair root lysate as a template. In AS-PCR, the target regions of the G- or A-alleles of both genes are allele-specifically amplified in a single PCR tube. In the PCR-RFLP analysis, the two genes are amplified simultaneously in a single tube, and then a portion of the PCR product is double-digested with restriction enzymes MslI and Eam1104I for 5 min. The resulting reaction products of each method are electrophoresed side by side, and the genotypes are determined from the DNA band patterns. With the optimized protocol, the whole process from template preparation to genotyping can be completed in about 75 min. During PCR, students also perform an ethanol patch test to estimate their ability to metabolize alcohol. This series of experiments can help students learn the principles and applications of PCR/SNP analyses. By comparing the genotypes revealed by PCR and the phenotypes revealed by the patch tests, students can gain a better understanding of the clinical value of genetic testing., (© 2023 International Union of Biochemistry and Molecular Biology.)

Background/aim: Ultrafine bubbles (UFBs) have been extensively researched owing to their promising physical and biological properties. However, determining the lifespan or ideal concentration of UFBs for various biological events is challenging. This study aimed to determine the maximum concentration and longest lifespan of UFBs and to verify the validity of UFBs for assessing cell properties., Materials and Methods: A generator system (HMB-H0150+P001, TOSSLEC Corporation Limited, Kyoto, Japan) generated UFBs using various gases. The size and concentration of UFBs in ultrapure water and cell culture medium were measured through a nanoparticle tracking analysis method., Results: The UFB concentration increased when the generator operated in a time dependent manner. The mean size of UFBs was approximately 120 nm. In the UFB lifespan, the concentration decreased by approximately 30% within the first two weeks of generation and was stable for up to 6 months. The UFB size increased by approximately 20% within the first two weeks of generation and demonstrated minor changes until the 6th month. The number of cells differed significantly with various concentrations of nitrogen gas UFBs., Conclusion: The generator system can generate UFBs with multiple concentrations within a suitable temperature. Consequently, the solution containing UFBs could be widely acceptable in cell culture systems., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Atmospheric pressure measurements based on microelectromechanical systems (MEMSs) can extend accessibility to altitude information. A differential pressure sensor using a thin cantilever and an air chamber is a promising sensing element for sub-centimeter resolution. However, its vulnerability to wind and the lack of height estimation algorithms for real-time operation are issues that remain to be solved. We propose a sensor "cap" that cancels the wind effect and noise by utilizing the airflow around a sphere. A set of holes on the spherical cap transmits only the atmospheric pressure to the sensor. In addition, we have developed a height estimation method based on a discrete transfer function model. As a result, both dynamic pressure and noise are suppressed, and height is estimated under a 5 m/s wind, reconstructing the trajectory with an estimation error of 2.8 cm. The developed sensing system enhances height information in outdoor applications such as unmanned aerial vehicles and wave height measurements.

Super-resolution vibrational microscopy is promising to increase the degree of multiplexing of nanometer-scale biological imaging because of the narrower spectral linewidth of molecular vibration compared to fluorescence. However, current techniques of super-resolution vibrational microscopy suffer from various limitations including the need for cell fixation, high power loading, or complicated detection schemes. Here, we present reversible saturable optical Raman transitions (RESORT) microscopy, which overcomes these limitations by using photoswitchable stimulated Raman scattering (SRS). We first describe a bright photoswitchable Raman probe (DAE620) and validate its signal activation and depletion characteristics when exposed to low-power (microwatt level) continuous-wave laser light. By harnessing the SRS signal depletion of DAE620 through a donut-shaped beam, we demonstrate super-resolution vibrational imaging of mammalian cells with excellent chemical specificity and spatial resolution beyond the optical diffraction limit. Our results indicate RESORT microscopy to be an effective tool with high potential for multiplexed super-resolution imaging of live cells.

Background/aim: This study aimed to evaluate the learning curve and perioperative outcomes of robot-assisted hysterectomy (RAH)., Patients and Methods: We retrospectively analyzed data from 45 patients who underwent RAH using the da Vinci Xi surgical system. The learning curve was evaluated using the cumulative summation method. Demographic data and various perioperative parameters, including total operative time, docking time, and console time, were obtained from the medical records., Results: Cumulative summation analysis indicated that proficiency regarding hysterectomy time was reached after 33 cases. There were two unique phases of the learning curve for console time: the introduction phase identified by the bottom point in the curve, and the proficient phase, identified by an upward line after the bottom point in the curve. There were no significant differences between the two phases in terms of patient age and body mass index. Total operative time, docking time, and console time were significantly decreased in the proficient phase compared with those in the introduction phase. There was a significant reduction in blood loss during operation in the proficient phase. The perioperative complication rates were 12.1% in the introduction phase and 0% in the proficient phase (p=0.5606). No blood transfusion or conversion to laparotomy was required in either phase., Conclusion: The introduction and proficient phases identified by cumulative summation analysis demonstrated progressive improvement of surgical performance in surgeons carrying out RAH., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)