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Objectives: This crossover randomized controlled clinical trial (RCT) aimed to evaluate the clinical applicability of three-dimensional printed dentures (CAD-3DPs) by comparing two fabricated complete dentures, CAD-3DPs and conventional complete dentures (CCDs), and assess the non-inferiority of CAD-3DPs. The hypothesis was that CAD-3DPs would be inferior to CCDs in terms of the oral health-related quality of life (OHRQoL) and patient satisfaction., Methods: This single-blind RCT was conducted at two university hospitals. The participants included adult patients with edentulous maxillary and mandibular arches, who had existing complete dentures and were willing to use new complete dentures. Eighteen participants were assigned to two groups: CCD-CAD-3DP and CAD-3DP-CCD, based on the order of denture delivery. Both sets of maxillary and mandibular CCDs and CAD-3DPs were delivered to all the participants. The OHRQoL using Oral Health Impact Profile for Edentulous Patients (OHIP-EDENT-J) was considered the primary outcome. General satisfaction using a 100-mm visual analog scale was also evaluated as a suboutcome., Results: Based on the non-inferior test on the total score of the OHIP-EDENT and each score of the seven conceptual subdomains, the lower limit of the 95 % confidence interval was < 2.65 in seven domains. Therefore, CAD-3DP was judged to be non-inferior to CCD. Patient satisfaction was not significantly different between the CCD and CAD-3DP groups (p > 0.05)., Conclusions: This RCT revealed that CAD-3DP is comparable to CCD based on the OHIP-JDENT scores and patient satisfaction., Clinical Significance: CAD-3DP is clinically applicable and comparable to CCD in terms of patient-reported outcomes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Maiko Iwaki reports financial support was provided by Japanese Dental Science Federation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Non-permeable disaccharides are widely used as cryoprotectant agents due to their low cytotoxicity, but their protective effect is insufficient when the disaccharides are present only extracellularly. On the other hand, cryoprotectant agent (CPA)-free cryopreservation has been recently achieved by instantaneously inkjet-freezing cells as tiny droplets. However, CPA-free cryopreservation requires skilled handling operations due to instability of the vitreous water without the CPA. In this study, the effectiveness of separately adding two types of disaccharides in inkjet freezing of 3T3 cells was evaluated and the following results were obtained. First, trehalose showed the highest effect at 0.57 M, twice the plasma osmolarity, with a maximum cell viability of over 90 % when freezing 70 pL droplets. However, higher concentrations of trehalose decreased cell viability due to damage caused by dehydration. Similarly, sucrose gave cell viability close to 90 % at 0.57 M with 70 pL droplets, and higher concentrations decreased cell viability. Next, the relationship between minimum trehalose concentrations to prevent intracellular and extracellular ice crystal formation and droplet size was analyzed. The results indicated that trehalose of less than 0.57 M was able to inhibit intracellular ice crystal formation even in the largest droplet used in this study, 450 pL, while trehalose of nearly 0.57 M was required to inhibit extracellular ice crystal formation in the smallest droplet, 70 pL. In other words, the suppression of extracellular ice crystals by the addition of CPA was shown to be crucial in improving the viability of inkjet superflash freezing., Competing Interests: Declaration of Competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Society for Cryobiology. Published by Elsevier Inc. All rights reserved.)

Background: Although photodynamic-diagnosed transurethral resection of bladder cancer (PDD-TURBT) and Bacillus Calmette-Guérin (BCG) intravesical instillation are the two representative therapies for non-muscle invasive bladder cancer (NMIBC), no studies directly compare their efficacy. We evaluated the outcome of PDD-TURBT alone compared with white light TURBT with intravesical BCG therapy and analyzed the efficacy of both therapies depending on the characteristics of the tumors., Methods: We retrospectively analyzed intermediate- and high-risk NMIBC patients treated with PDD-TURBT alone (the PDD group) or white light TURBT with BCG therapy (the white light group) using propensity score matched analysis., Results: In the propensity score matched cohort, the 1-, 2-, and 3-year recurrence-free survival rates for the PDD group were 77.6 %, 64.1 %, and 48.1 %, respectively, compared to 84.6 %, 75.1 %, and 75.1 % for the white light group (p = 0.44, 0.27, 0.17, respectively). The difference in recurrence rates between the two groups tended to become more pronounced over time, although there was no significant difference. In the univariate and multivariate analysis, recurrence, multiplicity, and tumor grade were the significant prognostic factors of recurrence in the PDD group (p = 0.010, 0.047, 0.048, respectively). Long-term RFS was similar in the PDD and white light groups when the population was limited to the primary and single tumors, suggesting that PDD-TURBT alone may be sufficient in this spectrum of patients., Conclusions: PDD-TURBT alone is insufficient to control the long-term recurrence of bladder cancer but can be effective in selected cases such as primary and single tumors., (Copyright © 2024. Published by Elsevier B.V.)

Background and Purpose: Successful first-pass reperfusion is associated with better functional outcomes after mechanical thrombectomy (MT) for acute ischemic stroke, but its treatment strategies remain unclear., Materials and Methods: We retrospectively recruited patients who underwent MT for M1 occlusion between December 2020 and May 2023 at our institution. The locations of susceptibility vessel sign (SVS) on magnetic resonance imaging were classified into M1 only, M1 to single M2 branch, or M1 to both M2 branches. Patients were included in the SVS tracing group when the stent retriever of the first pass covered the entire SVS length. Successful reperfusion was defined as a modified Thrombolysis in Cerebral Infarction scale 2b-3. Any intracranial hemorrhage detected at 24-hour postoperatively was included as a hemorrhagic complication., Results: The SVS was detected in M1 only, M1 to single M2 branch, and M1 to both M2 branches in 8, 22, and 4 patients, respectively. Among the 34 patients, 27 were included in the SVS-tracing group. Successful first-pass reperfusion was significantly more frequent in the SVS-tracing group compared with the non-SVS tracing group (odds ratio, 14.4; 95% confidence interval, 2.0 - 101; P = 0.007). The procedural time was significantly reduced in the SVS tracing group (median, 29 [interquartile range, 22 - 49] minute vs. 63 [43 - 106] minute; P = 0.043). There was a trend toward less frequent hemorrhagic complications in the SVS tracing group (odds ratio, 0.17; 95% confidence interval, 0.029 - 1.0; P = 0.052)., Conclusions: This study provides a thrombus imaging-based MT strategy to efficiently achieve first-pass reperfusion in M1 occlusion., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Tecovirimat's application in treating mpox remains under-researched, leaving gaps in clinical and virological understanding., Methods: The Tecopox study