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Streptococcus pneumoniae serotype 35B, a non-vaccine type, is a major contributor to the increase in pneumococcal infection post-vaccination. We aimed to understand the mechanism of its spread by characterizing 35B. The serotype, type 1 pilus (T1P) positivity, and antimicrobial susceptibility of 319 isolates in 2018-2022 were analysed and compared with those of isolates in 2014-2017 to find the changes. 35B accounted for 40 (12.5%) isolates. T1P positivity was notably higher in 35B (87.5%) than in the other serotypes. To confirm the role of T1P, an adhesion factor, we compared adherence to A549 cells between T1P -positive 35B isolates and their T1P -deficient mutants, showing contribution of T1P to adherence. Penicillin-non-susceptible rate of 35B was 87.5%, and meropenem-resistant 35B rate was 35.0%, which increased from 14.5% of 2014-2017 ( p  = 0.009). Multilocus sequence typing was performed in 35B strains. Prevalence of clonal complex 558, harbouring T1P and exhibiting multidrug non-susceptibility, suggested the advantages of 35B in attachment and survival in the host. The emergence of ST156 isolates, T1P -positive and non-susceptible to β-lactams, has raised concern about expansion in Japan. The increase of serotype 35B in pneumococcal diseases might have occurred due to its predominant colonizing ability after the elimination of the vaccine-serotypes.

Purpose: This study aimed to clarify the differences in the pathophysiology of maxillary sinus fungus balls (FB) among different case groups and to identify which patients with maxillary sinus FB would be suitable for outpatient procedures., Methods: Thirty-four patients diagnosed with maxillary sinus FB between January 2017 and December 2021 were divided into two groups (O and S). We retrospectively compared the clinical and imaging characteristics, and the treatment outcomes between the groups. Group O comprised 12 patients (13 sides) treated in an outpatient clinic and Group S comprised 15 patients (16 sides) treated with endoscopic sinus surgery (ESS)., Results: Compared to Group S, Group O had more patients with an enlarged maxillary sinus membranous portion, and shadows indicative of fungal masses (P < 0.01 and P < 0.05, respectively). In particular, the anteroposterior ratio of the open maxillary sinus membranous area was 0.68 ± 0.16 in Group O and 0.5 ± 0.12 in Group S. After surgery, Group O exhibited greater anteroposterior expansion of the maxillary sinus membranous portion compared to Group S (P < 0.01). Additionally, Group O had more patients with shadows in sinuses other than the maxillary sinus (P < 0.01) and medial displacement of the uncinate process (P < 0.01) than Group S. In addition, Group O required fewer procedures and hospital visits than Group S (P < 0.001 and P < 0.01, respectively)., Conclusions: Determining the indications for outpatient procedures while considering the pathophysiology of maxillary sinus FB can significantly benefit patients and medical professionals in terms of safety and medical costs., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Aim: Sodium picosulfate plus magnesium citrate (SP + MC) is a well-tolerated bowel preparation agent. However, Japan currently approves only two methods of taking SP + MC: the day-before and split-dose preparation, without approval of same-day preparations. This study aimed to evaluate the efficacy and safety of same-day SP + MC preparations., Methods: This was a multicenter, single-arm, nonrandomized, open-label study. We enrolled 145 Japanese patients between June and December 2023. The patients received two sachets of SP + MC dissolved in 300 ml of water and 1200 mL or more of clear liquid on the day of colonoscopy. Bowel cleansing efficacy, adverse events (AEs), and patient satisfaction were evaluated., Results: Of the enrolled patients, 137 underwent colonoscopy according to our protocol. Bowel preparation was adequate in 133 patients (97.1%). The mean total Boston Bowel Preparation Score was 8.3 ± 1.2. Five patients experienced AEs (3.6%): two (1.5%), abdominal pain; one (0.73%), ischemic enteritis; one (0.73%), vomiting or nausea; and one (0.73%), headache. All AEs were treated conservatively. None of the patients exhibited abnormal blood test results or clinical symptoms after receiving SP + MC. Regarding patient satisfaction, all patients were able to take SP + MC as directed; 136 (99.2%) expressed a preference for this bowel preparation for future colonoscopies., Conclusion: The same-day SP + MC preparation showed high bowel-cleansing efficacy and satisfaction in Japanese patients without serious AEs., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Aspergillus spp. are rare causes of surgical site infections (SSIs). Specifically, Aspergillus section Nigri, commonly identified as Aspergillus niger through morphological findings, has infrequently been reported as an abdominal SSI pathogen., Case Presentation: An 86-year-old woman with a history of hypertension, chronic kidney disease, and atrial fibrillation who was taking 6 mg of prednisolone daily for rheumatoid arthritis was admitted to our hospital because of sudden abdominal pain. She was diagnosed with sigmoid colon perforation and underwent an open Hartmann operation on the day of admission. Subsequently, a superficial abdominal SSI was detected. Through analysis of the calmodulin gene, Aspergillus welwitschiae, which is classified within the Aspergillus section Nigri, was identified as the responsible pathogen. The minimum inhibitory concentration of voriconazole (VRCZ) was 2 mg/L. Surgical removal of the infected tissue and VRCZ administration was effectively used to treat the infection., Conclusions: Given the reported low susceptibility of Nigri section species to azoles, identification and drug susceptibility testing of these fungi are highly important., (© 2024. The Author(s).)

Objectives: To describe the oral health-related quality of life (OHRQoL) and its potential influencing factors within the Myanmar population., Methods: Data were from the first national oral health survey, involving 3,513 participants aged 15-18 years, 35-44 years, and 60-74 years from 21 selected townships in Myanmar. Self-administered questionnaire-based surveys, conducted from December 2016 to January 2017, included socio-demographics, behavioral factors, self-reported oral conditions (number of teeth present, teeth and gingival conditions), and inquiries regarding OHRQoL (a set of 12 questions with 5 response options) using the recommended questions from WHO Oral Health Surveys., Results: The most prevalent oral health issues were difficulties in chewing (32.2%) and biting foods (30.8%). In bivariate analysis, older individuals, rural residents, and participants with higher educational levels were associated with OHRQoL. In multiple regression analysis, self-reported number of teeth, teeth and gingival conditions were strong predictors of OHRQoL in all age groups., Conclusion: Self-rated oral health conditions predicted quality of life due to oral problems. The development of national oral health policies and strategies is imperative to facilitate early detection of oral health problems and promote the awareness of oral health importance., (Copyright© 2024 Dennis Barber Ltd.)

