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Abstract Rectal neuroendocrine carcinoma is rare with poor prognosis. We report herein a case of advanced moderately differentiated neuroendocrine carcinoma of the rectum with relatively favorable prognosis treated by postoperative adjuvant chemoradiation therapy. A 58-year-old Japanese female was referred and colonofiberscopy revealed an easy-bleeding irregular tumor in the lower rectum, which was pathologically diagnosed as a neuroendocrine carcinoma. Surgical treatment consisted of abdominoperineal resection and lymph node dissection. The tumor invaded deeply into perirectal tissues, and 9 of 11 lymph node metastases were observed. Immunohistochemically, chromogranin A showed diffuse and strong staining, and the MIB-1 labeling index was 18.3 ± 5.6, supporting the high proliferation of the tumor. Some nucleus of the tumor showed positive staining for p21/WAF1. A total dose of 46 Gy of radiotherapy was delivered with 800 mg of daily oral doxifluridine. At 5 years post-surgery, the patient demonstrated no clinical evidence of intrapelvic recurrence or distant metastases.

Abstract Many meiosis-specific proteins in Schizosaccharomyces pombe contain coiled-coil motifs which play essential roles for meiotic progression. For example, the coiled-coil motifs present in Meu13 and Mcp7 are required for their function as a putative recombinase cofactor complex during meiotic recombination. Mcp6/Hrs1 and Mcp5/Num1 control horsetail chromosome movement by astral microtubule organization and anchoring dynein respectively. Dhc1 and Ssm4 are also required for horsetail chromosome movement. It is clear from these examples that the coiled-coil motif in these proteins plays an important role during the progression of cells through meiosis. However, there are still many unanswered questions on how these proteins operate. In this paper, we briefly review recent studies on the meiotic coiled-coil proteins in Sz. pombe.

The study aimed to determine the acute effects of subtetanic neuromuscular electrical stimulation (NMES) combined with active recovery between sprint exercises on blood lactate accumulation, sprint performance, and muscle fatigue. Sixteen healthy young individuals [23(4) years, 10 males] underwent a 1-min rest followed by sprint interval training consisting of four 15-sec maximal sprint exercises with three 5-min active cycling sessions. Participants engaged in voluntary cycling at 40% of peak oxygen consumption, with or without NMES (VOLES or VOL; interventions). Blood lactate concentration ([La] b ) was assessed at the end of the rest and each intervention periods. Mean power was assessed during each sprint exercise session. Maximum voluntary contraction (MVC) of the knee extensor was measured before and after sprint interval training to evaluate muscle fatigue. The [La] b was significantly higher in VOLES than in VOL (main effect, P=0.037). Mean power did not differ between conditions (main effect and interaction, P>0.050). MVC after sprint interval exercise was significantly lower in VOLES than in VOL (interaction, P<0.001). Subtetanic NMES combined with voluntary cycling enhanced blood lactate accumulation and induced greater voluntary fatigue but resulted in similar peripheral muscle fatigue and sprint exercise performance compared with voluntary cycling without NMES., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

