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Miki Uchino,1 Motoko Kawashima,1 Minako Kaido,1 Kazuhisa Suwaki,2 Yuichi Uchino,1 Ichiro Kawachi,3 Kazuno Negishi,1 Kazuo Tsubota1 1Department of Ophthalmology, Keio University School of Medicine, Tokyo, 2Santen Pharmaceutical Co., Ltd, Osaka, Japan; 3Department of Social and Behavioral Sciences, Harvard T. H. Chan School of Public Health, Boston, MA, USA Purpose: To validate a paper-based visual acuity (PBVA) questionnaire.Methods: In 2015, a cross-sectional survey was conducted among 301 young and middle-aged, mostly male, Japanese subjects. The participants were asked to self-rate their visual acuity (VA) on a scale from 1 to 5. Self-ratings of VA were categorized into three groups: good (1 and 2), normal (3), and poor (4 and 5). For objective validation, we performed a functional VA (FVA) assessment in the same subjects.Results: A total of 301 subjects answered the PBVA and completed the FVA test including initial VA. We found out that the result of PBVA was significantly correlated with FVA test and initial VA (r=0.33, P

Motoko Kawashima,1 Miki Uchino,1,2 Norihiko Yokoi,3 Yuichi Uchino,1,2 Murat Dogru,1 Aoi Komuro,3 Yukiko Sonomura,3 Hiroaki Kato,3 Shigeru Kinoshita,3 Kazuo Tsubota1 1Department of Ophthalmology, Keio University School of Medicine, Shinjuku-ku, 2Ryogoku Eye Clinic, Sumida-ku, Tokyo, 3Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan Purpose: To investigate the association of dry eye disease with sleep quality. Methods: In 2011, a cross-sectional survey was conducted among all the employees, mainly young and middle-aged Japanese office workers, who used visual display technology, at a company in Osaka, Japan (N=672; age range =26–64 years). The participants were classified according to the Japanese dry eye diagnosis criteria by dry eye examination results including the Schirmer test, fluorescein and lissamine green staining, tear film break-up time, and symptom questionnaire into three groups as follows: definite dry eye disease, probable dry eye disease, and no dry eye disease. To determine sleep quality, Japanese version of the Pittsburgh Sleep Quality Index (global score) was implemented. The global score (range =0–21) was calculated by summing seven sleep variable scores (scale, 0–3); scores ≥5.5 indicated poor sleep. Results: The total mean global score was 5.1±2.3 (completed N=383); 45% of the dry eye disease participants reported having poor sleep quality, while 34% of the no dry eye disease participants did so, with a significant difference found in the global score (P=0.002). Furthermore, a statistically significant association was observed between the global score and dry eye disease (P=0.005). Conclusion: Poor sleep quality is associated with dry eye disease, especially with dry eye symptoms. Keywords: dry eye, sleep quality, symptom, questionnaire, Pittsburgh Sleep Quality Index, tear film break-up time, visual display terminals

J Neurol Neurosurg Psychiatry 2004;75:453-458. doi: 10.1136/jnnp.2003.010827 Objective: To evaluate the safety and efficacy of removing large acoustic neurinomas (≥3 cm) by the retrosigmoid approach. Methods: Large acoustic neurinomas (mean [...]

Objective: To determine the antioxidant supplementation effect on accommodation among VDT users. Design: A double blind randomized placebo controlled study. Registered under Clinical Trials.gov Identifier No. NCT00877201. Participants and Controls: Fourty right eyes of 40 healthy VDT users (30 females, 10 males, mean age: 43.8±2.8 years, range: 40–49 years). 20 subjects (15 females, 5 males; mean age: 44.0±2.7 years, range: 40–49 years). Methods: Subjects were required to take an antioxidant supplement, 20 age and sex matched subjects (15 females, 5 males; mean age: 43.6±3.1 years, range: 40–49 years) were required to take placebo medication for 4 weeks. Results: The mean of the change in accommodation power was significantly higher in the group receiving antioxidant supplements (0.20±0.50 Diopter(D)) compared to the placebo group (−0.12±0.48(D)) (p<0.05). Conclusions: Antioxidant supplementation was observed to improve accommodation in Japanese Visual Display Terminal (VDT) Users. [ABSTRACT FROM AUTHOR]

