Search

While nonocclusive mesenteric ischemia (NOMI) has been reported in a significant percentage of adults who were resuscitated after cardiac arrest, it is rare in children. This report presents the first known Japanese case of pediatric NOMI after return of spontaneous circulation following cardiac arrest. A 16-month-old boy experienced cardiac arrest due to asphyxiation from foreign bodies in the airway. After receiving 10 doses of adrenaline, with a maximum arrest time of 95 minutes, the patient achieved return of spontaneous circulation. However, 40 hours after onset, the patient developed NOMI, resulting in refractory hypotensive shock with decreased blood pressure, distended abdomen, and increased intravesical pressure. The patient was successfully rescued with two laparotomies and was discharged. Although NOMI is uncommon in children, appropriate treatment can be lifesaving.

Purpose: Drug resistance and severe pelvic pain often warrant surgical intervention for treating deep endometriosis (DE); however, damage to the autonomic nervous system can occur because of anatomical considerations. We aimed to investigate the advantages of robotic technology in enabling precise dissection, even in DE., Methods: We retrospectively compared the surgical outcomes of robot-assisted (RA) and conventional laparoscopic (CL) nerve-sparing modified radical hysterectomies (NSmRHs) for DE., Results: Between the two groups (RA-NSmRH group, n = 50; CL-NSmRH group, n = 18), no differences were identified based on patient demographics, such as age, body mass index, previous surgery, revised American Society of Reproductive Medicine classification, Enzian classification, uterine weight, number of removed DE lesions, and concomitant procedures. All patients in both groups achieved complete removal of the DE lesions with complete bilateral pelvic autonomic nerve preservation. The mean operative time (OT) was significantly longer (130 ± 46 vs. 98 ± 22 min, p < 0.01), and estimated blood loss (EBL) was lower (35 ± 44 vs. 131 ± 49 ml, p < 0.01) in the RA-NSmRH group than in the CL-NSmRH group. The hospitalization days (4.3 ± 1.3 vs. 4.1 ± 0.2 days, p = 0.45) and perioperative complications with Clavien-Dindo classification ≥ grade III (0% vs. 0%) were not significant in both the groups. None of the patients required self-catheterization after surgery., Conclusion: Compared with CL-NSmRH, RA-NSmRH was associated with longer OT and lower EBL, whereas the number of hospitalization days and complications were similar in both groups. Our results imply that nerve-sparing surgery can be safely and reproducibly performed using conventional or robotic laparoscopic modalities to treat DE., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The archaeal mevalonate pathway is a recently discovered modified version of the eukaryotic mevalonate pathway. This pathway is widely conserved in archaea, except for some archaeal lineages possessing the eukaryotic or other modified mevalonate pathways. Although the pathway seems almost exclusive to the domain Archaea, the whole set of homologous genes of the pathway is found in the metagenome-assembled genome sequence of an uncultivated bacterium, Candidatus Promineifilum breve, of the phylum Chloroflexota. To prove the existence of the archaea-specific pathway in the domain Bacteria, we confirmed the activities of the enzymes specific to the pathway, phosphomevalonate dehydratase and anhydromevalonate phosphate decarboxylase, because only these two enzymes are absent in closely related Chloroflexota bacteria that possess a different type of modified mevalonate pathway. The activity of anhydromevalonate phosphate decarboxylase was evaluated by carotenoid production via the archaeal mevalonate pathway reconstituted in Escherichia coli cells, whereas that of phosphomevalonate dehydratase was confirmed by an in vitro assay using the recombinant enzyme after purification and iron-sulfur cluster reconstruction. Phylogenetic analyses of some mevalonate pathway-related enzymes suggest an evolutionary route for the archaeal mevalonate pathway in Candidatus P. breve, which probably involves horizontal gene transfer events.IMPORTANCEThe recent discovery of various modified mevalonate pathways in microorganisms, such as archaea and Chloroflexota bacteria, has shed light on the complexity of the evolution of metabolic pathways, including those involved in primary metabolism. The fact that the archaeal mevalonate pathway, which is almost exclusive to the domain Archaea, exists in a Chloroflexota bacterium provides valuable insights into the molecular evolution of the mevalonate pathways and associated enzymes. Putative genes probably involved in the archaeal mevalonate pathway have also been found in the metagenome-assembled genomes of Chloroflexota bacteria. Such genes can contribute to metabolic engineering for the bioproduction of valuable isoprenoids because the archaeal mevalonate pathway is known to be an energy-saving metabolic pathway that consumes less ATP than other mevalonate pathways do., Competing Interests: The authors declare no conflict of interest.

This study aimed to assess ginger extract's impact on ocular and peripheral blood flow and its potential to alleviate eye fatigue and shoulder stiffness. This study included 100 healthy individuals aged 20-73 years with eye fatigue and shoulder stiffness. Participants were randomly assigned to receive either placebo capsules or ginger extract capsules daily for eight weeks. Ocular blood flow, peripheral blood flow, eye fatigue (visual analog scale [VAS]), shoulder stiffness (VAS), body warmth (VAS), and shoulder muscle stiffness were assessed at weeks 0, 4, and 8, respectively. No improvement in ocular blood flow was observed under the study conditions. Conversely, peripheral blood flow in deep areas was enhanced in females ( p = 0.033). Subgroup analysis by age (≥51 or <51 years) revealed that ginger's effect on enhancing peripheral blood flow in deep vessels was restricted in females under 51 ( p = 0.017). Similarly, subjective complaints of eye fatigue and shoulder stiffness were improved by ginger consumption in females under 51. Body warmth was favorably changed significantly in males ≥51 years due to ginger consumption. The muscle stiffness showed no statistically significant changes. In conclusion, ginger consumption reduces eye fatigue and shoulder stiffness by enhancing peripheral blood flow in relatively young females.

Objective: The da Vinci SP Surgical System (SP) received regulatory approval for use in gynecological surgeries in Japan in 2023. Given the advantages of the precision of a robot, less pain, and the cosmesis of single-port surgery, the da Vinci SP is expected to be further used for minimally invasive surgeries. To the best of our knowledge, this is the first report of the use of SP for the treatment of rectal endometriosis with segmental bowel resection., Setting: An urban general hospital. Stepwise demonstration of the technique with narrated video footage., Participants: The patient was a 46-year-old woman presented with chronic pelvic pain, pain on defecation and constipation. Magnetic resonance imaging showed uterine large fibroid, left ovarian endometrioma, and 38mm of rectal endometriosis, with complete cul-de-sac obliteration., Interventions: We made a 30-mm vertical incision at the umbilicus, then placed the access port, and inserted three articulating instruments and a camera. An assistant port was placed in the right lower quadrant for using the linear stapler. The surgical steps were completely identical to conventional multiport laparoscopic robotic surgery. This suggests that conventional laparoscopic or robotic skills are highly transferrable to SP. SP offer several advantages, including high-resolution three-dimensional visualization, articulating instruments, and improved dexterity and range of motion. In addition, the umbilical access port was particularly useful for proximal bowel resection, specimen retrieval, and anvil positioning during bowel resection. The total operative time was 216 minutes. The estimated blood loss was 100 ml without any complications. The uterine weight was 800 g. The postoperative course was uneventful, with no perioperative complications, including no postoperative bladder dysfunction or low anterior resection syndrome [1, 2]., Conclusion: The use of SP with the access port for segmental bowel resection for rectal endometriosis is technically safe and feasible, with good cosmesis and less pain., Competing Interests: Declaration of competing interest None, (Copyright © 2024. Published by Elsevier Inc.)