X-ray therapy aims to eliminate tumours while minimizing side effects. Intense mucositis is sometimes induced when irradiating the oral cavity with a dental metal crown (DMC). However, the underlying mechanisms of such inducing radiosensitization by DMC remain uncertain. This study explored the radiosensitizing mechanisms around DMCs in an interdisciplinary approach with cell experiments and Monte Carlo simulation with the PHITS code. Clonogenic survival and nuclear 53BP1 foci of a cell line derived from cervical cancer cells (HeLa cells) were measured post-irradiation with therapeutic X-rays near high-Z materials such as Pb or Au plates, and the experimental sensitizer enhancement ratio (SER) was obtained. Meanwhile, the dose enhancement ratio (DER) and relative biological effectiveness for DNA damage yields were calculated using the PHITS code, by considering the corresponding experimental condition. The experiments show the experimental SER values for cell survival and 53BP1 foci near metals are 1.2-1.4, which agrees well with the calculated DER values. These suggest that the radiosensitizing effects near metal are predominantly attributed to the dose increase. In addition, as a preclinical evaluation, the spatial distributions of DER near DMC are calculated using Computed Tomography Digital Imaging and Communications in Medicine (CT-DICOM) data and a simple tooth model. As a result, the DER values evaluated using the CT-DICOM data were lower than those from a simple tooth model. These findings highlight the challenge of evaluating radiosensitizing effects near DMCs using Digital Imaging and Communications in Medicine (DICOM) images due to volume-averaging effects and emphasize the need for a high-resolution (<1 mm) dose assessment method unaffected by these effects., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Objective : The diagnostic efficacy of the apparent diffusion coefficient (ADC) in diffusion-weighted magnetic resonance imaging (DW-MRI) for lymph node metastasis in biliary tract cancer was investigated in the present study. Methods : In total, 112 surgically resected lymph nodes from 35 biliary tract cancer patients were examined in this study. The mean and minimum ADC values of the lymph nodes as well as the long-axis and short-axis diameters of the lymph nodes were assessed by computed tomography (CT). The relationship between these parameters and the presence of histological lymph node metastasis was evaluated. Results : Histological lymph node metastasis was detected in 31 (27.7%) out of 112 lymph nodes. Metastatic lymph nodes had a significantly larger short-axis diameter compared with non-metastatic lymph nodes ( p = 0.002), but the long-axis diameter was not significantly different between metastatic and non-metastatic lymph nodes. The mean and minimum ADC values for metastatic lymph nodes were significantly reduced compared with those for non-metastatic lymph nodes ( p < 0.001 for both). However, the minimum ADC value showed the highest accuracy for the diagnosis of histological lymph node metastasis, with an area under the curve of 0.877, sensitivity of 87.1%, specificity of 82.7%, and accuracy of 83.9%. Conclusions : The minimum ADC value in DW-MRI is highly effective for the diagnosis of lymph node metastasis in biliary tract cancer. Accurate preoperative diagnosis of lymph node metastasis in biliary tract cancer should enable the establishment of more appropriate treatment strategies.

The intrinsic radiosensitivity index (RSI) and genomic-adjusted radiation dose (GARD) were reported to be able to predict the surviving fraction at 2 Gy and therapeutic effect when delivering actual treatment doses using the gene expression profiles of clinical cases. Given the impact of p16 status, a surrogate marker of the human papillomavirus (HPV) infection, on radiosensitivity, we attempted to apply the RSI and GARD to estimate p16-associated radiosensitivity in head and neck squamous cell carcinoma (HNSC). For this purpose, The Cancer Genome Atlas (TCGA) dataset was employed. In the GARD calculation, we assumed that p16-positive patients received 60 Gy in 30 fractions, while p16-negative patients received 70 Gy in 35 fractions. p16 positivity was associated with favorable characteristics compared to negative patients. The RSI and GARD analyses demonstrated increased radiosensitivity and high therapeutic effect in p16-positive patients, compared to p16-negative patients. Additionally, tumor microenvironmental conditions predicted by other models were also significantly affected by p16 status. Collectively, the models used in this study could be a promising tool for estimating p16-associated radiosensitivity in HNSC., (© 2024 by Radiation Research Society. All rights of reproduction in any form reserved.)

A scoring system to discriminate between uncomplicated and complicated appendicitis is beneficial to determine the optimal treatment for acute appendicitis. We developed a scoring system to discriminate between uncomplicated and complicated appendicitis and assessed the clinical usefulness of the scoring system using external validation. A total of 299 patients with acute appendicitis were retrospectively reviewed. One hundred and ninety-nine patients were assigned to the model development group, while the other 100 patients were assigned to an external validation group. A scoring system for complicated appendicitis was created using a final multivariate logistic regression model with six independent predictors. The area under the receiver operating characteristic curve of the scoring system was 0.882 (95% confidence interval: 0.835-0.929). The cutoff point of the scoring system was 12, and the sensitivity and specificity were 82.9% and 86.2%, respectively. In the external validation group, the area under the receiver operating characteristic curve of the scoring system was 0.868 (95% confidence interval 0.794-0.942), and there was no significant difference between the groups in the area under the receiver operating characteristic curve (P = 0.750). Our newly developed scoring system may contribute to prompt determination of the optimal treatment for acute appendicitis., (© 2024. The Author(s).)