Rationale: Patients with atopic dermatitis undergoing penetrating keratoplasty (PKP) face a high risk of postoperative complications. Endothelial keratoplasty may be a safer alternative for such patients, including those with abnormal anterior chamber anatomy., Patient Concerns: 3 male patients, aged 33 to 44, presented with blurred vision at Keio University Hospital., Diagnosis: Bullous keratopathy was diagnosed through slit-lamp examination and specular microscopy. Two patients had well-controlled systemic atopic dermatitis, while 1 had blepharitis associated with atopic dermatitis. Two patients had peripheral anterior synechia, and 2 had undergone glaucoma surgery before keratoplasty., Interventions: Non-Descemet stripping endothelial keratoplasty (nDSAEK) was performed by a single surgeon., Outcomes: The best-corrected visual acuity ranged from 0.7 to 1.5 logMAR before surgery and from 0.2 to 2.3 logMAR after surgery. One year post-surgery, the graft remained clear in 2 cases; however, in the case of repeated glaucoma surgeries after nDSAEK, the graft became edematous. Corneal endothelial cell density was 1586 and 1988 cells/mm² in 2 cases and undetectable in the failed case. The follow-up period ranged from 2.5 to 9 years., Lessons: Despite the presence of peripheral anterior synechia or prior glaucoma surgery, some patients experienced a favorable long-term postoperative course following nDSAEK. This procedure may offer a safer alternative for treating patients with atopic dermatitis who have ocular complications that present a high risk for PKP., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Obesity and aging are major risk factors for several life-threatening diseases. Accumulating evidence from both rodents and humans suggests that the levels of nicotinamide adenine dinucleotide (NAD + ), a regulator of many biological processes, declines in multiple organs and tissues with aging and obesity. Administration of an NAD + intermediate, nicotinamide mononucleotide (NMN), replenishes intracellular NAD + levels and mitigates aging- and obesity-associated derangements in animal models. In this human clinical study, we aimed to investigate the safety and effects of 8-week oral administration of NMN on biochemical, metabolic, ophthalmologic, and sleep quality parameters as well as on chronological alterations in NAD + content in peripheral tissues. An 8-week, single-center, single-arm, open-label clinical trial was conducted. Eleven healthy, middle-aged Japanese men received two 125-mg NMN capsules once daily before breakfast. The 8-week NMN supplementation regimen was well-tolerated; NAD + levels in peripheral blood mononuclear cells increased over the course of NMN administration. In participants with insulin oversecretion after oral glucose loading, NMN modestly attenuated postprandial hyperinsulinemia, a risk factor for coronary artery disease (n = 3). In conclusion, NMN overall safely and effectively boosted NAD + biosynthesis in healthy, middle-aged Japanese men, showing its potential for alleviating postprandial hyperinsulinemia.

Background: The Japanese guideline for therapeutic strategy in HCC does not recognize any benefit of preoperative chemotherapy for potentially resectable hepatocellular carcinoma (HCC), and only upfront resec tion is recommended even for an advanced HCC. Data on preoperative chemotherapy for advanced HCC is still limited. Poor prognostic factors of HCC after resection are tumor more than 5 cm in diameter, multiple lesions, and gross tumor thrombosis, which constitute UICC7 Stage IIIA and IIIB HCC. There are no prospective studies about preoperative chemotherapy in these patients., Aim: To evaluate the benefit of preoperative chemotherapy for UICC7 Stage IIIA and IIIB potentially resectable HCC., Discussion: Our recent study demonstrated that the 5-year overall survival rate (OS) of patients diagnosed as UICC7 Stage IIIA and IIIB who had received upfront resection was only 16.5%. In contrast, the 5-year OS of UICC7 Stage IIIA and IIIB initially unresectable patients who had achieved conversion from unresectable to resect able status under successful hepatic infusion chemotherapy prior to resection was as high as 61.3%. Additionally, recent studies reported transarterial chemoembolization achieved outcomes comparable with those of resection. Therefore, we believe that patients with UICC7 Stage IIIA and IIIB should be considered borderline resectable. To evaluate this hypothesis we registered the present phase II clinical trial to assess the benefit of preoperative chemo therapy followed by hepatectomy in potentially resectable UICC7 Stage IIIA and IIIB HCC patients.

This study aimed to clarify local recurrence (LR) predictive factors following intraoperative microwave ablation (MWA) for colorectal liver metastases. The data from 195 patients with 1392 CRLM lesions, who were preoperatively diagnosed by gadolinium-enhanced MRI with diffusion-weighted imaging and dynamic CT and treated with intraoperative MWA (2450 MHz) with or without hepatectomy, from January 2005 to December 2019, were retrospectively reviewed and analyzed using logistic regression. In addition, the margins were measured on contrast-enhanced CT 6 weeks post-ablation. Overall, 1066 lesions were ablated. The LRs occurred in 44 lesions (4.1%) among 39 patients (20.0%). The multivariate analysis per patient showed that tumor size > 20 mm and ablation margin < 5 mm were significant predictors for LR. Furthermore, multivariate analysis per lesion revealed that segments 1, 7, and 8 and tumor size > 15 mm, ablation margin < 5 mm, tumor size > 20 mm, and proximity to the Glisson were significant LR predictors. Finally, the outcome of this study may help determine indications for MWA.