in Japan evaluated the efficacy and safety of tecovirimat in patients with smallpox or mpox, who were divided into oral tecovirimat and control groups. Patients with mpox enrolled between June 28, 2022, and April 30, 2023, were included. Demographic and clinical details along with blood, urine, pharyngeal swab, and skin lesion samples were gathered for viral analysis. A multivariable Tobit regression model was employed to identify factors influencing prolonged viral detection., Results: Nineteen patients were allocated to the tecovirimat group, and no patients were allocated to the control group. The median age was 38.5 years, and all patients were males. Ten patients (52.6%) were infected with human immunodeficiency virus (HIV). Sixteen patients (84.2%) had severe disease. Nine of the 15 patients (60.0%) (four patients withdrew before day 14) had negative PCR results for skin lesion specimens 14 days after inclusion. The mortality rates were 0% on days 14 and 30. No severe adverse events were reported. HIV status and the number of days from symptom onset to tecovirimat administration were associated with lower Ct values (p = 0.027 and p < 0.001, respectively). The median number of days when PCR testing did not detect the mpox virus in each patient was 19.5 days., Conclusion: Early tecovirimat administration might reduce viral shedding duration, thereby mitigating infection spread. Moreover, patients infected with HIV showed prolonged viral shedding, increasing the transmission risk compared to those without HIV., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: Acute glaucoma is a potential complication of carotid revascularization procedures such as endarterectomy or stenting. Although preoperative ocular hypoperfusion may predispose patients to postoperative glaucoma, the details of this complication have not been clarified., Methods: We retrospectively reviewed the medical records of consecutive patients who underwent carotid revascularization at our institution from January 2019 to December 2022. These patients were divided into glaucoma and nonglaucoma groups. Given the rarity of the event, a systematic literature review was performed to additionally include data from patients who developed acute glaucoma after carotid revascularization. Multivariate logistic regression was performed to identify the risk factors for acute glaucoma., Results: Thirty-five cases, including 2 from our institution, were included in the glaucoma group, and 130 were included in the nonglaucoma group. Most cases (79%) occurred within five days postoperatively. Multivariate analysis revealed that preoperative ocular symptoms were significantly associated with the development of postoperative glaucoma (odds ratio, 361.06; 95% confidence interval, 34.09-3824.27; P < 0.001). Preoperative neovascularization at the iris or anterior chamber angle, indicating severe ocular hypoperfusion, was found in 84% of patients with glaucoma. Permanent visual loss occurred in 41% of patients. The incidence of postoperative glaucoma at our institution was 1.5% (2/132). The positive predictive value of preoperative ocular symptoms for postoperative glaucoma was 0.25 (95% confidence interval, 0.18-0.32)., Conclusions: This study was the first to clarify the risk factors and characteristics of acute glaucoma after carotid revascularization., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly since 2019, and the number of reports regarding long COVID has increased. Although the distribution of long COVID depends on patient characteristics, epidemiological data on Japanese patients are limited. Hence, this study aimed to investigate the distribution of long COVID in Japanese patients. This study is the first nationwide Japanese prospective cohort study on long COVID., Methods: This multicenter, prospective cohort study enrolled hospitalized COVID-19 patients aged ≥18 years at 26 Japanese medical institutions. In total, 1200 patients were enrolled. Clinical information and patient-reported outcomes were collected from medical records, paper questionnaires, and smartphone applications., Results: We collected data from 1066 cases with both medical records and patient-reported outcomes. The proportion of patients with at least one symptom decreased chronologically from 93.9% (947/1009) during hospitalization to 46.3% (433/935), 40.5% (350/865), and 33.0% (239/724) at 3, 6, and 12 months, respectively. Patients with at least one long COVID symptom showed lower quality of life and scored higher on assessments for depression, anxiety, and fear of COVID-19. Female sex, middle age (41-64 years), oxygen requirement, and critical condition during hospitalization were risk factors for long COVID., Conclusions: This study elucidated the symptom distribution and risks of long COVID in the Japanese population. This study provides reference data for future studies of long COVID in Japan., Competing Interests: Conflict of Interest Norihiro Harada reports personal fees from AstraZeneca K.K., GlaxoSmithKline, Kyorin, Novartis Japan, Sanofi and grants from AstraZeneca, Daikin, Kyorin, SRL Medisearch, outside the submitted work. Other authors have no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Mpox virus is known to be transmissible from the onset of clinical manifestations. We report the first case in Japan of a man who contracted mpox through close contact with an individual with pre-symptomatic infection. Given that transmission before symptom onset has recently been reported from various countries, the importance of prophylaxis for reducing the risk of infection and controlling the disease should be emphasized., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: The relationship between the season of birth, allergen sensitization, and allergic rhinitis have been inconsistent, and there are no studies that simultaneously consider vitamin D and allergen exposure. This study aimed to determine the associations between the season of birth, house dust mite (HDM) and Japanese cedar pollen (JCP) sensitization, and allergic rhinitis and pollinosis, while taking vitamin D levels and allergen exposure into account., Methods: This study included 4323 participants in the Sub-Cohort Study of the Japan Environment and Children's Study. A logistic regression model was used to analyze the association between the season of birth and sensitization to JCP or HDM (judged by specific immunoglobulin E) at age 2 and allergic rhinitis or pollinosis at age 3, adjusted for HDM or JCP exposure and vitamin D levels with potential confounders., Results: Participants born in spring or summer were more likely to have pollinosis than were those born in winter (adjusted odds ratio [aOR]: 2.08, 95% confidence interval [CI]: 1.13-3.82 for spring; aOR: 1.89, 95% CI: 1.03-3.47 for summer). Participants born in summer were more likely to have HDM sensitization than were those born in winter (Der p 1, aOR: 1.53, 95% CI: 1.10-2.15; Der f 1, aOR: 1.44, 95% CI: 1.03-2.01). Exposure to JCP and HDM were associated with pollinosis and HDM sensitization, respectively., Conclusions: Spring and summer births were associated with the development of pollinosis, and summer birth was associated with HDM sensitization, even when vitamin D and allergen exposure were considered. Further studies on mechanisms other than vitamin D and allergen exposure are required., (Copyright © 2023 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.)