In this study, we devised a radiation protection tool specifically designed for healthcare professionals and students engaged in cardiac catheterization to easily monitor and evaluate scattered radiation distribution across diverse C-arm angles and arbitrary physician associated staff positions-scrub nurse and technologist positions. In this study, scattered radiation distributions in an angiography room were calculated using the Monte Carlo simulation of particle and heavy ion transport code system (PHITS) code. Four visualizations were performed under different C-arm angles with and without radiation protection: (1) a dose profile, (2) a 2D cross-section, (3) a 3D scattered radiation distribution, and (4) a 4D scattered radiation distribution. The simulation results detailing the scattered radiation distribution in PHITS were exported in Visualization Toolkit format and visualized through the open-source visualization application ParaView for analysis. Visualization of the scattered dose showed that dose distribution depends on the C-arm angle and the x-ray machine output parameters (kV, mAs s -1 , beam filtration) which depend upon beam angulation to the patient body. When irradiating in the posterior-anterior direction, the protective curtain decreased the dose by 62% at a point 80 cm from the floor, where the physician's gonads are positioned. Placing the protection board close to the x-ray tube reduced the dose by 24% at a location 160 cm from the floor, where the lens of the eye is situated. Notably, positioning the protection board adjacent to the physician resulted in a 95.4% reduction in incident air kerma. These visualization displays can be combined to understand the spread and direction of the scattered radiation distribution and to determine where and how to operate and place radiation protection devices, accounting for the different beam angulations encountered in interventional cases. This study showed that scatter visualization could be a radiation protection teaching aid for students and medical staff in angiography rooms., (© 2024 Society for Radiological Protection. Published on behalf of SRP by IOP Publishing Limited. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Purpose: Identification of the Adamkiewicz artery before aortic surgery is important for preventing postoperative complications due to spinal cord ischemia. The Adamkiewicz artery is difficult to identify due to its small diameter. Nitroglycerin has a vasodilatory effect and is used clinically to improve visualization of blood vessels on coronary computed tomography (CT) angiography. We investigated whether the vasodilatory effect of nitroglycerin could improve the ability to visualize the Adamkiewicz artery., Methods: We extracted 33 cases wherein contrast-enhanced CT images were taken before and after aortic aneurysm surgery. Nitroglycerin was administered for coronary artery evaluation on the preoperative CT. However, no nitroglycerin was administered before the postoperative CT. Aortic contrast-to-noise ratio, CT value, image noise, and diameter of the Adamkiewicz artery and anterior spinal artery were measured. The depiction of the Adamkiewicz artery was graded into four grades and evaluated. These measurements were performed by two independent reviewers., Results: In nitroglycerin-administered cases, the contrast-to-noise ratio and CT values were significantly higher (P < 0.001, P < 0.001, respectively); the Adamkiewicz artery and anterior spinal artery diameters were dilated (P = 0.005, P = 0.001, respectively). The Adamkiewicz artery score also improved significantly (P < 0.001). No significant difference was found in image noise., Conclusion: Nitroglycerin contributed to improving the Adamkiewicz artery's visualization., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Esophagogastroduodenoscopy is the most important tool to detect gastric cancer (GC). In this study, we developed a computer-aided detection (CADe) system to detect GC with white light imaging (WLI) and linked color imaging (LCI) modes and aimed to compare the performance of CADe with that of endoscopists., Methods: The system was developed based on the deep learning framework from 9,021 images in 385 patients between 2017 and 2020. A total of 116 LCI and WLI videos from 110 patients between 2017 and 2023 were used to evaluate per-case sensitivity and per-frame specificity., Results: The per-case sensitivity and per-frame specificity of CADe with a confidence level of 0.5 in detecting GC were 78.6% and 93.4% for WLI and 94.0% and 93.3% for LCI, respectively (p &lt; 0.001). The per-case sensitivities of nonexpert endoscopists for WLI and LCI were 45.8% and 80.4%, whereas those of expert endoscopists were 66.7% and 90.6%, respectively. Regarding detectability between CADe and endoscopists, the per-case sensitivities for WLI and LCI were 78.6% and 94.0% in CADe, respectively, which were significantly higher than those for LCI in experts (90.6%, p = 0.004) and those for WLI and LCI in nonexperts (45.8% and 80.4%, respectively, p &lt; 0.001); however, no significant difference for WLI was observed between CADe and experts (p = 0.134)., Conclusions: Our CADe system showed significantly better sensitivity in detecting GC when used in LCI compared with WLI mode. Moreover, the sensitivity of CADe using LCI is significantly higher than those of expert endoscopists using LCI to detect GC., (© 2024 S. Karger AG, Basel.)

Objectives: This study aimed to evaluate the clinical impact of preoperative endoscopic ultrasound-guided tissue acquisition (EUS-TA) on the prognosis and incidence of positive peritoneal lavage cytology (PLC) during laparotomy or staging laparoscopy in patients with resectable (R) or borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC)., Methods: We retrospectively collected data from patients diagnosed with body and tail PDAC with/without EUS-TA at our hospital from January 2006 to December 2021., Results: To examine the effect of EUS-TA on prognosis, 153 patients (122 in the EUS-TA group, 31 in the non-EUS-TA group) were analyzed. There was no significant difference in overall survival between the EUS-TA and non-EUS-TA groups after PDAC resection (P = 0.777). In univariate and multivariate analysis, preoperative EUS-TA was not identified as an independent factor related to overall survival after pancreatectomy [hazard ratio 0.96, 95 % confidence interval (CI) 0.54-1.70, P = 0.897]. Next, to examine the direct influence of EUS-TA on the results of PLC, 114 patients (83 in the EUS-TA group and 31 in the non-EUS-TA group) were analyzed. Preoperative EUS-TA was not statistically associated with positive PLC (odds ratio 0.73, 95 % CI 0.25-2.20, P = 0.583). After propensity score matching, overall survival and positive PLC were the same in both groups., Conclusions: EUS-TA had no negative impact on postoperative survival and PLC-positive rates in R/BR PDAC., Competing Interests: Declaration of competing interest All authors have no conflicts of interest directly relevant to the content of this article., (Copyright © 2024. Published by Elsevier B.V.)

There is a growing interest in development of novel vaccines against respiratory tract infections, due to COVID-19 pandemic. Here, we examined mucosal adjuvanticity and the mucosal booster effect of membrane vesicles (MVs) of a novel probiotic E. coli derivative lacking both flagella and potentially carcinogenic colibactin (Δ flhD Δ clbP ). Δ flhD Δ clbP -derived MVs showed rather strong mucosal adjuvanticity as compared to those of a single flagellar mutant strain (Δ flhD -MVs). In addition, glycoengineered Δ flhD Δ clbP -MVs displaying serotype-14 pneumococcal capsular polysaccharide (CPS14 + MVs) were well-characterized based on biological and physicochemical parameters. Subcutaneous (SC) and intranasal (IN) booster effects of CPS14 + MVs on systemic and mucosal immunity were evaluated in mice that have already been subcutaneously prime-immunized with the same MVs. With a two-dose regimen, an IN boost (SC-IN) elicited stronger IgA responses than homologous prime-boost immunization (SC-SC). With a three-dose regimen, serum IgG levels were comparable among all tested regimens. Homologous immunization (SC-SC-SC) elicited the highest IgM responses among all regimens tested, whereas SC-SC-SC failed to elicit IgA responses in blood and saliva. Furthermore, serum IgA and salivary SIgA levels were increased with an increased number of IN doses administrated. Notably, SC-IN-IN induced not only robust IgG response, but also the highest IgA response in both serum and saliva among the groups. The present findings suggest the potential of a heterologous three-dose administration for building both systemic and mucosal immunity, e.g . an SC-IN-IN vaccine regimen could be beneficial. Another important observation was abundant packaging of colibactin in MVs, suggesting increased applicability of Δ flhD Δ clbP -MVs in the context of vaccine safety.

Background: With recent dramatic developments in chemotherapy, attempts to incorporate surgery into the multidisciplinary treatment of unresectable pancreatic ductal adenocarcinoma with metastasis (UR-M PDAC) have emerged. Maintenance therapy with olaparib after chemotherapy including a platinum-based regimen, which inhibits the poly ADP-ribose polymerase (PARP) involved in DNA repair, was approved for UR-M PDAC with positive BRCA mutations., Case Presentation: A 47-year-old male patient with a high carbohydrate antigen 19-9 (CA19-9) level was diagnosed with PDAC in the pancreatic tail. Staging laparoscopy revealed occult liver metastasis. Because BRCA2 mutation was confirmed, triple combination chemotherapy with SOXIRI (S-1/oxaliplatin/irinotecan) was introduced and continued for 16 weeks, followed by 14 weeks of olaparib. After that, CA19-9 was normalized, and no obvious liver metastases of any size could be seen on imaging studies during chemotherapy. Since staging laparoscopy after chemotherapy proved that the liver metastasis had disappeared, laparoscopic distal pancreatectomy was performed, and curative resection was completed. After adjuvant chemotherapy with olaparib for 12 months, the patient is alive 36 months from his initial diagnosis and 27 months postoperatively without recurrence., Conclusion: We report a case of PDAC with liver metastasis and BRCA mutation-positivity who underwent conversion surgery and achieved long-term survival after irinotecan-based chemotherapy followed by maintenance therapy with olaparib., (© 2024. The Author(s).)