Other iatrogenic immunodeficiency lymphoproliferative disorders (oii-LPD) are defined as lymphoid proliferations or lymphomas that occur in patients taking immunosuppressive agents (ISA) for autoimmune disorders (AID). Although methotrexate and tumor necrosis factor-alpha inhibitors cause oii-LPD, the association between corticosteroids and lymphomagenesis remains unknown. Herein, we present the case of a 51-year-old woman with oii-LPD caused by corticosteroid use for autoimmune hemolytic anemia (AIHA). The diagnosis of AIHA was made in May 2016, and AIHA had been well-controlled for 5 years with oral prednisolone (PSL). During a regular follow-up visit in March 2022, an abnormal increase in atypical lymphoid cells in the peripheral blood was found. The bone marrow biopsy specimens showed local aggregations of large cells that were identified as lymphoplasmacytic cells and plasma cells, and that were positive for cluster of differentiation (CD)19 and CD20, with apparent nucleoli among the diffuse infiltration of atypical small lymphocytes. The large cells were partially positive for the Epstein-Barr encoding region in situ hybridization and latent membrane protein 1, which confirmed Epstein-Barr virus (EBV)-affected lymphomagenesis. To our knowledge, this is the first report of an oii-LPD case shown to be induced by corticosteroid use for AID.

Although small organic molecules in cells have been considered important to control the functions of proteins, their electronic fluctuation and the intermolecular interaction, which is physicochemical origin of the molecular functions, under physiological conditions, i.e., dilute aqueous solutions (0.18 mol L -1 ), has never been clarified due to the lack of observation methods with both accuracy and efficiency. Herein, the time evolutions of the interactions in dilute aqueous trimethylamine N-oxide (TMAO) and tert-butyl alcohol (TBA) solutions were analyzed via ab initio molecular dynamics simulations accelerated with the fragment molecular theory. It has been known that TMAO and TBA have similar structures, but opposite physiological functions to stabilize and destabilize proteins. It was clarified that TMAO induced stable polarization and charge-transfer interactions with water molecules near the hydrophilic group, and water molecules were caught even near the CH 3 - group. Those should affect protein stabilization. Understanding the solution dynamics will contribute to artificial chaperone design in next generation medicine., (© 2022. The Author(s).)

Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of B-cell lymphoma characterized by aggressive disease progression with a high incidence of central nervous system (CNS) involvement. We retrospectively analyzed 16 patients with de novo IVLBCL treated at our hospital between 2004 and 2018 with either standard therapy plus CNS-directed therapy or standard therapy alone. CNS-directed therapy was associated with a significantly better 2-year CNS-free survival (100% vs. 63%, p  = 0.0191), despite no significant effects on progression-free or overall survival. Further studies should assess CNS-focused treatment in patients with IVLBCL with or without primary CNS involvement., Competing Interests: Hiromichi Takahashi received honoraria from Bristol‐Myers Squibb. Takashi Hamada received honoraria from Bristol‐Myers Squibb. Masaru Nakagawa received honoraria from Bristol‐Myers Squibb. Noriyoshi Iriyama received honoraria from Novartis, Bristol‐Myers Squibb, Takeda, and Ono Parma. Katsuhiro Miura received honoraria from AstraZeneca, Chugai, Kyowa Kirin, Takeda, Bristol‐Myers Squibb, Nippon Shinyaku, SymBio, and Ono Parma. Yoshihiro Hatta received honoraria from Chugai, Kyowa Kirin, Janssen, Bristol‐Myers Squibb, Takeda, and Ono Parma. Hideki Nakamura received research grants from MSD, Asahi Kasei Pharma, Astellas, AbbVie, Japan Blood Products organization, Eisai, Otsuka Pharmaceutical, Ono Pharma, Kyowa Kirin, Sanofi, Shionogi, Daiichi Sankyo, Taiho, Takeda, Mitsubishi Tanabe, Chugai, Teijin Pharma, Eli Lilly, Nippon Kayaku, Nihon Pharmaceutical, Boehringer Ingelheim, and Pfizer. The other authors have no conflicts of interest to disclose., (© 2022 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

This study aimed to investigate the relationship between the severity of dry eye disease (DED) and galectin-3 concentration (gal-3) and its cleavage (gal-3C) in tear fluid. Twenty-eight DED patients and 14 controls were recruited at Keio University Hospital. The lissamine green conjunctival staining (LG) score, fluorescein corneal staining (FL) score, tear film break-up time (TBUT), Schirmer's test, and ocular symptoms questionnaire score (dry eye questionnaire score, DEQS) were evaluated. Furthermore, the correlation between these parameters and the concentrations of gal-3 in tears (ng/µg) and the detection rate of gal-3C (%) were analyzed. Gal-3 concentration in tears was positively correlated with the LG score (R = 0.60, p < 0.01), FL score (R = 0.49, p < 0.01), and DEQS (R = 0.45, p < 0.01), and negatively correlated with the TBUT score (R = -0.40, p < 0.01) and Schirmer's I value (R = -0.36, p < 0.01). The detection rate of gal-3C in tears was significantly associated with the severity of DED, especially with the LG ( p < 0.01) and FL ( p < 0.01) scores. Therefore, the concentration of gal-3 and the detection rate of gal-3C in tears had a significant relationship with the severity of ocular surface barrier disruption.