Objective: Transcranial electrical stimulation motor evoked potentials (TES-MEP) are widely used to monitor motor function; however, broad current spread and induced body movement are limitations of this technique. We herein report a localized stimulation technique for TES-MEP that induces unilateral MEP responses., Methods: The stimulation of C1(+)-C4(-) or C2(+)-C3(-) was performed to induce right- or left-sided muscle contraction, respectively, in 70 patients. Electromyography was recorded by placing electrodes on the bilateral abductor pollicis brevis (APB) and abductor hallucis (AH) muscles. Stimulation conditions were regulated in the range to induce unilateral muscle contractions contralateral to the anodal stimulation. The thresholds and amplitudes of TES-MEP were retrospectively analyzed., Results: The thresholds of APB were lower than those of AH in 47 patients, AH thresholds were lower than those of APB in 6 patients, and both APB and AH started to respond at the same intensity in 15 patients. This technical stimulation induced contralateral limb contractions with a suprathreshold stimulation of 129.4 ± 35.6 mA (mean ± standard deviation) in 68 patients (97%). Amplitudes in the suprathreshold stimulation of APB and AH responses were 727.5 ± 695.7 and 403.3 ± 325.7 μV, respectively., Conclusions: The C1(+)-C4/C2(+)-C3(-) stimulation in TES-MEP enables a localized stimulation to induce unilateral MEP responses., Significance: Our stimulation technique enables the stable and safe monitoring of unilateral limbs, and contributes to the reliable monitoring of motor function in neurosurgery., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: The differential diagnosis of neuropathic pain, especially discrimination between neuropathic pain caused by spinal canal stenosis (SCS) and neuropathic pain associated with causes other than SCS, is sometimes difficult; however, it is important for surgical application., Methods: We established a reliable method for measuring lysophosphatidylcholine (LPC), a precursor of lysophosphatidic acids which are known as being pain initiators, using a liquid chromatography-tandem mass spectrometry method, and measured the LPC concentrations in the cerebrospinal fluid (CSF) in patients with SCS (SCS group; n = 76), patients with neuropathic pain caused by non-SCS diseases (Others group; n = 49), and control subjects without pain (control group; n = 92)., Results: Both within-run and between-run CV(%) were almost < 10 %, suggesting an enough performance for clinical introduction. The CSF concentrations of LPC (16:0) and LPC (18:0) were higher in the SCS group than those in the Control or Others group; the concentrations of LPC (18:1), LPC (18:2), LPC (20:4), LPC (22:6) levels were higher in the SCS group than those in the control or others group, but they were also higher in the Others group than those in the control group. The areas under the curve in the ROC curve analyses of LPC (18:1) for discriminating between the SCS and control groups, others and control groups, and SCS and others groups were 0.994, 0.860, and 0.869, respectively., Conclusions: LPC measurement in the CSF is useful for the differential diagnosis of neuropathic pain, especially for surgical decision-making, which is expected for clinical introduction., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Anterior nasal sampling (AN) might be more convenient for patients than NP sampling to diagnose coronavirus disease. This study investigated the feasibility of rapid antigen tests for AN sampling, and the factors affecting the test accuracy., Methods: This single-center prospective study evaluated one qualitative (ESP) and two quantitative (LUMI and LUMI-P) rapid antigen tests using AN and NP swabs. Symptomatic patients aged 20 years or older, who were considered eligible for reverse-transcription quantitative polymerase chain reaction using NP samples within 9 days of onset were recruited. Sensitivity, specificity, and positive and negative concordance rates between AN and NP samples were assessed for the rapid antigen tests. We investigated the characteristics that affected the concordance between AN and NP sampling results., Results: A total of 128 cases were recruited, including 28 positive samples and 96 negative samples. The sensitivity and specificity of AN samples using ESP were 0.81 and 1.00, while those of NP samples were 0.94 and 1.00. The sensitivity of AN and NP samples was 0.91 and 0.97, respectively, and specificity was 1.00, for both LUMI and LUMI-P. The positive concordance rates of AN to NP sampling were 0.87, 0.94, and 0.85 for ESP, LUMI, and LUMI-P, respectively. No factor had a significant effect on the concordance between the sampling methods., Conclusions: ESP, LUMI, and LUMI-P showed practical diagnostic accuracy for AN sampling compared to NP sampling. There was no significant factor affecting the concordance between AN and NP sampling for these rapid antigen tests., Competing Interests: Declaration of competing interest K.Yamamoto received research grants from Fujirebio Inc. for their submitted work, and received research grants from Mizuho Medy, Co., Ltd., and VisGene Inc., outside the submitted work. S. Yagi, H. Nojima, and K. Yamakawa are employees of Fujirebio Inc. N. Ohmagari received grants from Sanofi K.K., Japan, and Eiken Chemical Co. Ltd., Japan, outside the submitted work., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objective: In elderly populations, the enlargement of the perivascular space is related to small vessel disease and the glymphatic system. Enlarged perivascular spaces (EPVS) in the basal ganglia (EPVS-BG) and EPVS in the centrum semiovale (EPVS-CSO) are associated with different pathophysiological processes. However, the prevalence of EPVS and the factors associated with EPVS location in healthy middle-aged individuals are still unclear. We aimed to determine the prevalence of EPVS and the factors associated with EPVS location among healthy individuals in their 40 s METHODS: This study included 5000 consecutive healthy individuals who underwent screening for brain diseases in Japan from August to December 2018. Of them, the data of individuals in their 40 s were extracted and analyzed. The associations of age, sex, body mass index, smoking and drinking history, and medical history with EPVS location were investigated. Similar analyses were performed for the other age groups. A literature review on the factors associated with EPVS location was also performed., Results: A total of 1720 individuals in their 40 s were finally included. The prevalence of EPVS-BG and EPVS-CSO was 7.7% and 9.2%, respectively. Age (years), smoking history, and hypertension were associated with EPVS-BG; none of the studied factors were found to be associated with EPVS-CSO. In the elderly, the factors previously reported to be associated with EPVS-BG included atherosclerosis change, while the factors associated with EPVS-CSO were cerebral amyloid angiopathy-related formation., Conclusion: Both EPVS-BG and EPVS-CSO occurred among healthy individuals in their 40 s, but they did so rarely, and less prevalently than in older age groups. EPVS-BG and EPVS-CSO may represent early imaging signs of the atherosclerotic and cerebral amyloid angiopathy processes, respectively., Data Availability: The anonymized data for this study will be shared upon any qualified investigator's request to the corresponding author. Primary data from this study will be made available upon reasonable request in accordance with the review board of the research institute., Competing Interests: Declaration of Competing Interest Dr. Kitamura receives personal fees from Medical Network Systems, MNES Inc., related to this work. Mr. Tomoaki Hamano, as the CEO of SmartScan, Inc., receives officers' remuneration from SmartScan, Inc., and holds more than 5% of SmartScan shares. All the other authors report that they have no conflict of interest to disclose., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The pathophysiology underlying vertebrobasilar dolichoectasia (VBD) is largely unknown. However, a few reports have demonstrated that acute