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The adaptor protein human GRB2 plays crucial roles in mediating signal transduction from cell membrane receptors to RAS and its downstream proteins by recruiting SOS1. Recent studies have revealed that GRB2 also serves as a scaffold for liquid-liquid phase separation (LLPS) with SOS1 and transmembrane receptors, which is thought to regulate the magnitude of cell signalling pathways. In this study, we employed solution NMR spectroscopy to investigate the interactions of the full-length GRB2 with proline-rich motifs (PRMs) derived from ten potential GRB2-binding sites in SOS1, as well as a peptide from a phosphorylation site of EGFR. Our findings indicate that the binding affinity of the two SH3 domains of GRB2 for PRMs differs by a factor of ten to twenty, with the N-terminal SH3 domain (NSH3) exhibiting a markedly higher affinity. The interactions of PRMs with the SH3 domains affected not only the regions surrounding the PRM binding sites on the SH3 domains but also the linker area connecting the three domains and parts of the SH2 domain. Analysis of the interaction between the phosphorylated EGFR binding site and the SH2 domain revealed chemical shift perturbations in regions distal from the known binding site of SH2. Moreover, we observed that the inter-domain interactions of the two SH3 domains with the SH2 domain of GRB2 are asymmetric. These findings suggest that the local binding of PRMs and phosphorylated EGFR to GRB2 impacts the overall structure of the GRB2 molecule, including domain orientation and dimerisation, which may contribute to LLPS formation., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Short-stranded double-helical monometallofoldamers capable of M / P -switching were constructed by the complexation of two strands, each with two L-shaped units linked by a 2,2'-bipyridine, with a Zn(II) cation. The helix terminals of the "double-helical form" folded by π-π interactions can unfold in solution to equilibrate with the "open forms" that are favored at higher temperatures. Interestingly, the helical chirality of the monometallofoldamers with chiral side chains induced a single-handed helix sense and controlled M / P -switching depending on achiral solvent stimuli. For instance, the ( M )-helicity was favored in nonpolarized solvents (toluene, hexane, Et 2 O), whereas the ( P )-helicity was favored in Lewis basic solvents (acetone, DMSO). Circular dichroism (CD) and rotating-frame overhauser enhancement spectroscopy (ROESY) measurements revealed that the conformational change of the chiral side chains due to interaction of Lewis basic solvents with the double helices induced helicity bias. These novel double-helical monometallofoldamers possessed a stable helical structure and exhibited switchable chiroptical properties ( g abs ∼ 10 -3 -10 -2 ). In addition, the chiral strand exhibited chiral transfer and amplification abilities through the formation of chiral heteroleptic double-helical monometallofoldamers when mixed with an achiral strand.

Background/aim: Adjuvant capecitabine and oxaliplatin (CAPOX) therapy is standard strategy for colorectal cancer with risk of recurrence. Early dose reduction (EDR) of CAPOX therapy is commonly used in real-world practice. However, there is limited evidence regarding the effectiveness of CAPOX for patients who had EDR. Therefore, this study aimed to clarify the risks of EDR and its effect on long-term outcomes and body composition factors., Patients and Methods: Patients who received CAPOX therapy after radical surgery for colorectal cancer between June 2013 and December 2021 were included. EDR was defined as dose reduction within four courses of CAPOX therapy. Body composition factors were measured for 1 year following surgery to determine the EDR effects., Results: Eighty-four patients were included; 35 (42%) of them had EDR. The multivariate analysis revealed that underweight [odds ratio (OR)=4.95, 95% confidence interval (CI)=1.13-21.7, p=0.03] was a risk factor for EDR. Relapse-free survival (RFS) was significantly better in the non-EDR group (p=0.01). The 5-year RFS rates for the non-EDR and EDR groups were 88.7% and 65.4%, respectively. The multivariate analysis revealed that age >65 years [hazard ratio (HR)=3.97; 95% CI=1.16-13.62, p=0.03] and EDR (HR=7.62; 95% CI=1.71-33.91, p=0.005) were associated with poorer RFS. The 1-year body composition analysis revealed decreases in all factors in the EDR group., Conclusion: Preoperative underweight status was associated with EDR, which resulted in decreased RFS and body composition factors when compared with the non-EDR group. Therefore, avoiding EDR and early nutritional intervention after EDR may improve outcomes., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

This population-based study aimed to evaluate the incidence of urinary tract infections following hip and knee arthroplasty (HPRO and KPRO) and identify urinary tract infection risk factors among Polish patients. The analysis included data from 83,525 patients, with incidence rates of 0.7% and 0.49% after HPRO and KPRO, respectively. We identified women, individuals over 65 years old, residents of long-term care facilities, patients with chronic circulatory, endocrine, or digestive diseases, and those operated on due to trauma as targets for infection prevention and control., (Copyright © 2024 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

A 46-year-old female presented persistent right lower abdominal pain for 4 days. Computed tomography revealed an enlarged appendix with a surrounding low-attenuation mass. The patient was diagnosed with appendiceal abscess-forming appendicitis and initially treated with antibiotics. However, owing to the manifestation of nausea as a side effect, laparoscopic appendectomy was performed 3 days after the initial consultation. Intraoperative examination revealed mucinous material on the surface of the appendix and within the abdominal cavity, leading to the decision to perform an appendectomy with partial cecum resection and excision of the omentum with mucinous deposits. Pathological examination confirmed the diagnosis of a perforating low-grade appendiceal mucinous neoplasm and pseudomyxoma peritonei. The patient was subsequently referred to a specialized center for ongoing management, and at 9 months postoperatively, surveillance is being conducted. Low-grade appendiceal mucinous neoplasms can progress to pseudomyxoma peritonei through perforation; however, an optimal treatment approach has not yet been established. In particular, patients in advanced stages of the disease often require challenging management decisions. This case is reported along with a review of the literature to provide further guidance.