The aim of this study was to determine the effects of subtetanic neuromuscular electrical stimulation combined with voluntary exercise between repeated Wingate tests on sprint exercise performance and blood lactate accumulation during sprint interval training. Fifteen healthy young males volunteered. After 1-min baseline, participants underwent the Wingate test twice. They performed a 4-min intervention between tests: neuromuscular electrical stimulation with free-weight cycling or voluntary cycling alone [43.6 (8.0) watts], which matched oxygen consumption with neuromuscular electrical stimulation with free-weight cycling. The blood lactate concentration was assessed at the end of the baseline, at 3-min intervention, and on recovery at 1, 3, 5, and 10 min after the second Wingate test. Peak and mean blood lactate concentration during recovery were significantly greater with neuromuscular electrical stimulation with free-weight cycling than voluntary cycling alone (P>0.036 and P=0.011, respectively). Peak power, mean power, and rate of decline (fatigue index) were not significantly different between conditions in both Wingate tests (condition/interaction all P>0.300, partial η 2 <0.1). Subtetanic neuromuscular electrical stimulation combined with voluntary exercise indicated similar exercise performance and fatigue levels during Wingate tests, but enhanced blood lactate accumulation compared to oxygen consumption-matched voluntary cycling during sprint interval training., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Diffusing alpha-emitters radiation therapy (Alpha-DaRT) is a unique method, in which interstitial sources carrying 224 Ra release a chain of short-lived daughter atoms from their surface. Although DNA damage response (DDR) is crucial to inducing cell death after irradiation, how the DDR occurs during Alpha-DaRT treatment has not yet been explored. In this study, we temporo-spatially characterized DDR such as kinetics of DNA double-strand breaks (DSBs) and cell cycle, in two-dimensional (2D) culture conditions qualitatively mimicking Alpha-DaRT treatments, by employing HeLa cells expressing the Fucci cell cycle-visualizing system. The distribution of the alpha-particle pits detected by a plastic nuclear track detector, CR-39, strongly correlated with γH2AX staining, a marker of DSBs, around the 224 Ra source, but the area of G2 arrested cells was more widely spread 24 h from the start of the exposure. Thereafter, close time-lapse observation revealed varying cell cycle kinetics, depending on the distance from the source. A medium containing daughter nuclides prepared from 224 Ra sources allowed us to estimate the radiation dose after 24 h of exposure, and determine surviving fractions. The present experimental model revealed for the first time temporo-spatial information of DDR occurring around the source in its early stages., (© 2024. The Author(s).)

Objective: To determine whether Aquacel Ag Hydrofiber dressings containing ionic silver are superior to film dressings for preventing superficial surgical site infections (SSI) in patients undergoing elective gastrointestinal surgery., Background: Multiple clinical trials have assessed the effectiveness of silver-containing wound dressings; however, systematic reviews failed to find any advantages of these dressings and concluded that there was insufficient evidence to indicate that they prevented wound infections. This study aimed to evaluate the efficacy of Aquacel Ag Hydrofiber dressings for preventing superficial SSIs in patients undergoing gastrointestinal surgery., Methods: Patients undergoing elective gastrointestinal surgery were randomly assigned to receive either Aquacel Ag Hydrofiber (study group) or film dressings (control group). The primary end point was superficial SSI within 30 days after surgery (UMIN Clinical Trials Registry ID: 000043081)., Results: A total of 865 patients (427 study group, 438 control group) were qualified for primary end-point analysis. The overall rate of superficial SSIs was significantly lower in the study group than in the control group (6.8% vs 11.4%, P = 0.019). There was no significant difference in superficial SSI rates between the groups in patients undergoing upper gastrointestinal surgery; however, the rate was significantly lower in the study group in patients undergoing lower gastrointestinal surgery ( P = 0.042). Multivariate analysis identified Aquacel Ag Hydrofiber dressings as an independent factor for reducing superficial SSIs (odds ratio, 0.602; 95% confidence interval, 0.367-0.986; P = 0.044)., Conclusions: Aquacel Ag Hydrofiber dressings can reduce superficial SSIs compared to film dressings in patients undergoing elective gastrointestinal surgery, especially lower gastrointestinal surgery., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

The sphingolipid metabolic pathway, an important signaling pathway, plays a crucial role in various physiological processes including cell proliferation, survival, apoptosis, and immune regulation. The liver has the unique ability to regenerate using bioactive lipid mediators involving multiple sphingolipids, including ceramide and sphingosine 1-phosphate (S1P). Dysregulation of the balance between sphingomyelin, ceramide, and S1P has been implicated in the regulation of liver regeneration and diseases, including liver fibrosis and hepatocellular carcinoma (HCC). Understanding and modulating this balance may have therapeutic implications for tumor proliferation, progression, and metastasis in HCC. For cancer therapy, several inhibitors and activators of sphingolipid signaling, including ABC294640, SKI-II, and FTY720, have been discussed. Here, we elucidate the critical roles of the sphingolipid pathway in the regulation of liver regeneration, fibrosis, and HCC. Regulation of sphingolipids and their corresponding enzymes may considerably influence new insights into therapies for various liver disorders and diseases.