intramural hematoma (IMH) in VBD is associated with stroke. We aimed to investigate the clinical and radiological features of IMH in VBD and the role of IMH in predicting rupture and patient outcomes., Methods: We retrospectively reviewed the medical records of patients treated in 2 stroke centers between January 2012 and December 2021. Patients presenting with VBD and stroke were eligible for study inclusion. We excluded patients with stroke caused by arterial dissection or artery-to-artery embolism. IMH was defined as a crescent-shaped area of high signal density in the vessel wall on axial computed tomography in the absence of an intimal flap, double lumen, and pearl-and-string sign., Results: Six patients were analyzed. All presented with symptoms of brainstem/cerebellar infarction without headache. Interobserver agreement for the presence or absence of IMH was excellent (100%). IMH was detected in 5 patients. The positive predictive value of IMH for rupture was 80% (95% confidence interval, 28%-99.5%). The median time from symptom onset to rupture was 2.5 days (range, 1.5-4). Median computed tomography values were significantly higher within the IMH than those in the lumen of the basilar artery (70 vs. 44.5 Hounsfield units; P = 0.008). The modified Rankin scale score on day 30 after onset was 5 in 1 patient and 6 in the remaining 5., Conclusions: IMH in patients with VBD presenting with brainstem/cerebellar infarction should be regarded as a sign associated with a high risk of rupture., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Indications for adjuvant chemotherapy for advanced gastric cancer are determined based on the pathological diagnosis. However, macroscopic diagnoses have been reported as predictors of peritoneal recurrence and survival. This study investigated the predictability of peritoneal recurrence and survival based on macroscopically (sT) and pathologically (pT) diagnosed serosal invasion to identify more sensitive predictors of peritoneal recurrence., Methods: This study included 396 patients who underwent R0 resection without adjuvant chemotherapy with S-1 in the JCOG0110 study. Tumor depth limited to the subserosa (SS) was defined as serosal invasion negative (T-), while tumors with serosal invasion (SE, SI) were defined as serosal invasion positive (T+). The predictability of peritoneal recurrence based on sT and pT was evaluated using the Fine and Gray model. Cox regression analyses were performed for overall survival (OS) and relapse-free survival (RFS) with sT or pT as covariates., Findings: A total of 150 patients (37.9%) were sT+ and 82 (26.3%) were pT+. Sixty-two patients (15.7%) were sT+/pT+, 88 (22.2%) were sT+/pT-, 20 (5.1%) were sT-/pT+, and 226 (57.1%) were sT-/pT-. Both sT and pT were found to be independent predictors of peritoneal recurrence, OS, and RFS. The 5-year RFS rates of sT+/pT+, sT+/pT-, sT-/pT+, and sT-/pT-patients were 45.2%, 63.6%, 55.0%, and 81.8%, respectively., Conclusion: Intraoperatively diagnosed macroscopic serosal invasion showed a similar predictive value for peritoneal recurrence as pathologically diagnosed serosal invasion. The establishment of a novel staging system incorporating macroscopic serosal invasion is recommended., Competing Interests: Declaration of competing interest MT reports lecture fees from Taiho Pharmaceutical, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol-Myers Squibb, Yakult Honsha, Takeda Pharmaceutical, Eli Lilly Japan KK, Pfizer Pharmaceutical, Daiichi Sankyo, Johnson and Johnson, Medtronic Japan, Intuitive Japan, Olympus outside the submitted work. JM reports the funding from National Cancer Center, Japan and the Ministry of Labour and Welfare, Japan for the present study, and personal fees from Chugai Pharmaceutical, outside the submitted work. TS reports personal fees from Taiho Pharma, Chugai Pharma, Ono Pharma, Eli Lilly, outside the submitted work. TY reports grants from Eli Lilly japan, personal fees from MSD, BMS, Ono, Taiho, Lilly, Chugai, Pfizer, Nihon Kayaku, Terumo, Otsuka, Myarisan, EA pharma, Astra-Zeneca, Covidien, Johnson and Johnson outside the submitted work. NB received a research grant from Ono and Takeda and honorarium from Taiho, Ono, Bristol-Myers Squibb outside the submitted work. MS reports lecture fees from Taiho Pharmaceutical and Eli Lilly, travel support from Eli Lilly outside the submitted work, and has served as Chairman of the board of directors of the Japan Gastric Cancer Association and member of the Guideline committee of the Japan Gastric cancer Association during the study period. All the other authors declare no competing interests. Red lines represent serosal invasion positive and blue lines represent serosal invasion negative. The C-index was calculated using the Fine and Gray model., (Copyright © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Deaths of home-care patients with coronavirus disease (COVID-19) have become a social problem. One of their causes is hypoxemia without dyspnea which delays seeking medical attention. This was a retrospective study including patients registered in the COVID-19 Registry Japan, in which hospitalized patients with COVID-19 in 227 participating healthcare facilities were enrolled. The enrolled patients were divided into two groups: non-dyspneic patients with a peripheral capillary oxygen saturation (SpO 2 ) ≤ 93% on admission (the hypoxemia without dyspnea group) and non-dyspneic patients with an SpO 2 > 93% (the control group). We conducted a multivariate logistic regression analysis to identify the factors associated with hypoxemia without dyspnea. 21544 patients were enrolled, 1035 (4.8%) patients were in the hypoxemia without dyspnea group, and 20509 (95.2%) patients were in the control group. The median respiratory rate (RR) of the hypoxemia without dyspnea group was higher than that of the control group (31/min vs. 18/min, p < 0.001). Age> 65, male, body mass index> 25, smoking, chronic obstructive pulmonary disease, other chronic lung disease, and diabetes mellitus were the independent factors associated with hypoxemia without dyspnea. Patients with those background should be closely monitored. RR is an important indicator of hypoxemia, even in the absence of dyspnea., Competing Interests: Conflict of Interest All authors report no conflicts of interest relevant to this article., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: To alleviate the overflow of coronavirus disease 2019 (COVID-19) patients in hospitals, less invasive and simple criteria are required to triage the patients. We evaluated the relationship between COVID-19 severity and fatty liver on plain computed tomography (CT) scan performed on admission., Methods: In this retrospective cohort study, we considered all COVID-19 patients at a large tertiary care hospital between January 31 and August 31, 2020. COVID-19 severity was categorized into severe (moderate and severe) and non-severe (asymptomatic and mild) groups, based on the Japanese National COVID-19 guidelines. Fatty liver was detected on plain CT scan. Multivariate logistic regression analysis was performed to evaluate factors associated with severe COVID-19., Results: Of 222 patients (median age: 52 years), 3.2%, 58.1%, 20.7%, and 18.0% presented with asymptomatic, mild, moderate, and severe COVID-19, respectively. Although 59.9% had no fatty liver on plain CT, mild, moderate, and severe fatty liver occurred in 13.1%, 18.9%, and 8.1%, respectively. Age and presence of fatty liver were significantly associated with severe COVID-19., Conclusion: Our study showed that fatty liver on plain CT scan on admission can become a risk factor for severe COVID-19. This finding may help clinicians to easily triage COVID-19 patients., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Introduction: The ability to predict which patients with a history of coronavirus disease (COVID-19) will exhibit a high antibody titer is necessary for more efficient screening of potential convalescent plasma donors. We aimed to identify factors associated with a high immunoglobulin G (IgG) titer in Japanese convalescent plasma donors after COVID-19., Methods: