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To establish a new rat model of craniofacial myalgia, and to clarify which central nervous system pathways are activated in the model.Craniofacial myalgia, represented by myogenous temporomandibular disorder and tension-type headache with pericranial tenderness, is more common in female patients. The pain is thought to be a type of multifactorial disorder with several coexisting causes. To our knowledge, there are no models of craniofacial muscle hyperalgesia caused by multiple types of stimuli.We injected nerve growth factor into the trapezius muscle of female and male rats and repeatedly stimulated the masseter muscle (MM) electrically for 10 days. We determined the mechanical head-withdrawal threshold of MM and extent of phosphorylated extracellular signal-related kinase 1/2 (pERK) immunoreactivity in various regions of the lower brainstem. We conducted retrograde tract-tracing to determine the projection of mechanosensitive MM-innervating secondary neurons to the lateral parabrachial nucleus. Finally, we administered morphine in rats to determine whether increases of pERK immunoreactivity were dependent on noxious inputs.In female rats, but not male rats, the mechanical head-withdrawal threshold was decreased significantly from days 9 to 12. The number of pERK-immunoreactive neurons in the brainstem was increased significantly in female rats in the group with both stimuli compared to rats in other groups with a single stimulus. Mechanosensitive MM-innervating neurons in the brainstem projected to the parabrachial nucleus. Morphine administration blocked the increase in the number of pERK-immunoreactive neurons in both the brainstem and parabrachial nucleus.We established a model of craniofacial myalgia by combining trapezius and MM stimuli in female rats. We found mechanical hyperalgesia of the MM and activation of the pain pathway from the brainstem to parabrachial nucleus. The model reflects the characteristics of patients with craniofacial myalgia and might be helpful to clarify the pathogenic mechanisms underlying these disorders.

The international partnership GEOMME seeks to develop collaborative activities in research and education on climate-induced geohazards in South Korea, Japan, and Norway. The partnership focuses on excellence in education and research to increase societal resilience against climate-induced geohazards. The objective of the GEOMME partnership is to increase the adaptive capacity of the partner nations to climate change through research-based education, knowledge exchange, and international collaboration. Activities centre on four scientific themes: (1) geohazards in a changing climate, (2) geohazards over large spatial scales, (3) advanced modelling and monitoring techniques, and (4) green solutions for hazard- and risk mitigation – including Nature-Based Solutions.A novel aspect of the GEOMME partnership is the collective development of four education packages – each focusing on one of the scientific themes. The target audience is graduate students, researchers and practitioners. Education packages consist of two components – an online module and an in-person research- and experience-based course. The online modules are standalone introductions to the scientific themes and are openly accessible. The modules promote rapid accessibility to international perspectives in geohazards education and research, guiding interested parties towards an understanding of these complex topics. The modules will live on beyond the project period, hosted by GEOMME partners. Intensive research- and experience-based courses are implemented as a follow-up to the online modules and allow affiliated partners to further develop in-depth expertise in the topic areas. The content of the education packages reflects the state-of-the-art in research and current state-of-practice in applications within the domains of the three partner countries.This contribution will present the approach of combining digital and in-person research-based teaching methodologies for geosciences, and experiences and challenges from early-stage implementation.The GEOMME partnership is financed through INTPART program the Research Council of Norway (project number 322469). The INPART program seeks to promote long-term international partnerships to enhance the quality of higher education and research in Norway. The GEOMME partnership is running between 2021 and 2026.

This study analyzed the outcomes of docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy and DCF plus concurrent radiotherapy (DCF-RT), both followed by conversion surgery, if possible, in patients with cT4b esophageal cancer.Forty-six patients with cT4b esophageal cancer, including borderline cT4b lesions, were eligible. Borderline cT4b lesions were treated with induction DCF therapy. For definitive cT4b lesions, definitive DCF-RT was administered. Patients unsuitable for induction DCF therapy or DCF-RT were treated with other therapies. After treatment, conversion surgery (CS) was performed for the residual tumor in resectable cases.Induction DCF therapy was administered to 12 patients (group A), and DCF-RT was provided to 18 patients (group B). Meanwhile, other therapies were provided to 16 patients (group C). The 1-, 3-, and 5-year overall survival (OS) rates were 66.7, 30.0, and 15.0%, respectively, in group A; 66.7, 37.5, and 37.5%, respectively, in group B; and 62.5, 0, and 0%, respectively, in group C. DCF-RT tended to prolong survival, albeit without significance (p=0.1040). The group A + B had significantly better overall survival than group C (p=0.0437). Fourteen patients underwent CS (30.4%), and patients who underwent CS had significantly better overall survival than those who did not undergo surgery (p=0.0291).Induction DCF or DCF-RT is promising for the treatment of cT4b esophageal cancer. Effective CS including combined resection of the invaded organ can contribute to improved therapeutic outcomes.