Background: Cognitive abnormalities associated with electroconvulsive therapy (ECT) are limited to the first few days after treatment. Mismatch negativity (MMN) is an event-related potential that reflects an automatic auditory change detection process under nonattention conditions and cognitive function in psychotic disorders and may be trait- or state-dependent. This study aimed to report the changes in MMN and cognitive function after two ECT treatments in a female patient who underwent maintenance ECT for atypical psychosis., Case Presentation: A 67-year-old Japanese woman with atypical psychosis was admitted to our hospital for the maintenance of ECT. She received two ECT treatments. We measured her duration-MMN (MMN-D) at baseline, the day after two ECT treatments, and approximately 40 days after the two ECT treatments. After the two ECT treatments, the peak latency of the MMN on the following day was delayed compared with that before the first ECT treatment. Forty days after the two ECT treatments, the peak latency reverted to the baseline. The Brief Assessment of Cognition in Schizophrenia scores measured at the same time point also showed a similar temporary decrease in scores., Conclusion: Peak latency prolongation in MMN-D may reflect transient cognitive abnormalities after ECT. MMN can be useful to evaluate cognitive dysfunction, one of the adverse events of ECT. However, future studies are needed to examine the reproducibility and to examine the results in diseases other than atypical psychosis., Competing Interests: The authors declare that they have no competing financial interests or personal relationships that may have influenced the work reported in this study., (© 2024 The Author(s). Psychiatry and Clinical Neurosciences Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

We developed a surgical support system that visualises important microanatomies using artificial intelligence (AI). This study evaluated its accuracy in recognising the thoracic nerves during lung cancer surgery. Recognition models were created with deep learning using images precisely annotated for nerves. Computational evaluation was performed using the Dice index and the Jaccard index. Four general thoracic surgeons evaluated the accuracy of nerve recognition. Further, the differences in time lag, image quality and smoothness of movement between the AI system and surgical monitor were assessed. Ratings were made using a five-point scale. The computational evaluation was relatively favourable, with a Dice index of 0.56 and a Jaccard index of 0.39. The AI system was used for 10 thoracoscopic surgeries for lung cancer. The accuracy of thoracic nerve recognition was satisfactory, with a recall score of 4.5 ± 0.4 and a precision score of 4.0 ± 0.9. Though smoothness of motion (3.2 ± 0.4) differed slightly, nearly no difference in time lag (4.9 ± 0.3) and image quality (4.6 ± 0.5) between the AI system and the surgical monitor were observed. In conclusion, the AI surgical support system has a satisfactory accuracy in recognising the thoracic nerves., (© 2024. The Author(s).)

Introduction: This case study aimed to demonstrate how cooking class activities held in collaboration with the Ajinomoto Foundation (TAF) and a consumer cooperative after the Great East Japan Earthquake contributed to the resilience of the affected community., Methods: With reference to the logic model, evaluation indicators for the case study were established. We focused on the Iwate Seikatsu Kyodo Kumiai (Iwate Co-op). We organized 120 continuation cases out of the eight-and-a-half-year activity records of the project owned by TAF (April 2012 to March 2020). The Iwate Co-op was one of the 120 continuing cases and had special features, including awareness that its members were responsible for the community., Results: The collaboration revealed three effects. First, owing to the encounter and collaboration with TAF, the cooking class was continuously conducted even after TAF withdrew from the disaster-affected areas. Second, the Iwate Co-op trained some of its members as food support staff to run the cooking class independently and was actively involved in obtaining the necessary budget for the operation, consequently leading to the independent activation of member activities. Third, they developed a cooking class project in inland areas other than disaster-stricken areas, assuming that they could incorporate the project into their existing activities, as food problems affected people beyond disaster victims., Conclusion: The collaborative food support project of the Iwate Co-op and TAF contributed to the resilience of the affected people and communities by strengthening bonds and solidarity among residents and organizations. The key to success was the fusion of a traditional sense of independence in the co-op with TAF's mission and technical know-how. The partnership between the Iwate Co-op and TAF allowed the former to aim toward developing food support activities in the affected areas, accelerating the resilience of the community in the Iwate Prefecture., Competing Interests: KKo was employed by Miyako Co-op, Iwate Co-op. KN and KF were employed by Kamaishi Co-op, Iwate Co-op. KKa was employed by Kesen Co-op, Iwate Co-op. HK and YN were employed by Organization/Management Headquarters, Iwate Co-op. MY was employed by The Ajinomoto Foundation. Co-author YK has received research funding from TAF. 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., (Copyright © 2024 Ito, Konno, Nozaki, Fukushi, Kanno, Kawamura, Nakamura, Yamada, Kuroda, Kuchii, Kinoshita, Nabetani and Fukuda.)

Antiviral agents are highly sought after. In this study, a novel alkylated decalin-type polyketide, alaspelunin, was isolated from the culture broth of the fungus Talaromyces speluncarum FMR 16671, and its structure was determined using spectroscopic analyses (1D/2D NMR and MS). The compound was condensed with alanine, and its absolute configuration was determined using Marfey's method. Furthermore, the antiviral activity of alaspelunin against various viruses was evaluated, and it was found to be effective against both severe acute respiratory syndrome coronavirus 2 and pseudorabies (Aujeszky's disease) virus, a pathogen affecting pigs. Our results suggest that this compound is a potential broad-spectrum antiviral agent., (© 2024. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

Objective: To demonstrate the efficacy of the double-bipolar method in a benign hysterectomy., Design: Stepwise demonstration of the technique with a narrative video., Setting: The double-bipolar method was first reported in 2011 [1] and is gaining popularity in Japan; however, its usefulness in robot-assisted hysterectomy is under-reported. When unexpected bleeding occurs during robot-assisted hysterectomy using a monopolar technique, corrective measures may be prolonged and often require changing forceps. The Maryland forceps have 4 functions, including incision, dissection, grasping, and coagulation, which enable rapid responses to bleeding and reduce forceps changes and cost. Previously, we reported the usefulness of the double-bipolar technique in other surgical procedures [2,3]. Herein, we present a case of robot-assisted hysterectomy using this technique at an urban general hospital, including detailed insights into its execution., Interventions: A 45-year-old female patient presented to our hospital with painful menstrual bleeding. Magnetic resonance imaging revealed an 8-cm myoma in the posterior wall of the uterine cervix. Consequently, a robot-assisted hysterectomy was performed using right-handed Maryland forceps (Intuitive, Sunnyvale, CA) and the ForceTriad TM Energy Platform (Medtronic, Minneapolis, MN) in the macro mode, with an output of 60 W. This configuration ensured a consistent electronic output, regardless of the electrical resistivity of the target tissues, facilitating precise incisions using a momentary high voltage [4]. The surgical duration was 60 minutes, and the estimated blood loss was 5 mL., Conclusion: The highly versatile double-bipolar method uses one forceps for incision, dissection, coagulation, and grasping and is useful in gynecological surgery. VIDEO ABSTRACT., (Copyright © 2024 AAGL. Published by Elsevier Inc. All rights reserved.)