Background and Purpose: Ionizing radiation (IR) induces DNA double-strand breaks (DSBs), leading to micronuclei formation, which has emerged as a key mediator of inflammatory responses after IR. This study aimed to investigate the signaling cascade in inflammatory gene expression using fibroblasts harboring DNA damage response deficiency after exposure to IR., Materials and Methods: Micronuclei formation was examined in human dermal fibroblasts derived from patients with deficiencies in ATM, ATR, MRE11, XLF, Artemis, or BRCA2 after IR. RNA-sequencing analysis was performed to assess gene expression, pathway mapping, and the balance of transcriptional activity using the transcription factor-based downstream gene expression mapping (TDEM) method developed in this study., Results: Deficiencies in ATM, ATR, or MRE11 led to increased micronuclei formation after IR compared to normal cells. RNA-seq analysis revealed significant upregulation of inflammatory expression in cells deficient in ATM, ATR, or MRE11 following IR. Pathway mapping analysis identified the upregulation of RIG-I, MDA-5, IRF7, IL6, and interferon stimulated gene expression after IR. These changes were pronounced in cells deficient in ATM, ATR, or MRE11. TDEM analysis suggested the differential activation of STAT1/3-pathway between ATM and ATR deficiency., Conclusion: Enhanced micronuclei formation upon ATM, ATR, or MRE11 deficiency activated the cGAS/STING, RIG-I-MDA-5-IRF7-IL6 pathway, resulting in its downstream interferon stimulated gene expression following exposure to IR. Our study provides comprehensive information regarding the status of inflammation-related gene expression under DSB repair deficiency after IR. The generated dataset may be useful in developing functional biomarkers to accurately identify patients sensitive to radiotherapy., 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.)

Purpose: Recent radiation therapy (RT), such as intensity modulated radiation therapy and particle RT, has improved the concentration of the radiation field targeting tumors. However, severe adverse effects still occur, possibly due to genetic factors in patients. We aimed to investigate the mechanism of exacerbated inflammation during RT., Methods and Materials: Dermal fibroblasts derived from a patient with severe inflammatory adverse effects during RT were compared with 2 normal human dermal fibroblasts. Micronuclei formation, G2/M-checkpoint arrest, DNA damage signaling and repair, and inflammatory gene expression were comprehensively examined., Results: We found greater micronuclei formation in radiation-sensitive fibroblasts (RS-Fs) after ionizing radiation (IR). RS-Fs exhibited premature G2/M-checkpoint release after IR, which triggers micronuclei formation because RS-Fs undergo mitosis with unrepaired DNA double-strand breaks (DSBs). Additionally, we found that DSB end-resection and activation of the ATR-Chk1 pathway were impaired in RS-Fs after IR. Consistent with the increase in the formation of micronuclei, which can deliver cytosolic nucleic acids resulting in an innate immune response, the expression of genes associated with inflammatory responses was highly upregulated in RS-Fs after IR., Conclusions: Although this is a single case of RT-dependent adverse effect, our findings suggest that impaired G2/M-checkpoint arrest due to the lack of DSB end-resection and activation of the ATR-Chk1 pathway causes exacerbated inflammation during RT; therefore, genes involved in G2/M-checkpoint arrest may be a predictive marker for unexpected inflammatory responses in RT., Competing Interests: 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., (© 2024 Published by Elsevier Inc. on behalf of American Society for Radiation Oncology.)