Few studies have investigated the relationship between nutritional status and comprehensive assessment of oral hypofunction, especially protein intake-related sarcopenia. Thus, we explored these relationships in a large-scale cross-sectional cohort study using the seven-item evaluation for oral hypofunction and Diet History Questionnaire for nutritional assessment. We used the data from 1004 individuals who participated in the 2019 health survey of the residents of Tarumizu City, Kagoshima Prefecture, Japan for analysis. We found that individuals with oral hypofunction were significantly older with a lower skeletal muscle index. Although there were few foods that had a significant difference between the groups with and without oral hypofunction, the consumption of beans and meats was significantly lower in women and men in the oral hypofunction group, respectively. According to the lower limit of the tentative dietary goal defined in Japan, comprehensive evaluation of oral hypofunction was significantly and independently associated with protein intake in both men and women (odds ratio, 1.70; 95% confidence interval, 1.21-2.35). In conclusion, we found that oral hypofunction was associated with targeted protein intake for sarcopenia and frailty prevention in middle-aged and older community-dwelling adults. Comprehensive evaluation of oral function with intervention in cases of hypofunction could inform clinicians to better prevent sarcopenia.

Adapter proteins CRK and CRKL participate in a variety of signaling pathways, including cell adhesion, and fate regulation of mammalian cells. However, the molecular functions of CRK/CRKL in epigenetic regulation remain largely unknown. Here, we developed a pipeline to evaluate cell morphology using high-content image analysis combined with chemical screening of kinase and epigenetic modulators. We found that CRK/CRKL modulates gene regulatory networks associated with cell morphology through epigenetic alteration in mouse embryonic fibroblasts. Integrated epigenome and transcriptome analyses revealed that CRK/CRKL is involved in super-enhancer activity and upregulation of Cdt1, Rin1, and Spp1 expression for the regulation of cell morphology. Screening of a library of 80 epigenetic inhibitors showed that histone H3 modifiers, euchromatic histone methyltransferase 2 and mitogen- and stress-activated kinase 1, may be important for CRK/CRKL-mediated morphological changes. Taken together, our results indicate that CRK/CRKL plays a critical role in gene regulatory networks through epigenetic modification. DATABASES: Chromatin immunoprecipitation sequencing and RNA sequencing data were deposited in the DNA Data Bank of Japan under DRA011080 and DRA011081 accession numbers, respectively., (© 2021 Federation of European Biochemical Societies.)

Background/aim: We assessed the prognosis of patients with refractory or relapsed multiple myeloma (RRMM) by focusing on the change in absolute lymphocyte counts (ALCs) after lenalidomide and dexamethasone (Ld) initiation., Patients and Methods: In total, 72 patients with RRMM were treated with Ld. ALCs were evaluated before treatment and at 1, 2, and 3 months after Ld initiation. The median ALCs in the entire cohort before and at 1, 2, 3 months after Ld initiation were 1,131, 1,059, 1,222, and 1,162/μl, respectively., Results: ALCs before Ld initiation did not affect time to next treatment (TNT) or overall survival (OS). However, the patients with ALCs equal to or greater than the median at 3 months showed relatively better TNT than those with lower lymphocyte counts, with a significant difference. OS was also significantly longer in patients with higher ALCs., Conclusion: Immunomodulation by lenalidomide may improve prognosis in patients with RRMM., Competing Interests: NI received honoraria and speaker fees from Bristol-Myers Squibb, Celgene K.K., Takeda Pharma Co., Ltd., and Ono Parma Co., Ltd. KM received honoraria and speaker fees from Celgene K.K., Takeda Pharma Co., Ltd., and Ono Parma Co., Ltd. HT, MN, and TH reports honoraria and speaker fees from Bristol-Myers Squibb. YH received speaker fees and honoraria from Celgene K.K., Janssen Pharmaceutical K.K., Bristol-Myers Squibb, Takeda Pharma Co., Ltd., and Ono Parma Co., Ltd. MT received honoraria from Janssen Pharmaceutical K.K., Bristol-Myers Squibb, Takeda Pharma Co., Ltd., and Ono Parma Co., Ltd., supports for extension lectures from Bristol-Myers Squibb, and scholarship funds from Takeda Pharma Co., Ltd. and Ono Parma Co., Ltd. Also, MT is part of an international clinical trial evaluating an investigational drug that was developed by Bristol-Myers Squibb for the treatment of Sjögren’s syndrome and has cooperative research with Celgene K.K. TN received scholarship funds from Roche Diagnostics K.K. and salary as an instruction doctor of the ethics from the Health Sciences Research Institute, Inc. The remaining co-authors declare no competing financial interests., (Copyright 2021, International Institute of Anticancer Research.)