Objective: To demonstrate the anatomical and technical highlights of nerve-sparing deep endometriosis (DE) surgery with rectal discoid resection using a newer single-port robotic system., Design: Step-by-step demonstration of this method was provided with narrated video footage., Setting: The surgery was performed at an urban general hospital. Single-port laparoscopic surgery is a useful surgical approach in gynecology because of the excellent cosmetic results but shows challenges including reduced intracorporeal triangulation and conflict with nonarticulating instruments. The range of indications is thus limited., Patient: A 46-year-old woman was referred with severe pelvic pain, dysmenorrhea, and pain on defecation. Magnetic resonance imaging revealed uterine adenomyosis, bilateral ovarian endometriomas, and 3 cm of rectal endometriosis. Computed tomography colonography confirmed 38% stenosis of the rectum., Intervention: A newer single-port robotic system was used., Main Outcome Measures: The main outcome measures were technical safety and feasibility of intrapelvic complex DE surgery using a newer single-port robotic platform., Results: The procedure was performed using nine steps with a da Vinci SP surgical system (Intuitive Surgical, Sunnyvale, California). Importantly, the surgical steps were completely identical to conventional multiport laparoscopic or robotic surgery. This suggests that conventional laparoscopic or robotic skills are highly transferrable to the newer system. The surgical steps are as follows: The newer single-port system offered several advantages, including high-resolution three-dimensional visualization, articulating instruments (intracorporeal instrument triangulation), and improved dexterity and range of motion. These advantages allow precise dissection even in difficult situations such as DE., Conclusions: This appears to be the first reported use of the da Vinci SP for nerve-sparing DE surgery or rectal discoid resection. The newer single-port robotic system can provide the same quality of surgery as conventional multiport laparoscopic and robotic platforms with cosmetic advantages for the treatment of complex pelvic pathologies., Competing Interests: Declaration of Interests K.K. has nothing to disclose. S.Y. has nothing to disclose. M.S. has nothing to disclose. S.S. has nothing to disclose.M.A. has nothing to disclose., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Hepatic adipogenesis has common mechanisms with adipocyte differentiation such as PPARγ involvement and the induction of adipose tissue-specific molecules. A previous report demonstrated that integrator complex subunit 6 (INTS6) is required for adipocyte differentiation. This study aimed to investigate INTS6 expression and its role in hepatic steatosis progression. The expression of INTS6 and PPARγ was examined in the liver of a mouse model of steatohepatitis and in paired liver biopsy samples from 11 patients with severe obesity and histologically proven metabolic dysfunction associated steatohepatitis (MASH) before and one year after bariatric surgery. To induce hepatocellular steatosis in vitro, an immortalized human hepatocyte cell line Hc3716 was treated with free fatty acids. In the steatohepatitis mouse model, we observed hepatic induction of INTS6, PPARγ, and adipocyte-specific genes. In contrast, β-catenin which negatively regulates PPARγ was reduced. Biopsied human livers demonstrated a strong positive correlation (r 2  = 0.8755) between INTS6 and PPARγ mRNA levels. After bariatric surgery, gene expressions of PPARγ, FABP4, and CD36 were mostly downregulated. In our in vitro experiments, we observed a concentration-dependent increase in Oil Red O staining in Hc3716 cells after treatment with the free fatty acids. Alongside this change, the expression of INTS6, PPARγ, and adipocyte-specific genes was induced. INTS6 knockdown using siRNA significantly suppressed cellular lipid accumulation together with induction of β-catenin and PPARγ downregulation. Collectively, INTS6 expression closely correlates with PPARγ. INTS6 suppression significantly reduced hepatocyte steatosis via β-catenin-PPARγ axis, indicating that INTS6 could be a novel therapeutic target for treating MASH., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A pair of novel chiral Zn(II) complexes coordinated by Schiff-base type ligands derived from BINOL (1,1'-bi-2-naphthol), R-/S-Zn, were synthesized. X-ray crystallography revealed the presence of two crystallographically independent complexes; one has a distorted trigonal-bipyramidal structure coordinated by two binaphthyl ligands and one disordered methanol molecule (molecule A), while the other has a distorted tetrahedral structure coordinated by two binaphthyl ligands (molecule B). Numerous CH⋯π and CH⋯O interactions were identified, contributing to the formation of a 3-dimensional rigid network structure. Both R-/S-Zn exhibited fluorescence in both CH 2 Cl 2 solutions and powder samples, with the photoluminescence quantum yields (PLQYs) of powder samples being twice as large as those in solutions, indicating aggregation-induced enhanced emission (AIEE). The AIEE properties were attributed to the restraint of the molecular motion arising from the 3-dimensional intermolecular interactions. CD and CPL spectra were observed for R-/S-Zn in both solutions and powders. The dissymmetry factors, g abs and g CPL values, were within the order of 10 -3 to 10 -4 magnitudes, comparable to those reported for chiral Zn(II) complexes in previous studies.

Background: AT-rich interaction domain 1A (ARID1A) has been proposed as a new biomarker for predicting response to immune checkpoint inhibitors (ICIs). The predictive value of ARID1A for predicting ICI effectiveness has not been reported for endometrial cancer. Therefore, we investigated whether ARID1A negativity predicts ICI effectiveness for endometrial cancer treatment., Methods: We evaluated ARID1A expression, tumor-infiltrating lymphocytes (CD8+), and immune checkpoint molecules (PD-L1/PD-1) by immunostaining endometrial samples from patients with endometrial cancer. Samples in which any of the four mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2) were determined to be negative via immunostaining were excluded. In the ARID1A-negative group, microsatellite instability (MSI) status was confirmed via MSI analysis., Results: Of the 102 samples investigated, 25 (24.5%) were ARID1A-negative. CD8 and PD-1 expression did not differ significantly between the ARID1A-negative group and the ARID1A-positive group; however, the ARID1A-negative group showed significantly lower PD-L1 expression. Only three samples (14.2%) in the ARID1A-negative group showed high MSI. Sanger sequencing detected three cases of pathological mutation in the MSH2-binding regions. We also established an ARID1A-knockout human ovarian endometriotic epithelial cell line (HMOsisEC7 ARID1A KO), which remained microsatellite-stable after passage., Conclusion: ARID1A negativity is not suitable as a biomarker for ICI effectiveness in treating endometrial cancer.

Photonic computing is widely used to accelerate the computational performance in machine learning. Photonic decision making is a promising approach utilizing photonic computing technologies to solve the multi-armed bandit problems based on reinforcement learning. Photonic decision making using chaotic mode-competition dynamics has been proposed. However, the experimental conditions for achieving a superior decision-making performance have not yet been established. Herein, we experimentally investigate mode-competition dynamics in a chaotic multimode semiconductor laser in the presence of optical feedback and injection. We control the chaotic mode-competition dynamics via optical injection and observe that positive wavelength detuning results in an efficient mode concentration to one of the longitudinal modes with a small optical injection power. We experimentally investigate two-dimensional bifurcation diagram of the total intensity of the laser dynamics. Complex mixed dynamics are observed in the presence of optical feedback and injection. We experimentally conduct decision making to solve the bandit problem using chaotic mode-competition dynamics. A fast mode-concentration property is observed at positive wavelength detunings, resulting in fast convergence of the correct decision rate. Our findings could be useful in accelerating the decision-making performance in adaptive optical networks using reinforcement learning.