Aims: This study aims to evaluate the periodontal status and its changes among Japanese older adults over a 10-year period., Methods and Results: A total of 206 dentate older adults aged 70 years who completely participated in 10 years of oral examination were included. The community periodontal index (CPI) was used to assess the gingival and periodontal pocket status, while the loss of attachment (LA) scoring system was used to report the extensive LA. A higher score in CPI (Code 3 and Code 4) and more extensive attachment loss were found in a majority of participants. During follow-up evaluation, mean number of sextants with CPI code 4 remained stable, while CPI code 3 significantly decreased particularly in male participants. Whereas, sextants without attachment loss significantly decreased on average. The mean number of missing sextants significantly increased from 1.1 to 1.9, and 5.8% of subjects had all sextants excluded in the follow-up., Conclusion: This study indicated that majority of the older people experienced severe periodontal disease and this condition remained stable during 10-year period. Additionally, the incidence of tooth loss increased as individuals aged. Regular oral care and maintenance are highly recommended for older population., (© 2024 Special Care Dentistry Association and Wiley Periodicals LLC.)

Introduction: This study aimed to assess the efficacy of combined administration of dipeptidyl peptide-4 (DPP4) and sodium-glucose cotransporter-2 (SGLT2) inhibitors on metabolic disorders and their preferable and complementary effects., Methods: The effectiveness of a 24-week intervention on metabolic parameters (including glucose profile), physical functions (grip strength and calf circumference), and health-related quality of life (HR-QOL) was analyzed using the International Physical Activity Questionnaire and Geriatric Depression Scale 5. A total of 39 patients with type-2 diabetes mellitus (T2DM) treated with the combination of DPP4 and SGLT2 inhibitors were included in this multicenter pilot study., Results: Combination therapy significantly reduced the HbA1c level (median [interquartile range]) after 24 weeks (pretreatment: 7.7% [7.3-8.2] vs. posttreatment: 7.1% [6.6-7.9], P < 0.001). The grip strength significantly increased after 24 weeks (1.7 ± 2.7 kg, P < 0.001), while the mean calf circumference and body mass index significantly decreased. In particular, administration of the SGLT2 inhibitor significantly increased total physical activity in participants aged ≥65 years ( P = 0.003), while psychological QOL did not significantly improve., Conclusions: Combination therapy with DPP4 and SGLT2 inhibitors decreased HbA1c levels and improved physical function in patients with T2DM. This study confirmed the effectiveness of combination therapy for metabolic disorders and suggested its beneficial and complementary effects. Therefore, advances in treatment plans to achieve further improvements in glucose profiles using DPP4 and SGLT2 inhibitors are recommended to enhance the QOL of patients with T2DM. Clinical trial number: University Hospital Medical Information Network Center: UMIN000045375., Competing Interests: None, (Copyright © Japan Medical Association.)

The immunoproteasome subunit LMP7 (β5i)/LMP2 (β1i) dual blockade has been reported to suppress B cell differentiation and activation, suggesting that the dual inhibition of LMP7/LMP2 is a promising approach for treating autoimmune diseases. In contrast, the inhibition of the constitutive proteasome subunit β5c correlates with cytotoxicity against non-immune cells. Therefore, LMP7/LMP2 dual inhibitors with high selectivity over β5c may be desirable for treating autoimmune diseases. In this study, we present the optimization and discovery of α-amido boronic acids using cryo-electron microscopy (cryo-EM). The exploitation of structural differences between the proteasome subunits led to the identification of a highly selective LMP7/LMP2 dual inhibitor 19. Molecular dynamics simulation based on cryo-EM structures of the proteasome subunits complexed with 19 explained the inhibitory activity profile. In mice immunized with 4-hydroxy-3-nitrophenylacetyl conjugated to ovalbumin, results indicate that 19 is orally bioavailable and shows promise as potential treatment for autoimmune diseases., 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 Ltd. All rights reserved.)

Purpose: The retrolabyrinthine approach is a surgical method designed to preserve hearing after surgery. When paired with intraoperative monitoring and an endoscope, this approach has demonstrated high rates of postoperative hearing preservation. However, the long-term prognosis of hearing preservation after utilizing this approach for vestibular schwannomas remains unexplored. This study aimed to examine the long-term outcomes of preserved hearing, providing insights into the suitability of the retrolabyrinthine approach for hearing preservation surgery., Methods: This study included 34 patients with preserved hearing after vestibular schwannoma surgery using the retrolabyrinthine approach at a single center. Long-term hearing prognosis and requirement for additional interventions were retrospectively examined., Results: Immediate after post-operative hearing preservation rate was 71.7%. Among the 34 patients with preserved hearing post-vestibular schwannoma surgery, four (11.8%) required additional interventions. Other patients experienced a gradual deterioration in their hearing status, with an approximate 10 dB decline during the 5-year follow-up; however, a serviceable hearing level persisted long after the surgery in these individuals., Conclusions: This study indicated the rationale for the retrolabyrinthine approach as a hearing preservation surgery for vestibular schwannomas, emphasizing its long-term hearing prognosis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction. Maternal screening tests and prophylactic antibiotics are important to prevent neonatal and infant group B streptococcal (GBS) infections. Hypothesis/Gap Statement. The performance of enrichment broth media for GBS screening that are available in Japan is unclear. Whole-genome data of GBS isolates from pregnant women in Japan is lacking. Aim. The aim of this study was to compare the protocol performance of six enrichment broths and two subculture agar plates, which were all available in Japan, for GBS detection. In addition, we showed whole-genome data of GBS isolates from pregnant women in Japan. Methodology. We collected 133 vaginal-rectal swabs from pregnant women visiting clinics and hospitals in Nagasaki Prefecture, Japan, and compared the protocol performance of 6 enrichment broths and 2 subculture agar plates. All GBS isolates collected in this study were subjected to whole-genome sequencing analysis. Results. We obtained 133 vaginal-rectal swabs from pregnant women at 35-37 weeks of gestation from 8 private clinics and 2 local municipal hospitals within Nagasaki Prefecture, Japan. The detection rate of the protocol involving the six enrichment broths and subsequent subcultures varied between 95.5 and 100 %, depending on the specific choice of enrichment broth. The GBS carriage rate among pregnant women in this region was 18.8 %. All 25 isolates derived from the swabs were susceptible to penicillin, whereas 48 and 36 % of the isolates demonstrated resistance to erythromycin and clindamycin, respectively. The distribution of serotypes was highly diverse, encompassing seven distinct serotypes among the isolates, with the predominant serotype being serotype V ( n = 8). Serotype V isolates displayed a tendency towards increased resistance to erythromycin and clindamycin, with all resistant isolates containing the ermB gene. Conclusion. There was no difference in performance among the culture protocols evaluated in this study. GBS strains isolated from pregnant women appeared to have greater genomic diversity than GBS strains detected in neonates/infants with invasive GBS infections. To confirm this result, further studies with larger sample sizes are needed.