This cross-sectional study included volunteers undergoing screening for convalescent plasma donation after COVID-19. Serum anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S-protein IgG antibodies were measured using a high-sensitivity chemiluminescence enzyme immunoassay., Results: IgG antibodies were measured in 581 patients, 534 of whom had full information of selected independent variables. Multiple linear regression analysis revealed that increasing age (1.037 [1,025, 1.048]), days from symptom onset to sampling (0.997 [0.995, 0.998]), fever (1.664 [1.226, 2.259]), systemic corticosteroid use during SARS-CoV-2 infection (2.382 [1.576, 3.601]), and blood type AB (1.478 [1.032, 2.117]) predict antibody titer., Conclusion: Older participants, those who experienced fever during infection, those treated with systemic corticosteroids during infection, those from whom samples were obtained earlier after symptom onset, and those with blood type AB are the best candidates for convalescent plasma donation. Therefore, these factors should be incorporated into the screening criteria for convalescent plasma donation after SARS-CoV-2 infection., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Palmoplantar pustulosis (PPP) is a chronic pustular dermatosis on the palms and soles. Dental focal infections are known as the major worsening factor for PPP. Recent our study of oral microbiome demonstrated dysbiosis in PPP patients. While almost half of the PPP patients improved after treatment of dental focal infections, a certain number of patients did not improve., Objective: To investigate the oral microbial factors affecting the clinical course of PPP after treatment of dental focal infection., Methods: The oral microbiota of healthy controls (n = 10), improved (n = 7) and not-improved (n = 6) patients were analyzed by sequencing of bacterial 16S ribosomal RNA gene., Results: The UniFrac analysis suggested the differences of oral microbiota between improved and not-improved patients. The prevalence of the phylum Proteobacteria was lower in improved patients than in not-improved patients. When the alpha microbial diversity was assessed by Shannon index, Pielou's index and the average operational taxonomic units (OTUs), not-improved patients had a lower-diversity microbiota compared to improved patients. The degree of changes of oral microbiota after dental focal infection treatment was higher in improved patients than in not-improved patients. Six genera showed significant correlation with blood test data of PPP patients., Conclusion: Our findings suggested that oral microbial compositions and diversity could account for the distinct clinical course of PPP patients after treatment of dental focal infection. Oral microbiome analysis of PPP patients may provide a predictive factor for clinical responsiveness to dental focal infection treatment., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2021 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)

Objective: The present study investigated the effects of the stimulus polarity and location of motor evoked potential (MEP) to establish a stimulation protocol., Methods: Nineteen patients who intraoperatively underwent MEP in bipolar direct cortical stimulation were enrolled in the present study. Somatosensory evoked potentials (SEP) of the contralateral median nerve stimulation were recorded to determine stimulation sites. MEP was performed under two settings in all patients: 1. Anodal bipolar stimulation: an anode on the precentral gyrus and a cathode on the postcentral gyrus, 2. Cathodal bipolar stimulation: a cathode on the precentral gyrus and an anode on the postcentral gyrus. MEP amplitudes and the coefficient of variation (CV) at a stimulation intensity of 25 mA and the thresholds of induced MEP were compared between the two settings., Results: An electrical stimulation at 25 mA induced a significantly higher amplitude in cathodal bipolar stimulation than in anodal bipolar stimulation. Cathodal bipolar stimulation also showed significantly lower thresholds than anodal stimulation. CV did not significantly differ between the two groups., Conclusions: These results indicate that cathodal bipolar stimulation is superior to anodal bipolar stimulation for intraoperative MEP monitoring., Significance: MEP in cathodal bipolar cortical stimulation may be used in a safe and useful evaluation method of motor fiber damage that combines sensitivity and specificity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: Hair dye use frequently induces allergic contact dermatitis, and on rare occasions induces immunoglobulin E-mediated immediate urticaria, anaphylaxis, and asthma. The effects of hair dye use during pregnancy on offspring have been studied for carcinogenicity, but not for development of allergies. This study aimed to assess the association between hair dye use during pregnancy and allergic disease in children at 3 years old., Methods: Data of 77,303 participants from the Japan Environment and Children's Study, which is a prospective birth cohort recruited from January 2011 to March 2014, were used. We examined the associations between using hair dye during pregnancy and allergic diseases (food allergy, asthma, atopic dermatitis and allergic rhinitis) in children after adjustment for covariates by multivariable logistic regression., Results: Among mothers who were exposed to hair dye during pregnancy, 50.0% were exposed in hair salons, 21.3% had home use, and 9.5% had occupational exposure. The percentages of doctor-diagnosed allergies at 3 years old were 6.3% for food allergies, 7.7% for asthma, 7.3% for atopic dermatitis, and 4.6% for allergic rhinitis. In univariable analyses, hair dye use at home and occupational exposure was significantly associated with asthma respectively (odds ratio [OR] 1.15, 95% CI 1.07-1.24 for at home; OR 1.18, 95% CI 1.08-1.28 for occupational exposure). Hair dye use at home were significantly associated with doctor-diagnosed allergic rhinitis at 3 years old (OR 1.12, 95% CI 1.02-1.22). After adjustment for covariates, these associations for asthma decreased and were no longer significant (aOR 1.06, 95% CI 0.98-1.14 for at home; aOR 1.09, 95% CI 1.00-1.20 for occupational exposure, p = 0.057), also for allergic rhinitis (aOR 1.07, 95% CI 0.97-1.19). Doctor-diagnosed allergic rhinitis at 3 years old was significantly associated with hair dye use at home in the most frequent use group (aOR for quite often versus never 1.78, 95% CI 1.22-2.60)., Conclusion: Both home and occupation use of hair dye during pregnancy showed a trend of increased odds of allergic rhinitis and asthma in offspring at 3 years. However, the only association that reached significance was in frequency of use analyses between the highest frequency of home hair dye users and allergic rhinitis., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The aim of this study was to describe the clinical and radiological findings of COVID-19 patients with "silent hypoxia," who had no dyspnea on admission even though their oximetry saturation was less than 94%. This retrospective cohort study included all COVID-19 patients (n = 270) at a large tertiary care hospital between January 31 and August 31, 2020. Clinical and radiological characteristics of patients who met our criteria of "silent hypoxia", which included those who reported no dyspnea even though oximetry saturation was <94%, were extracted. Eight patients (3.0%) met the criteria for "silent hypoxia." The median age was 61 years (interquartile range [IQR]: 48.8-72.3), and five (62.5%) were men. All patients had consolidation on CT and showed a moderate to high COVID-19 CT severity score (median: 13.5, IQR: 10.8-15.3). The median FIO2 of the maximum oxygen required was 55 (IQR: 28-70)%. Two patients (25.0%) were intubated, and one patient (12.5%) underwent extracorporeal membrane oxygenation. Some COVID-19 patients with "silent hypoxia" may develop severe disease. Close and accurate monitoring of patients using arterial blood gas and pulse oximetry is necessary, regardless of their symptoms., (Copyright © 2021. Published by Elsevier Ltd.)