Although endometriosis is a benign disease, it is associated with cancer-related gene mutations, such as KRAS or PIK3CA . Endometriosis is associated with elevated levels of inflammatory factors that cause severe pain. In a previous study, we demonstrated that KRAS or PIK3CA mutations are associated with the activation of cell proliferation, migration, and invasion in a patient-derived immortalized endometriotic cell line, HMOsisEC10. In this study, we investigated the effects of these mutations on progesterone resistance. Since the HMOsisEC10 had suppressed progesterone receptor (PR) expression, we transduced PR-B to HMOsisEc10 cell lines including KRAS mutant and PIK3CA mutant cell lines. We conducted a migration assay, invasion assay, and MTT assay using dienogest and medroxyprogestrone acetate. All cell lines showed progesterone sensitivity with or without mutations. Regarding inflammatory factors, real-time quantitative RT-PCR revealed that the KRAS mutation cell line exhibited no suppression of Cox-2 and mPGES-1 on progesterone treatment, whereas IL-6, MCP-1, VEGF, and CYP19A1 were significantly suppressed by progesterone in both mutated cell lines. Our results suggest that KRAS mutation and PIK3CA mutation in endometriotic cells may not be associated with progesterone resistance in terms of aggressiveness. However, KRAS mutations may be associated with progesterone resistance in the context of pain.

Background Uterine weight is an important factor in determining the complexity of a hysterectomy. Although greater uterine weight increases operative time and blood loss in open or laparoscopic surgery, it remains uncertain whether this applies to robot-assisted hysterectomy. This study aimed to investigate the effect of uterine weight on the surgical outcomes of robot-assisted hysterectomy. Methods We conducted a retrospective cohort study involving 872 patients who underwent robot-assisted hysterectomies at our institution between January 2019 and June 2022. Of these, 724 cases were analyzed and classified into four groups based on uterine weight: <250 g (377 patients), 250-500 g (253 patients), 500-750 g (69 patients), and ≥750 g (25 patients). We performed univariate analysis with the following endpoints: operation time, blood loss, postoperative hospital stay, complication rate, conversion to laparotomy rate, and blood transfusion rate. Results Operating time and blood loss increased significantly with greater uterine weight in the four groups (both p-values <0.01), but postoperative hospital stay and complication rate did not increase (p = 0.448, p = 0.679, respectively). None of the patients underwent conversion to laparotomy or blood transfusion. Conclusion Although the operating time for robot-assisted hysterectomy and blood loss increased with greater uterine weight, the complications and length of postoperative hospital stay were similar between groups. Robot-assisted hysterectomy is safe in cases of much uterine weight., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Higuchi et al.)

Background: The global impact of the coronavirus disease 2019 (COVID-19) pandemic on public health has been significant. Upper gastrointestinal endoscopy for screening and diagnosis decreased along with new gastric cancer (GC) diagnoses., Methods: This study assesses how the pandemic affected GC mortality using data from Hiroshima Prefecture, comparing mortality rates between patients diagnosed during the pandemic (2020 and 2021) and pre-pandemic (2018 and 2019) periods. The crude hazard ratios (HRs) and HRs adjusted for age, sex, clinical stage, treatment status, and travel distance to the nearest GC screening facility were estimated using Cox regression models. Subgroup and sensitivity analyses were also performed., Results: A total of 9571 patients were diagnosed, with 4877 eligible for follow-up. The median age was 74 years, and 69% were male. The median follow-up period was 157 days, with events per 1000 person-years at 278 and 374 in the pre-pandemic and pandemic periods, respectively (crude HR, 1.37; adjusted HR, 1.17). The sensitivity and subgroup analyses yielded consistent results., Conclusions: The COVID-19 pandemic increased mortality risk in patients with GC. Further studies are required to observe long-term outcomes and identify the disparities contributing to the increased mortality risk.

We previously showed through clinical trials that one plant-derived lactic acid bacteria (LAB) can improve constipation. We preliminarily found that the plant-derived LAB Lactococcus lactis BM32-1 can grow in a mixture of sericin and fibroin, which are extracted from silk and have been reported to help promote health. Thus, in the present study, we evaluated the favorable effect of a sericin/fibroin mixture (S/F-M), which was extracted from silk prepared from cocoons reared in an aseptic rearing system using an artificial diet, fermented with the BM32-1 strain through a clinical trial. The trial was conducted at Hiroshima University from June to October 2022 as a double-blind, placebo-controlled, randomized parallel-group comparative study with 50 eligible subjects (aged 23-71) who had an average defecation frequency of less than 5 times per week. The subjects were instructed to drink 100 mL of fermented S/F-M or placebo every day. After the 12 weeks of the clinical trial period, the average defecation frequency increased significantly-1.4 times higher than that at baseline in the test group-as compared with the placebo group. Furthermore, the fecal microbiota was also compared before and after treatment, revealing that intake of the fermented S/F-M significantly multiplied the relative abundance of the genera Enterococcus and Clostridium , which have been reported to contribute to the amelioration of constipation by improving the gut microbiota and producing butyric acid, respectively. In conclusion, the S/F-M fermented using the BM32-1 strain improves defecation frequency through alteration of the gut microbiota., Competing Interests: None., (©2024 BMFH Press.)

Objectives: The objective of this study was to compare the surgical outcomes for pelvic lymph node dissection (PLND) performed through conventional laparoscopic surgery (CLS) versus robot-assisted surgery (RAS) in patients with gynecologic malignancies., Materials and Methods: Perioperative data, including operative time, estimated blood loss, and complications, were retrospectively analyzed in 731 patients with gynecologic malignancies who underwent transperitoneal PLND, including 460 and 271 in the CLS and RAS groups, respectively. Data were statistically analyzed using the Chi-square test or Student's t -test as appropriate. P < 0.05 was considered statistically significant., Results: The mean age was 50 ± 14 years and 53 ± 13 years in the RAS and CLS groups ( P < 0.01), respectively. The mean body mass index was 23.4 ± 4.8 kg/m 2 and 22.4 ± 3.6 kg/m 2 in the RAS group and CLS groups ( P < 0.01), respectively. The operative time, blood loss, and number of resected lymph nodes were 52 ± 15 min, 110 ± 88 mL, and 45 ± 17, respectively, in the RAS group and 46 ± 15 min, 89 ± 78 mL, and 38 ± 16, respectively, in the CLS group (all P < 0.01). The rate of Clavien-Dindo Grade ≥ III complications was 6.3% and 8.7% in the RAS and CLS groups, respectively ( P = 0.17)., Conclusion: Shorter operative time and lower blood loss are achieved when PLND for gynecologic malignancies is performed through CLS rather than RAS. However, RAS results in the resection of a greater number of pelvic lymph nodes., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Gynecology and Minimally Invasive Therapy.)

Pain is subjective, warranting tailored responses in pharmacotherapy and nursing support. Despite this, the evidence for suitable nursing support for pain is not well established in terminally ill patients such as those with cancer; therefore, it is necessary to provide support in consideration of changes in physical symptoms and quality of life. However, interventional studies for such patients are often difficult. There have been no comprehensive studies to date on non-pharmacological support that can be implemented by nurses. Therefore, with the aim of examining nursing support applicable at the end of life, this scoping review comprehensively mapped nursing support for pain in cancer patients at all stages of the disease. This study complies with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and the Arksey and O'Malley framework. All available published articles from the time of database establishment to January 31, 2022, were systematically searched for in PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), CENTRAL, and the Ichushi Web database of the Japanese Society of Medical Abstracts. Overall, 10,385 articles were screened, and 72 were finally included. Both randomized controlled trials (RCTs) (n = 62) and non-RCTs (n = 10) were included. Twenty-two types of nursing support were identified. Eighteen of them showed positive results; five of them were provided only to terminally ill patients, three of which were effective, namely, comfort care, foot bath, and combined therapy. It is important to examine the applicability of types of nursing support in clinical practice in the future., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Morikawa et al.)