Background: Sarcopenic obesity is associated with gastrointestinal cancer prognosis through systemic inflammation. However, in patients with adenocarcinoma of the esophagogastric junction (AEG), the relationship between the inflammation-based prognostic score (IBPS), muscle loss, visceral fat mass, and prognosis has not been sufficiently evaluated. We investigated the prognostic value of the preoperative IBPS and the visceral fat area ratio to the psoas muscle area (V/P ratio) in patients with AEG undergoing surgery., Methods: We retrospectively analyzed 92 patients with AEG who underwent surgery. The prognostic value of the preoperative neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio, systemic inflammation response index, C-reactive protein-to-albumin ratio, prognostic nutritional index, modified Glasgow Prognostic Score, and V/P ratio at the third lumbar vertebra was investigated using univariate and multivariate survival analyses., Results: Multivariate analysis revealed that a high pathological stage (p = 0.0065), high PLR (p = 0.0421), and low V/P ratio (p = 0.0053) were independent prognostic factors for poor overall survival (OS). When restricted to patients with body mass index (BMI) ≥ 25 kg/m 2 , a high V/P ratio was a poor prognostic factor (p = 0.0463) for OS. Conversely, when restricted to patients with BMI < 25 kg/m 2 , a low V/P ratio was a poor prognostic factor (p = 0.0021) for OS., Conclusions: Both PLR and V/P ratios may be useful prognostic biomarkers in surgical cases of AEG. V/P ratio and BMI may provide an accurate understanding of the muscle and fat mass's precise nature and may help predict AEG prognosis., (© 2023. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Background/aim: Chemotherapy and immunotherapy have been recently developed as potentially useful first-line treatments for unresectable, advanced, or recurrent esophageal cancer. We performed a retrospective study of the therapeutic effectiveness of triplet chemotherapy with docetaxel, nedaplatin, and 5-fluorouracil therapy for advanced, recurrent, and unresectable advanced esophageal cancer at our hospital and compared the regimen's results with those of current and possible future treatment options., Patients and Methods: The study cohort comprised 101 patients who received docetaxel, nedaplatin, and 5-fluorouracil for advanced or recurrent esophageal cancer at Gunma University from May 2008 to December 2017. We retrospectively evaluated the results of this combination chemotherapy and postulated future treatment strategies., Results: The overall response and disease control rates, the latter including stable disease, for docetaxel, nedaplatin, and 5-fluorouracil were 33.6% and 61.4%, respectively. The median overall survival and progression-free survival were 12.26 months and 5.1 months, respectively. In patients with recurrence, the median overall and progression-free survivals were 14.97 months (449 days) and 5.1 months (152 days), respectively. No study patients developed acute kidney injury and there were no treatment-related deaths. However, leukopenia and neutropenia were frequent hematologic toxicities., Conclusion: Treatment with docetaxel, nedaplatin, and 5-fluorouracil for advanced or recurrent esophageal cancer is particularly useful for recurrent cases and has the advantage of not causing severe renal dysfunction., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Intrathoracic esophagogastric anastomosis following minimally invasive Ivor-Lewis esophagectomy is a technically demanding surgical technique that can result in serious intrathoracic infections when anastomotic leakage occurs. Herein, we report a novel side-overlap esophagogastric anastomosis with pleural closure for esophagogastric junction cancer., Methods: The 3 key points of our novel technique were the following: (1) overlap esophagogastric anastomosis and closure of the entry hole were all performed using a linear stapler; (2) the pleura was closed to separate the anastomotic site from the thoracic cavity; and (3) the mediastinal drain was inserted transhiatally from the abdominal cavity., Results: This modified anastomosis procedure was performed on 8 consecutive patients at our institution. The median overall/thoracoscopic operating time and estimated blood loss were 652.5/241.5 min and 89 mL, respectively. No mortality or serious postoperative complications occurred, and the median postoperative hospital stay was 22 days (range, 17 to 37 d)., Conclusion: This novel thoracoscopic overlap esophagogastric reconstruction procedure with pleural closure is safe and feasible., Competing Interests: The author declares no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objectives : The number of residents of long-term care facilities (LTCFs) is expected to increase. Determining the epidemiological situation in the context of organizational conditions is therefore extremely important for planning the necessary future activities in the field of infection prevention. The aim of this study was to analyze the prevalence rates in Polish nursing vs. residential homes, in the context of the medical and functional burdens of residents and the organizational conditions of both types of units. Material and Methods : the data that were analyzed came from a point prevalence survey of infections and antibiotic consumption in LTCFs, conducted in accordance with the HALT-3 protocol in Poland in 2017, between April and June. Results : This study included a total of 2313 residents in 24 LTCFs. The most common risk factors for infections in the study population were urinary and fecal incontinence (77.0%), impaired mobility (the patient was in a wheelchair or lying down) (68.7%), and impaired spatial and temporal orientation (52.5%). The median prevalence in nursing homes (NHs) was 3.2% and that in residential homes (RHs) was 0.7%, but without statistical significance. The median for the entire group was 2.6%. A total of 93 healthcare-related infections were detected in 91 residents. The most frequently reported forms of infections were urinary tract infections, lower respiratory tract infections, and skin infections. A statistically significant positive correlation was found only between the percentage of residents with pressure ulcers and other wounds and the incidence of gastrointestinal infections (correlation coefficient = 0.413, p < 0.05). Infection prevention and control measures were implemented mainly in nursing homes, and in residential homes, only hand hygiene procedures were commonly available. Conclusions : For the two types of LTCFs, the epidemiological situation in terms of nosocomial infections is diverse. Consequently, both types of facilities require different approaches to infection control and prevention and outcomes analysis.