Twelve years after the first edition of The Guideline for Gynecological Practice, which was jointly edited by The Japan Society of Obstetrics and Gynecology and The Japan Association of Obstetricians and Gynecologists, the 5th Revised Edition was published in 2023. The 2023 Guidelines includes 5 additional clinical questions (CQs), which brings the total to 103 CQ (12 on infectious disease, 30 on oncology and benign tumors, 29 on endocrinology and infertility and 32 on healthcare for women). Currently, a consensus has been reached on the Guidelines, and therefore, the objective of this report is to present the general policies regarding diagnostic and treatment methods used in standard gynecological outpatient care that are considered appropriate. At the end of each answer, the corresponding Recommendation Level (A, B, C) is indicated., (© 2024 The Authors. Journal of Obstetrics and Gynaecology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Obstetrics and Gynecology.)

Background/Objectives : This study aims to compare the clinical findings, particularly symptomatic diplopia, associated with an inferomedial orbital strut fracture versus intact strut and to determine the clinical significance of the inferomedial orbital strut in patients with orbital floor and medial orbital wall fractures. Methods : A 10-year retrospective observational study involving orbital blowout fracture cases was conducted in our institution. Patients with fractures of the orbital floor medial to the infraorbital groove and medial orbital wall, as seen on computed tomography (CT) scans, were included in this study. Patients with concomitant orbital rim fracture and those with old orbital fractures were excluded. Fracture of the inferomedial orbital strut was diagnosed via coronal CT images and patients were classified into those with an inferomedial orbital strut fracture and those without. Results : A total of 231 orbits from 230 patients was included in the study (fractured strut on 78 sides and intact strut on 153 sides). Approximately 2/3 of patients in both groups had the field of binocular single vision in primary position upon first examination ( p = 0.717). Patients with strut fractures demonstrated only comminuted or open fractures, while those without strut fractures showed diverse fracture patterns ( p < 0.001). Conclusions : Inferomedial orbital strut fracture does not automatically result in diplopia in patients with orbital blowout fractures. The integrity of the orbital periosteum plays a more essential role in hampering extraocular muscle displacement, thereby preventing symptomatic diplopia in these patients., Competing Interests: The authors declare no conflicts of interest.

Metastatic pheochromocytomas and paragangliomas (PPGLs) are rare endocrine malignancies with limited effective treatment options. The association between the tumor microenvironment (TME) with somatostatin receptor 2 (SSTR2) and hypoxia-induced factor-2α (HIF-2α) in PPGLs, critical for optimizing combination therapeutic strategies with immunotherapy, remains largely unexplored. To evaluate the association of SSTR2 and HIF-2α immunoreactivity with the TME in patients with PPGLs, we analyzed the expression of SSTR2A, HIF-2α, and TME components, including tumor-infiltrating lymphocytes (CD4 and CD8), tumor-associated macrophages (CD68 and CD163), and PD-L1, using immunohistochemistry in patients with PPGLs. The primary outcome was to determine the association of the immune profiles with SSTR2A and HIF-2α expression. Among 45 patients with PPGLs, SSTR2A and HIF2α were positively expressed in 21 (46.7%) and 14 (31.1%) patients, respectively. The median PD-L1 immunohistochemical score (IHS) was 2.0 (interquartile range: 0-30.0). Positive correlations were observed between CD4, CD8, CD68, and CD163 levels. A negative correlation was found between the CD163/CD68 ratio (an indicator of M2 polarization) and SSTR2A expression (r = -0.385, p = 0.006). HIF-2α expression showed a positive correlation with PD-L1 IHS (r = 0.348, p = 0.013). The co-expression of PD-L1 (HIS > 10) and HIF-2α was found in seven patients (15.6%). No associations were observed between SDHB staining results and the CD163/CD68 ratio, PD-L1, or SSTR2A expression. Our data suggest the potential of combination therapy with immunotherapy and peptide receptor radionuclide therapy or HIF-2α inhibitors as a treatment option in selected PPGL populations.

Tissue folds are structural motifs critical to organ function. In the intestine, bending of a flat epithelium into a periodic pattern of folds gives rise to villi, finger-like protrusions that enable nutrient absorption. However, the molecular and mechanical processes driving villus morphogenesis remain unclear. Here, we identify an active mechanical mechanism that simultaneously patterns and folds the intestinal epithelium to initiate villus formation. At the cellular level, we find that PDGFRA+ subepithelial mesenchymal cells generate myosin II-dependent forces sufficient to produce patterned curvature in neighboring tissue interfaces. This symmetry-breaking process requires altered cell and extracellular matrix interactions that are enabled by matrix metalloproteinase-mediated tissue fluidization. Computational models, together with in vitro and in vivo experiments, revealed that these cellular features manifest at the tissue level as differences in interfacial tensions that promote mesenchymal aggregation and interface bending through a process analogous to the active dewetting of a thin liquid film., Competing Interests: Declaration of interests Z.J.G. and C.S.M. hold patents related to the MULTI-seq barcoding method., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Lactononadecapeptide (LNDP; NIPPLTQTPVVVPPFLQPE), a casein-derived peptide comprising 19 residues, is known for its capacity to enhance cognitive function. This study aimed to explore the transepithelial transport and stability of LNDP. Results showed that LNDP retained over 90% stability after 2 h of treatment with gastrointestinal enzymes. The stability of LNDP on Caco-2 cell monolayers ranged from 93.4% ± 0.9% to 101.1% ± 1.2% over a period of 15-60 min, with no significant differences at each time point. The permeability of LNDP across an artificial lipid membrane was very low with the effective permeability of 3.6 × 10 -11 cm/s. The Caco-2 assay demonstrated that LNDP could traverse the intestinal epithelium, with an apparent permeability of 1.22 × 10 -6 cm/s. Its transport was significantly inhibited to 67.9% ± 5.0% of the control by Gly-Pro, a competitor of peptide transporter 1 (PEPT1). Furthermore, PEPT1 knockdown using siRNA significantly inhibited LNDP transport by 77.6% ± 1.9% in Caco-2 cell monolayers. The LNDP uptake in PEPT1-expressing HEK293 cells was significantly higher (54.5% ± 14.6%) than that in mock cells. These findings suggest that PEPT1 plays a crucial role in LNDP transport, and LNDP exhibits good resistance to gastrointestinal enzymes.

This paper presents treatment strategies for orbital necrotizing fasciitis (NF) in a case of a 33-year-old male diagnosed with orbital NF, which developed after dental root canal treatment. Although orbital NF is rare, it is rapidly progressive and can easily lead to the loss of tissue and visual function, sometimes to a life-threatening extent. Prompt and adequate treatment has been a challenge yet remains quite essential. In addition to the conventional approach to NF, such as immediate antibiotic administration and drainage, orbital NF patients like this case were often treated by incorporating additional steps, which include: 1) performing minimally invasive but adequate removal of necrotic tissue through intraoperative use of ultrasound equipment and postoperative use of proteolytic enzyme-containing ointment for chemical debridement; 2) managing intraorbital pressure by lateral cantholysis and orbital floor removal (decompression); and 3) maintaining the aerobic conditions of the wound after surgical drainage via orbital wall removal. Thus far, satisfactory results in patients with extensive NF of the orbit, including the presented case, were achieved with regards to preserving periorbital tissues, vision, and ocular motility through a multidisciplinary approach. These should be considered as optional means of preserving the orbital tissue and visual function., Competing Interests: Declaration of Competing Interest The authors have no financial or conflicts of interest to disclose., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Golli-myelin basic proteins, encoded by the myelin basic protein gene, are widely expressed in neurons and oligodendrocytes in the central nervous system. Further, prior research has shown that Golli-myelin basic protein is necessary for myelination and neuronal maturation during central nervous system development. In this study, we established Golli-myelin basic protein-floxed mice to elucidate the cell-type-specific effects of Golli-myelin basic protein knockout through the generation of conditional knockout mice (Golli-myelin basic proteins fl/fl ; E3CreN), in which Golli-myelin basic proteins were specifically deleted in cerebellar granule neurons, where Golli-myelin basic proteins are expressed abundantly in wild-type mice. To investigate the role of Golli-myelin basic proteins in cerebellar granule neurons, we further performed histopathological analyses of these mice, with results indicating no morphological changes or degeneration of the major cellular components of the cerebellum. Furthermore, behavioral analysis showed that Golli-myelin basic proteins fl/fl ; E3CreN mice were healthy and did not display any abnormal behavior. These results suggest that the loss of Golli-myelin basic proteins in cerebellar granule neurons does not lead to cerebellar perturbations or behavioral abnormalities. This mouse model could therefore be employed to analyze the effect of Golli-myelin basic protein deletion in specific cell types of the central nervous system, such as other neuronal cells and oligodendrocytes, or in lymphocytes of the immune system., (© 2024. The Author(s).)