Speech-sound stimuli have a complex structure, and it is unclear how the brain processes them. An event-related potential (ERP), known as mismatch negativity (MMN), is elicited when an individual's brain detects a rare sound. In this study, MMNs were measured in response to an omitted segment of a complex sound consisting of a Japanese vowel. The results indicated that the latency from onset in the right hemisphere was significantly shorter than that in the frontal midline and left hemispheres during left ear stimulation. Additionally, the results of latency from omission showed that the latency of stimuli omitted in the latter part of the temporal window of integration (TWI) was longer than that of stimuli omitted in the first part of the TWI. The mean peak amplitude was found to be higher in the right hemisphere than in the frontal midline and left hemispheres in response to left ear stimulation. In conclusion, the results of this study suggest that would be incorrect to believe that the stimuli have strictly the characteristics of speech-sound. However. the results of the interaction effect in the latencies from omission were insignificant. These results suggest that the detection time for deviance may not be related to the stimulus ear. However, the type of deviant stimuli on latencies was found to be significant. This is because the detection of the deviants was delayed when a deviation occurred in the latter part of the TWI, regardless of the stimulation of the ear., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Primary extraovarian dysgerminoma (EOD) is a very rare disease. There is no literature about primary EOD involving the uterine cervix. We herein present details of a unique case of primary EOD involving the uterine cervix. A 46-year-old woman with uterine cervical tumor was referred to our institution with atypical genital bleeding. A polypoid tumor localized to the uterine cervix was found. Cervical biopsy detected malignant components of likely nonepithelial cell origin. Preoperative imaging examinations showed a uterine cervical tumor measuring ~5 cm, suggestive of malignancy without distant or lymph node metastases. The patient underwent abdominal radical hysterectomy with pelvic lymph node dissection according to the standard treatment for stage IB3 cervical cancers. The pathological diagnosis was dysgerminoma involving the uterine cervix and the right fallopian tube. Immunohistochemical results were as follows: SALL4 (+), octamer-binding transcription factor 4 (+), D2-40 (+), and c-Kit (+). She received 3 cycles of adjuvant chemotherapy with bleomycin, etoposide, and cisplatin. The disease did not recur up to 14 months after surgery. This is the first-ever published case of primary EOD involving the uterine cervix among previously reported EOD cases. Reported cases of EOD in female genital tract are also reviewed. Our case provides more extensive insights for pathologists to consider the differential diagnosis of cervical lesions. In our case, combination therapy involving a surgical approach-according to cervical cancers and adjuvant chemotherapy as used for ovarian dysgerminomas-was effective. Future verification is needed regarding the best approach for treating uterine cervical dysgerminomas., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 by the International Society of Gynecological Pathologists.)

Although elevated serum levels of soluble CD40 ligand (sCD40L) were reported in patients with cancer, the importance of high sCD40L levels in clinical oncology remains unknown. We conducted a post hoc analysis of the AMATERASU randomized clinical trial of vitamin D3 supplementation (2000 IU/day) in patients with digestive tract cancer to assess its significance. Serum sCD40L levels were measured by ELISA in 294 residual samples, and were divided into tertiles. In patients with colorectal cancer (CRC), 5-year relapse-free survival (RFS) rates in the middle and highest tertiles were 61.6% and 61.2%, respectively, which was significantly lower than 83.8% in the lowest tertile. A Cox proportional hazard analysis showed that the lowest tertile had a significantly lower risk of relapse or death than the highest tertile even with multivariate adjustment (hazard ratio (HR), 0.30; 95% confidence interval (CI), 0.11-0.80; p = 0.016). In the subgroup of CRC patients with the highest tertile of sCD40L, the 5-year RFS rate in the vitamin D group was 77.9%, which was significantly higher than 33.2% in the placebo group (HR, 0.30; 95% CI, 0.11-0.81; p = 0.018 [ P interaction = 0.04]). In conclusion, elevated sCD40L might be a biomarker of poor prognosis in patients with CRC, but vitamin D supplementation might improve RFS in patients with high sCD40L.

Developmental factors for autism spectrum disorders (ASDs) have been an ongoing debate despite an increasing number of reports on genetic factors. Recent studies have suggested maternal intake of selective serotonin reuptake inhibitors (SSRIs) as a possible developmental factor elevating the risk for ASD in offspring. Here, we show that maternal exposure of mice to an SSRI, Fluoxetine (FLX), induces abnormal ultrasonic vocalizations (USVs), an indicator of ASD-related behavior. We tested the effect of FLX intake during pregnancy, lactation, or both. We found that the lactation and both conditions decreased the number of USVs emitted by offspring pups. An index for assessing the syllables' frequency modulation revealed that highly modulated syllables appeared to be inhibited only in both conditions. Furthermore, we found that the number of serotonergic neurons at adulthood was reduced in the progeny of mice treated with FLX in all conditions. In addition, maternal exposure to FLX through pregnancy and lactation induced a high death rate of early post-natal pups. These suggest that the maternal exposure to SSRIs affects early development of offsprings as well as the serotonergic system. Focusing on vocal communication, our results indicate that intake of an SSRI during lactation increases the risk of abnormal USVs in pups, and provides potential insights into the development of ASD., Competing Interests: Declaration of competing interest The authors have no real or perceived conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: We performed our standard air leak, leak percentage, and cuff leak percentage tests in pediatric patients intubated with microcuff pediatric tracheal tubes (MPTTs) just before extubation. We examined the association between test findings and the subsequent occurrence of post-extubation laryngeal edema (PLE)., Design: Prospective, single-center, observational study., Setting: PICU (June 1, 2020 to May 31, 2021)., Patients: Pediatric patients intubated and scheduled for extubation during the day shift in the PICU., Interventions: Multiple pre-extubation leak tests were performed on each patient immediately before extubation. In our center, the standard leak test is positive if a leak is audible at 30 cm H 2 O applied pressure with the MPTT cuff deflated. Two other tests were calculated in the pressure control-assist control ventilator mode using the following formulas: leak percentage with deflated cuff = (inspiratory tidal volume [V t ]-expiratory V t ) × 100/inspiratory V t ; cuff leak percentage = (expiratory V t with inflated cuff-expiratory V t with deflated cuff) × 100/expiratory V t with inflated cuff., Measurements and Main Results: The diagnostic criteria for PLE was made by at least two healthcare professionals and included upper airway stricture with stridor-requiring nebulized epinephrine. Eighty-five pediatric patients (< 15 yr) who had been intubated for at least 12 hours using the MPTT were included. Positive rates for the standard leak, leak percentage (cutoff 10%), and cuff leak percentage (cutoff 10%) tests were 0.27, 0.20, and 0.64, respectively. The standard leak, leak percentage, and cuff leak tests showed sensitivities of 0.36, 0.27, and 0.55, respectively; and specificities of 0.74, 0.81, and 0.35, respectively. PLE occurred in 11 of 85 patients (13%), and there were no instances of needing reintubation., Conclusions: The pre-extubation leak tests in current practice for intubated pediatric patients in the PICU all lack diagnostic accuracy for PLE., Competing Interests: Dr. Fujii disclosed work for hire. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Background: We believe that parental presence before the induction of anesthesia for surgery among children with a cleft palate/lip would be effective in mitigating their preoperative anxiety., Objective: We assessed the states of patients with a cleft palate/lip when their parents accompanied them into operating rooms and clarified their and their parents' cognition using a questionnaire., Methods: Data were collected via nursing observation when patients and their parents entered the operating room. Furthermore, an anonymous questionnaire was administered to patients and parents after the operation regarding their feelings about parental presence in the operating room., Results: In total, nine patients cried when they entered the surgical room. Furthermore, six patients and three parents reported preoperative anxiety. In addition, eight patients agreed that they were satisfied with the presence of their parents before induction., Conclusion: Approximately half of the patients cried. However, the presence of parents before the induction of anesthesia was effective in reducing anxiety among most patients and their parents.