Background/aim: Impact of second-line chemotherapy in unresectable advanced/recurrent gastric/esophagogastric junction cancer (AGC) remains unclear. This retrospective analysis aimed to identify factors affecting prognosis in chemotherapy for patients with AGC, including the importance of progression-free survival in second-line chemotherapy (PFS-2)., Patients and Methods: Data from a total of 109 patients with AGC that received second-line treatment were analyzed with the aim of clarifying prognostic factors. Furthermore, the correlation between PFS-2 and clinical characteristics and the association between PFS-2 and inflammation-based and/or nutritional markers were investigated., Results: Multivariate analysis identified the following prognostic factors: ECOG PS ≥1, presence of peritoneal dissemination, metastasis in two or more organs, and taxane use on second-line chemotherapy. Short PFS-2 was strongly associated with prognosis in the univariate analysis [hazard ratio (HR)=3.107, 95% confidence interval (CI)=1.969-4.904, p<0.001]. The duration of PFS-2 was significantly correlated with ECOG PS (p=0.019), liver metastasis rates (p=0.035) and taxane use on second-line chemotherapy (p=0.001). In addition, weight loss rate during first-line treatment (p=0.042), white blood cell count (p=0.008), C-reactive protein (p=0.032), c-reactive protein to albumin ratio (p=0.039), prognostic index (p=0.028), and modified Glasgow prognostic score (p=0.027) were significantly associated with the duration of PFS-2., Conclusion: The duration of PFS-2 significantly correlated with ECOG PS, liver metastasis, and taxane use on second-line treatment, and strongly affected OS. It was suggested that the presence of malnutrition and inflammation at the start of second-line therapy had a negative impact on PFS-2 and OS., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The glass catfish is a freshwater fish with electroreceptors on its body surface. In this study, we investigated its behavioral response to sinusoidal electrical stimulation with a dipole wider than its body length and the spiking patterns of its electroreceptors. We observed that sinusoidal electric stimulation with a large dipole distance elicited in the glass catfish an avoidance movement whose frequency range is frequency-dependent. The movements were prominent in the frequency range between 10-20 Hz. When the stimulation strength increased, the movements were also found in the low-frequency range. In electrophysiological experiments, periodic interspike intervals of the electroreceptors were modulated by sinusoidal electrical stimuli. The stimulation introduced irregularity in the spiking patterns. The local variability of the spike modulations was significantly higher in the frequency range of 4-40 Hz and was particularly sensitive at 20 Hz. The avoidance movements and an increase in the local variability in the spike patterns were found around 20 Hz. Our results indicate that the glass catfish avoids sinusoidal electrical stimulation in a frequency-dependent manner, and this is associated with local modulations in the spiking patterns of the electroreceptors., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2023. Published by The Company of Biologists Ltd.)

Background/aim: Establishment of powerful and easy-to-evaluate biomarkers that can predict immune checkpoint inhibitor sensitivity in patients with gastric cancer (GC) would be highly useful. The albumin-derived neutrophil-to-lymphocyte ratio (Alb-dNLR) score reportedly is an excellent measure of both immunity and nutritional status. However, the association between nivolumab treatment sensitivity and Alb-dNLR in GC has also not been adequately investigated. This multicenter retrospective study was designed to evaluate the association of Alb-dNLR with therapeutic sensitivity of nivolumab in GC patients., Patients and Methods: This was a retrospective multicenter study with patients from five sites. The data from 58 patients who received nivolumab for postoperative recurrent or unresectable advanced GC between October 2017 and December 2018 were analyzed. Blood tests had been performed before nivolumab administration. We analyzed the correlation between the Alb-dNLR score and clinicopathological factors, including best overall response., Results: Of the 58 patients, 21 (36.2%) comprised the disease control (DC) group and 37 (63.8%) comprised the progressive disease (PD) group. The nivolumab treatment responses were subjected to receiver operating characteristic analysis. The cutoff value was set to 2.90 g/dl for Alb and to 3.55 for dNLR. All eight patients in the high Alb-dNLR group had PD (p=0.0049). The low Alb-dNLR group had significantly better overall survival (p=0.0023) and progression-free survival rates (p<0.0001)., Conclusion: The Alb-dNLR score was a very simple and sensitive predictor of nivolumab therapeutic sensitivity and has very good biomarker properties., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: To discover the positive therapeutic effects of nivolumab in patients with advanced gastric cancer (AGC), it is necessary to establish a useful biomarker to predict therapeutic efficacy. This multicenter retrospective study sought to evaluate the predictive impact of inflammation-based prognostic score (IBPS) on the therapeutic efficacy of nivolumab in patients with AGC., Patients and Methods: In this retrospective study, we evaluated 58 AGC patients treated with nivolumab from October 2017 to November 2018 at five institutes. Patients were categorized follows: progressive disease (PD) or disease control (DC). Blood chemistry tests were performed immediately before and after two courses of nivolumab; the correlation between best overall response and IBPS was investigated. Transition of each blood serum marker was also assessed., Results: Of 58 patients, 37 (63.8%) were in the PD group and 21 (36.2%) in the DC group. No positive correlation was noted between IBPS and therapeutic efficacy of nivolumab both immediately before and after two courses of nivolumab. However, the neutrophil-lymphocyte ratio (NLR) (p=0.045) and prognostic index (PI) (p=0.0042) before nivolumab and NLR (p=0.025), PI (p=0.0030) and Glasgow prognostic score (GPS) (p=0.043) after nivolumab were significantly correlated with treatment sensitivity. Furthermore, a decrease in PNI was an independent prognostic factor to predict nivolumab resistance on univariate analyses (p=0.0051)., Conclusion: Although no association between IBPS and therapeutic sensitivity was found, it is important to focus on the transition of PNI to predict therapeutic efficacy of nivolumab., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Ischemic colitis affects the left colon in elderly individuals and localization on the right side, especially in the cecum, is rare. We report a case of gangrenous ischemic colitis localized in the cecum of a patient undergoing hemodialysis., Case Presentation: A 73-year-old man had been undergoing hemodialysis for chronic renal failure caused by diabetic nephropathy. He experienced frequent vomiting, diarrhea, and abdominal pain. Contrast-enhanced computed tomography revealed thickening of the cecal wall, poor enhancement, dilation of the cecum, and intrahepatic portal emphysema. No obvious abnormal findings were observed in the appendix. The patient was diagnosed with cecal necrosis and ileocecal resection was performed. Histopathological examination revealed gangrenous ischemic colitis of the cecum. He was discharged 12 days after surgery without postoperative complications., Conclusion: It is important to consider the possibility of ischemic colitis of the right colon in the event of renal failure requiring dialysis, to ensure that opportunities for surgical intervention are not missed., (© 2023. The Author(s).)