Oral microbiota is reportedly associated with gut microbiota and influences colorectal cancer (CRC) progression; however, the details remain unclear. This study aimed to evaluate the role of oral microbiota in CRC progression. Fifty-two patients with CRC and 51 healthy controls were included. Saliva and stool samples were collected, and microbiota were evaluated using 16S rRNA analysis and next-generation sequencing. Comparative analysis was performed on both groups. Linear discriminant analysis effect size (LEfSe) revealed the presence of indigenous oral bacteria, such as Peptostreptococcus , Streptococcus , and Solobacterium spp., at a significantly higher relative abundance in saliva and stool samples of CRC patients compared with controls. Next, CRC patients were divided into early stage (Stage I, II; n = 26; 50%) and advanced stage (Stage III, IV; n = 26; 50%) disease. LEfSe revealed that S. moorei was present at a significantly higher relative abundance in the advanced-stage group compared with the early-stage group, again consistent for both saliva and stool samples. Among bacterial species with significantly higher relative abundance in CRC patients, P. stomatis , S. anginosus , S. koreensis , and S. moorei originated from the oral cavity, suggesting indigenous oral bacteria may have promoted initiation of CRC carcinogenesis. Furthermore, S. moorei may influence CRC progression.

Background: Few reports have described the association between rheumatoid arthritis (RA) cervical lesions and osteoporosis, especially in patients with vertical subluxation (VS) that could be induced by the collapse of lateral masses in the upper cervical spine. Therefore, this study aimed to investigate the prevalence and risk factors for cervical lesions in patients with RA under current pharmacological treatments with biological agents, and to investigate the relationship between osteoporosis and VS development., Methods: One hundred eighty-five consecutive patients with RA who underwent both cervical plain radiography and bone mineral density (BMD) scanning were enrolled. RA cervical lesions included atlantoaxial subluxation (AAS), VS, and subaxial subluxation (SAS). We assigned patients with AAS, VS, or SAS to the cervical-lesion group, and all other patients to the non-cervical-lesion group. Radiological findings, BMD, and clinical data on RA were collected. We used multivariate logistic regression analyses to assess the risk factors for cervical lesions in patients with RA., Results: The cervical-lesion and non-cervical-lesion groups included 106 and 79 patients, respectively. There were 79 patients with AAS, 31 with VS, and 41 with SAS. The cervical-lesion group had a younger age of RA onset, longer RA disease duration, higher RA stage, and lower femoral neck BMD than the non-cervical-lesion group. Multivariate analyses showed that the risk factors for RA cervical lesions were prednisolone usage, biological agent usage, and higher RA stage. Prednisolone usage and femoral neck BMD were the risk factors for VS., Conclusions: Cervical lesions were confirmed in 57 % of the patients. Prednisolone usage, biological agent usage, and higher RA stage were significant risk factors for cervical lesions in patients with RA. The general status of osteoporosis might contribute to the development of VS.

Background/aim: Here, we investigated whether bortezomib as a maintenance therapy affected outcomes in transplant-ineligible patients with multiple myeloma (MM)., Patients and Methods: Following induction therapy with bortezomib, maintenance therapy with bortezomib (1.3 mg/m 2 ) and dexamethasone (20 mg) was administered once or twice every 4 weeks until disease progression. The endpoints of this study were time to next treatment and overall survival., Results: Seventy-six newly diagnosed, transplant-ineligible patients were treated with a bortezomib-based regimen; 28 discontinued induction therapy, 27 did not receive maintenance therapy after induction therapy (the non-maintenance group), and 21 did (the maintenance group). In the three groups, the median times to the next required treatment were 3, 14, and 37 months, respectively. The 3-year overall survival rates were 55%, 69%, and 85%, respectively. There were no significant differences in patient characteristics between the non-maintenance and maintenance groups, except for poorer estimated glomerular filtration rates in the maintenance group., Conclusion: Bortezomib maintenance therapy may be a useful option for transplant-ineligible patients with MM., Competing Interests: NI received honoraria and speaker fees from Bristol-Myers Squibb, Takeda Pharma Co., Ltd., and Ono Parma Co., Ltd. KM received honoraria and speaker fees from Takeda Pharma Co., Ltd., and Ono Parma Co., Ltd. HT, MN, and TH reports honoraria and speaker fees from Bristol-Myers Squibb. YH received speaker fees and honoraria from Janssen Pharmaceutical K.K., Bristol-Myers Squibb, Takeda Pharma Co., Ltd., and Ono Parma Co., Ltd. MT received honoraria from Janssen Pharmaceutical K.K., Bristol-Myers Squibb, Takeda Pharma Co., Ltd., and Ono Parma Co., Ltd.; supports for extension lectures from Bristol-Myers Squibb; and scholarship funds from Takeda Pharma Co., Ltd. and Ono Parma Co., Ltd. Furthermore, MT is a part of an international clinical trial on investigational drug that was developed by Bristol-Myers Squibb for the treatment of Sjögren’s syndrome. The remaining co-authors declare no competing financial interests., (Copyright 2021, International Institute of Anticancer Research.)