Polymerase proofreading-associated polyposis (PPAP) is a rare disease with autosomal-dominant inheritance caused by germline variants in the POLE and POLD1 genes. PPAP has been reported to increase the risk of multiple cancers, including colon, duodenal, and endometrial cancers. Herein, we report a case in which multiple duodenal tumors led to the detection of a POLE mutation. A 43-year-old woman underwent esophagogastroduodenoscopy (EGD). Multiple duodenal tumors were detected, and all lesions were treated endoscopically. The patient had a history of multiple colorectal cancers and endometrial cancer along with a family history of cancer; hence, genetic testing was performed, and POLE variant, c.1270C > G (p.Leu424Val) was detected. Hereditary colorectal cancer syndromes should be considered in patients with colorectal cancer who have multiple cancers or a family history of cancer, and multigene panel sequencing is useful in confirming the diagnosis. In addition, duodenal tumors frequently coexist in patients with PPAP-carrying POLE variants, while the endoscopic treatment for duodenal tumors becomes safe and useful with several new approaches. Therefore, surveillance EGD is necessary in such patients for the early detection and treatment of duodenal tumors., (© 2024. Japanese Society of Gastroenterology.)

Background: This study evaluated the effectiveness of NUDT15 codon 139 genotyping in optimizing thiopurine treatment for inflammatory bowel disease (IBD) in Japan, using real-world data, and aimed to establish genotype-based treatment strategies., Methods: A retrospective analysis of 4628 IBD patients who underwent NUDT15 codon 139 genotyping was conducted. This study assessed the purpose of the genotyping test and subsequent prescriptions following the obtained results. Outcomes were compared between the Genotyping group (thiopurine with genotyping test) and Non-genotyping group (thiopurine without genotyping test). Risk factors for adverse events (AEs) were analyzed by genotype and prior genotyping status., Results: Genotyping test for medical purposes showed no significant difference in thiopurine induction rates between Arg/Arg and Arg/Cys genotypes, but nine Arg/Cys patients opted out of thiopurine treatment. In the Genotyping group, Arg/Arg patients received higher initial doses than the Non-genotyping group, while Arg/Cys patients received lower ones (median 25 mg/day). Fewer AEs occurred in the Genotyping group because of their lower incidence in Arg/Cys cases. Starting with < 25 mg/day of AZA reduced AEs in Arg/Cys patients, while Arg/Arg patients had better retention rates when maintaining ≥ 75 mg AZA. Nausea and liver injury correlated with thiopurine formulation but not dosage. pH-dependent mesalamine reduced leukopenia risk in mesalamine users., Conclusions: NUDT15 codon 139 genotyping effectively reduces thiopurine-induced AEs and improves treatment retention rates in IBD patients after genotype-based dose adjustments. This study provides data-driven treatment strategies based on genotype and identifies risk factors for specific AEs, contributing to a refined thiopurine treatment approach., (© 2024. The Author(s).)

Abstract: We have recently shown that including the blood flow from the lateral thoracic artery (LTA) in addition to the thoracoacromial artery in the pectoralis major muscle musculocutaneous (PMMC) flap (bipedicle PMMC flap) can increase the perfusion of the flap. We also developed the concept of the supercharged PMMC flap, in which the LTA included in the flap was once cut and anastomosed to a cervical artery under a microscope. It is an effective solution to maintain the additional blood flow from the LTA, when the length of the LTA is compromised for reconstruction. The mandibular reconstruction of an oral cancer patient was performed with a supercharged PMMC flap. Intraoperative indocyanine green angiography was performed in a single pedicle, bipedicle, and supercharged conditions, and the videos were analyzed with a quantitative assessment system of perfusion using some parameters. As a result, blood supply from the LTA was essential for flap survival in this patient, and supercharging from the cervical artery improved flap perfusion compared with the perfusion in the bipedicle condition. The supercharged PMMC flap can resolve the compromise of pedicle length and be also hemodynamically advantageous, thus making the reconstruction more reliable than the conventional technique., Competing Interests: Conflicts of interest and sources of funding: This study received funding from institutional sources only., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Cold snare polypectomy (CSP)-dedicated snares (DSs) may have a higher resection ability than conventional snares. However, a model that can accurately and objectively evaluate and compare the resection ability of each snare has yet to be determined, and characteristics of snare parts that increase resection ability remain unknown. Therefore, we elucidated DSs' resection ability and all characteristics of the parts required for acquiring high resection ability., Methods: An ex vivo model for evaluating resection ability was generated using human colons obtained from forensic autopsy specimens. The force required to resect a 15 mm wide human colonic mucosa (FRR) was measured using this model; if the FRR is small, the resection ability is high. Next, after measuring the stiffness of each snare part, the correlation between the stiffness and resection ability was analyzed., Results: The force required to resect using SnareMaster Plus, Micro-Tech Cold Snare, Captivator Cold, Exacto Cold Snare, or Captivator II was 13.6 ± 1.0, 12.5 ± 1.2, 7.4 ± 1.2, 6.5 ± 1.0, and 28.7 ± 3.7 N, respectively. All DSs had significantly lower FRR than the conventional snare (Captivator II) and had higher resection ability (P < 0.001). A negative correlation was found between FRR and sheath or wire spindle stiffness, with correlation coefficients of 0.72 (P = 0.042) or 0.94 (P < 0.001), respectively. Moreover, 1 × 7 type wire rings had significantly higher friction coefficients than 1 × 3 type wire rings (P < 0.002)., Conclusion: Sheath and wire spindle stiffness should be increased to increase resection ability; 1 × 7 type wire rings may be suitable for CSP-snare parts., (© 2023 Japan Gastroenterological Endoscopy Society.)

Purpose: This study aims to determine the incidence of pure orbital fractures with concomitant lacrimal drainage system injuries., Methods: A retrospective observational study involving 956 sides from 940 pure orbital blowout fracture patients was conducted in our institution. Patients with concomitant orbital rim fracture and those with old orbital fractures were excluded., Results: A total of 13 sides (1.4%) from 13 patients were included in the study. Canalicular laceration, bony nasolacrimal canal fracture, and lacrimal sac wall laceration were found in 9, 4, and 1 patients, respectively (one overlapping). Majority of the injuries resulted from either sports or falls. Inferomedial orbital strut fracture (23.1% vs. 7.6%; p  = .075) and orbital floor fracture occurring lateral to the infraorbital groove (30.8% vs. 9.9%; p  = .035) tended to be higher in patients with lacrimal drainage system injuries., Conclusion: There is a 1.4% incidence rate of pure orbital fractures with concomitant lacrimal drainage system injuries among the Japanese population included in this study. Inferomedial orbital strut fractures and orbital floor fracture lateral to the infraorbital groove were found to have higher association with lacrimal drainage system injuries.