A focused ion beam (FIB) can precisely mill samples and freely form any nanostructure even on surfaces with curvature, like a nanowire surface, which are difficult to implement by using conventional fabrication techniques, e.g. electron beam lithography. Thus, this tool is promising for nanofabrication; however, fabrication damage and contamination are critical issues, which deteriorate optical properties. In this work, we investigated the protective performance of Al 2 O 3 against the FIB process (especially by a gallium ion). Nanowires were coated with Al 2 O 3 as a hard mask to protect them from damage during FIB nanofabrication. To estimate the protective performance, their emission properties by photoluminescence measurement and time-resolved spectroscopy were compared with and without Al 2 O 3 coating conditions. From the results, we confirmed that the Al 2 O 3 coating protects the nanowires. In addition, the nanowires also showed lasing behavior even after FIB processing had been carried out to implement nanostructures. This indicates that their optical properties are well maintained. Thus, our study proves the usefulness of FIBs for future nanofabrication., (© 2023 IOP Publishing Ltd.)

Introduction: We investigated whether the infiltration of tumor-infiltrating lymphocytes (TILs) in gastric cancer (GC), as evaluated by hematoxylin and eosin (H&E) staining, could be a prognostic marker. We also explored on the relationship between TILs and mechanistic target of rapamycin (mTOR) and how it regulates immune effector responses in GC., Methods: A total of 183 patients with available data on TIL were included. TIL infiltration was evaluated using H&E staining. We also conducted immunohistochemistry to determine mTOR expression., Results: Positive TIL infiltration was defined as TILs ≥20%. There were 72 (39.3%) and 111 (60.7%) positive and negative cases, respectively. TILs positivity significantly correlated with both absence of lymph node metastasis (p = 0.037) and negative p-mTOR expression (p = 0.040). TIL infiltration correlated with a significantly better overall (p = 0.046) and disease-free (p = 0.020) survival., Conclusion: mTOR possibly suppresses TIL infiltration in GC. H&E staining is an effective tool for evaluating the immune status of GC patients. H&E staining may be used in clinical practice to monitor treatment response in GC., (© 2023 S. Karger AG, Basel.)

Background: Patients with critical limb ischemia (CLI) still have a high rate of lower limb amputation, which is associated with not only a decrease in quality of life but also poor life prognosis. Implantation of adipose-derived regenerative cells (ADRCs) has an angiogenic potential for patients with limb ischemia., Objectives: We investigated safety, feasibility, and efficacy of therapeutic angiogenesis by cell transplantation (TACT) of ADRCs for those patients in multicenter clinical trial in Japan., Methods: The TACT-ADRC multicenter trial is a prospective, interventional, open-labeled study. Patients with CLI (Fontaine class III-IV) who have no other option for standard revascularization therapy were enrolled in this study. Thirty-four target ischemic limbs of 29 patients were received freshly isolated autologous ADRCs implantation., Results: The overall survival rate at a post-operative period and at 6 months follow-up was 100% at any time points. As a primary endpoint for efficacy evaluation, 32 limbs out of 34 (94.1%) were free from major amputation for 6 months. Numerical rating scale (from 6 to 1) as QOL score, ulcer size (from 317 mm 2 at to 109 mm 2 ), and 6-min walking distance (from 255 to 369 m) improved in 90.6%, 83.3%, and 72.2% patients, respectively., Conclusions: Implantation of autologous ADRCs could be safe and effective for the achievement of therapeutic angiogenesis in the multicenter settings, as a result in no major adverse event, optimal survival rate, and limb salvage for patients with no-conventional option against critical limb ischemia. TRN: jRCTb040190118; Date: Nov. 24th, 2015., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Platelet activation in the hemodialysis (HD) circuit often causes thrombocytopenia. However, its clinical and pathophysiological significance has rarely been explored. Herein, we investigated the predictive value of thrombocytopenia for cardiovascular events (CVE) in maintenance HD patients and attempted to explore its mechanistic background considering recent knowledge of platelet dynamics. We conducted a retrospective cohort study on HD patients with the composite primary endpoint of predicting CVE, i.e., myocardial infarction, ischemic stroke, and cardiovascular death. Baseline clinical data were analyzed and explored. Multivariate Cox regression analysis showed that platelet decrease was independently associated with CVE. Thrombocytopenia was correlated with the disuse of antiplatelet therapy (APT) and macrocytosis. These findings are possibly associated with platelet activation and senescent hematopoiesis. The prognostic significance of thrombocytopenia was more prominent in patients undergoing APT, implying the presence of APT-resistant platelets in such patients. To fully explain these results, we hypothesized that HD-activated platelets induce the biological aging of hematopoiesis, which is presumably extramedullary in the lung, where activated platelets could deliver massive amounts of inflammatory cytokines and reactive oxidative species. This results in the production of qualitatively altered and hyper-reactive platelets, a process that could form a vicious cycle that induces CVE-associated thrombocytopenia. Further investigations focusing on the dynamics of the biological aging of platelets in HD patients are warranted.