In situ meteorological data are essential to better understand ongoing environmental changes in the Arctic. Here, we present a dataset of quality-controlled meteorological observations by two automatic weather stations in northwest Greenland from July 2012 to the end of August 2020. The stations were installed in an accumulation area on the Greenland Ice Sheet (SIGMA-A site, 1490 m a.s.l.) and near the equilibrium line of the Qaanaaq Ice Cap (SIGMA-B site, 944 m a.s.l.). We describe the two-step sequence of quality-control procedures that we used to create increasingly reliable datasets by masking erroneous data records. We analyzed the resulting 2012–2020 time series of air temperature, positive degree-days, snow height, surface albedo, and histograms of longwave radiation (a proxy of cloud formation frequency). We found that snow height increased and albedo remained steady at the SIGMA-A site, whereas high air temperatures and clear-sky conditions prevailed while snow height and albedo decreased in the summers of 2015, 2019, and 2020 at the SIGMA-B site. Therefore, it appears that these weather conditions led to notable snow height degradation at the SIGMA-B site but not at the SIGMA-A site. We anticipate that this quality-control method and these datasets will aid in climate studies of northwest Greenland as well as contribute to the advancement of broader polar climate studies.

Background Anastomotic disorder of the reconstructed gastric conduit is a life‐threating morbidity after thoracic esophagectomy. Although there are various reasons for anastomotic disorder, the present study focused on dislocation of the gastric conduit (DGC). Methods The study cohort comprised 149 patients who underwent transthoracic esophagectomy. The relationships between DGC and peri‐ and postoperative morbidities were analyzed retrospectively. Data were analyzed to determine whether body mass index (BMI) and extension of the gastric conduit were related to DGC. Uni‐ and multivariate Cox regression analyses were performed to identify the factors associated with anastomotic disorder. Results DGC was significantly related to anastomotic leakage (P, Anastomotic disorder is a life‐threating morbidity after esophagectomy. Anastomotic leakage, stricture, and mediastinal abscess/empyema are significantly related to dislocation of the gastric conduit.

Introduction: The COVID-19 outbreak abruptly restricted gastrointestinal (GI) endoscopy services during the first wave of the pandemic. We aimed to assess the impact of COVID-19 on the practice of GI endoscopy in Asian countries. Methods: This was an International Questionnaire-based Internet Survey conducted at multiple facilities by the International Gastrointestinal Consensus Symposium. A total of 166 respondents in Japan, China, Hong Kong, South Korea, Philippines, Thailand, Indonesia, and Singapore participated in this study. Results: The volume of endoscopic screening or follow-up endoscopies and therapeutic endoscopies were markedly reduced during the first wave of the pandemic, which was mainly attributed to the decreased number of outpatients, cancellations by patients, and adherence to the guidelines of academic societies. The most common indications for GI endoscopy during the first wave were GI bleeding, cholangitis or obstructive jaundice, and a highly suspicious case of neoplasia. The most common GI symptoms of COVID-19 patients during the infected period included diarrhea, nausea, and vomiting. The pandemic exacerbated some GI diseases, such as functional dyspepsia and irritable bowel syndrome. There were cases with delayed diagnosis of cancers due to postponed endoscopic procedures, and the prescription of proton pump inhibitors/potassium-competitive acid blockers, steroids, immunosuppressive agents, and biologics was delayed or canceled. The personal protective equipment used during endoscopic procedures for high-risk patients were disposable gloves, disposable gowns, N95 or equivalent masks, and face shields. However, the devices on the patient side during endoscopic procedures included modified surgical masks, mouthpieces with filters, and disposable vinyl boxes or aerosol boxes covering the head. Furthermore, the time for education, basic research, clinical research, and daily clinical practice decreased during the first wave. Conclusion: This study demonstrated that the COVID-19 pandemic profoundly affected the method of performing GI endoscopy and medical treatment for patients with GI diseases in Asian countries.

