Genomic adaptive potential to cold environments in the invasive red swamp crayfish.

Biological invasion refers to the introduction, spread, and establishment of non-native species in a novel habitat. The ways in which invasive species successfully colonize new and different environments remain a fundamental topic of research in ecology and evolutionary biology. Here, we investigated the genomic and transcriptomic characteristics of the red swamp crayfish (Procambarus clarkii), a widespread invader in freshwater environments. Targeting a recently colonized population in Sapporo, Japan that appears to have acquired a high degree of cold tolerance, RNA-seq analysis revealed differentially expressed genes in response to cold exposure, and those involved in protease inhibitors and cuticle development were considered top candidates. We also found remarkable duplications for these gene families during evolution and their concerted expression patterns, suggesting functional amplification against low temperatures. Our study thus provides clues to the unique genetic characteristics of P. clarkii, possibly related to cold adaptation.

Long-Term Results of Gamma Knife Radiosurgery for Trigeminal Neuralgia.

OBJECTIVE: Although the short- to medium-term efficacy of Gamma Knife therapy for drug-resistant essential trigeminal neuralgia has been reported, long-term evaluations are limited. We evaluated patient data obtained at least 10 years post-treatment and examined the significance of this treatment using new end points. METHODS: Among 249 consecutive patients with essential trigeminal neuralgia who were treated with Gamma Knife radiosurgery (retrogasserian target/4-mm single isocenter/90 Gy at 100%) at our institution between January 2003 and October 2011, 103 patients who were followed up for at least 10 years (mean, 174 [120-219] months) after treatment and whose data were amenable to accurate evaluation, were included in this retrospective study. Herein, we used the Barrow Neurological Institute (BNI) pain intensity scale as a clinical evaluation method for pain and the BNI numbness scale to evaluate complications (namely facial dysesthesia). RESULTS: The initial and final follow-up pain attack cessation (BNI pain intensity score I-IIIa) rate was 82.5% (85 of 103) and 58.2% (60 of 103), respectively. Furthermore, sensory impairment (BNI numbness score ≥ II) at the last follow-up was observed in 24.3% (25 of 103) of the cases, while very bothersome status (BNI numbness score IV) was observed in 2.9% of the cases. CONCLUSIONS: Gamma Knife radiosurgery for essential trigeminal neuralgia showed good therapeutic effects during long-term follow-up. Serious complications of significant concern in the short- to mid-term follow-up, resolved spontaneously. Therefore, the indications for treatment should be expanded to include patients who strongly desire Gamma Knife therapy.

Development of new gastric endoscopic submucosal dissection training model: A reproducibility evaluation study.

Background and study aims Gastric endoscopic submucosal dissection (ESD) is a highly technical procedure mainly due to the distinctive shape of the stomach and diverse locations of lesions. We developed a new gastric ESD training model (G-Master) that could accurately recreate the location of the stomach and assessed the reproducibility of located lesions in the model. Methods The model comprises a simulated mucous membrane sheet made of konjac flour and a setting frame, which can simulate 11 locations of the stomach. We assessed the reproducibility of each location in the model by assessing the procedure speed and using a questionnaire that was distributed among experts. In the questionnaire, each location was scored on a six-point scale for similarity of locations. Results The mean score for all locations was high with > 4 points. Regarding locations, lower anterior and posterior walls had medium scores with 3 to 4 points. The procedure speed was slower in the greater curvature of the upper and middle gastric portions, where ESD is considered more difficult than the overall procedure speed. Conclusions The new gastric ESD training model appears to be highly reproducible for each gastric location and its application for training in assuming actual gastric ESD locations.

Humanized substitutions of Vmat1 in mice alter amygdala-dependent behaviors associated with the evolution of anxiety.