Objectives: Improvement of patient visual outcome is very important in the treatment of clinoidal meningioma (CLM). The purpose of this study is to determine the association between arachnoid preservation and visual outcome., Patients: Fifteen patients with CLMs that caused visual impairment underwent surgery in our hospital. The patients included 4 men and 11 women, and the mean age was 53.3 years., Methods: The clinical findings of these patients were retrospectively reviewed. We divided the patients into two groups based on the presence or absence of the arachnoid membrane. Group 1 comprised cases in which arachnoid preservation was intraoperatively confirmed. Group 2 comprised cases in which the arachnoid membrane was not preserved. The Landolt C chart was used to evaluate visual acuity, and dynamic visual field tests using Goldmann perimetry were used to evaluate the visual field. Results were compared before and after surgery., Results: The visual acuity of the ipsilateral eye was significantly improved in Group 1 (p = 0.038). There were no other significant differences between the two groups in terms of tumor volume, patient age, and symptom duration., Conclusions: Patients in which arachnoid preservation could be intraoperatively confirmed had good improvement in visual acuity. Further research with an increased number of cases is needed to confirm these findings., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Severe hypotension is a notable adverse event caused by administration of 5-aminolevulinic acid (5-ALA) during photodynamic diagnosis-assisted transurethral resection of bladder tumor (PDD-TURBT). Hypotension can be prolonged following induction of anesthesia and may require continuous administration of a vasopressor. Here, we investigated the risk factors for severe hypotension caused by oral administration of 5-ALA., Methods: A total of 128 patients with bladder tumors who underwent PDD-TURBT using 5-ALA were included in this study. Clinicopathological data were collected retrospectively and the correlations between the incidence of severe hypotension and clinicopathological factors were analyzed., Results: Severe hypotension developed in 8 cases (6.3 %). Age ≥ 80 years, body mass index (BMI) ≥ 25 (kg/m 2 ), and estimated glomerular filtration rate (eGFR) < 45 (mL/min/1.73 m 2 ) were significantly correlated with severe hypotension (P = 0.003, 0.017, and 0.027, respectively). Severe hypotension developed in 1 of 89 cases (1.1 %) which have 0 or 1 risk factor, and in 3 of 31 cases (9.7 %) which have 2 risk factors, whereas it developed in 4 of 8 cases (50 %) which have all risk factors. Patients with all risk factors developed severe hypotension significantly more frequently compared with patients with 1 or fewer risk factors (P < 0.001)., Conclusion: Age ≥ 80 years, BMI ≥ 25, and eGFR < 45 are risk factors for severe hypotension in PDD-TURBT using 5-ALA. The risk of developing severe hypotension is extremely high in patients who have all factors. Adjustment of the 5-ALA dose may be desirable in those patients., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Aneurysmal subarachnoid hemorrhage (aSAH) in the elderly often has a poor prognosis even after surgical treatment in the acute phase. Additionally, subarachnoid clots are the strongest predictors of cerebral vasospasm and tend to be thicker and heavier due to cerebral atrophy. We aimed to compare the conventional surgical treatment in such patients and identify the independent predictors of a favorable outcome after aggressive surgical clot removal., Methods: We included 40 patients with aSAH aged 70 or older. Each patient underwent aneurysmal clipping. We used the modified Rankin Scale to assess the primary outcome of neurologic status at discharge. We performed univariate analysis using the following factors: sex, age, neurologic, and general medical condition, radiographic data, aneurysm location, treatment approach, and timing of the aneurysm surgery. We divided the patients into irrigation and nonirrigation groups. We focused mainly on subarachnoid clots and analyzed them semiquantitatively using computed tomography., Results: Clot removal was significantly greater in the irrigation group (n = 21) than in the nonirrigation group (n = 19). The period of intrathecal drainage was significantly shorter in the irrigation group (P = 0.002). The rate of occurrence of new low-density areas on CT scans was higher in the nonirrigation group. Outcomes were better in the irrigation group (P = 0.010)., Conclusions: In elderly patients with aSAH in the acute phase, aggressive surgical clot removal after clipping showed favorable outcomes by facilitating early out-of-bed mobilization., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Some studies have reported that long-term prognosis after pneumonia is poor. Our aim was to determine predictors of long-term outcomes with special attention to community-acquired pneumonia (CAP) etiology., Methods: We studied 1930 patients who were hospitalized with CAP from January 2002 through November 2017 at Saitama Cardiovascular and Respiratory Center and were discharged alive. We conducted a retrospective study for calculation of survival rate using the Kaplan-Meier method and analysis of prognostic factors by multivariate analysis using a Cox proportional hazard model., Results: The median follow-up period was 442.5 (range 1-5514) days. During this period, 321 patients died. Median survival time was 11.9 years, and 1-year and 5-year survival rates were 93.8% and 74.0%, respectively. Among the patients' demographics factors, old age, poor performance status (PS) score, pneumococcal vaccination history, some underlying respiratory diseases, and chronic heart failure were significant independent factors of poor prognosis. Among pathogens, Streptococcus pneumoniae (hazard ratio [HR]: 1.35, 95% confidence interval [CI]: 1.03, 3.07, P = 0.038) and Pseudomonas aeruginosa (HR: 1.68, 95% CI: 1.07, 2.64, P = 0.024) were significant independent factors of poor prognosis, whereas influenza virus tended to predict a good prognosis (HR: 0.60, 95% CI: 0.36, 1.02, P = 0.058). Respiratory disease accounted for 59% of all causes of death after CAP, and the rate of death from pneumonia was the largest at 22%., Conclusion: Not only age, general condition, and comorbidities but also specific pathogens were predictors of long-term prognosis after hospital discharge for CAP., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Information on the effectiveness of personal protective equipment (PPE) for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among healthcare workers (HCWs), especially among HCWs with frequent contact with patients with SARS-CoV-2, is limited., Methods: We conducted a prospective cohort study on 49 HCWs who worked in close contact with patients with SARS-CoV-2 infection. HCWs had blood samples taken every 2 weeks to test for SARS-CoV-2 antibodies using two different types of assay., Results: Forty-nine participants (31 nurses, 15 doctors, 3 other workers) were enrolled. In total, 112 blood samples are obtained from participants. The median work days in 2 weeks was 9 (interquartile range (IQR): 5-10) days. In a single work day, 30 of the 49 participants (61.5%) had contact with patients with suspected or conformed SARS-CoV-2 at least 8 times, and approximately 60% of participants had more than 10 min of contact with a single patient. The median self-reported compliance to PPE was 90% (IQR: 80-100%). Seven participants tested positive for SARS-CoV-2 antibody using enzyme-linked immunosorbent assay (ELISA); however, none were seropositive for SARS-CoV-2 neutralizing antibody, so the positive ELISA results were assumed to be false-positive., Conclusions: The study provides evidence that appropriate PPE is sufficient to prevent infection amongHCWs. It is necessary to establish a system that provides a stable supply of PPE for HCWs to perform their duties., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objective: Grade 2 meningioma is more likely to recur than grade 1 meningioma. Recurrence decreases overall survival in patients with grade 2 meningioma. However, the clinical course of grade 2 meningioma with several repeated recurrences is poorly understood. The purpose of this study was to clarify the clinical characteristics of grade 2 meningioma with repeated recurrences., Methods: This study included 28 patients with grade 2 meningioma treated at our institution from January 1994 to December 2017. The relationship between survival and factors including age, sex, number of recurrences, malignant transformation, radiation therapy, tumor location, MIB-1 labeling index, Simpson grade, Karnofsky Performance Status, and surgical interval were analyzed., Results: The average age at the initial operation was 53.4 years. The number of recurrences was 3.7 times on average during the follow-up of 113.9 months after the initial operation. An increasing number of recurrences resulted in shortening of the surgical interval, increase in the MIB-1 labeling index, and decrease in Karnofsky Performance Status. In fatal cases, the average surgical interval before death was approximately 1 year. Three factors were related to poor prognosis: number of recurrences (odds ratio, 1.620; P = 0.030), malignant transformation (odds ratio, 10.625; P = 0.019), and high MIB-1 labeling index (odds ratio, 1.089; P = 0.044)., Conclusions: Shortening of the surgical interval within 1 year because of multiple recurrences led to death in patients with grade 2 meningioma. Malignant transformation was the most potent among the poor prognostic factors., (Copyright © 2020. Published by Elsevier Inc.)