Objective: To report the long-term outcomes of the arterial switch operation for transposition of the great arteries., Methods: The data of 35 patients who underwent an arterial switch operation between April 2006 and May 2021 were retrospectively examined; five had double-outlet right ventricles, three had side-by-side transposition, and 27 had d-transposition. The punch-out technique was the basic method for coronary transplantation; however, if coronary artery kinking after additional peeling was a concern, the trap-door technique was used. In aortic reconstruction, the caliber difference between the neoascending aorta and the native pulmonary artery was fixed using the pulmonary artery flap. In pulmonary reconstruction, the pulmonary artery was bilaterally exposed over the second branch., Results: The median age at operation and follow-up duration were 10.0 (8.0-12.5) days and 72.9 (40.7-139.5) months, respectively. Thirty-four patients survived, and one was lost to follow-up ([coronary transplantation]: right coronary artery, punch-out = 31, trap-door = 2; left coronary artery, punch-out = 28, trap-door = 7; [aortic regurgitation]: no-slight = 27, mild = 6, moderate = 1; [pulmonary regurgitation]: no-slight = 22, mild = 11, moderate = 1). Slight coronary bending occurred in two patients; ischemia was not observed. Catheter stent placement was performed in one of three patients with stenosis at the pulmonary artery bifurcation. Catheter balloon dilation was performed in one patient with supravalvular pulmonary stenosis. There were no cases of coronary, aortic, or pulmonary artery reoperations. The 15-year cumulative reintervention avoidance rate was 91.0%., Conclusions: There were no deaths or reoperations during the long-term follow-up period, and arterial switch operation outcomes at our hospital were satisfactory., (© 2022. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

Although aryl hydrocarbon receptors (AhRs) are related to the metabolic pathway of xenobiotics, recent studies have revealed that this receptor is also associated with the life cycle of viruses and inflammatory reactions. For example, flutamide, used to treat prostate cancer, inhibits hepatitis C virus proliferation by acting as an AhR antagonist, and methylated-pelargonidin, an AhR agonist, suppresses pro-inflammatory cytokine production. To discover a novel class of AhR ligands, we screened 1000 compounds derived from fungal metabolites using a reporter assay and identified methylsulochrin as a partial agonist of the aryl hydrocarbon receptor. Methylsulochrin was found to inhibit the production of hepatitis C virus (HCV) in Huh-7.5.1 cells. Methylsulochrin also suppressed the production of interleukin-6 in RAW264.7 cells. Furthermore, a preliminary structure-activity relationship study using sulochrin derivatives was performed. Our findings suggest the use of methylsulochrin derivatives as anti-HCV compounds with anti-inflammatory activity.

Importance: Recent meta-analyses of randomized clinical trials found that daily vitamin D3 supplementation had beneficial effects on cancer mortality, although the results are still controversial., Objective: To examine whether vitamin D supplementation reduces the risk of relapse or death in a supgroup of patients with digestive tract cancer who were p53 immunoreactive., Design, Setting, and Participants: This was a post hoc subgroup analysis of the AMATERASU randomized, double-blind, placebo-controlled clinical trial. This trial included patients at a single university hospital in Japan with digestive tract cancers between January 2010 and February 2018 followed up for a median (IQR) of 3.5 (2.5-5.3) years to compare the effects of vitamin D supplementation with placebo and was reported in 2019. Patients from among 417 participants in the AMATERASU trial whose residual serum samples were available were included. Data were analyzed from October 20 to November 24, 2022., Interventions: Vitamin D3 (2000 IU/d) supplementation or placebo., Main Outcomes and Measures: The primary outcome was 5-year relapse or death. The subgroup of patients who were p53 immunoreactive was defined by positivity for anti-p53 antibodies in serum and nuclear accumulation of p53 oncosuppressor protein in more than 99% of cancer cells, which is considered a biomarker for p53 missense mutations. Anti-p53 antibody levels were measured using chemiluminescent enzyme immune assay. Immunohistochemical staining data of p53 protein in cancer tissue in pathologic specimens were obtained from a previous study and divided into 4 grades., Results: Among 392 patients with digestive tract cancer (mean [SD] age, 66 [10.7] years; 260 males [66.3%]), there were 37 patients with esophageal cancer (9.4%), 170 patients with gastric cancer (43.4%), 2 patients with small bowel cancer (0.5%), and 183 patients with colorectal cancer (46.7%). Serum anti-p53 antibody was detectable in 142 patients (36.2%), and p53-immunohistochemistry grade showed a positive association with serum anti-p53 antibody levels (coefficient = 0.19; P < .001). In the p53-immunoreactive subgroup (80 patients), relapse or death occurred in 9 of 54 patients (16.7%) in the vitamin D group and 14 of 26 patients (53.8%) in the placebo group; 5-year relapse-free survival (RFS) was significantly higher in the vitamin D group (13 patients [80.9%]) than the placebo group (1 patient [30.6%]; hazard ratio [HR], 0.27; 95% CI, 0.11-0.61; P = .002). This was significantly different from 272 patients in the non-p53 immunoreactive subgroup, in which vitamin D had no effect on 5-year RFS (vitamin D: 35 of 158 patients [22.2%] vs placebo: 24 of 114 patients [21.1%]; HR, 1.09; 95% CI, 0.65-1.84) (P for interaction = .005)., Conclusions and Relevance: This study found that vitamin D supplementation reduced the risk of relapse or death in the subgroup of patients with digestive tract cancer who were p53 immunoreactive., Trial Registration: Identifier: UMIN000001977.

Objective: To analyze the time trends of recidivism of acquired cholesteatoma using the Kaplan-Meier method., Study Design: We conducted a retrospective, observational study of 256 patients having their first cholesteatoma surgery. The cumulative recidivism-free rate was calculated using Kaplan-Meier survival analysis related to the follow-up period, pathophysiology, the extent of the disease, and recidivism pathologies., Results: Pars flacida cholesteatoma with tympanic cavity progression had a high likelihood of recurrence disease. Pars tensa cholesteatoma led to more recurrence of the disease than the residual disease. In both pars flacida and pars tensa cholesteatoma, the incidence of disease recurrence increased even 3 years after surgery. On the contrary, the incidence of residual disease peaked within 3 years after surgery, and thereafter, the incidence of residual disease tended to be small. In particular, pars flacida cholesteatoma extending into the mastoid cavity or tympanic cavity tended to recur up to 5 years postoperatively., Conclusions: We calculated the cumulative recidivism-free rates of 256 patients with cholesteatoma using Kaplan-Meier survival analysis. These results can lead to better estimates of the length of the follow-up period., Level of Evidence: Level IV evidence from case-control studies., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2023, Otology & Neurotology, Inc.)