The human vesicular monoamine transporter 1 (VMAT1) harbors unique substitutions (Asn136Thr/Ile) that affect monoamine uptake into synaptic vesicles. These substitutions are absent in all known mammals, suggesting their contributions to distinct aspects of human behavior modulated by monoaminergic transmissions, such as emotion and cognition. To directly test the impact of these human-specific mutations, we introduced the humanized residues into mouse Vmat1 via CRISPR/Cas9-mediated genome editing and examined changes at the behavioral, neurophysiological, and molecular levels. Behavioral tests revealed reduced anxiety-related traits of Vmat1 Ile mice, consistent with human studies, and electrophysiological recordings showed altered oscillatory activity in the amygdala under anxiogenic conditions. Transcriptome analyses further identified changes in gene expressions in the amygdala involved in neurodevelopment and emotional regulation, which may corroborate the observed phenotypes. This knock-in mouse model hence provides compelling evidence that the mutations affecting monoaminergic signaling and amygdala circuits have contributed to the evolution of human socio-emotional behaviors.

Two cases with fulminant type 1 diabetes that developed long after cessation of immune checkpoint inhibitor treatment.

Various immune-related adverse events (irAEs), including fulminant type 1 diabetes (FT1D), are known to be associated with immune checkpoint inhibitors (ICIs). We experienced two lung adenocarcinoma cases who developed fulminant type 1 diabetes long after discontinuation of ICI therapies. One, a 74-year-old male, received nivolumab and developed fulminant type 1 diabetes 44 days after the last infusion. The other, an 85-year-old male, received atezolizumab and developed fulminant type 1 diabetes 171 days after the last infusion. Clinical ICI treatment guidelines recommend laboratory tests during ICI treatments but the necessity of tests in patients whose ICI therapy has been discontinued is not clearly described. These cases indicate that blood glucose monitoring should be continued at least for several months, and that patients should be informed of the possibility of fulminant type 1 diabetes after ICI discontinuation, because fulminant type 1 diabetes progresses rapidly and can be life-threatening if not promptly recognized.

Factors of technical difficulty in conventional and traction-assisted esophageal endoscopic submucosal dissection.

BACKGROUND: The traction assisted (TA) method has reduced the technical difficulty associated with esophageal endoscopic submucosal dissection (ESD). However, it is unclear which factors associated with difficulty have been improved by the TA-ESD method. We aimed to evaluate and compare difficulty factors between conventional and TA-ESD. METHODS: We retrospectively enrolled patients treated by ESD from Apr 2010 to Jun 2014 for the conventional ESD cohort and from Jan 2016 to Dec 2019 for the TA-ESD cohort. Difficult cases were defined as; (1) ≥ 120 min ESD procedure time, (2) intraoperative perforation, or (3) piecemeal resection. We explored and compared the factors associated with technical difficulty in each cohort. RESULTS: The conventional and TA-ESD cohorts included 285 (299 lesions) and 387 (421 lesions) patients, respectively. For difficult cases, the conventional and TA-ESD cohorts had 91 (30%) and 71 (17%) lesions, respectively. Multivariate logistic regression showed that ≥ 30 mm lesion length (odds ratio (OR) 6.85, 95% confidence interval (CI) 3.47-13.50), lower esophagus (OR 2.37, 95% Cl 1.34-4.21), > 1/2 circumference (OR 2.26, 95% CI 1.28-3.99), and left wall (OR 2.72, 95% CI 1.42-5.20) in the conventional ESD cohort, and ≥ 30 mm lesion length (21.30, 95% CI 4.75-95.30), lower esophagus (OR 3.05, 95% CI 1.52-6.13), and > 1/2 circumference (OR 6.40, 95% CI 3.06-13.40) in the TA-ESD cohort, were independently associated with technical difficulty. CONCLUSIONS: TA-ESD can reduce the difficulty in cases including lesions in the left wall; however, cases in the lower esophagus and large lesions were still difficult to simplify.

Late-stage macrolactonisation enabled by tandem acyl transfers followed by desulphurisation.