Aim：To clarify the short-term results of robot-assisted rectal cancer surgery performed at our department.Materials and Methods：Twenty-five patients with rectal cancer who underwent robot-assisted surgery at our department between May 2020 and March 2021 were enrolled in this study. The safety and short-term outcomes of this procedure were evaluated.Results：The mean age of the patients was 69.2±9.3 years（18 men and 7 women）. The locations of cancer included the sigmoid region of the rectum（8 cases）, the upper rectum（5 cases）, the lower rectum（10 cases）, and the anal canal（2 cases）. The surgical techniques were as follows：anterior rectal resection（14 cases）（temporary ileostomy in 4 cases：29％）, Hartmann’s operation（4 cases）, and perineal rectal amputation（7 cases）. The median operation time was 306（195-622）minutes, with 40（1-460）ml of blood loss and 169（85-377）minutes of console operation time. There were no cases of conversion to open surgery. Preoperative treatment was performed in 7 patients. The pathological stages were as follows：stage I：3 cases；stage II：9 cases；stage III：9 cases；stage IV：3 cases. The median number of dissected lymph nodes was 11（2-24）, and the tumor diameter was 44.8 ±18.6 mm. Postoperative complications were observed in 3 patients（12％）：paralytic bowel obstruction（1 case）, outlet syndrome（1 case）, and enteritis（1 case）. No suture failure, sexual dysfunction, or urinary dysfunction was observed. The median postoperative hospital stay was 14（8-69）days.Conclusion：Robot-assisted rectal cancer surgery is safe and effective in terms of short-term outcomes. In the future, it will be necessary to improve safety further by standardizing each technique and to develop an education system from a perspective different from that of laparoscopy. It is considered necessary to further investigate the recurrence rate and survival rate by continuing this method for a long period of time.

Objectives：The surgical method and the timing of surgical intervention for refractory ulcerative colitis（UC）remain controversial. Several studies have reported that the nutritional indicators are useful for predicting of postoperative complications. This study aimed to clarify the relationship between nutritional status and outcome of surgery for UC.Methods：This was a single-institution, retrospective study of patients with UC who underwent surgery between 2006 and 2019, excluding those who underwent emergency surgery. The Controlling Nutritional（CONUT）score and Onodera’s prognostic nutrition index（OPNI）were used as indicators of nutritional status. The moderate cut-off point was determined using the receiver operating characteristic curve.Results：A total of 51 UC patients underwent surgery between 2006 and 2019. Thirty-five UC patients were included in this study after excluding those who underwent surgery for emergency indications such as perforation, toxic megacolon. 57％（n＝20）of the patients received three-stage surgery. Postoperative complications（Clavien-Dindo classification＞II）occurred in 40％（n＝14）of patients. The prevalence of surgical site infection was 12％. The areas under the curve for the frequency of surgical site infection were 0.72 and 0.75 for CONUT and OPNI, respectively. The cut-off value for CONUT was 8.00（sensitivity：84％, specificity：50％）and OPNI was 46.5（sensitivity：44.8％, specificity：100％）. The malnutrition cohort as identified using CONUT and OPNI had a higher rate of postoperative complications than non-malnutritionl cohort（p＝0.04, p＝0.01）.Conclusion：Nutritional status indicators are useful for determining the operative method for the treatment of UC.

_ Leg placement and removal are the two most critical operational modes for dynamically positioned jack-ups when working close to an offshore asset. Any positional deviation may lead to collision and damage to the asset. The industry operates with a weak link between the dynamic positioning (DP) system and the jacking system. Current DP systems operate without any sensors identifying the hydrodynamic force variations on the legs and spudcans, which vary between different leg and spudcan designs. When the spudcan is near to the sea bottom, the hydrodynamic force must be reported to avoid large positional deviations driven by the DP system. This article promotes a mechanism to measure these forces using Computational Fluid Dynamics (CFD) analysis to analyze the jack-up behavior, when the spudcan assembly is operating close to the sea bottom. Introduction A jack-up’s dynamic positioning (DP) control system requires minimum 23–30 minutes for the mathematical model to learn the vessel’s hydrodynamic behavior and response to the environment. Although when moving between locations, DP jack-up vessels provide time for the DP model to learn the hydrodynamic behavior, the spudcan that holds the vessel position and headings does not allow the mathematical model to learn. The residual current remains constant until the spudcan is in the seabed. As a result, the DP mathematical model-building process does not help the DP system to estimate the additional forces in the form of residual current. Soon after the spudcan detaches from the seabed, the vessel drift occurs because the vessel thrusters’ response need a rapid response of thrust and azimuth (directions). The DP system manufacturers currently use a sensorless approach to account for the hydrodynamic forces on the legs and spudcans to build a factor into the mathematical model. The jack-up DP system addresses two simultaneous forces on the legs. The leg element in the air is subject to aerodynamic effects and the leg and spudcan elements in the water are subject to hydrodynamic effects. DP systems currently use drag coefficients (Cd) to compute drag forces, however the hydrodynamic force variations during the complete lowering and raising processes are never completely considered. This weak link in the overall operation leads to positional error and is generally unrecognized by the vessel operators. The risk falls to DP officer and the jacking master to handle. The DP and jacking simultaneous operations mode (SIMOPS) may easily last between 15 and 90 minutes, depending on jacking speed, operational water depth, and field procedures, on approach to the asset. The area of operation is close to the asset, which increases the risk of collision with the asset. Most of the studies on jack-up vessels focus on impact force acting on the leg during touchdown or penetrations, such as Elkadi et al. (2014) and Kreuzer et al. (2014).