The receptor potentials of taste receptor cells remain unclear. Here, we demonstrate that taste receptor cells generate oscillating depolarization ( n = 7) with action potentials in response to sweet, bitter, umami, and salty taste substances. At a lower concentration of taste substances, taste receptor cells exhibited oscillations in membrane potentials with a low frequency and small magnitude of depolarization. Although the respective waves contained no or 1-2 action potentials, the taste receptor cells generated action potentials continuously in the presence of taste stimuli. Both the frequency and magnitude of oscillations increased when the concentration was increased, to 0.67-1.43 Hz ( n = 3) and Δ39-53 mV ( n = 3) in magnitude from -64.7 ± 4.2 to -18.7 ± 5.9 mV, which may activate the ATP-permeable ion channels. In contrast, a sour tastant (10-mM HCl) induced membrane depolarization (Δ19.4 ± 9.5 mV, n = 4) with action potentials in type III taste receptor cells. Interestingly, NaCl (1 M) taste stimuli induced oscillation ( n = 2) or depolarization (Δ10.5 ± 5.7 mV at the tonic component, n = 9). Our results indicate that the frequency and magnitude of oscillations increased with increasing taste substance concentrations. These parameters may contribute to the expression of taste "thickness.", 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 © 2022 Nakao, Tateno and Ohtubo.)

Introduction: We investigated whether the expression of prospero homeobox protein-1 (PROX1) in gastric cancer (GC) could be a prognostic marker. We also focused on the relationship between PROX1 and LGR5 and Wnt/β-catenin activity in GC., Methods: A total of 196 patients who underwent potentially curative surgery were collected and reviewed retrospectively. Immunohistochemistry was conducted and evaluated the expression PROX1, LGR5, Wnt3a, and β-catenin expression. And we evaluated the relationship between PROX1 expression and clinicopathological features., Results: The PROX1 low-expression group consisted of 105 patients (53.6%) and the high-expression group consisted of 91 patients (46.4%). For LGR5 expression, 76 patients (38.8%) were classified as low-expression, and 120 patients (61.2%) were classified as high-expression. The PROX1 low-expression group was significantly younger (p = 0.0095), had more intestinal type (p = 0.014), and had smaller tumor size (p = 0.013). The PROX1 high-expression group was significantly correlated with high LGR5 expression (p < 0.0001) and high Wnt3a expression (p = 0.012). In addition, there were significantly more cases of postoperative recurrence in the PROX1 high-expression group (p = 0.013)., Conclusion: Our findings demonstrate that PROX1 correlated with the cancer stemness markers LGR5 and Wnt3a signaling in GC and had a poor prognosis including postoperative recurrence., (© 2022 S. Karger AG, Basel.)