Recent studies reported the presence of oncogenic mutations in normal endometrial glands, but the biological significance remains unclear. The present study investigated the status of KRAS/PIK3CA driver mutations in normal endometrial glands as well as spheroids derived from single glands. The normal endometria of surgically removed uteri (n = 3) were divided into nine regions, and 40 endometrial single glands were isolated from each region. The DNAs of 10 glands in each region were extracted and subjected to Sanger sequencing for KRAS or PIK3CA driver mutations, while the remaining 30 glands were conferred to a long-term spheroid culture, followed by Sanger sequencing. Immunohistochemical analyses of stem cell (Axin2, ALDH1A1, SOX9) markers were undertaken for spheroids. Sanger sequencing successfully detected oncogenic mutations of KRAS or PIK3CA in a single gland. Twenty-five of the 270 glands (9.3%) had mutations in either KRAS or PIK3CA, and the mutation frequency in each endometrial region varied from 0% to 50%. The droplet digital PCR showed high mutation allele frequency (MAF) of PIK3CA mutation, suggestive of clonal expansion of mutated cells within a gland. Over 60% of the collected spheroids had PIK3CA mutations, but no KRAS mutations were detected. Immunohistochemically, spheroids were mainly composed of cells with stem cell marker expressions. High MAF of PIK3CA mutation in a single gland as well as frequent PIK3CA mutation in stem cell-rich spheroids that originated from a single gland suggest the role of PIK3CA mutation in stem cell propagation. This information could improve our understanding of endometrial physiology as well as stem cell-oriented endometrial regeneration and carcinogenesis., (© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Autoimmune diseases triggered by coronavirus disease 2019 (COVID-19) mRNA vaccination have been emerging. Here, we report the case of a 27-year-old Japanese man with autoimmunity-related neutrophilic dermatosis, occurring as an initial cutaneous manifestation of systemic lupus erythematosus with Sjögren syndrome after the second dose of the Pfizer/BioNTech COVID-19 vaccination. The patient presented with urticarial erythema and partially annular erythema on the trunk and extremities with severe pruritus. Histopathological analysis showed vacuolar degeneration at the dermo-epidermal junction and interstitial neutrophil infiltration. We reviewed eight patients, including the aforementioned patient, with exacerbation or new-onset of SLE after COVID-19 vaccination and found the patient had relatively mild symptoms, itchy annular erythema, and positive anti-SS-A/SS-B antibodies. COVID-19 mRNA vaccination can induce the production of type-I interferon, which plays a crucial role in the pathogenesis of SLE and may cause autoimmunity-related neutrophilic dermatosis in susceptible individuals. In the case that itchy annular erythema develops approximately 2 weeks after the vaccination, the possibility of systemic or cutaneous lupus erythematosus should be considered. For an accurate diagnosis, dermatologists should obtain a recent vaccination history and perform complete antibody profiling and skin biopsy for patients presenting with annular or erythema multiforme-like lesions., (© 2023 Japanese Dermatological Association.)

The analysis of a chemical reaction along the ground-state potential energy surface in conjunction with an unknown spin state is challenging because electronic states must be separately computed several times using different spin multiplicities to find the lowest energy state. However, in principle, the ground state could be obtained with just a single calculation using a quantum computer without specifying the spin multiplicity in advance. In the present work, ground-state potential energy curves for PtCO were calculated as a proof-of-concept using a variational quantum eigensolver (VQE) algorithm. This system exhibits a singlet-triplet crossover as a consequence of the interaction between Pt and CO. VQE calculations using a statevector simulator were found to converge to a singlet state in the bonding region, while a triplet state was obtained at the dissociation limit. Calculations performed using an actual quantum device provided potential energies within ±2 kcal/mol of the simulated energies after error mitigation techniques were adopted. The spin multiplicities in the bonding and dissociation regions could be clearly distinguished even in the case of a small number of shots. The results of this study suggest that quantum computing can be a powerful tool for the analysis of the chemical reactions of systems for which the spin multiplicity of the ground state and variations in this parameter are not known in advance., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Type II endometrial cancer (EC) is responsible for most endometrial cancer-related deaths due to its aggressive nature, late-stage detection, and high tolerance to standard therapies. Thus, novel treatment strategies for type II EC are imperative. For patients with mismatch repair-deficient (dMMR) tumors, immunotherapy with immune checkpoint inhibitors represents a promising therapeutic strategy. However, the prevalence of dMMR tumors in type II EC patients remains unclear. In this study, using immunohistochemistry, we evaluated the expression of mismatch repair (MMR) proteins, tumor-infiltrating lymphocytes (CD8+), and immune checkpoint molecules (PD-L1) in 60 patients with type II EC (16, 5, 17, and 22 were endometrioid G3, serous, de-differentiated, and carcinosarcoma cases, respectively) to investigate the therapeutic effect of immune checkpoint inhibitors. Approximately 24 cases (40%) had a loss of MMR protein expression. The positivity rate of CD8+ ( p = 0.0072) and PD-L1 ( p = 0.0061) expression was significantly associated with the dMMR group. These results suggest immune checkpoint inhibitors (anti-PD-L1/PD-1 antibodies) could effectively treat type II EC with dMMR. The presence of dMMR might be a biomarker for a positive response to PD-1/PD-L1 immunotherapy in type II EC.

Tumor heterogeneity remains an ongoing challenge in the field of cancer therapy. Intratumor heterogeneity significantly complicates the diagnosis of cancer and presents challenging clinical problems due to resistance to drug therapy. This study aimed to elucidate the genetic changes histologically (mucinous cystadenoma (MCA), mucinous borderline tumor (MBT), and mucinous ovarian carcinoma (MOC)) in a portion of mucinous ovarian tumors within the same sample. Seven tumor samples obtained from different patients were used to evaluate the genetic mutations in each component. Intratumor genetic heterogeneity was observed in all patients; among them, BRAF (V600E) and p53 (T118I, P142S, T150I, and T170M) point mutations were observed in the MBT component, while KRAS (G12D and G13D) and PIK3CA (E545K) mutations were found in the MOC component. The current findings suggest that diverse genetic alterations occur in mucinous tumors, according to tumor histology. Tumor heterogeneity and genetic diversity in mucinous ovarian tumors might be the cause of treatment failure. Knowledge of intertumor heterogeneity may lead to an increased understanding of the tumor response to treatment.

Background: The role of surgery in primary central nervous system lymphoma (PCNSL) is to allow pathological diagnosis from tumor biopsy. However, PCNSL is often difficult to distinguish from other tumors, particularly glioblastoma multiforme (GBM). Quantitative evaluations to facilitate differentiation between PCNSL and GBM would be useful. Here, we investigated the best examinations for exact differentiation of PCNSL from GBM among preoperative examinations, including imaging studies and tumor markers., Methods: Various examinations were performed for 68 patients with PCNSL , including serum soluble interleukin 2 receptor, β2-microglobulin (MG) in cerebrospinal fluid (CSF), diffusion-weighted imaging, 11 C-methionine-positron emission tomography (PET), and 18 F-fluorodeoxyglucose (FDG)-PET. These results were compared with findings from 28 patients with consecutive GBM who underwent the same examinations to evaluate the utility and accuracy of different investigations., Results: CSF β2-MG ≥2.0 mg/L was relatively specific for PCNSL, offering 95.0% sensitivity and 85.7% specificity. Tumor-to-contralateral normal brain tissue ratio ≥2.4 on 18 F-FDG-PET was also quite specific for PCNSL, offering 83.8% sensitivity and 95.2% specificity. No other examinations displayed any significant differences in quantitative differential markers between PCNSL and GBM., Conclusions: Both β2-MG ≥2.0 mg/dL in CSF and tumor-to-contralateral normal brain tissue ratio ≥2.4 from 18 F-FDG-PET allow quantitative differentiation of PCNSL from GBM, potentially representing clinically useful indicators. These findings could lead to innovative methods for differentiating PCNSL from GBM as well as new treatment strategies for other brain tumors., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Photonic computing has attracted increasing interest for the acceleration of information processing in machine learning applications. The mode-competition dynamics of multimode semiconductor lasers are useful for solving the multi-armed bandit problem in reinforcement learning for computing applications. In this study, we numerically evaluate the chaotic mode-competition dynamics in a multimode semiconductor laser with optical feedback and injection. We observe the chaotic mode-competition dynamics among the longitudinal modes and control them by injecting an external optical signal into one of the longitudinal modes. We define the dominant mode as the mode with the maximum intensity; the dominant mode ratio for the injected mode increases as the optical injection strength increases. We deduce that the characteristics of the dominant mode ratio in terms of the optical injection strength are different among the modes owing to the different optical feedback phases. We propose a control technique for the characteristics of the dominant mode ratio by precisely tuning the initial optical frequency detuning between the optical injection signal and injected mode. We also evaluate the relationship between the region of the large dominant mode ratios and the injection locking range. The region with the large dominant mode ratios does not correspond to the injection-locking range. The control technique of chaotic mode-competition dynamics in multimode lasers is promising for applications in reinforcement learning and reservoir computing in photonic artificial intelligence.