Background: The development of immunohistochemical staining has revealed that gastric adenocarcinoma with the gastric phenotype can be divided into the foveolar, fundic gland, and pyloric gland phenotypes. Gastric adenocarcinoma of the pyloric gland type is difficult to diagnose using biopsy because of its low atypia and rarity. Herein, we describe a case of gastric adenocarcinoma of the pyloric gland type that was diagnosed immunohistochemically after endoscopic resection., Case Presentation: A 67-year-old man was referred to our hospital for the diagnosis and treatment of a 30-mm elevated lesion on the lesser curvature side of the middle of the gastric body. Although four biopsies were performed, it was difficult to determine whether the lesion was benign or malignant. Therefore, endoscopic submucosal dissection was performed, and the presence of tumor cells infiltrating the submucosa with venous invasions was identified. Immunohistochemical staining revealed that the tumor cells were positive for MUC5AC and MUC6 and negative for Pepsinogen I and H + /K + -ATPase. From the above findings, he was diagnosed as having gastric adenocarcinoma with pyloric gland type. The patient underwent a laparoscopic distal gastrectomy and was discharged without any adverse events., Conclusions: Gastric adenocarcinoma of the pyloric gland type is a rare disease, and endoscopic resection can serve as a viable diagnostic option for this condition when it is difficult to diagnose using biopsy. Immunohistochemical pathology images can aid in the diagnosis of gastric adenocarcinoma of the pyloric gland type., (© 2024. The Author(s).)

Background and Aims: This retrospective study aimed to compare the short- and long-term outcomes of endoscopic submucosal dissection and laparoscopic and endoscopic cooperative surgery in patients with superficial non-ampullary duodenal epithelial tumors., Patients and Methods: We investigated consecutive patients with SNADETs > 10 mm in size who underwent ESD (ESD group) or LECS (LECS group) between January 2015 and March 2021. The data was used to analyze the clinical course, management, survival status, and recurrence between the two groups., Results: A total of 113 patients (100 and 13 in the ESD and LECS groups, respectively) were investigated. The rates of en bloc resection and curative resection were 100% vs. 100% and 93.0% vs. 77.0% in the ESD and LECS groups, respectively, with no significant difference. The ESD group had shorter resection and suturing times than the LECS group, but there were no significant difference after propensity score matching. There were also no differences in the rates of postoperative adverse event (7.0% vs. 23.1%; P = 0.161). The 3-year overall survival (OS) rate was high in both the ESD and LECS groups (97.6% vs. 100%; P = 0.334). One patient in the ESD group experienced recurrence due to liver metastasis; however, no deaths related to SNADETs were observed., Conclusion: ESD and LECS are both acceptable treatments for SNADETs in terms of a high OS rate and a low long-term recurrence rate, thereby achieving a comparable high rate of curative resection. Further studies are necessary to compare the outcomes of ESD and LECS for SNADETs once both techniques are developed further., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A total of 739 patients underwent RARP as initial treatment for PCa from November 2011 to October 2018. Data on BCR status, clinical and pathological parameters were collected from the clinical records. After excluding cases with neoadjuvant and/or adjuvant therapies, presence of lymph node or distant metastasis, and positive SM, a total of 537 cases were eligible for the final analysis. The median follow-up of experimental cohort was 28.0 (interquartile: 18.0-43.0) months. We identified the presence of International Society of Urological Pathology grade group (ISUP-GG) ≥ 4 (Hazard ratio (HR) 3.20, 95% Confidence Interval (95% CI) 1.70-6.03, P < 0.001), lymphovascular invasion (HR 2.03, 95% CI 1.00-4.12, P = 0.049), perineural invasion (HR 10.7, 95% CI 1.45-79.9, P = 0.020), and maximum tumor diameter (MTD) > 20 mm (HR 1.9, 95% CI 1.01-3.70, P = 0.047) as significant factors of BCR in the multivariate analysis. We further developed a risk model according to these factors. Based on this model, 1-year, 3-year, and 5-year BCR-free survival were 100%, 98.9%, 98.9% in the low-risk group; 99.1%, 94.1%, 86.5% in the intermediate-risk group; 93.9%, 84.6%, 58.1% in the high-risk group. Internal validation using the bootstrap method showed a c-index of 0.742 and an optimism-corrected c-index level of 0.731. External validation was also carried out using an integrated database derived from 3 other independent institutions including a total of 387 patients for the final analysis. External validation showed a c-index of 0.655. In conclusion, we identified risk factors of biochemical failure in patients showing negative surgical margin after RARP and further developed a risk model using these risk factors., (© 2024. The Author(s).)

Ulcerative colitis (UC) is a chronic disorder of the large intestine with inflammation and ulceration. The incidence and prevalence of UC have been rapidly increasing worldwide, but its etiology remains unknown. In patients with UC, the accumulation of eosinophils in the large intestinal mucosa is associated with increased disease activity. However, the molecular mechanism underlying the promotion of intestinal eosinophilia in patients with UC remains poorly understood. Here, we show that uridine diphosphate (UDP)-glucose mediates the eosinophil-dependent promotion of colonic inflammation via the purinergic receptor P2Y14. The expression of P2RY14 mRNA was upregulated in the large intestinal mucosa of patients with UC. The P2Y14 receptor ligand UDP-glucose was increased in the large intestinal tissue of mice administered dextran sodium sulfate (DSS). In addition, P2ry14 deficiency and P2Y14 receptor blockade mitigated DSS-induced colitis. Among the large intestinal immune cells and epithelial cells, eosinophils highly expressed P2ry14 mRNA. P2ry14-/- mice transplanted with wild-type bone marrow eosinophils developed more severe DSS-induced colitis compared with P2ry14-/- mice that received P2ry14-deficient eosinophils. UDP-glucose prolonged the lifespan of eosinophils and promoted gene transcription in the cells through P2Y14 receptor-mediated activation of ERK1/2 signaling. Thus, the UDP-glucose/P2Y14 receptor axis aggravates large intestinal inflammation by accelerating the accumulation and activation of eosinophils., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Japanese Society for Immunology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Safe water supply is usually inadequate in areas without water treatment plants and even in a city under emergency conditions due to a disaster, even though safe water is essential for drinking and other various purposes. The purification of surface water from a river, lake, or pond requires disinfection and removal of chemical pollutants. In this study, we report a water purification strategy using seashell-derived calcium oxide (CaO) via disinfection and subsequent flocculation with polyphosphate for chemical pollutant removal. Seashell-derived CaO at a concentration (2 g L -1 ) higher than its saturation concentration caused the >99.999% inactivation of bacteria, mainly due to the alkalinity of calcium hydroxide (Ca(OH) 2 ) produced by hydration. After the disinfection, the addition of sodium polyphosphate at 2 g L -1 allowed for the flocculation of CaO/Ca(OH) 2 particles with adsorbing chemical pollutants, such as Congo red, dichlorodiphenyltrichloroethane, di(2-ethylhexyl)phthalate, and polychlorinated biphenyls, for removing these pollutants; purified water was obtained through filtration. Although this purified water was initially highly alkaline (pH ∼ 12.5), its pH decreased into a weak alkaline region (pH ∼ 9) during exposure to ambient air by absorbing carbon dioxide from the air with the precipitating calcium carbonate. The advantages of this water purification strategy include the fact that the saturation of CaO/Ca(OH) 2 potentially serves as a visual indicator of disinfection, that the flocculation by polyphosphate removes excessive CaO/Ca(OH) 2 as well as chemical pollutants, and that the high pH and Ca 2+ concentrations in the resulting purified water are readily decreased. Our findings suggest the usability of seashell-derived material-polymer assemblies for water purification, especially under emergency conditions due to disasters., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