Rationale: With Duchenne muscular dystrophy (DMD) being the most common and most severe type of muscular dystrophy, DMD patients are at risk for complications from general anesthesia due to impaired cardiac and respiratory functions as the pathological condition progresses. In recent years, advances in multidisciplinary treatment have improved the prognosis of DMD patients, and the number of patients requiring surgery has increased. Remimazolam is a benzodiazepine derivative similar to midazolam. Its circulatory stability and the fact that it has an antagonist make it superior to propofol.There are no reports of pediatric patients with DMD undergoing total intravenous anesthesia with remimazolam., Patient Concerns: A 4-year boy was scheduled for single-incision laparoscopic percutaneous extraperitoneal closure for inguinal hernia under general anesthesia, but the surgery was postponed because his serum creatine phosphokinase level was extremely high., Diagnosis: He was diagnosed with DMD. According to the results of the genetic test, exon deletion of the DMD gene was detected using multiplex ligation-dependent probe amplification, although he had no symptoms of DMD except for elevated serum levels of creatine phosphokinase, etc., Intervention: He was admitted for the same surgical purpose. Anesthesia was induced with 3 mg of intravenously administered remimazolam. He lost the ability to respond to verbal commands. After the intravenous administration of 100 μg of fentanyl, a continuous infusion of remifentanil (1.0 μg/kg/min) and remimazolam (15 mg/h) was started, and the endotracheal tube was inserted smoothly after the administration of 10 mg of rocuronium with which the muscle twitches disappeared in train-of-four monitoring. At the end of the surgery, 15 mg of flurbiprofen was administered intravenously. After surgery, we injected 40 mg of sugammadex to confirm a train-of-four count of 100%., Outcomes: Although the dose of remimazolam was reduced to 5 mg/h 30 minutes before the end of the surgery, it took 20 minutes after the discontinuation of remimazolam for the patient to open his eyes upon verbal command. On postoperative Day 2, he was discharged from the hospital without any complications., Lessons: Remimazolam was shown to be safe to use for general anesthesia in a pediatric patient with DMD., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Although a significant association between periodontal disease and atherosclerotic cardiovascular disease has been reported, their cause-to-effect relationship remains controversial. This randomized controlled clinical trial aimed to investigate the effect of advanced self-care on atherosclerotic cardiovascular disease-related vascular function markers flow-mediated brachial artery dilatation (FMD) and serum asymmetric dimethylarginine (ADMA) level in patients with early-stage periodontal disease. The study was designed as a parallel group, 3-month follow-up, open-label, randomized controlled trial. The control group received standard care for periodontal diseases, whereas the test group additionally applied disinfectant using a custom-fabricated prescription tray for advanced self-care twice a day. Overall, 110 patients provided data for FMD and serum ADMA level. No significant improvements in FMD were observed in the control (mean increase, -0.1%; 95% confidence interval [CI], -1.0-0.8; P = 0.805) or test (mean increase, -0.3%; 95% CI, -1.1-0.4; P = 0.398) group. No significant changes in serum ADMA levels were observed (mean reduction, 0.01 μmol/L; 95% CI, -0.00-0.02; P = 0.366 and mean reduction, 0.00 μmol/L; 95% CI, -0.01-0.01; P = 0.349, respectively). No significant between-group differences were found in FMD (mean difference, -0.2%; 95% CI, -1.4-0.9; p = 0.708) or serum ADMA levels (mean difference, 0.01 nmol/L; 95% CI, -0.00-0.03; p = 0.122). Significant improvements in the average probing pocket depth were observed in the control and test groups. The bleeding on probing score in the test group was significantly reduced, while that in the control group was reduced, although not significantly. Periodontal care for a 3-month duration did not provide better endothelial function although improvements of periodontal status in patients with early-stage periodontal diseases. This trial is registered in UMIN Clinical Trials Registry (www.umin.ac.jp/ctr/; ID: UMIN000023395)., Competing Interests: Dr. Khairul Matin and Dr. Nobuhiro Hanada received a research grant from Medoc International Co. Ltd. Dr. Nobuhiro Hanada received a research grant from Shiken Corp. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no other competing interests to declare. Medoc International Co. Ltd.: http://www.medoc.co.jp/company Shiken Corp.: https://www.shiken-jp.com.

For the construction of helical foldamers composed of π-frameworks, the choice of appropriate π-π stacking units and π-spacers connecting them is important. The transfer of helicity between the minimal helix structural units is also an essential factor in the construction of homochiral helical foldamers. Tetramers 4 a-4 d, which have four L-shaped dibenzopyrrolo[1,2-a]naphthyridine units, were synthesized to investigate the interplay and cooperativity of the helical structures. Tetramer 4 a bridged with a biphenyl unit formed a homochiral bishelical structure with π-π stacking between the L-shaped units (3.3 Å), consisting only of (P,P)- and (M,M)-enantiomers without the (P,M)-diastereomer, owing to interplay through the axial chirality of biphenyl unit in the solid state. Similarly, in solution, thermodynamic stabilization of the two helix formations worked cooperatively to favor the bishelical form of 4 a. Furthermore, bishelical foldamer 4 a emitted intense fluorescence (Φ=0.86)., (© 2021 Wiley-VCH GmbH.)

We present a case of colorectal cancer with temporomandibular joint dysfunction and discuss the management of the case. Type IIIb temporomandibular disorder involves anterior dislocation of the articular disk, trismus and difficult intubation. A 68-year-old woman was scheduled for colectomy. The day before surgery, the patient had temporomandibular pain. On examination, the mouth opening was 13 mm. We diagnosed type IIIb temporomandibular disorder. A simple splint was fabricated with gauze and she bit it. The mouth opening was 55 mm on the day of surgery. The pain disappeared, and intubation was uneventful. Temporomandibular disorders are generally treated by dentists. It is beneficial for general hospitals without a dentistry department to employ a dental anaesthesiologist to assist in potentially difficult intubations in patients with temporomandibular disorders., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Retroperitoneal leiomyoma is a very rare disease, with little reported information on its origin. Herein, we report a case of a large retroperitoneal leiomyoma that developed from the pelvic floor. A 44-year-old woman had a large mass protruding outside the body from the right hip. Imaging revealed a large tumor developing from the pelvic floor to the buttocks. It was difficult to identify the place of origin. Upon preoperative biopsy, the patient was diagnosed with retroperitoneal leiomyoma. Tumor removal with abdominoperineal and partial vaginal resection was performed. Based on the histological findings of the surgical specimens, she was diagnosed with a retroperitoneal leiomyoma (gynecologic type) via immunohistochemistry, the tumor cells were positive for αSMA, desmin, estrogen receptor(ER), and progesterone receptor(PgR), but negative for myoglobin, S-100, CD34, and MIB-1.This is a case of a large retroperitoneal leiomyoma that was successfully removed via abdominoperineal and partial vaginal resection., (© 2021. Japanese Society of Gastroenterology.)