Background: Watch and wait(W & W)for rectal cancer after chemoradiotherapy(CRT)is attracting attention., Purpose: To examine regimens and indications from the results of follow-up of cases undergoing W & W in our department., Materials and Methods: CRT(SOX therapy 2-5 cycles, 45 Gy)was performed on patients with lower rectal cancer over a period of 2016 to 2020, and 7 patients with clinical complete response(cCR)were followed up., Results: With a median follow-up of 33 months(10-74), 4 of 7 patients(57.1%)remained in cCR. Two patients had local relapse more than a year after the start of treatment, were able to undergo salvage surgery, and are alive after surgery. Patients with lateral lymph node metastasis before CRT had para-aortic lymph node metastasis at 8 months., Conclusions: Patients with maintained cCR were those with localized, node-negative disease. On the other hand, in patients with lymph node metastasis, including lateral metastasis, it was not possible to perform salvage surgery due to distant metastasis. Careful case selection and follow-up are necessary in the future.

A 38-year-old woman was admitted to our hospital due to severe anemia. CT showed a 13×12 cm tumor with moderately enhanced wall thickening in the right upper abdomen. The huge tumor located adjacent to the jejunum and compressed the right transverse colon. Hemorrhagic necrosis and air were observed within the tumor, suspecting tumor penetration into the jejunum. The patient was diagnosed with abdominal GIST with jejunal infiltration. Laparotomy revealed a 13× 11 cm solid mass with intra-tumoral hemorrhage and invasion into the jejunum, located in the transverse mesocolon. Tumor resection combined with partial jejunectomy and transverse colectomy were performed. Immunohistochemical findings of the resected specimen was positive for c-kit and DOG-1, and the MIB-1 positive rate was 10%. Three weeks after the operation, re-anastomosis was performed due to transverse colon anastomotic stricture. She was discharged 45 days after first operation. Currently, 9 months after the operation, patient has been prescribed imatinib and is alive without recurrence.

Purpose: Concentration- and time-dependent effect of lactate on physiological adaptation (i.e., glycolytic adaptation and mitochondrial biogenesis) have been reported. Subtetanic neuromuscular electrical stimulation (NMES) with voluntary exercise (VOLES) can increase blood lactate accumulation. However, whether this is also true that VOLES can enhance the blood lactate accumulation during sprint exercise is unknown. Thus, we investigated whether VOLES before the Wingate test can enhance blood lactate accumulation without compromising Wingate exercise performance., Methods: Fifteen healthy young males (mean [SD], age: 23 [4] years, body mass index: 22.0 [2.1] kg/m 2 ) volunteered. After resting measurement, participants performed a 3-min intervention: VOLES (NMES with free-weight cycling) or voluntary cycling alone, which matched exercise intensity with VOLES (VOL, 43.6 [8.0] watt). Then, they performed the Wingate test with 30 min free-weight cycling recovery. The blood lactate concentration ([La] b ) was assessed at the end of resting and intervention, and recovery at 1, 3, 5, 10, 20, and 30 min., Results: [La] b during intervention was higher with VOLES than VOL (P = 0.011). The increase in [La] b after the Wingate test was maintained for longer with VOLES than VOL at 10- and 20-min recovery (P = 0.014 and 0.023, respectively). Based on the Wingate test, peak power, mean power, and the rate of decline were not significantly different between VOLES and VOL (P = 0.184, 0.201, and 0.483, respectively)., Conclusion: The combination of subtetanic NMES with voluntary exercise before the Wingate test has the potential to enhance blood lactate accumulation. Importantly, this combined approach does not compromise Wingate exercise performance compared to voluntary exercise alone., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Ampullary adenomas are premalignant lesions. However, biliary obstruction causing jaundice is rare. Duodenal intussusception secondary to an ampullary adenoma rarely occurs because of the fixed position of the duodenum in the retroperitoneum. Herein, we have described a rare case of ampullary adenoma with jaundice caused by duodenal intussusception., Case Presentation: A 40-year-old woman presenting with vomiting and yellowish discoloration of the skin was admitted to another hospital. The patient had experienced recurrent epigastric pain and vomiting for the past 18 months. Blood test results showed elevated levels of bilirubin (3.9 mg/dL), and abdominal computed tomography (CT) showed a 60-mm hypovascular mass in the third part of the duodenum and a left lateral shift of the dilated common bile duct. The patient was referred to our hospital for further evaluation. She recovered from hyperbilirubinemia spontaneously (levels of bilirubin, 1.0 mg/dL), and the CT showed a tumor shift from the third part of the duodenum to the second part and improvement of the dilated common bile duct. Hypotonic duodenography revealed a tumor that moved easily from the second to the third portion of the patient's position. Upper gastrointestinal endoscopy revealed a large papillary tumor occupying the second part of the duodenum, which was diagnosed as an adenoma through biopsy. The possibility of malignancy could not be negated owing to the presence of jaundice and an elevated carbohydrate antigen 19-9 level (76.0 U/mL). Pancreaticoduodenectomy was performed. The resected specimen showed a 60 × 40 × 40-mm pedunculated ampullary mass with submucosal elongation. The pathological examination indicated that the ampullary tumor was a high-grade intestinal adenoma. The postoperative course was uneventful, and the patient was discharged 26 days postoperatively., Conclusions: This report describes a rare case of a patient with an ampullary adenoma presenting with jaundice resulting from duodenal intussusception. Owing to the possibility of a postoperative cancer diagnosis which may have caused the biliary obstruction and the difficulty in making an accurate preoperative diagnosis, it is imperative to choose the appropriate surgical procedure such as a pancreaticoduodenectomy., (© 2024. The Author(s).)