In thermoelectric and other inorganic materials research, the significance of half-Heusler (HH) compositions following the 18-electron rule has drawn interest in developing and exploiting the potential of intermetallic compounds. For the fabrication of thermoelectric modules, in addition to high-performance materials, having both p- and n-type materials with compatible thermal expansion coefficients is a prerequisite for module development. In this work, the p-type to n-type transition of valence balanced/unbalanced HH composition of Mg 1- x V x NiSb was demonstrated by changing the Mg:V chemical ratio. The Seebeck coefficient and power factor of Ti-doped Mg 0.57 V 0.33 Ti 0.1 NiSb are -130 μV K -1 and 0.4 mW m -1 K -2 at 400 K, respectively. In addition, the reduced lattice thermal conductivity (κ L < 2.5 W m -1 K -1 at 300 K) of n-type compositions was reported to be much smaller than κ L of conventional HH materials. As high thermal conductivity has long been an issue for HH materials, the synthesis of p- and n-type Mg 1- x V x NiSb compositions with low lattice thermal conductivity is a promising strategy for producing high-performance HH compounds. Achieving both p- and n-type materials from similar parent composition enabled us to fabricate a thermoelectric module with maximum output power P max ∼ 63 mW with a temperature difference of 390 K. This finding supports the benefit of exploring the huge compositional space of valence balanced/unbalanced quaternary HH compositions for further development of thermoelectric devices.

Background and Objective: Several endoscopic resection methods have been developed as less invasive treatments for superficial non-ampullary duodenal epithelial tumours. This study aimed to compare outcomes of conventional endoscopic mucosal resection and underwater endoscopic mucosal resection for superficial non-ampullary duodenal epithelial tumours, including resection depth and rate of the muscularis mucosa contained under the lesion., Methods: This single-centre retrospective cohort study conducted from January 2009 to December 2021 enrolled patients who underwent conventional endoscopic mucosal resection and underwater endoscopic mucosal resection for superficial non-ampullary duodenal epithelial tumours and investigated their clinicopathological outcomes using propensity score matching., Results: Of the 285 superficial non-ampullary duodenal epithelial tumours, 98 conventional endoscopic mucosal resections and 187 underwater endoscopic mucosal resections were included. After propensity score matching, 64 conventional endoscopic mucosal resections and 64 underwater endoscopic mucosal resections were analysed. The R0 resection rate was significantly higher in underwater endoscopic mucosal resection cases than in conventional endoscopic mucosal resection cases (70.3% vs. 50.0%; P = 0.030). In the multivariate analysis, a lesion diameter > 10 mm (odds ratio 7.246; P = 0.001), being in the 1st-50th treatment period (odds ratio 3.405; P = 0.008), and undergoing conventional endoscopic mucosal resection (odds ratio 3.617; P = 0.016) were associated with RX/R1 resection. Furthermore, in underwater endoscopic mucosal resection cases, the R0 rate was significantly higher for lesions diameter ≤10 mm than >10 mm, and was significantly higher in the 51st-treatment period than in the 1st-50th period. Conventional endoscopic mucosal resection and underwater endoscopic mucosal resection cases showed no significant difference in resection depth and muscularis mucosa containing rate., Conclusions: Underwater endoscopic mucosal resection may be more acceptable than conventional endoscopic mucosal resection for superficial non-ampullary duodenal epithelial tumours ≤ 10 mm. A steep early learning curve may be acquired for underwater endoscopic mucosal resection. Large multicentre prospective studies need to be conducted to confirm the effectiveness of underwater endoscopic mucosal resection., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: In this study, we investigated infection-related tumor growth, focusing on myeloid-derived suppressor cells (MDSCs) in clinical and experimental settings., Patients and Methods: In the clinical study, a total 109 patients who underwent gastrectomy or esophagectomy were included. Blood samples were collected from a preoperative time point through 3 months after surgery, and MDSCs were analyzed using flow cytometry. In animal experiments, peritonitis model mice were created by CLP method. We investigated the number of splenic MDSCs in these mice using flow cytometry. Malignant melanoma cells (B16F10) were inoculated on the back of the mice, and tumor growth was monitored. We compared the level of MDSC infiltration around the tumor and the migration ability between CLP and sham-operated mice-derived MDSCs. Finally, we focused on PD-L1 + MDSCs to examine the effectiveness of anti-PD-L1 antibodies on tumor growth in CLP mice., Results: In patients with postoperative infectious complication, MDSC number was found to remain elevated 3 months after surgery, when the inflammatory responses were normalized. CLP mice showed increased numbers of MDSCs, and following inoculation with B16F10 cells, this higher number of MDSCs was associated with significant tumor growth. CLP-mice-derived MDSCs had higher levels of accumulation around the tumor and had more enhanced migration ability. Finally, CLP mice had increased numbers of PD-L1 + MDSCs and showed more effective inhibition of tumor growth by anti-PD-L1 antibodies compared to sham-operated mice., Conclusion: Long-lasting enhanced MDSCs associated with infection may contribute to infection-related tumor progression., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Pseudomyxoma peritonei (PMP) of pancreatic origin arising from an intraductal papillary mucinous neoplasm (IPMN) is rare. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has been established as the optimal treatment for PMP. However, the benefits and safety of CRS with HIPEC for treating PMP of pancreatic origin remain unclear. Herein, we describe a case of PMP of pancreatic origin that was treated with CRS and HIPEC without postoperative complications. A 75-year-old woman was referred to our department. Computed tomography (CT) revealed a multilocular cystic tumor in the pancreatic tail, notable mucinous ascites in the abdominal cavity, and scalloping of the liver and spleen. CT did not reveal the appendix, and the ovaries were normal in size. The patient was diagnosed with PMP of pancreatic origin, and CRS and HIPEC were performed. Intraoperatively, the pancreatic tumor was perforated, and there was a large amount of mucinous ascites. We performed distal pancreatectomy in addition to CRS and HIPEC, with no intraoperative complications. The postoperative course was uneventful, and the patient survived after 6 months without recurrence. CRS with HIPEC may be a feasible treatment option for PMP of pancreatic origin., (© 2023. Japanese Society of Gastroenterology.)

Conventional clip closure of mucosal defects after duodenal endoscopic submucosal dissection decreases the incidence of delayed adverse events, but may result in incomplete closure, depending on size or location. This study aimed to assess the effectiveness of the underwater clip closure method for complete duodenal defect closure without the difficulties associated with conventional closure methods. We investigated 19 patients with 20 lesions who underwent endoscopic submucosal dissection of the duodenum and subsequent mucosal defect closure in underwater conditions at our facility between February 2021 and January 2022. The success rate of the underwater clip closure method was defined as the complete endoscopic closure of the mucosal defect; a success rate of 100% was achieved. The median resected specimen size was 34.3 mm, the median procedure time for mucosal defect closure was 14 min, and the median number of clips used per patient was 12. No delayed adverse events were observed. The underwater clip closure method is a feasible option for complete closure of mucosal defects, regardless of the size or location of a duodenal endoscopic submucosal dissection., (© 2023 Japan Gastroenterological Endoscopy Society.)

