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Cirrhosis is a chronic condition that can lead to liver failure. Currently, the viable option for decreasing mortality is liver transplantation. However, transplant surgery is highly invasive. Therefore, cell-based therapy has been developed as an alternative. Based on promising findings from preclinical research, some new trials have been registered. One of them was autologous bone marrow cell infusion therapy and found that ameliorating liver fibrosis activated liver regeneration. Now, majority of trials focus on low-immunogenicity mesenchymal stem cells (MSCs) appropriate for allogeneic administration. However, despite about 20 years of research, only a limited number of cell-based therapies have entered routine practice. Furthermore, potential shortcomings of cell-based therapy include a limit on the number of cells, which may be administered, as well as their failure to infiltrate target organs. On the other hand, these research show that MSCs act as “conducting cells” and regulate host cells including macrophages via extracellular vesicles (EVs) or exosome signals, leading to ameliorate liver fibrosis and promote regeneration. Therefore, the concept of cell-free therapy, which makes use of cell-derived EVs or exosomes, is attracting attention. Cell-free therapies may be safely administered in large doses and are able to infiltrate target organs. However, development of cell-free therapy exhibits its own set of challenges and such therapy may not be completely curative in the context of liver disease. This review describes the history of cell-based therapy research and recent advances in cell-free therapy, as well as discussing the need for more effective therapies.

We analyzed genome-wide single-nucleotide polymorphism data of 11,069 Japanese individuals recruited from all 47 prefectures of Japan to clarify their genetic structure. The principal component analysis at the prefectural level enabled us to study the relationship between geographical location and genetic differentiation. The results revealed that the mainland Japanese were not genetically homogeneous, and the genetic structure could be explained mainly by the degree of Jomon ancestry and the geographical location. One of the interesting findings was that individuals in the Shikoku region (i.e., Tokushima Prefecture, Kagawa Prefecture, Ehime Prefecture, and Kochi Prefecture) were genetically close to Han Chinese. Therefore, the genetic components of immigrants from continental East Asia in the Yayoi period may have been well maintained in Shikoku. The present results will be useful for understanding the peopling of Japan, and also provide suggestions for recruiting subjects in genetic association studies.

Microwave-assisted de-emulsification is attractive in the processes of petroleum production and refining. The main advantage of microwaves is their direct influence on the surfactant layer at the oil/water interface. Previously, an effective interfacial modification was demonstrated by pulsed microwave irradiation. However, the effect of the modification diminished during the off interval of the pulse irradiation. In this study, two-stage microwave irradiation with different powers and durations was applied as a method to maintain an interfacial effect. The power of the second stage was changed to optimise the modification. Quick modification was obtained by high-power irradiation followed by low-power irradiation. It was confirmed a sustained modification was maintained by a moderate power of the second irradiation. This observation indicates a re-adsorption or re-structure process after the first irradiation is suppressed by the second irradiation. The results open new opportunities to optimise microwave operation in oil/water systems.

The Japanese archipelago is a terminal location for human migration, and the contemporary Japanese people represent a unique population whose genomic diversity has been shaped by multiple migrations from Eurasia. We analyzed the genomic characteristics that define the genetic makeup of the modern Japanese population from a population genetics perspective from the genomic data of 9,287 samples obtained by high-coverage whole-genome sequencing (WGS) by the National Center Biobank Network. The dataset comprised populations from the Ryukyu Islands and other parts of the Japanese archipelago (Hondo). The Hondo population underwent two episodes of population decline during the Jomon period, corresponding to the Late Neolithic, and the Edo period, corresponding to the Early Modern era, while the Ryukyu population experienced a population decline during the shell midden period of the Late Neolithic in this region. Haplotype analysis suggested increased allele frequencies for genes related to alcohol and fatty acid metabolism, which were reported as loci that had experienced positive natural selection. Two genes related to alcohol metabolism were found to be 12,500 years out of phase with the time when they began to increase in the allele frequency; this finding indicates that the genomic diversity of Japanese people has been shaped by events closely related to agriculture and food production.