Background: Validation and standardization of methodologies for microbial community measurements by high-throughput sequencing are needed to support human microbiome research and its industrialization. This study set out to establish standards-based solutions to improve the accuracy and reproducibility of metagenomics-based microbiome profiling of human fecal samples., Results: In the first phase, we performed a head-to-head comparison of a wide range of protocols for DNA extraction and sequencing library construction using defined mock communities, to identify performant protocols and pinpoint sources of inaccuracy in quantification. In the second phase, we validated performant protocols with respect to their variability of measurement results within a single laboratory (that is, intermediate precision) as well as interlaboratory transferability and reproducibility through an industry-based collaborative study. We further ascertained the performance of our recommended protocols in the context of a community-wide interlaboratory study (that is, the MOSAIC Standards Challenge). Finally, we defined performance metrics to provide best practice guidance for improving measurement consistency across methods and laboratories., Conclusions: The validated protocols and methodological guidance for DNA extraction and library construction provided in this study expand current best practices for metagenomic analyses of human fecal microbiota. Uptake of our protocols and guidelines will improve the accuracy and comparability of metagenomics-based studies of the human microbiome, thereby facilitating development and commercialization of human microbiome-based products. Video Abstract.

Oral hypofunction is a new concept that addresses the oral function of older adults. Few studies have investigated the relationship between oral hypofunction and general health conditions such as frailty, sarcopenia, and mild cognitive impairment. This paper explores these relationships in a large-scale, cross-sectional cohort study. The relationships of oral hypofunction with frailty, sarcopenia, and mild cognitive impairment were examined using data from 832 individuals who participated in the 2018 health survey of the residents of Tarumizu City, Kagoshima Prefecture, Japan. Individuals with frailty, sarcopenia, and mild cognitive impairment had significantly higher rates of oral hypofunction. Frailty was independently associated with deterioration of the swallowing function (odds ratio 2.56; 95% confidence interval, 1.26-5.20), and mild cognitive impairment was independently associated with reduced occlusal force (odds ratio 1.48; 95% confidence interval, 1.05-2.08) and decreased tongue pressure (odds ratio 1.77; 95% confidence interval, 1.28-2.43). There was no independent association found between sarcopenia and oral function. In conclusion, early intervention for related factors such as deterioration of the swallowing function in frailty, reduced occlusal force, and decreased tongue pressure in mild cognitive impairment could lead to the prevention of general hypofunction in older adults.

Background: Chronic ocular graft-versus-host disease (oGVHD) is an ocular comorbidity of graft-versus-host disease (GVHD) that usually occurs concurrently with systemic manifestations. Failure to detect and treat oGVHD in its early stages may lead to progression of ocular signs and symptoms leading to oGVHD that is refractory to conventional treatment., Case Presentation: We report the clinical course of a 19-year-old male and a 59-year-old female with severe and progressive chronic oGVHD without concurrent systemic signs of chronic graft-versus-host disease (cGVHD). Although their systemic conditions had been stable, both suffered from severe oGVHD and were referred to our clinic. Both cases exhibited marked improvement in conjunctival inflammation and fibrotic changes after amniotic membrane transplantation (AMT). Both cases underwent keratoplasty eventually to stabilize ocular surface conditions and to improve visual function., Conclusions: We reported the clinical outcomes of 2 cases of chronic oGVHD without concurrent systemic comorbidities that were treated with AMT. The clinician should be aware that cGVHD may persist in target organs even in the absence of concurrent systemic comorbidities following seemingly successful systemic treatment. A multidisciplinary team approach is essential in the early detection and therapeutic intervention for chronic oGVHD.

This population-based cross-sectional study was performed to determine the mean corneal endothelial cell density (ECD), coefficient of variation (CV), and hexagonality (HEX), and their associations with myopia in Japanese adults living in Chikusei city. Of 7109 participants with available data, 5713 (2331 male and 3382 female) participants were eligible for analysis. After assessing the relationship between participant characteristics and spherical equivalent refraction (SER), the association of SER with the abnormal value of ECD (< 2000 cells/mm), CV (≥ 0.40), and HEX (≤ 50%) were determined using the logistic regression models adjusting for potential confounders (age, intraocular pressure, keratometric power, height, and antihypertensive drug use). In male participants, there was no statistically significant relationships between SER and endothelial parameters. In female participants, compared to emmetropia, SER ≤ - 6 D had significantly higher odds ratio (OR) of having the abnormal value of CV (OR = 2.07, 95% confidence interval [CI] 1.39-3.10) and HEX (OR = 2.04, 95% CI 1.29-3.23), adjusted for potential confounders, indicating that the high myopia was associated with the abnormal values of CV and HEX. Further adjustment for contact lenses wear partly attenuated these associations. Association between the SER and ECD was not detected.