We have developed a rapid genus identification method for poisonous plants. The real-time PCR using the TaqMan ® probe method was employed for detection, with the amplified targets being the "trnL (UAA)-intron" or "trnL-trnF intergenic spacer" regions of chloroplast DNA. The targeted plants were selected six genera (Aconitum, Colchicum, Veratrum, Brugmansia, Scopolia and Narcissus), which have been implicated in many instances of food poisoning in Japan. A tissue lysis solution was used for DNA extraction, which can be completed within approximate 30 min. A master mix corresponding to the tissue lysis solution was used for real-time PCR reagents. As a result, we were able to complete the entire process from DNA extraction to genus identification in 4 to 5 hr. The detection sensitivity was estimated at approximately 1 pg of DNA for all six plant genera. Remarkably, an amplification plot was discerned even with the crude cell lysates of all samples. It was also possible to obtain amplification curves for three plant samples that had been subjected to simulated cooking (boiling). This study suggests that the developed method can rapidly identify six genera of poisonous plants.

Purpose: To report adult patients with an orbital trapdoor fracture with extraocular muscle entrapment., Methods: We retrospectively reviewed 566 adult patients (>18 years) with a pure orbital fracture who were referred to us from January 2016 to May 2023. The following data were collected: age, sex, affected side, causes of injury, concomitant ocular injury and nasal bone fracture, presence or absence of oculocardiac reflex and infraorbital nerve hypesthesia, period from injury to surgery, follow-up period, and pre- and postoperative limitation of extraocular muscle motility and fields of a binocular single vision., Results: We found 5 patients (0.9%) with an orbital trapdoor fracture with extraocular muscle entrapment (age range, 19-47 years; all males; 2 right and 3 left). Causes of injury included performing a bench press, fall, assault, boxing, and bicycle accident. Entrapment of the inferior and medial recti muscles was seen in 2 and 3 patients, respectively. None of the patients had any sign of oculocardiac reflex. After surgical reduction, the field of binocular single vision became normal in 3 patients and was incompletely recovered in 2 patients, in whom consultation with us was delayed., Conclusion: Adults with extraocular muscle entrapment may not present with an oculocardiac reflex. Urgent release of an entrapped muscle is, however, still recommended to avoid permanent limitation of extraocular muscle motility., Competing Interests: The authors have no financial or conflicts of interest to disclose., (Copyright © 2023 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Aims: Ursodeoxycholic acid is the first-line treatment for primary biliary cholangitis, and treatment response is one of the factors predicting the outcome. To prescribe alternative therapies, clinicians might need additional information before deciphering the treatment response to ursodeoxycholic acid, contributing to a better patient prognosis. In this study, we developed and validated machine learning (ML) algorithms to predict treatment responses using pretreatment data., Methods: This multicenter cohort study included collecting datasets from two data samples. Data 1 included 245 patients from 18 hospitals for ML development, and was divided into (i) training and (ii) development sets. Data 2 (iii: test set) included 51 patients from our hospital for validation. An extreme gradient boosted tree predicted the treatment response in the ML model. The area under the curve was used to evaluate the efficacy of the algorithm., Results: Data 1 showed that patients complying with the Paris II treatment response had significantly lower serum alkaline phosphatase and total bilirubin levels than those who did not respond. Three factors, total bilirubin, total protein, and alanine aminotransferase levels were selected as essential variables for prediction. Data 2 showed that patients complying with the Paris II criteria had significantly high prothrombin time and low total bilirubin levels. The area under the curve of extreme gradient boosted tree was good for (ii) (0.811) and (iii) (0.856)., Conclusions: We demonstrated the efficacy of ML in predicting the treatment response for patients with primary biliary cholangitis. Early identification of cases requiring additional treatment with our novel ML model may improve prognosis., (© 2023 Japan Society of Hepatology.)

Liquid cell transmission electron microscopy (LC-TEM) is a unique technique that permits in situ observations of various phenomena in liquids with high spatial and temporal resolutions. One difficulty with this technique is the control of the environmental conditions in the observation area. Control of the temperature ranging from room temperature to minus several tens of degrees Celsius, is desirable for controlling the supersaturation in various materials and for observing crystallization more easily. We have developed a cooling transmission electron microscopy specimen holder that uses Peltier devices, and we have combined it with a liquid cell to realize accurate temperature control in LC-TEM. We evaluated this system by using water as a specimen. Motionless bubbles, shown to be voids containing pressurized gas, formed in the specimen sometime after the temperature had reached -12°C. An electron diffraction pattern showed that the specimen turned into ice Ih after the formation of these bubbles, confirming that our system works properly and can induce crystallization. In addition, we analyzed the behavior of bubbles formed in the ice Ih, and we discussed the formation of these bubbles and their internal pressure., Competing Interests: Conflict of Interest The authors declare that they have no competing interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Microscopy Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Our previous study revealed that changes of the intracellular Cl - concentration ([Cl - ] i ) affected cell proliferation in cancer cells. However, the role of Cl - on cell migration and invasion in cancer cells remains unanalyzed. Therefore, the aim of the present study is to investigate whether changes of [Cl - ] i affects cell migration and invasion of cancer cells. In human prostate cancer DU145 cells, cell migration and invasion were enhanced by culturing in the low Cl - medium (replacement of Cl - by NO 3 - ). We also found that DU145 cells in the low Cl - condition caused significant transient ERK1/2 activation followed by an increase of MMP-1 mRNA levels. Inhibition of ERK1/2 activation in the low Cl - condition reduced enhancement of MMP-1 mRNA levels and decreased cell migration and invasion. These observations indicate that [Cl - ] i plays important roles in metastatic function by regulating the ERK1/2 signaling pathway in human prostate cancer cells, and intracellular Cl - would be one of the key targets for anti-cancer therapy., 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 © 2023 Elsevier Inc. All rights reserved.)

A 50-year-old male was referred to our hospital for the further evaluation and treatment of abdominal pain. He was diagnosed with complicated appendicitis using computed tomography. After conservative treatment, he underwent an interval appendectomy. A histopathological examination revealed a goblet cell carcinoid(GCC)of the appendix with subserosal invasion. He underwent laparoscopic ileocecal resection with D3 lymph node dissection. Histopathological findings showed neither residual tumor nor lymph node metastasis. The patients is currently followed as an outpatient without recurrence. Here we report our experience with GCC, a rare disease.

Background: In recent years, site-directed therapies (SDTs) targeting progressive lesions in patients with oligometastatic prostate cancer have attracted attention. However, whether they effectively treat oligoprogressive castration-resistant prostate cancer (CRPC) remains unclear. Here, we investigated the efficacy of SDT in patients with oligoprogressive CRPC and identified prognostic factors., Methods: We reviewed 59 patients with oligoprogressive CRPC who underwent SDT targeting prostate or metastatic lesions between April 2014 and March 2022. We evaluated the associations between several pretreatment clinical variables and treatment procedures and a >50% prostate-specific antigen (PSA) response, progression-free survival (PFS), and time to next treatment (TTNT)., Results: A PSA response of >50% was observed in 66% of patients. The median PFS and TTNT were 8.3 months and 9.9 months, respectively. Patients with PSA doubling time ≥6 months showed a higher >50% PSA response rate (87% vs. 45%; P  < 0.001), longer PFS (median, 15.0 vs. 5.0 months; P  < 0.001), and longer TTNT (median, 16.3 vs. 5.9 months; P  < 0.001) than patients with PSA doubling time <6 months. In multivariate analyses, a PSA doubling time of ≥6 months independently predicted a >50% PSA response, favorable PFS, and TTNT ( P  = 0.037, 0.025, and 0.017, respectively)., Conclusion: PSA doubling time of ≥6 months may be a key indicator of the favorable efficacy of SDT for oligoprogressive CRPC., (© 2023 The Asian Pacific Prostate Society. Published by Elsevier B.V.)