BackgroundSeveral well-trained expert instructors who completed the “Train-The-Trainer (TTT)” course are required to disseminate the safe use of surgical energy devices, which can be learned through the Fundamental Use of Surgical Energy (FUSE) program. This study aimed to explore whether the hybrid FUSE TTT course is feasible and effective, which can improve teaching skills of surgical energy.MethodsThe hybrid TTT course, which was designed to train FUSE-certified personnel as instructors, comprised three virtual sessions spread over 5 h in total and a 1-day in-person training, followed by a 100-min FUSE electrosurgery hands-on workshop in practice as an instructor. The participants reported on self-confidence regarding knowledge of various energy devices or adverse events before, immediately after, and 6 months after the course. Participants and experienced FUSE instructors assessed the trainees’ presentation skills at the beginning of the in-person training and after the hands-on workshop. The primary outcomes were the feasibility and completion rate of the entire course.ResultsSeventeen participants completed the entire couse; most (94%) were satisfied with the course. Self-confidence in knowledge about various contents improved significantly: the fundamentals of electrosurgery (post, p < 0.001; 6 months, p = 0.01), mechanism and prevention of adverse events (post, p = 0.001; 6 months, p = 0.04), monopolar instruments (post, p = 0.002; 6 months, p = 0.01), bipolar instruments (post, p = 0.01; 6 months, p = 0.06), and integration with other medical devices (post, p = 0.006; 6 months, p = 0.02). The presentation skill index scores of self- and peer assessments improved after the in-person training (self-assessment [pre 44 vs. post 56, p < 0.001], peer assessment [pre 39 vs. post 68, p < 0.001]).ConclusionsThe hybrid TTT course can provide FUSE-certified personnel with an improved self-confidence concerning knowledge of surgical energy and improve their presentation skills with midterm retention. This can help build trainees’ self-confidence as instructors.

BackgroundAlthough the da Vinci™ Surgical System is the most predominantly used surgical robot worldwide, other surgical robots are being developed. The Japanese surgical robot hinotori™ Surgical Robot System was launched and approved for clinical use in Japan in November 2022. We performed the first robotic gastrectomy for gastric cancer using hinotori in the world. Here, we report our initial experience and evaluation of the feasibility and safety of robotic gastrectomy for gastric cancer using hinotori.MethodsA single-institution retrospective study was conducted. Between November 2022 and October 2023, 24 patients with gastric cancer underwent robotic gastrectomy with hinotori. Five ports, including one for an assistant, were placed in the upper abdomen, and gastric resection with standard lymphadenectomy and intracorporeal reconstruction were performed. The primary endpoint was the postoperative complication rate within 30 days after surgery. The secondary outcomes were surgical outcomes, including intraoperative adverse events, operative time, blood loss, and the number of dissected nodes.ResultsOf the 24 patients, 16 (66.7%) were male. The median age and body mass index were 73.5 years and 22.9 kg/m2, respectively. Twenty-three patients (95.8%) had tumors in the middle to lower stomach. Sixteen (66.7%) and seven (29.2%) patients had clinical stage I and II diseases, respectively. Twenty-three (95.8%) patients underwent distal gastrectomy. No patient had postoperative complications of Clavien–Dindo classification IIIa or higher, whereas two (8.3%) had the grade II complications (enteritis and pneumonia). No intraoperative adverse events, including conversion to other approaches, were observed. All patients received R0 resection. The median operative and console times were 400 and 305 min, respectively. The median blood loss was 14.5 mL, and the number of lymph nodes dissected was 51.5.ConclusionsThis study found that robotic gastrectomy with standard lymphadenectomy for gastric cancer using hinotori can be safely performed.

BackgroundUlcerative colitis (UC) is a chronic inflammatory disease of the colon with an intractable, recurrent course. The goal of UC therapy is to target mucosal healing because immune-suppressive therapy for UC frequently results in relapse. However, few drugs directly target mucosal healing. We, therefore, aim to evaluate the therapeutic effect of an investigational drug on intestinal epithelial cells in an in vitro UC model using human colonic organoids.MethodsColonic organoids were isolated from human colon and cultured. A mixture of cytokines and bacterial components were used to mimic UC in humans. The effect of the investigational drug on colonic organoid was evaluated by microarray analysis and 3D immunofluorescence. The enrichment of stem cells was assessed with a colony formation assay.ResultsInflammatory stimulation resulted in a significant induction of inflammatory-related genes in colonic organoids whereas cell differentiation was suppressed. Treatment with the investigational drug KAG-308 showed reciprocal dynamics of gene expression to inflammatory stimulation, which resulted in not only the suppression of immune response but also the promotion of cellular differentiation towards secretory lineages. Moreover, SPDEF and Reg4 were identified as novel targets for the enrichment of intestinal epithelial stem cells and mucosal healing.ConclusionsThe establishment of in vitro UC model using human colonic organoid could reveal the effects and targets of investigational drugs in intestinal epithelial cells under inflammation conditions. Further maturation of this system might be more efficient to predict the effect on UC, as compared with the use of animal model, for the development of new drugs.