Intramolecular S-acylation of a thiol-installed threonine with a thioester unit, followed by S-O acyl transfer and subsequent desulphurisation, allows the synthesis of lactone peptides. A protocol has been developed enabling the cyclisation of a linear peptide, a reaction which has not been achieved by conventional methods.

The safety and feasibility of endoscopic submucosal dissection using a flexible three-dimensional endoscope for early gastric cancer and superficial esophageal cancer: A prospective observational study.

BACKGROUND AND AIM: Endoscopic submucosal dissection (ESD) is performed as one of standard treatments for patients with early gastric cancer (EGC) and superficial esophageal squamous cancer (SESCC). A prototype of a flexible endoscope with a 3-D system has been recently developed. This study aimed to investigate the safety and feasibility of ESD using a 3-D flexible endoscope (3-D ESD) for EGC and SESCC. METHODS: This single-center, prospective, observational study enrolled patients who underwent planned 3-D ESD. The clinical outcomes, including the incidence of adverse events and treatment results, were analyzed. Visibility and manipulation during 3-D ESD were evaluated using a visual analog scale (VAS). We also evaluated the effect of the 3-D system on the endoscopist using VAS and the critical flicker fusion frequency (CFFF). RESULTS: We analyzed 47 EGC and 20 SESCC cases. There are no bleeding cases that required transfusion and perforation during 3-D ESD in both EGC and SESCC patients. However, the incidence of delayed bleeding and delayed perforation was 1.5% (one case) each. The mean VAS scores for recognizing the submucosal layer during the submucosal dissection, visual perception of blood vessel, and depth perception were 72.7 ± 22.2, 74.7 ± 21.8, and 78.2 ± 19.9, respectively. In contrast, the mean VAS score for manipulation was 25.4 ± 19.7. Among endoscopists, there was no significant difference in the VAS of eyestrain and headache before and after ESD, and there was no significant difference in the CFFF. CONCLUSION: The safety and feasibility of 3-D ESD for EGC and SESCC are acceptable in both patients and endoscopists.

Long-term clinical outcomes of patients diagnosed with pT1a-muscularis mucosae with lymphovascular invasion or pT1b after endoscopic resection for cT1N0M0 esophageal squamous cell carcinoma.

BACKGROUND: Endoscopic resection (ER) is performed for early esophageal squamous cell carcinoma (ESCC) cases. Additional esophagectomy or chemoradiotherapy is recommended for non-curative resection (NCR) even with pathologically negative vertical margins (pVM0); however, their clinical outcomes remain unknown. We examined the long-term clinical outcomes of NCR for ESCCs according to additional treatments. METHODS: We retrospectively analyzed the data of patients who underwent ER for cT1N0M0 ESCC between 2009 and 2017 judged to have NCR, which defined when pathologically diagnosed as invading the submucosa (SM) or muscularis mucosae (MM) involving lymphovascular invasion (LVI), pVM0, and endoscopically judged as negative horizontal margin. Additional esophagectomy (involving three-field lymphadenectomy), chemoradiotherapy [mainly cisplatin and 5-fluorouracil with concurrent radiotherapy (41.4 Gy)], or observation was undertaken. Thereafter, computed tomography was performed every 6-12 months. The cumulative recurrence (CRR) and recurrence-free survival (RFS) rates were evaluated. RESULTS: Eighty-nine patients were included. Among them, 14 had pathologically diagnosed pMM with LVI; 9 and 6, and 32 and 28 patients had pSM1 and pSM2 without and with LVI. Twenty-one patients underwent observation, whereas 18 and 50 underwent esophagectomy and chemoradiotherapy. During the 60.6-month median follow-up period, nine patients had recurrence; among them, six patients had occurrence at > 4 years after ER. The 5-year CRR/RFS rates were 35.7%/48.1%, 13.4%/80.4%, and 0.0%/98.0% in the observation, esophagectomy, and chemoradiotherapy groups, respectively (observation vs. chemoradiotherapy; P < 0.001). CONCLUSIONS: Additional treatments showed better long-term outcomes than observation for patients with NCR. As recurrence may occur at > 4 years after ER, careful long-term follow-up examinations are needed.

