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We investigated whether intra-arterial administration of carboplatin using Calvert's formula is useful for avoiding thrombocytopenia in targeted chemoradiotherapy in patients with squamous cell cancer of the oral cavity and oropharynx. Carboplatin was infused intra-arterially under digital subtraction angiography in 28 patients. In the first group of patients, the dose of carboplatin was calculated according to the body surface area (BS group). In the second group, the dose was calculated using Calvert's formula (AUC group). The value for AUC (area under concentration vs time curve; mg?ml-1?min-1) in the formula was set at 4.5. All patients received concurrent radiotherapy (30?Gy) and were given oral tegafur-uracil (UFT®, 400-600?mg?day-1). The AUC group showed a significantly lower percentage platelet reduction than the BS group (49.0±22.0 vs 65.1±23.2%; P=0.045) and also tended to have a higher platelet nadir count (10.9±4.2 vs 8.4±5.8 × 104; P=0.27) without reducing the antitumour effect. The value of 4.5 for target AUC is recommended clinically. However, AUC of Calvert's formula could not predict thrombocytopenia associated with intra-arterial chemoradiotherapy due to the variability of the actual AUC.British Journal of Cancer (2004) 90, 2062-2066. doi:10.1038/sj.bjc.6601818 www.bjcancer.com Published online 20 April 2004 [ABSTRACT FROM AUTHOR]

The biomimetic design of a transition metal complex based on the iron(iv)-oxo porphyrin π-cation radical species in cytochrome P450 enzymes has been studied extensively. Herein, we translate the functions of this iron(iv)-oxo porphyrin π-cation radical species to an α-ketoacyl phosphonium species comprised of non-metal atoms and utilize it as a light-activated oxygenation auxiliary for ortho -selective oxygenation of anilines. Visible light irradiation converts the α-ketoacyl phosphonium species to the excited state, which acts as a transiently generated oxidant. The intramolecular nature of the process ensures high regioselectivity and chemoselectivity. The auxiliary is easily removable. A one-pot protocol is also described., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Previous research has revealed that several emotions can be perceived via touch. What advantages does touch have over other nonverbal communication channels? In our study, we compared the perception of emotions from touch with that from voice to examine the advantages of each channel at the emotional valence level. In our experiment, the encoder expressed 12 different emotions by touching the decoder's arm or uttering a syllable /e/, and the decoder judged the emotion. The results showed that the categorical average accuracy of negative emotions was higher for voice than for touch, whereas that of positive emotions was marginally higher for touch than for voice. These results suggest that different channels (touch and voice) have different advantages for the perception of positive and negative emotions., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

The authors have developed a micro-vibration actuator using filiform SMA wire electrically driven by periodic electric current. While applying the SMA actuators to tactile displays, we discovered a phenomenon that the deformation caused by a given stress to an SMA wire generated a change in the electrical resistance. With this characteristic, the SMA wire works as a micro-force sensor with high sensitivity, while generating micro-vibration. In this paper, the micro-force sensing ability of an SMA transducer is described and discussed. Experiments are conducted by sliding the SMA sensor on the surface of different objects with different speeds, and the sensing ability is evaluated to be related with human tactile sensation.

Objective: The goal of this study was to evaluate how listening to different types of music while studying affects learning., Methods and Materials: We conducted a survey to discover people's music listening habits. We designated calculation tasks or memorization tasks and asked students to work on the tasks while listening to nothing or listening to music The types of Western music had three categories: the accent of the singer, the pitch, and the speed. The participants were divided into six groups based on what tasks they did and what types of music they listened to., Results: There was no correlation between the preference of study environment, whether students usually listen to Western music or any music while studying, and the task scores. We found that there was not much difference between the scores of calculations when listening to nothing or listening to some kind of music., Conclusions: It seems that the ideal type of music a student should listen to depends on what they study. It might be a good idea to listening to slow music or music at a low pitch when doing calculation tasks. On the other hand, when doing memorization tasks, it might be a good idea to play music that you have never listened to before., Competing Interests: The authors have declared that no conflicts of interest exist., (© 2022 The Juntendo Medical Society.)