Introduction: WHO core components of healthcare-associated infections (HAIs) prevention and control include their surveillance system. In Poland, there are no widespread multi-center infection surveillance networks based on continuous, targeted, active methodology. One of the most important form of HAIs are surgical site infections (SSIs). The aim of this study was to analyze the incidence of SSIs, in the context of seasonal differentiation. Seasonal differentiation could be connected with weather conditions, but it also can be affected by personnel absence due to holidays and furlough. The second aspect may influence organization of work and increased absenteeism may contribute to lowering the quality of patient care. Healthcare associated infections are the phenomenon which can be especially affected by such factors., Methods: The data used originate from the targeted, active surveillance reports obtained from the six years period, based on the ECDC recommendations., Results: Highest incidence rates of SSIs were found after operations performed in June and August, equal to 1.8% and 1.5% respectively and the lowest in October was 0.8%. These differences were statistically significant: for June incidence: OR 1.6, 95% CI 1.03-2.5, p = 0.015. Another approach showed a significant difference between the level of incidence in the period from November to January together with from June to August (1.35%), comparing to the rest of the year (1.05%). Also the rates of enterococcal and Enterobacterales infections were significantly higher for the period comprising months from November till January and from June to August. In Poland these are periods of increased number of absences associated with summer, national and religious holidays., Conclusions: Our results show that the short-term surveillance data limited to several days or months are not sufficient to obtain a valuable description of the epidemiological situation due to HAI. Efforts should be undertaken in order to implement wide net of hospital acquired infections, including SSI on the country level.

It is very difficult to treat patients with liver metastasis presenting with jaundice or cachexia. We herein report a successfully treated case of huge liver metastasis of gastrointestinal stromal tumor (GIST) that initially showed jaundice and cachexia. The patient was a woman in her early 40 s. She had a history of duodenal GIST 4 years before this admission. She was admitted to our hospital for abdominal fullness and anorexia. Abdominal computed tomography revealed huge liver metastasis of GIST. She showed jaundice and cancer cachexia with a modified Glasgow Prognostic Score of 2. After applying nutritional support, 400 mg of imatinib was administered. Although leg edema transiently worsened, the withdrawal of imatinib and administration of diuretics improved it. Imatinib was re-administered, and nutritional support was continued. The total bilirubin level decreased, and the serum albumin level increased. The tumor gradually decreased in size. Finally, she received surgical resection after 16 months of treatment with imatinib. Although adjuvant imatinib administration was continued after surgery, and no recurrence was observed as of 18 months after surgery.

Preeclampsia is a pregnancy-induced disorder that is characterized by hypertension and is a leading cause of perinatal and maternal-fetal morbidity and mortality. HLA-G is thought to play important roles in maternal-fetal immune tolerance, and the associations between HLA-G gene polymorphisms and the onset of pregnancy-related diseases have been explored extensively. Because contiguous genomic sequencing is difficult, the association between the HLA-G genotype and preeclampsia onset is controversial. In this study, genomic sequences of the HLA-G region (5.2 kb) from 31 pairs of mother-offspring genomic DNA samples (18 pairs from normal pregnancies/births and 13 from preeclampsia births) were obtained by single-molecule real-time sequencing using the PacBio RS II platform. The HLA-G alleles identified in our cohort matched seven known HLA-G alleles, but we also identified two new HLA-G alleles at the fourth-field resolution and compared them with nucleotide sequences from a public database that consisted of coding sequences that cover the 3.1-kb HLA-G gene span. Intriguingly, a potential association between preeclampsia onset and the poly T stretch within the downstream region of the HLA-G*01:01:01:01 allele was found. Our study suggests that long-read sequencing of HLA-G will provide clues for characterizing HLA-G variants that are involved in the pathophysiology of preeclampsia.

Helical structures were constructed by using π-spacer-bridged dimers of dibenzopyrrolo[1,2-a][1,8]naphthyridine, which has a highly fluorescent L-shaped π-extended skeleton. Three dimers with biphenylene (dimer 1), phenanthrene (dimer 2), and m-phenylene (dimer 3) spacers, as well as a fixed-helical dimer 4 where two quinolone rings were covalently cross-linked, were designed and prepared. 1 H NMR and ROESY spectra revealed that dimers 1 and 2 adopted helical forms in solution, whereas dimer 3 did not. The helical conformation of 1 was strengthened by addition of either polar or nonpolar solvents to the chloroform solution, which suggested that π-π stacking was the main contributor to the stabilization of the helical structure. All of the dimers, including fixed-helical dimer 4, emitted fluorescence with high quantum yields (ϕ=0.79-0.86)., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Random pulses contribute to stochastic resonance in neuron models, whereas common random pulses cause stochastic-synchronized excitation in uncoupled neuron models. We studied concurrent phenomena contributing to phase synchronization and stochastic resonance following induction by a weak common random pulse in uncoupled non-identical Hodgkin-Huxley type neuron models. The common random pulse was selected from a gamma distribution and the degree of synchronization depended on the corresponding shape parameter. Specifically, a low shape parameter of the weak random pulse induced well-synchronized spiking in uncoupled neuron models, whereas a high shape parameter of the weak random pulse or a weak periodic pulse caused low degrees of synchronization. These were improved by concurrent inputs of periodic and random pulses with high shape parameters. Finally, the output pulse was synchronized with the periodic pulse, and the common random pulse revealed periodic responses in the present neuron models.