Efficacy and safety of second photodynamic therapy for local failure after salvage photodynamic therapy for esophageal cancer.

OBJECTIVES: Photodynamic therapy (PDT) is an optional salvage treatment for local failure of esophageal squamous cell carcinoma (ESCC) after chemoradiotherapy; however, local failure after PDT sometimes occurs. In such cases, second PDT is sometimes attempted, but its outcomes remain unclear. This study aimed to evaluate the efficacy and safety of second PDT. METHODS: We enrolled patients who underwent PDT for local failure of ESCC after chemoradiotherapy. We retrospectively evaluated local-complete response (L-CR) rate and clinical outcomes of first and second PDT. The indications for PDT were lesions within the muscle layer, <3 cm in size, and <3/4 of the esophageal circumference; not suitable for salvage surgery; and absence of metastasis. Second PDT was avoided when lesions were apparently refractory to first PDT, e.g. persistence of submucosal tumor-like protruded component or rapid regrowth of tumor at the ulceration after first PDT. L-CR was defined as endoscopic disappearance of tumor and post-PDT ulcer and absence of cancer cells histologically. RESULTS: Among 82 patients who underwent first PDT, 27 underwent second PDT. The L-CR rates with first and second PDT were 63.0% and 40.7%, respectively. The 2-year overall survival rates after second PDT in patients with L-CR and local-nonCR were 79.5% and 40.5%, respectively. Five of 11 patients with L-CR survived without any recurrence. No grade ≥3 adverse events occurred. CONCLUSIONS: Second PDT demonstrated excellent safety and acceptable efficacy; therefore, it could be a useful treatment for local failure after first PDT.

Long-term clinical outcome after endoscopic resection of esophageal squamous cell carcinoma invading the muscularis mucosae without lymphovascular invasion.

BACKGROUND AND AIMS: Lymph node recurrence (LNR) after endoscopic resection (ER) in patients with esophageal squamous cell carcinoma (ESCC) pathologically invading the muscularis mucosae (pMM) without lymphovascular invasion (LVI) has been reported as non-negligible in the ER guidelines for esophageal cancer by the Japan Gastroenterological Endoscopy Society. However, these data were not regarded as high-level evidence because several retrospective case series were tabulated without sufficient long-term follow-up. Hence, this guideline stated that the administration of additional treatment after ER could not be determined for this population. This study aimed to clarify the long-term clinical outcomes after ER of pMM ESCC without LVI. METHODS: Between January 2009 and November 2017, we enrolled followed patients who underwent ER and were diagnosed with pMM ESCC without LVI with no additional treatments. We retrospectively investigated the cumulative recurrence rate and recurrence-free, overall, and disease-specific survival at 5 years after ER. RESULTS: Eighty-seven patients were enrolled. During the median follow-up period of 64 months (range, 12-117), 3 patients developed lymph node and/or distant recurrence, and 2 of these cases occurred more than 3 years after ER; all 3 patients died of the primary disease. The 5-year cumulative recurrence rate was 4.3%, and the 5-year recurrence-free, disease-specific, and overall survival rates were 88.8%, 98.2%, and 91.7%, respectively. CONCLUSIONS: The long-term outcome for patients with pMM ESCC without LVI was favorable after ER; however, this population had a risk of recurrence directly leading to death. Long-term follow-up is necessary, with attention to the timing of recurrence.

Functional differences between TSHR alleles associate with variation in spawning season in Atlantic herring.