A small hydroponic system that can use sustainable energy such as solar power has been developed. However, the amount of power generated is not constant, and in the case of unstable weather, enough power cannot be obtained. Therefore, it is necessary to store the generated energy in a battery. In order to design low-cost charging equipment, it is necessary to use a smaller battery and to estimate the remaining charge capacity (state of charge: SOC) accurately. To provide an accurate SOC estimation for such systems, a fusion of CI (current integral) and OCV (open circuit voltage) methods is proposed. When using this method, it is necessary to frequently disconnect the electronic load. In these experiments, the optimum disconnection duration, the effects on plants of frequent battery disconnection, and cutting off of the lighting were investigated.

The clinical utility of plasma cell-free DNA in precision cancer medicine has not been established. A pilot study was conducted to investigate the clinical utility of comprehensive genomic profiling by liquid biopsy in a Japanese population. In this PROFILE study, 102 patients with advanced solid tumors who showed progression with standard systemic therapy underwent liquid biopsy between August 2017 and February 2020. Liquid biopsy was performed using Guardant360. Of the 102 patients, 56 were women, and the median age was 65 years. Regarding the types of cancer, 31 were hepatobiliary and pancreatic cancer, 17 were gastrointestinal cancer, and 13 were breast cancer. Frequently altered genes were TP53 (53.9%, 46/102), KRAS (25.5%, 26/102), PIK3CA (19.6%, 20/102), and EGFR (17.6%, 18/102). At least one genetic aberration was detected in 92 patients (90.2%). Actionable mutation was discovered in 88 patients (86.3%), and 67 patients (65.7%) were clinical trial candidates. Of the 102 patients, 22 (21.6%) were able to receive biomarker-matched therapy. Their best responses were as follows: 1 complete response, 3 partial responses, 7 stable diseases, and 11 progressive diseases. Additionally, the treated patients were divided on the basis of matching scores (≥ 50% vs. < 50%). The patients were divided into high and low groups. The high group had a higher disease control rate (DCR) of 75% compared with 20% in the low group (P = 0.010). The results indicate that liquid biopsy is useful for identifying actionable mutations associated with the clinical response of selected patients.

Hiroharu Kamioka,1 Yasunori Mori,2 Takahiko Horiuchi,3 Takahito Hayashi,4 Koichiro Ohmura,5 Satoru Yamaguchi,6 Mitsutoshi Kato7 1Faculty of Regional Environment Science, Tokyo University of Agriculture, Tokyo, Japan; 2Mie Prefecture Health and Environment Research Institute, Yokkaichi, Mie, Japan; 3Department of Internal Medicine, Kyushu University Beppu Hospital, Beppu, Oita, Japan; 4Department of Legal Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan; 5Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan; 6Department of Oriental Medicine, Saitama Medical University, Saitama, Japan; 7Kato Clinic of Internal Medicine, Tokyo, JapanCorrespondence: Hiroharu KamiokaFaculty of Regional Environment Science, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-Ku, Tokyo 156-8502, JapanTel/Fax +81 35477 2587Email h1kamiok@nodai.ac.jpPurpose: To clarify the relationship between daily hot water bathing (HWB) at home and glycemic control in middle-aged and elderly ambulatory patients with type 2 diabetes mellitus (T2DM).Methods: We defined hemoglobin A1c (HbA1c) as the main outcome. We set 7.0% based on the mean value of the dependent variable as the cut-off point for analysis. Frequency of HWB was an explanatory variable. A two-sample t-test was used to compare between groups with continuous variables. Multiple logistic regression analysis was performed for frequency, adjusted age, sex, BMI, T2DM duration (Model 1), and other confounding factors (Model 2). Odds ratio (OR) and 95% confidence interval (95% CI) were calculated.Results: Among 838 patients, there was a significant difference (p< 0.001) in age between males (n=528, 62.8± 8.7 years) and females (n=310, 65.0± 8.1 years). In Model 1, compared with participants who used HWB more than seven times a week, those with poorly controlled HbA1c were significantly associated with low frequency of HWB: four to six times a week (OR 1.32, 95% CI 0.87– 1.99) and less than three times a week (OR 1.43, 95% CI 0.98– 2.10); p-value for overall trend was 0.041. In Model 2, p-value for overall trend was 0.138.Conclusion: A higher frequency of HWB was moderately associated with a decreased risk of poor glycemic control in middle-aged and elderly ambulatory patients with T2DM.Keywords: hot water bathing, type 2 diabetes, hemoglobin A1c, middle-aged and elderly ambulatory patients