We developed a novel dual-energy (DE) virtual monochromatic (VM) very-deep super-resolution (VDSR) method with an unsharp masking reconstruction algorithm (DE–VM–VDSR) that uses projection data to improve the nodule contrast and reduce ripple artifacts during chest digital tomosynthesis (DT). For estimating the residual errors from high-resolution and multiscale VM images from the projection space, the DE–VM–VDSR algorithm employs a training network (mini-batch stochastic gradient-descent algorithm with momentum) and a hybrid super-resolution (SR) image [simultaneous algebraic reconstruction technique (SART) total-variation (TV) first-iterative shrinkage–thresholding algorithm (FISTA); SART–TV–FISTA] that involves subjective reconstruction with bilateral filtering (BF) [DE–VM–VDSR with BF]. DE-DT imaging was accomplished by pulsed X-ray exposures rapidly switched between low (60 kV, 37 projection) and high (120 kV, 37 projection) tube-potential kVp by employing a 40° swing angle. This was followed by comparison of images obtained employing the conventional polychromatic filtered backprojection (FBP), SART, SART–TV–FISTA, and DE–VM–SART–TV–FISTA algorithms. The improvements in contrast, ripple artifacts, and resolution were compared using the signal-difference-to-noise ratio (SDNR), Gumbel distribution of the largest variations, radial modulation transfer function (radial MTF) for a chest phantom with simulated ground-glass opacity (GGO) nodules, and noise power spectrum (NPS) for uniform water phantom. The novel DE–VM–VDSR with BF improved the overall performance in terms of SDNR (DE–VM–VDSR with BF: 0.1603, without BF: 0.1517; FBP: 0.0521; SART: 0.0645; SART–TV–FISTA: 0.0984; and DE–VM–SART–TV–FISTA: 0.1004), obtained a Gumbel distribution that yielded good images showing the type of simulated GGO nodules used in the chest phantom, and reduced the ripple artifacts. The NPS of DE–VM–VDSR with BF showed the lowest noise characteristics in the high-frequency region (~0.8 cycles/mm). The DE–VM–VDSR without BF yielded an improved resolution relative to that of the conventional reconstruction algorithms for radial MTF analysis (0.2–0.3 cycles/mm). Finally, based on the overall image quality, DE–VM–VDSR with BF improved the contrast and reduced the high-frequency ripple artifacts and noise.

A geographical gradient of height has existed in Japan for approximately 100 years. People in northern Japan tend to be taller than those in southern Japan. The differences in annual temperature and day length between the northern and southern prefectures of Japan have been suggested as possible causes of the height gradient. Although height is well known to be a polygenic trait with high heritability, the genetic contributions to the gradient have not yet been explored. Polygenic score (PS) is calculated by aggregating the effects of genetic variants identified by genome-wide association studies (GWASs) to predict the traits of individual subjects. Here, we calculated the PS of height for 10,840 Japanese individuals from all 47 prefectures in Japan. The median height PS for each prefecture was significantly correlated with the mean height of females and males obtained from another independent Japanese nation-wide height dataset, suggesting genetic contribution to the observed height gradient. We also found that individuals and prefectures genetically closer to continental East Asian ancestry tended to have a higher PS; modern Japanese people are considered to have originated as result of admixture between indigenous Jomon people and immigrants from continental East Asia. Another PS analysis based on the GWAS using only the mainland Japanese was conducted to evaluate the effect of population stratification on PS. The result also supported genetic contribution to height, and indicated that the PS might be affected by a bias due to population stratification even in a relatively homogenous population like Japanese.

Background The background is that intravenous adrenaline administration is recommended for advanced cardiovascular life support in adults and endotracheal administration is given low priority. The reason is that the optimal dose of adrenaline in endotracheal administration is unknown, and it is ethically difficult to design studies of endotracheal adrenaline administration with non-cardiopulmonary arrest. We otolaryngologists think so because we administered adrenaline to the vocal folds for hemostasis after intracordal injection under local anesthesia, but have had few cases of vital changes. We hypothesized that examining vital signs before and after adrenaline administration for hemostasis would help determine the optimal dose of endotracheal adrenaline. Methods We retrospectively examined the medical records of 79 patients who visited our hospital from January 2018 to December 2020 and received adrenaline in the vocal folds and trachea for hemostasis by intracordal injection under local anesthesia to investigate changes in heart rate and systolic blood pressure before and after the injection. Results The mean heart rates before and after injection were 83.96 ± 18.51 (standard deviation) beats per minute (bpm) and 81.50 ± 15.38 (standard deviation) bpm, respectively. The mean systolic blood pressure before and after the injection were 138.13 ± 25.33 (standard deviation) mmHg and 135.72 ± 22.19 (standard deviation) mmHg, respectively. Heart rate and systolic blood pressure had P -values of 0.136, and 0.450, respectively, indicating no significant differences. Conclusions Although this study was an observational, changes in vital signs were investigated assuming endotracheal adrenaline administration. The current recommended dose of adrenaline in endotracheal administration with cardiopulmonary arrest may not be effective. In some cases of cardiopulmonary arrest, intravenous and intraosseous routes of adrenaline administration may be difficult and the opportunity for resuscitation may be missed. Therefore, it is desirable to have many options for adrenaline administration. Therefore, if the optimal dose and efficacy of endotracheal adrenaline administration can be clarified, early adrenaline administration will be possible, which will improve return of spontaneous circulation (ROSC) and survival discharge rates.