The underlying molecular mechanisms that determine long day versus short day breeders remain unknown in any organism. Atlantic herring provides a unique opportunity to examine the molecular mechanisms involved in reproduction timing, because both spring and autumn spawners exist within the same species. Although our previous whole genome comparisons revealed a strong association of TSHR alleles with spawning seasons, the functional consequences of these variants remain unknown. Here we examined the functional significance of six candidate TSHR mutations strongly associated with herring reproductive seasonality. We show that the L471M missense mutation in the spring-allele causes enhanced cAMP signaling. The best candidate non-coding mutation is a 5.2 kb retrotransposon insertion upstream of the TSHR transcription start site, near an open chromatin region, which is likely to affect TSHR expression. The insertion occurred prior to the split between Pacific and Atlantic herring and was lost in the autumn-allele. Our study shows that strongly associated coding and non-coding variants at the TSHR locus may both contribute to the regulation of seasonal reproduction in herring.

[Mobile Thrombus in the Ascending Aorta Detected Incidentally in the Patient with Fever before Surgery for Esophageal Cancer:Report of a Case].

A mobile thrombus in the ascending aorta is extremely rare. A 57-year-old man was referred to our hospital with suspected esophageal cancer. Following thorough evaluation, he was diagnosed with esophageal cancer( UtMt type0-Ⅱa T1b, Mt type0-Ⅱc T1a N0M0 cStageⅠ) and tongue cancer in situ. He was administered preoperative chemotherapy comprising fluorouracil and cisplatin. The patient developed fever on day four of the first course of the chemotherapy. Contrast-enhanced chest and abdominal computed tomography revealed a mobile thrombus in the ascending aorta with bilateral partial renal infarction. We initiated intravenous unfractionated heparin and oral warfarin as anticoagulant therapy. The thrombus did not disappear despite ten-day treatment;therefore, he underwent aortic thrombectomy under hypothermic circulatory arrest with retrograde cerebral perfusion. Intraoperatively, we detected a pedunculated mobile thrombus attached to the aorta. His postoperative course was uneventful and he was treated at discharge with warfarin. He underwent video-assisted thoracoscopic esophagectomy postoperatively and was discharged without any complication. Currently, he showed no recurrent thrombus or cancer.

Over 1000 nm Near-Infrared Multispectral Imaging System for Laparoscopic In Vivo Imaging.

In this study, a laparoscopic imaging device and a light source able to select wavelengths by bandpass filters were developed to perform multispectral imaging (MSI) using over 1000 nm near-infrared (OTN-NIR) on regions under a laparoscope. Subsequently, MSI (wavelengths: 1000-1400 nm) was performed using the built device on nine live mice before and after tumor implantation. The normal and tumor pixels captured within the mice were used as teaching data sets, and the tumor-implanted mice data were classified using a neural network applied following a leave-one-out cross-validation procedure. The system provided a specificity of 89.5%, a sensitivity of 53.5%, and an accuracy of 87.8% for subcutaneous tumor discrimination. Aggregated true-positive (TP) pixels were confirmed in all tumor-implanted mice, which indicated that the laparoscopic OTN-NIR MSI could potentially be applied in vivo for classifying target lesions such as cancer in deep tissues.

Diagnostic ability of Japan Narrow-Band Imaging Expert Team classification for colorectal lesions by magnifying endoscopy with blue laser imaging versus narrow-band imaging.