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that shows progressive muscle weakness. A few treatments exist including symptomatic therapies, which can prolong survival or reduce a symptom; however, no fundamental therapies have been found. As a therapeutic strategy, enhancing muscle force is important for patients' quality of life. In this study, we focused on skeletal muscle-specific myosin regulatory light chain kinase (skMLCK), which potentially enhances muscle contraction, as overexpression of skMLCK was thought to improve muscle function. The adeno-associated virus serotype 6 encoding skMLCK (AAV6/skMLCK) and eGFP (control) was produced and injected intramuscularly into the lower limbs of SOD1 G37R mice, which are a familial ALS model. AAV6/skMLCK showed the successful expression of skMLCK in the muscle tissues. Although the control did not affect the muscle force in both of the WT and SOD1 G37R mice, AAV6/skMLCK enhanced the twitch force of SOD1 G37R mice and the tetanic force of WT and SOD1 G37R mice. These results indicate that overexpression of skMLCK can enhance the tetanic force of healthy muscle as well as rescue weakened muscle function. In conclusion, the gene transfer of skMLCK has the potential to be a new therapy for ALS as well as for other neuromuscular diseases.

Background: The objective of this study was to compare the prognostic impact of sarcopenia in patients with head and neck cancer (HNC) treated with surgery or radiation., Methods: We systematically searched electronic databases to identify articles reporting the impact of sarcopenia on the prognosis of patients with HNC. Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) were extracted and pooled. HR according to treatment modality were estimated using random-effects models. Statistical analyses were carried out using the Comprehensive Meta-Analysis software., Results: In total, 18 studies enrolling 3,233 patients were included. Sarcopenia was associated with poor OS in both surgery and radiotherapy groups (hazard ratio [HR] 2.50, 95% confidence interval [CI] 1.95-3.21; HR 1.63, 95% CI 1.40-1.90, respectively). The HR was significantly higher in the surgery group than in the radiotherapy group (p = 0.004), with similar results obtained for DFS (HR 2.59, 95% CI 1.56-4.31; HR 1.56, 95% CI 1.24-1.97 for the surgery and radiotherapy groups, respectively) and DSS (HR 2.96, 95% CI 0.73-11.95; HR 2.67, 95% CI 1.51-4.73 for the surgery and RT groups, respectively)., Conclusions: Sarcopenia was a poor prognostic factor for HNC, regardless of the treatment modality. However, the adverse effects of sarcopenia on survival were more prominent in the surgery group than in the radiotherapy group. Sarcopenia assessment is required for appropriate treatment decision-making., Competing Interests: The authors have declared that no competing interests exist.

Sarcopenia, which is characterized by a decrease in muscle quantity or quality, is commonly observed in patients with cancer. Recent research has reported contradictory results on the association between sarcopenia and the efficacy of immune checkpoint inhibitors (ICIs). We conducted a systematic review and meta-analysis to investigate this discrepancy. We systematically searched three electronic databases to identify articles reporting on the association between sarcopenia and treatment outcomes in patients with solid cancers who received ICIs. The outcomes assessed were hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios (ORs) for objective response rate (ORR), disease control rate (DCR), and toxicity. Pooled estimates and their 95% confidence intervals (CIs) were calculated. A total of 2501 patients from 26 studies were analysed. Sarcopenia was observed in 44.7% (95% CI: 38.2-51.3) of the patients and was significantly associated with poor survival (HR = 1.55, 95% CI = 1.32-1.82 for OS and HR = 1.61, 95% CI = 1.35 to 1.93 for PFS). The HRs (95% CIs) for OS according to the diagnostic measures used were 1.97 (0.88-4.41) for psoas muscle index (PMI), 1.41 (0.87-2.28) for skeletal muscle density (SMD), and 1.43 (1.23-1.67) for skeletal mass index (SMI). The HRs (95% CIs) for PFS were 1.86 (1.08-3.21) for PMI, 1.27 (0.94-1.71) for SMD, and 1.38 (1.11-1.71) for SMI. Poor radiological response to ICI therapy was observed in patients with sarcopenia (OR = 0.52, 95% CI = 0.34-0.80 for ORR and OR = 0.45, 95% CI = 0.30-0.67 for DCR). The ORs for ORR (95% CIs) were 0.56 (0.15-2.05) for PMI and 0.78 (0.56-1.09) for SMI. The oncologic outcomes associated with melanoma and non-small cell lung cancer (NSCLC) were comparable with those observed overall (HR for OS = 2.02, 95% CI = 1.26-3.24 for melanoma and HR for OS = 1.61, 95% CI = 1.19-2.18 for NSCLC). In contrast, the occurrence of severe toxicity was not associated with sarcopenia (OR = 1.13, 95% CI = 0.51-2.52). Poor survival and poor response in patients with sarcopenia indicate a negative association between sarcopenia and efficacy of ICIs. Sarcopenia's predictive ability is consistent across various tumour types. For the selection of patients who may respond to ICIs pre-therapeutically, the presence of sarcopenia should be assessed in clinical practice., (© 2021 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