Background: Pancreatic trauma is a rare condition with a wide presentation, ranging from hematoma or laceration without main pancreatic duct involvement, to massive destruction of the pancreatic head. The optimal diagnosis of pancreatic trauma and its management approaches are still under debate. The East Association of Surgery for Trauma (EAST) guidelines recommend operative management for high-grade pancreatic trauma; however, several reports have reported successful outcomes with nonoperative management (NOM) for grade III/IV pancreatic injuries. Herein, we report a case of grade IV pancreatic injury that was nonoperatively managed through endoscopic and percutaneous drainage., Case Presentation: A 47-year-old Japanese man was stabbed in the back with a knife; upon blood examination, both serum amylase and lipase levels were within normal limits. Contrast-enhanced computed tomography (CT) showed extravasation of the contrast medium around the pancreatic head and a hematoma behind the pancreas. Abdominal arterial angiography revealed a pseudo aneurysm in the inferior pancreatoduodenal artery, as well as extravasation of the contrast medium in that artery; coil embolization was thus performed. On day 12, CT revealed a wedge-shaped, low-density area in the pancreatic head, as well as consecutive pseudocysts behind the pancreas; thereafter, percutaneous drainage was performed via the stab wound. On day 22, contrast radiography through the percutaneous drain revealed the proximal and distal parts of the main pancreatic duct. The injury was thus diagnosed as a grade IV pancreatic injury based on the American Association for the Surgery of Trauma guidelines. On day 26, an endoscopic nasopancreatic drainage tube was inserted across the disruption; on day 38, contrast-enhanced CT showed a marked reduction in the fluid collection. Finally, on day 61, the patient was discharged., Conclusions: Although the EAST guidelines recommend operative treatment for high-grade pancreatic trauma, NOM with appropriate drainage by endoscopic and/or percutaneous approaches may be a promising treatment for grade III or IV trauma.

The aim of the present study was to determine the factors associated with reduced clinical benefits of personalized peptide vaccination (PPV) for pancreatic cancer. Phase II PPV clinical trials comprising 309 (8 non-advanced and 301 advanced-stage) patients with pancreatic cancer were conducted. Two to four peptides were selected among a set of 31 different peptides as vaccine candidates for personalized peptide vaccination based on human leukocyte antigen types and preexisting peptide-specific IgG levels, and subcutaneously injected. The selected peptides were subcutaneously injected. Of the 309 patients, 81 failed to complete the 1st PPV cycle due to rapid disease progression, and their median overall survival [2.1 months; 95% confidence interval (CI), 1.8-2.7] was significantly shorter than that of the remaining 228 patients (8.4 months; 95% CI, 8.4-9.9; P<0.01). 'Immune boosting' was defined when IgG levels before vaccination increased more than 2-fold after vaccination. Immune boosting was observed in the majority of patients with PPV irrespective of whether or not they received concomitant chemotherapy. Additionally, patients demonstrating immune boosting exhibited longer survival rates. Although the positive-response rates and peptide-specific IgG levels in pre- and post-vaccination samples differed among the 31 peptides, patients exhibiting immune boosting in response to each of the vaccinated peptides demonstrated longer survival times. Pre-vaccination factors associated with reduced clinical benefits were high c-reactive protein (CRP) levels, high neutrophil counts, lower lymphocyte and red blood cell counts, advanced disease stage and the greater number of chemotherapy courses prior to the PPV treatment. The post-vaccination factors associated with lower clinical benefits were PPV monotherapy and lower levels of immune boosting. In conclusion, pre-vaccination inflammatory signatures, rather than pre- or post-vaccination immunological signatures, were associated with reduced clinical benefits of personalized peptide vaccination (PPV) for pancreatic cancer., (Copyright: © Uchino et al.)

We report a complete genome sequence of Blautia producta JCM 1471 T The genome consists of a single circular chromosome of 6,197,116 bp with a G+C content of 45.7%. The genome was annotated as containing 5 complete sets of rRNA genes, 70 tRNA genes, and 5,516 protein-coding sequences., (Copyright © 2020 Tourlousse et al.)

We report the complete genome sequence of Flavonifractor plautii JCM 32125 T (=VPI 0310 T ). The genome consists of a single circular chromosome of 3,985,392 bp (G+C content, 60.9%) and was predicted to contain 3 complete sets of rRNA genes, 63 tRNA genes, and 3,764 protein-coding sequences., (Copyright © 2020 Tourlousse et al.)

We announce the complete genome sequence of Megamonas funiformis JCM 14723 T (YIT 11815 T ). The genome consists of a circular chromosome (2,522,577 bp, 31.5% G+C content) and a plasmid of 46,189 bp (29.4% G+C content). The genome was predicted to contain 6 rRNA operons, 53 tRNA genes, and 2,440 protein-coding sequences., (Copyright © 2020 Tourlousse et al.)

We report a complete genome sequence of Collinsella aerofaciens JCM 10188 T (=VPI 1003 T ). The genome consists of a circular chromosome (2,428,218 bp with 60.6% G+C content) and two extrachromosomal elements. The genome was predicted to contain 5 sets of rRNA genes, 58 tRNA genes, and 2,079 protein-encoding sequences., (Copyright © 2020 Tourlousse et al.)