Background and study aims The Japan Narrow-band imaging (NBI) Expert Team (JNET) classification was proposed for evaluating colorectal lesions. However, it remains unknown whether the JNET classification can be applied to magnifying endoscopy with image-enhanced endoscopies other than NBI. This study aimed to compare the diagnostic ability of JNET classification by magnifying endoscopy with blue laser imaging (ME-BLI) and with ME-NBI. Patients and methods We retrospectively assessed consecutive patients diagnosed per the JNET classification by ME-BLI (BLI group) or ME-NBI (NBI group) between March 2014 and June 2017. We compared the diagnostic value of JNET classification between the groups with one-to-one propensity score matching. Results Four hundred and seventy-one propensity score-matched pairs of lesions were analyzed. In the BLI and NBI groups, the overall diagnostic accuracies were 92.1 % and 91.7 %, respectively, and those for differentiating between neoplastic and non-neoplastic polyps were 96.6 % and 96.8 %, respectively. The positive predictive value by each JNET classification in BLI vs. NBI group was 90.6 % vs. 96.2 % in Type 1, 94.3 % vs. 94.6 % in Type 2A, 57.7 % vs. 42.3 % in Type 2B, and 100 % vs. 91.7 % in Type 3. The negative predictive value was 97.0 % vs. 96.9 % in Type 1, 88.1 % vs. 82.8 % in Type 2A, 98.0 % vs. 98.2 % in Type 2B, and 98.5 % vs. 98.7 % in Type 3. No statistical difference in the diagnostic results was found between the groups. Conclusions The diagnostic ability of the JNET classification by ME-BLI and ME-NBI was comparable, with the former also applicable for diagnosis of colorectal lesions.

Clinical features and risk factors of gastric cancer detected by esophagogastroduodenoscopy in esophageal cancer patients.

BACKGROUND: Gastric cancer is the most frequent primary cancer-associated with esophageal cancer and is most commonly detected by endoscopic surveillance. However, the clinical features of synchronous or metachronous gastric cancer that could be detected by esophagogastroduodenoscopy in esophageal cancer patients are unknown. METHODS: We reviewed the clinical records of all esophageal cancer patients (n = 1379) registered in the cancer registration database who underwent initial treatment between April 2010 and October 2015. We retrospectively analyzed the proportions of synchronous and metachronous gastric cancer cases, the cumulative incidence rate of metachronous gastric cancer in total and by esophageal cancer treatments (endoscopic resection, esophagectomy, and chemoradiotherapy), and the clinical features of esophageal cancer patients with synchronous or metachronous gastric cancer. RESULTS: Overall, 67 (5.3% of 1275) esophageal cancer patients with synchronous gastric cancer and 40 (5.1% of 791) esophageal cancer patients with metachronous gastric cancer were analyzed. The 5-year cumulative incidence rate of metachronous gastric cancer was 5.6% in total, 7.8% after endoscopic resection, 4.7% after esophagectomy, and 4.1% after chemoradiotherapy for esophageal cancer. From the results of multivariate analysis, the risk factors for synchronous gastric cancer were male (odds ratio 13.3) and moderate/severe atrophic gastritis (odds ratio 17.9), and the risk factor of metachronous gastric cancer was moderate/severe atrophic gastritis (hazard ratio 27.6) in patients with esophageal cancer. CONCLUSIONS: The incidence rates of synchronous and metachronous gastric cancer with esophageal cancer were both over 5%. Careful endoscopic observation is required for moderate and severe atrophic gastritis at detecting concomitant gastric cancer in esophageal cancer patients.

New isoflavone glucosides in yabumame (Amphicarpaea bracteata (L.) Fernald subsp. edgeworthii (Benth.) H.Ohashi var. japonica (Oliv.) H.Ohashi) and their effect on leukotriene B4 production in mast cells.