Cell cryopreservation stops the biological activity of cells by placing them in the frozen state, and can be used to preserve cells without subculturing, which can cause contamination and genetic drift. However, the freezing process used in cryopreservation can injure or damage the cells due to the cytotoxicity of cryoprotecting agents (CPAs). We have previously reported a CPA-free cryopreservation method based on inkjet technology. In this method, the vitrified cells were exposed to the room temperature atmosphere during the transport of the cells using tweezers, which caused devitrification due to the increased temperature and often lowered the cell viability. In the present study, we developed an automatic thawing apparatus that transports the vitrified cells rapidly into a prewarmed medium using a spring hinge. Observations with a high-speed camera revealed that the spring hinge drops the cells into the prewarmed medium within 20 ms. All heat-transfer simulations for the apparatuses with different designs and rotation speeds showed that the cells remained below the glass-transition temperature during the transport. Finally, the apparatus was evaluated using mouse fibroblast 3T3 cells. The cell viability was improved and its reproducibility was enhanced using this apparatus. The results indicate that the combination of superflash freezing with the rapid thawing process represents a promising approach to circumvent the problems typically associated with the addition of CPAs., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Excessive extracellular matrix deposition, in particular collagen, is an important cause of lung fibrosis. Heat shock protein 47 (HSP47), a collagen-binding protein, plays an important role in the intracellular processing of procollagen. A small molecule that blocks the collagen chaperone function of HSP47 has been reported as an HSP47 inhibitor. The aim of this study was to assess the effect of the HSP47 inhibitor on collagen synthesis and other fibrotic process in vitro. We evaluated collagen expression by western blot, and determined cell viability and migration by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and scratch test, respectively, in human and mouse lung fibroblasts. Treatment of lung fibroblasts with HSP47 siRNA decreased collagen type I expression. Similarly, the HSP47 inhibitor decreased collagen type I expression in transforming growth factor beta 1 (TGF-β1)-treated lung fibroblasts in a dose-dependent manner. The inhibitor also decreased the viability and cell migration ability of TGF-β1-treated lung fibroblasts. Overall, we demonstrated that HSP47 is a potential therapeutic target for pulmonary fibrosis. The small molecule HSP47 inhibitor may mediate antifibrotic effects by suppressing the overexpression of collagen, and inhibiting the viability and migration of fibroblasts. Further research is needed to clarify the therapeutic potential of this HSP47 inhibitor for pulmonary fibrosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: This study aimed to compare the functional outcome at discharge for unruptured cerebral aneurysms (UCAs) between surgical clipping and endovascular coiling in total, nonelderly (<65 years), and elderly (≥65 years) patients by nonbiased analysis based on a national database in Japan., Methods: A total of 15,671 patients with UCA were registered in the Diagnosis Procedure Combination, the nationwide database, from 2010 to 2015 in Japan. The outcome of the Barthel Index (BI) at discharge was investigated, and propensity score-matched analysis was conducted in total, nonelderly, and elderly patient groups., Results: Propensity score-matched analysis found no significant difference for in-hospital mortality between the 2 treatment methods in the total and both age-groups. The rate of morbidity of BI <90 at discharge was higher after surgical clipping than after endovascular coiling in the total (4.9% vs. 3.9%; P = 0.040; risk difference, -1.0%; 95% confidence interval, -3.6 to 2.3%) and the elderly age-group (8.1% vs. 5.0%; P < 0.001; risk difference, -3.1%; -4.8% to 1.5%), however, no significant association between the 2 treatment methods (2.4% vs. 2.6%; P = 0.67; risk difference, 0.22%; -0.79 to 1.22%) was found in the nonelderly group., Conclusions: In elderly patients with UCA, a better outcome at discharge after endovascular coiling was found. However, no significantly different functional outcome at discharge between surgical clipping and endovascular coiling for UCA in nonelderly patients was confirmed by propensity score-matched analysis from a nationwide database in Japan., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The purpose of the present study was to characterize current biopharmaceutics modeling and simulation software regarding the prediction of the fraction of a dose absorbed (Fa) in humans. As commercial software products, GastroPlus™ and Simcyp® were used. In addition, the gastrointestinal unified theoretical framework, a simple and publicly accessible model, was used as a benchmark. The Fa prediction characteristics for a total of 96 clinical Fa data of 27 model drugs were systematically evaluated using the default settings of each software product. The molecular weight, dissociation constant, octanol-water partition coefficient, solubility in biorelevant media, dose, and particle size of model drugs were used as input data. Although the same input parameters were used, GastroPlus™, Simcyp®, and the gastrointestinal unified theoretical framework showed different Fa prediction characteristics depending on the rate-limiting steps of oral drug absorption. The results of the present study would be of great help for the overall progression of physiologically based absorption models., (Copyright © 2020 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Objective: There has been no precise guide for treatment management of aneurysmal subarachnoid hemorrhage (aSAH) based on the patient's age and treatment method. This study clarifies each risk management for aSAH according to age and treatment method listed in a nationwide database., Methods: We compared 2 groups of patients (nonelderly, <65 years; elderly, ≥65 years) who underwent surgical clipping or endovascular coiling and were registered in a nationwide database in Japan from 2010 to 2015. The odds ratio (OR) and 95% confidence interval (CI) of each risk factor were calculated through multivariate logistic regression analysis for poor outcome according to a modified Rankin Scale score >2 at discharge for each group., Results: In all groups, the risk factors for poor outcome were older age, male sex, neurologic grade on admission, diabetes mellitus, and use of anticoagulation drugs. Inverse risk factors were a high-volume hospital, academic hospital, hypertension, and use of an antiplatelet drug (OR, 0.63-0.81; 95% CI, 0.56-0.88). Chronic heart disease was also a risk factor, but use of a statin drug (OR, 0.85-0.87; 95% CI, 0.76-0.97) and location other than on the anterior communicating artery (OR, 0.74-0.80; 95% CI, 0.67-0.91) were inverse risks in both the elderly and the endovascular coiling groups., Conclusions: Management for patients with aneurysmal subarachnoid hemorrhage was recommended in high-volume and academic institutes with the administration of antiplatelet drugs and consideration of several risk factors. Elderly patients undergoing endovascular coiling might be better given a statin drug, and patients with chronic heart failure or an anterior communicating artery aneurysm should be treated more carefully., (Copyright © 2019. Published by Elsevier Inc.)