In the management of patients with newly diagnosed glioblastoma, there is no standard duration for adjuvant temozolomide treatment. This study aimed to assess the feasibility of finalizing adjuvant temozolomide treatment on the basis of methionine uptake in methionine positron emission tomography (Met-PET). We conducted a retrospective review of glioblastoma patients who underwent more than twelve cycles of temozolomide (extended temozolomide) treatment after resection and concomitant chemoradiotherapy with no evidence of recurrence on MRI. In addition to the methionine uptake value at the completion of extended temozolomide, local and distant recurrence and progression-free survival were also analyzed. Forty-four patients completed the extended temozolomide treatment. Among these, 18 experienced some type of tumor recurrence within one year. A Tmax/Nave value of 2.0 was the optimal cut-off value indicating progression. More than 80% of the patients with low methionine uptake completed the temozolomide treatment, and subsequent basic MRI observations showed no recurrence within one year after Met-PET. Subgroups with high uptake (≥2.0), even with continuation of temozolomide treatment, showed more frequent tumor progression than patients with low uptake (<2.0) who completed the extended temozolomide treatment (p < 0.001, odds ratio 14.7, 95% CI 3.46-62.3). The tumor recurrence rate increased in stepwise manner according to methionine uptake. Finalization of the extended temozolomide treatment on the basis of low uptake value was feasible with a low recurrence rate. Compared to MRI, Met-PET shows better ability to predict tumor progression in long-term glioblastoma survivors with extended temozolomide use.

Despite the importance of dry eye disease (DED) treatment, the rate of DED treatment discontinuation, especially discontinuation of ophthalmic follow-up, remains unknown. This study aimed to assess the prevalence and risk factors of ophthalmic follow-up discontinuation for DED. A cross-sectional survey of 1030 participants was conducted using a self-administered web-survey instrument. We collected lifestyle information, history of DED diagnosis, types of treatment, frequency of eye-drop usage, symptoms, and the reasons for discontinuing treatment. Statistical analyses including logistic regression were used to evaluate the risk factors of discontinuing ophthalmic follow-up for DED. A past history of clinical DED diagnosis was reported by 155 (15.0%) subjects. Of those, 130 had persistent DED, and 88 (67.7%) of the subjects reported discontinuation of ophthalmic follow-up for DED. The most prevalent reasons for ophthalmic follow-up discontinuation were time restrictions, followed by dissatisfaction with the DED treatment. Duration after DED diagnosis was the only significant risk factor for discontinuing ophthalmic follow-up after adjusting for age and sex (odds ratio = 1.09, 95% confidence interval = 1.02-1.17, p = 0.009). In conclusion, longer DED duration after diagnosis was a significant risk factor for discontinuing ophthalmic follow-up for DED. This study showed that DED ophthalmic follow-up discontinuation involves both medical and non-medical reasons. Clinicians need to be aware of them, and preventative effort is needed to avoid discontinuation.

Currently, the available treatment for dry eye disease (DED) varies. The present study aimed to investigate the characteristics of undiagnosed DED and patient-based self-care management for DED based on a web-based survey performed for Tear's Day in Japan; 1030 participants (301 women) responded; 155 participants (72 women) had a clinical diagnosis of DED. We defined undiagnosed DED ( n = 116; 54 women) as those with DED symptoms, as evaluated by a frequently used questionnaire despite not having a clinical diagnosis. A multivariate adjusted model indicated that younger age (odds ratio (OR), 0.97 for each one-year decrease; 95% confidence interval (CI), 0.95-0.99), female sex (OR, 2.12; 95% CI, 1.28-3.50), and prolonged visual display terminal usage (OR, 1.12; 95% CI, 1.04-1.21) were risk factors for undiagnosed DED. To investigate the efficacy of self-care management for DED, a sub-analysis was conducted. The number of self-care methods used was significantly higher among women than men. For undiagnosed DED, those with less than three self-care methods had a significantly worse Dry Eye-related Quality-of-Life Score compared with those with diagnosed DED. This study revealed risk factors for undiagnosed DED; individuals with those risk factors need to be clinically assessed and should not rely solely on self-care.

Background/aim: Autologous hematopoietic stem cell transplantation (ASCT) after high-dose chemotherapy is used to treat relapsed malignant lymphomas. Radiation therapy (RT) is applied after ASCT. We compared the incidence of myelosuppression after RT with and without autologous peripheral blood stem cell transplantation (auto-PBSCT)., Patients and Methods: We retrospectively analyzed 20 patients with malignant lymphomas who received RT, six of whom underwent auto-PBSCT. Univariate analysis using Pearson's Chi-squared test and multivariate analysis using the Cox proportional hazards regression model were performed to determine correlations between the development of grade two or more leukopenia and clinical factors., Results: Among patients with auto-PBSCT, grade two or more leukopenia occurred in five. The incidence of grade two or more leukopenia was significantly higher in patients with auto-PBSCT than in those without (p=0.014)., Conclusion: Hematopoietic functions after auto-PBSCT may be more vulnerable to RT than normal hematopoietic functions., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)