Yabumame (Amphicarpaea bracteata (L.) Fernald subsp. edgeworthii (Benth.) H.Ohashi var. japonica (Oliv.) H.Ohashi) is a legume plant that the Ainu people eat as a traditional food, although the bioactive ingredients other than vitamins have not been studied. In this study, the structures of yabumame isoflavone glucosides were determined and their effect on leukotriene (LT) B4, a chemical mediator of type I allergy, produced in mast cells, was investigated in vitro. Seven compounds were isolated from yabumame. Their structures were determined by spectroscopic and spectrometric analyses, which were genistein-7-O-ß-D-glucoside (1), formononetin-7-O-(2″-O-ß-D-glucosyl)-ß-D-glucoside (2), formononetin-7-O-ß-D-glucoside (3), biochanin A-7-O-(2″-O-ß-D-glucosyl)-ß-D-glucoside (4), formononetin-7-O-(6″-O-malonyl)-ß-D-glucoside (5), biochanin A-7-O-(2″-O-ß-D-glucosyl-6″-O-ß-D-glucosyl)-ß-D-glucoside (6), and biochanin A-7-O-(6″-O-malonyl)-ß-D-glucoside (7). Compounds 2, 4, and 6 were determined as new compounds. Compound 3 showed statistically significant suppressive effect on LTB4 production in mast cells, although the activity was not strong. On the other hand, biochanin A, an aglycone common to compounds 4, 6, and 7, strongly inhibited the LTB4 production. The results suggest that some of yabumame isoflavone glucosides might contribute to mitigate type I allergy. Seven isoflavone glucosides including 3 new compounds were found in yabumame and their anti-allergic effect was evaluated.

Distinction of surgically resected gastrointestinal stromal tumor by near-infrared hyperspectral imaging.

The diagnosis of gastrointestinal stromal tumor (GIST) using conventional endoscopy is difficult because submucosal tumor (SMT) lesions like GIST are covered by a mucosal layer. Near-infrared hyperspectral imaging (NIR-HSI) can obtain optical information from deep inside tissues. However, far less progress has been made in the development of techniques for distinguishing deep lesions like GIST. This study aimed to investigate whether NIR-HSI is suitable for distinguishing deep SMT lesions. In this study, 12 gastric GIST lesions were surgically resected and imaged with an NIR hyperspectral camera from the aspect of the mucosal surface. Thus, the images were obtained ex-vivo. The site of the GIST was defined by a pathologist using the NIR image to prepare training data for normal and GIST regions. A machine learning algorithm, support vector machine, was then used to predict normal and GIST regions. Results were displayed using color-coded regions. Although 7 specimens had a mucosal layer (thickness 0.4-2.5 mm) covering the GIST lesion, NIR-HSI analysis by machine learning showed normal and GIST regions as color-coded areas. The specificity, sensitivity, and accuracy of the results were 73.0%, 91.3%, and 86.1%, respectively. The study suggests that NIR-HSI analysis may potentially help distinguish deep lesions.

Effect of the cation structure on cellulose dissolution in aqueous solutions of organic onium hydroxides.

The solubility of cellulose was systematically assessed in organic onium/inium hydroxide aqueous solutions (OHAS) having assorted cations, such as phosphonium, ammonium, piperidinium, morpholinium, pyrrolidinium, and cholinium. From a dissolution test of cellulose in OHAS, it was confirmed that the single most important factor in the dissolution is the high concentration of OHAS. In addition, having a weaker hydrogen bond network around OH and H2O was found to be important to facilitate the cellulose dissolution. In NMR analysis, the OHAS with an excellent cellulose solubility, such as tetrabutylphosphonium hydroxide ([P4444]OH), exhibited a chemical shift of water (δH2O) integrated with that of OH in the low frequency region (∼4.9 ppm), while choline hydroxide ([Ch]OH) with poor cellulose solubility showed δH2O higher than 5.2 ppm. A higher δH2O means that the protons are deshielded due to a stronger hydrogen bond network around H2O and OH, which indicates a strong self-associating property of OHAS that is unfavourable for the cellulose dissolution. Assuming that the strong self-associating property can be reduced by improving the hydrophobicity of organic cations, the methyl group in N-butyl-N-methylmorpholinium hydroxide ([Mor14]OH) was replaced by a butyl chain to shield the positive charge. While [Mor14]OH dissolved only 5 wt% of cellulose, the solubility in the synthesised OHAS, N,N-dibutylmorpholinium hydroxide ([Mor44]OH), was successfully improved to 20 wt%. In the present paper, cellulose solubility was also analysed in relation to the Kamlet-Taft parameters.