The recent discovery of the archaeal modified mevalonate pathway revealed that the fundamental units for isoprenoid biosynthesis (isopentenyl diphosphate and dimethylallyl diphosphate) are biosynthesized via a specific intermediate, trans -anhydromevalonate phosphate. In this biosynthetic pathway, which is unique to archaea, the formation of trans -anhydromevalonate phosphate from ( R )-mevalonate 5-phosphate is catalyzed by a key enzyme, phosphomevalonate dehydratase. This archaea-specific enzyme belongs to the aconitase X family within the aconitase superfamily, along with bacterial homologs involved in hydroxyproline metabolism. Although an iron-sulfur cluster is thought to exist in phosphomevalonate dehydratase and is believed to be responsible for the catalytic mechanism of the enzyme, the structure and role of this cluster have not been well characterized. Here, we reconstructed the iron-sulfur cluster of phosphomevalonate dehydratase from the hyperthermophilic archaeon Aeropyrum pernix to perform biochemical characterization and kinetic analysis of the enzyme. Electron paramagnetic resonance, iron quantification, and mutagenic studies of the enzyme demonstrated that three conserved cysteine residues coordinate a [4Fe-4S] cluster-as is typical in aconitase superfamily hydratases/dehydratases, in contrast to bacterial aconitase X-family enzymes, which have been reported to harbor a [2Fe-2S] cluster., Competing Interests: The 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., (Copyright © 2023 Komeyama, Kanno, Mino, Yasuno, Shinada, Ito and Hemmi.)

We aimed to determine how surface roughness changes the effect of a liquid flow on the forces between two charged surfaces. This is because many applications require liquid to flow through charged confined areas and because all surfaces show a degree of roughness. We prepared films of different roughness by making mixed Langmuir films of silica nanoparticles (NPs) of two different diameters at air-100 mM NaCl aqueous interfaces and then by transferring and sintering these films to silicon wafers. Atomic force microscope (AFM) imaging showed that the film roughness decreased (1) with an NP diameter decrease and (2) an increased ratio of small NPs in a mixed film of small and larger NPs. This decrease was explained by a decreased NP aggregation in the film, due to the increased Brownian velocity that accompanies an NP diameter decrease. Force-separation curves were next measured with an AFM between a microsized silica particle (probe) and a smooth substrate (silicon wafer) or the rough NP films in 1 mM NaCl. In the absence of a liquid flow, the repulsive forces decreased with an increased substrate roughness. This reduction was explained by an increased difference between the real zero separation distance and apparent zero separation distance (the distance between the first point of mechanical contact between the probe and substrate) with an increased surface roughness. In the presence of a liquid flow, the repulsive forces decreased in the case of a smooth substrate. However, the repulsive forces were reduced less by a liquid flow for rough substrates. This result was explained by the difference in the effect of liquid flow on the diffuse layer for the smooth and rough surfaces. Surface roughness is postulated to modify the liquid flow trajectory near the surfaces and to cause ion concentration gradients near the surface. These factors are proposed to lessen the change in the diffuse layer brought about by a liquid flow. This would then reduce the change in the forces.

Cardiac remodeling has no established therapies targeting inflammation. CD4 + T-cell subsets have been reported to play significant roles in healing process after ischemic myocardial injury, but their detailed mechanisms of activation remain unknown. To explore immune reactions during cardiac remodeling, we applied a non-surgical model of coronary heart disease (CHD) induced by a high-fat diet (HFD-CHD) in SR-BI -/- /ApoeR61 h/h mice. Flow cytometry analyses throughout the period of progressive cardiac dysfunction revealed that CD4 + T Helper 1 (Th1) cells were predominantly activated in T-cell subsets. Probucol was reported to attenuate cardiac dysfunction after coronary artery ligation model (ligation-MI) in rats. To determine whether probucol suppress cardiac remodeling after HFD-CHD, we treated SR-BI -/- /ApoeR61 h/h mice with probucol. We found treatment with probucol in HFD-CHD mice reduced cardiac dysfunction, with attenuated activation of Th1 cells. RNA-seq analyses revealed that probucol suppressed the expression of CXCR3, a Th1-related chemokine receptor, in the heart. XCR1 + cDC1 cells, which highly expresses the CXCR3 ligands CXCL9 and CXCL10, were predominantly activated after HFD-CHD. XCR1 + cDC1 lineage skewing of pre-DC progenitors was observed in bone marrow, with subsequent systemic expansion of XCR1 + cDC1 cells after HFD-CHD. Activation of CXCR3 + Th1 cell and XCR1 + cDC1 cells was also observed in ligation-MI. Notably, post-MI depletion of XCR1 + cDC1 cells suppressed CXCR3 + Th1 cell activation and prevented cardiac dysfunction. In patient autopsy samples, CXCR3 + Th1 and XCR1 + cDC1 cells infiltrated the infarcted area. In this study, we identified a critical role of XCR1 + cDC1-activated CXCR3 + Th1 cells in ischemic cardiac remodeling., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Vanitaracin A, an anti-hepatitis B virus polyketide, has been previously isolated from Talaromyces sp. In the present study, we searched for novel compounds in the culture broth obtained from a vanitaracin A-producing fungus under various conditions. Three novel compounds (vanitaracin C, vanitaraphilone A, and 2-hydroxy-4-(hydroxymethyl)-6-methylbenzaldehyde) were isolated, and their structures were determined using spectroscopic methods (1D/2D NMR and MS). In addition, the antiviral spectrum of vanitaracin A was examined by measuring its antiviral activities against rabies virus, Borna disease virus 1, and bovine leukemia virus. This compound exhibited antiviral activity against bovine leukemia virus, which is the causative agent of enzootic bovine leukosis. The anti-bovine leukemia virus effects of other compounds isolated from the vanitaracin A-producing fungus, namely, vanitaracins B and C, vanitaraphilone A, and 2-hydroxy-4-(hydroxymethyl)-6-methylbenzaldehyde, were also evaluated. Vanitaracin B, vanitaraphilone A and 2-hydroxy-4-(hydroxymethyl)-6-methylbenzaldehyde were also found to exhibit activity against bovine leukemia virus. These findings reveal the broad-spectrum antiviral activity of the vanitaracin scaffold and suggest several candidates for the development of anti-bovine leukemia virus drugs., (© 2022. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)