TAS-102 improved the overall survival of metastatic colorectal cancer (CRC) patients with a median progression-free survival (PFS) in the RECOURSE trial. Subsequently, the combination of TAS-102 and bevacizumab was shown to extend the median PFS (C-TASK FORCE study). However, the study included patients who received second- and third-line treatment. Our study exclusively examined patients receiving this combination as a third-line treatment to investigate the clinical impact beyond cytotoxic doublets. This investigator-initiated, open-label, single-arm, multi-centered phase II study was conducted in Japan. Eligible CRC patients were refractory or intolerant to fluoropyrimidine, irinotecan, and oxaliplatin in first- and second-line therapy. TAS-102 (35 mg/m2) was given orally twice daily on days 1–5 and 8–12 in a 4-week cycle, and bevacizumab (5 mg/kg) was administered by intravenous infusion every 2 weeks. The primary endpoint was PFS and the secondary endpoints were time-to-treatment failure, response rate, overall survival (OS), and safety. Between June 2016 and August 2017, 32 patients were enrolled. All patients previously received bevacizumab. The median PFS was 4.5 months; the median overall survival was 9.3 months. Partial response was observed in two patients. The most common adverse events above grade 3 were neutropenia followed by thrombocytopenia. There were no non-hematological adverse events above grade 3 and no treatment-related deaths occurred. This study met its primary endpoint of PFS, which is comparable to the results of the C-TASK FORCE study. The TAS-102 and bevacizumab combination has the potential to be a therapeutic option for third-line treatment of metastatic CRC.

A prolonged period of winter monsoonal flow brought heavy sea-effect snowfall to the Hokuriku region along the west coast of the Japanese island of Honshu from 2 to 7 February 2010. Snowfall in some locations exceeded 140 cm, but the distribution within the event was highly variable. We examine the factors contributing to these variations using data from a Japan Meteorological Agency (JMA) C-band surveillance radar, JMA soundings, surface precipitation observations, and a Weather Research and Forecasting (WRF) Model simulation. There were three distinct periods during the event. Period 1 featured relatively weak flow with precipitation confined mainly to the coast and lowlands. Precipitation maxima were located where the flow ascended: 1) over terrain-blocked air, 2) at the foot of a high flow-normal barrier, or 3) relatively unimpeded over the lower mountain ranges. Flow strengthened during period 2, yielding stronger vertical velocities over the terrain with precipitation maxima shifting inland and to higher elevation. The flow strengthened further in period 3, with the precipitation maxima shifting higher in elevation and into the lee, with almost no precipitation falling in the lowlands. Thus, greater inland penetration and enhancement of precipitation occurred as the flow speed increased, but additional factors such as the subcloud sublimation of hydrometeors and the convective instability also contribute to differences between periods 2 and 3. These results illustrate the importance of incident flow strength in modulating the distribution and enhancement of snowfall in global lake- and sea-effect regions.

Within the wide field of snow mechanics the shear strength of snow is paramount. In the scientific literature a wide number of experimental and theoretical works exist with reference to the progressive shear failure of snow-snow interfaces under different conditions of internal and external actions. On the contrary, to our knowledge, few studies are devoted to the shear behaviour at the contact between a snow layer and a solid stiff material, although this topic could have various fields of application (e.g., glide avalanches, snow removal, snow-structure interaction, etc.). Here, we analyze results of experimental direct shear tests carried out in displacement control on a snow-mortar interface at given conditions of temperature and sintering times. We additionally use the Mohr-Coulomb failure criterion to represent shear strength along the interface both in failure and post-failure conditions.

In this case of medication overuse headache in a patient with myasthenia gravis, an acupuncturist identified the use of an over-the-counter analgesic that was not revealed to the attending physician. This case highlights the potential role of an acupuncturist as part of the medical care team involved in headache management.