Background: Although Lumipulse assays and conventional ELISA are strongly correlated, the precise relationship between their measured values remains undetermined., Objective: To determine the relationship between Lumipulse and ELISA measurement values., Methods: Patients who underwent cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarker measurements and consented to biobanking between December 2021 and June 2023 were included. The relationship between values measured via Lumipulse assays and conventional ELISA were evaluated by Passing-Bablok analyses for amyloid-β 1-42 (Aβ42), total tau (t-tau), and phospho-tau 181 (p-tau 181). Studies using both assays were systematically searched for in PubMed and summarized after quality assessment., Results: Regression line slopes and intercepts were 1.41 (1.23 to 1.60) and -77.8 (-198.4 to 44.5) for Aβ42, 0.94 (0.88 to 1.01) and 98.2 (76.9 to 114.4) for t-tau, and 1.60 (1.43 to 1.75) and -21.1 (-26.9 to -15.6) for p-tau181. Spearman's correlation coefficients were 0.90, 0.95, and 0.95 for Aβ42, t-tau, and p-tau181, respectively. We identified 13 other studies that included 2,117 patients in total. Aβ42 slope varied among studies, suggesting inter-lab difference of ELISA. The slope and intercept of t-tau were approximately 1 and 0, respectively, suggesting small proportional and systematic differences. Conversely, the p-tau181 slope was significantly higher than 1, distributed between 1.5-2 in most studies, with intercepts significantly lower than 0, suggesting proportional and systematic differences., Conclusions: We characterized different relationship between measurement values for each biomarker, which may be useful for understanding the differences in CSF biomarker measurement values on different platforms and for future global harmonization.

Background: Although subtetanic neuromuscular electrical stimulation (NMES) has been proposed as an exercise training and/or rehabilitation tool, the impact of NMES on the autonomic nervous system (ANS) is unclear. Thus, we hypothesized that NMES would alter ANS, i.e., increase sympathetic activity and decrease parasympathetic activity, in young individuals., Methods: Eighteen healthy young individuals (16 males, mean age: 22 [SD: 4] years, Body Mass Index: 21.7 [2.2] kg/m 2 ) volunteered. Blood pressure (BP), heart rate (HR), and R-R intervals were recorded during 6-minute resting, NMES, and recovery conditions. Short-term heart rate variability analysis of R-R intervals was performed for the frequency and time domains during each condition. Time domain indices included the root mean square of successive R-R interval differences (RMSSD), and the percentage of successive R-R intervals differing by more than 50ms (pRR50%). Frequency domain indices (fast Fourier transform) of R-R intervals included total power (TP), low-frequency (LF) power (0.04-0.15 Hz), and high-frequency (HF) power (0.15-0.4 Hz)., Results: BP was not altered but HR was significantly increased during NMES (P<0.001), and it returned to the resting level at recovery. RMSSD and pRR50 decreased from resting to NMES and returned at recovery conditions (P<0.05, respectively). TP and HF decreased from resting to NMES and returned at recovery conditions (P<0.05, respectively). LF increased from NMES to recovery (P<0.05). The LF/HF ratio showed no significant differences between conditions (P=0.210)., Conclusions: Cardiac ANS fluctuated by subtetanic NMES without BP elevation in healthy young individuals. Parasympathetic but not sympathetic activity was affected by NMES stimulation.