Background: Proteins, which comprise one of the major classes of biomolecules that constitute a cell, interact with other cellular factors during both their biogenesis and functional states. Studying not only static but also transient interactions of proteins is important to understand their physiological roles and regulation mechanisms. However, only a limited number of methods are available to analyze the dynamic behaviors of proteins at the molecular level in a living cell. The site-directed in vivo photo-cross-linking approach is an elegant technique to capture protein interactions with high spatial resolution in a living cell., Scope of Review: Here, we review the in vivo photo-cross-linking approach including its recent applications and the potential problems to be considered. We also introduce a new in vivo photo-cross-linking-based technique (PiXie) to study protein dynamics with high spatiotemporal resolution., Major Conclusions: In vivo photo-cross-linking enables us to capture weak/transient protein interactions with high spatial resolution, and allows for identification of interacting factors. Moreover, the PiXie approach can be used to monitor rapid folding/assembly processes of proteins in living cells., General Significance: In vivo photo-cross-linking is a simple method that has been used to analyze the dynamic interactions of many cellular proteins. Originally developed in Escherichia coli, this system has been extended to studies in various organisms, making it a fundamental technique for investigating dynamic protein interactions in many cellular processes. This article is part of a Special issue entitled "Novel major techniques for visualizing 'live' protein molecules" edited by Dr. Daisuke Kohda., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: This study aimed to clarify the risk factors of treatment for unruptured cerebral aneurysms (UCAs) in elderly patients by comparing the morbidity at discharge between surgical clipping and endovascular coiling in nonelderly (<65 years) and elderly (≥65 years) patients based on a national database in Japan., Methods: A total of 36,017, including 15,671 patients with UCA after exclusion of unknown location, were registered in the Diagnosis Procedure Combination, the nationwide database, from 2010 to 2015 in Japan. Outcome of Barthel Index at discharge was investigated and multivariate logistic regression analysis identified risk factors for morbidity of Barthel Index <90 at discharge in nonelderly and elderly patient groups., Results: Risk factors for morbidity at discharge were basilar artery aneurysm compared with internal carotid artery (ICA), diabetes mellitus (odds ratio [OR], 2.0-2.5; 95% confidence interval [CI], 1.6-3.7), antiplatelet drug, and anticoagulation drug; however, highest hospital volume compared with lowest was an inverse risk factor in both age groups. Endovascular coiling (OR, 0.4; 95% CI, 0.3-0.5) was a significantly inverse risk in the elderly group. Anterior communicating artery aneurysm compared with ICA was a significant risk (OR, 1.6; 95% CI, 1.0-2.6) in the nonelderly group; on the other hand, anterior communicating artery aneurysm (OR, 0.7; 95% CI, 0.5-0.95) and middle cerebral artery aneurysm (OR, 0.6; 95% CI, 0.5-0.8) compared with ICA were significantly inverse risks in the elderly group., Conclusions: Endovascular coiling after control of diabetes mellitus was recommended for the treatment of UCA in elderly patients. The ICA location of aneurysm in the elderly should be paid attention as the treatment risk., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Several intracranial pathologies present as a ring-enhancing lesion on conventional magnetic resonance imaging (MRI), creating diagnostic difficulty. We studied the characteristics of the anatomical border of gadolinium enhancement on T1-weighted imaging (WI) and hypointensity on T2WI to employ a simple technique of histogram-profile analysis of MRI for differentiation of various ring-enhancing intracranial lesions., Methods: After approval from the institutional review board, preoperative MRI (T2WI, postcontrast T1WI) scans were analyzed retrospectively in 18 patients with histologically confirmed brain abscess, 66 glioblastomas, 46 brain-metastases, and 16 tumefactive multiple sclerosis (MS). T2WI and postcontrast T1WI were overlapped, and histogram-profile analysis was performed with in-house image-fusion software. The pattern of differential-peaks in histogram-profile was assessed visually. Kaplan-Meier survival analysis incorporating histogram-profile patterns was performed in patients with glioblastoma., Results: The histogram-profile study revealed 4 distinct patterns. Pattern 1 showed no differential T2-hypointensity trough, pattern 2 had T2-hypointensity trough inside, whereas pattern 3 had T2-hypointensity trough overlapping the enhanced margin. Pattern 4 had T2-hypointensity trough immediately external to the enhanced margin. Pattern 1 was specific for tumefactive MS (93.3%), whereas pattern 4 was specific for glioblastoma (40.7%). Pattern 4 glioblastoma was subdivided into rim (T2-hypointensity ≥50% of circumference of contrast-enhanced tumor) and arc (T2-hypointensity <50% of circumference of contrast-enhanced tumor). Pattern 4 glioblastoma was further subdivided into group A (edema: T2-hyperintensity ≥50% of circumference of contrast-enhanced tumor) and group B (less edema: T2-hyperintensity <50% of circumference of contrast-enhanced tumor). Patients with pattern 3 glioblastoma (37.6%) had better survival compared with others (P = 0.0341) and pattern 4B had decreased survival compared with pattern 4A (P = 0.0001) and others (P = 0.0003)., Conclusions: Tumefactive MS and a subset of glioblastomas show specific patterns in histogram-profile analysis. The difference in anatomical border also determines difference in survival in glioblastoma. Histogram-profile analysis is a simple and efficient technique to differentiate these pathologies., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The aim of this study was to determine pore size of nylon mesh (NM) device suitable for cryosurvival of bovine mature oocytes and to apply the device to vitrification of large quantities of the oocytes. Ten to twelve oocytes were loaded onto an NM device (a square opening 37-, 57- or 77-μm on a side length). After removal of the excess volume of vitrification solution by paper absorption, the oocytes were vitrified-warmed, fertilized and cultured in vitro. Oocyte recovery and morphological survival were comparable among the three groups. However, blastocyst yield in the 37-μm group (39%) was higher than that in the 77-μm group (28%), and the yield in the 57-μm group (31%) was the intermediate. The 37-μm NM device was applicable for increased oocyte number >40 (blastocyst yield, 33%). These results suggest that 37-μm-pore sized NM can serve as cryodevice to vitrify large quantities of in vitro-matured bovine oocytes., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The purpose of the present study was to evaluate the prediction accuracy of a mechanism-based oral absorption model for the fraction of a dose absorbed (Fa) in dogs, focusing on poorly soluble drugs. As an open mechanism-based model, the gastrointestinal unified theoretical framework was used in this study. The prediction accuracy of the gastrointestinal unified theoretical framework was evaluated using Fa data in dogs (63 data sets for marketed drugs and proprietary compounds). For neutral compounds, Fa was accurately predicted, suggesting that the physiological parameters of dogs were appropriate except for gastrointestinal pH. An extensive literature survey on the small intestinal pH of dogs was then conducted. The result suggested that the pH value ranged between 6.5 and 7.5, with the midst value of 7.0, but there was a great variation among the literature. To confirm the appropriateness of this pH value, the Fa of free acid compounds was predicted by setting the small intestinal pH to 6.5, 7.0, and 7.5. The proportions of compounds with <2-fold error were 57%, 90%, and 76%, respectively. The results of the present study would enable an appropriate use of a mechanism-based model for drug discovery and development., (Copyright © 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)