The organ of Corti is an auditory organ located in the cochlea, comprising hair cells (HCs) and other supporting cells. Cellular shape changes of HCs are important for the development of auditory epithelia and hearing function. It was previously observed that HCs and inner sulcus cells (ISCs) demonstrate cellular shape changes similar to the apical constriction of the neural epithelia. Apical constriction is induced via actomyosin cable contraction in the apical junctional complex and necessary for the physiological function of the epithelium. Actomyosin cable contraction is mainly regulated by myosin regulatory light chain (MRLC) phosphorylation by myosin light chain kinase (MLCK). However, MRLC and MLCK isoforms expressed in HCs and ISCs are unknown. Hence, we investigated the expression patterns and roles of MRLCs and MLCKs in HCs. Droplet digital PCR revealed that HCs expressed MYL12A/B and MYL9, which are non-muscle MRLC and smooth muscle MLCK (smMLCK), respectively. Immunofluorescence staining throughout the organ of Corti demonstrated that only MYL12 was expressed in the apical portion of HCs, whereas MYL12 and MYL9 were expressed on ISCs. In addition, purified MYL12B was phosphorylated by smMLCK in vitro, and the harvested HCs contained phosphorylated MYL12. Furthermore, accompanied by the expansion of the cell area of outer HCs, MYL12 phosphorylation was reduced by ML-7, which is an inhibitor of smMLCK. In conclusion, MYL12 phosphorylation by smMLCK contributed to the apical constriction-like cellular shape change of HCs possibly relating to the development of auditory epithelia and hearing function., (© 2021. Association for Research in Otolaryngology.)

Background: This study aimed to examine the association between overtime work and the frequency of preventive dental visits among workers in Japan., Methods: A self-administered questionnaire was completed by 14,847 daytime-workers. We used a logistic regression model stratified by sex and age and adjusted for marital status, occupation, education, and oral status to investigate the association between overtime work hours and the frequency of preventive dental visits., Results: In total 1037 men (9.3%) and 511 women (13.9%) attended quarterly preventive dental visits, and 2672 men (23.9%) and 1165 women (31.8%) attended annual preventive dental visits. Overtime work was statistically significantly associated with quarterly preventive dental visits among men aged 50-59 years, with adjusted odds ratios (aOR) and 95% confidence intervals (CI) of 0.73 (0.56-0.95), 0.75 (0.54-1.04), and 0.55 (0.34-0.90) for < 20, 20-39, and ≥40 h overtime/month, respectively. No such trends were observed for men aged < 50 years and women of all ages. Overtime work of < 20, 20-40, and ≥40 h overtime/month was statistically significantly associated with annual preventive dental visits among men aged 40-49 years (aOR [95%CI]: 0.76 [0.61-0.95], 0.84 [0.65-1.09], and 0.72 [0.51-1.00], respectively) and 50-59 years (aOR [95%CI]: 0.75 [0.61-0.91], 0.76 [0.59-0.97], and 0.63 [0.45-0.88], respectively). No such trends were observed in men < 40 years and women of all ages., Conclusions: Our study revealed associations between overtime and preventive dental visits among male workers aged in their 40s and 50s.

Low protein rice (LPR) by-products were used as a source of novel multifunctional cationic peptides. The LPR by-products were separated by ampholyte-free isoelectric focusing (autofocusing) into 20 fractions containing peptides with different isoelectric points (pIs). Subsequently, the antimicrobial activity of each fraction was evaluated against four pathogenic microorganisms. In addition, the cationic peptides from fractions exhibiting antimicrobial activity were purified using reversed-phase high-performance liquid chromatography and identified using matrix-assisted laser/desorption ionization-time-of-flight mass spectroscopy. Of the 11 cationic peptides identified, five peptides with pI values greater than 9.31 and net charges greater than +2 were chemically synthesized for multiple functionalities, including antimicrobial, lipopolysaccharide (LPS)-neutralizing, and angiogenic activities. Among these five cationic peptides, only LPR-KRK, which had a net charge of +9, exhibited antimicrobial activity against three of the four pathogenic microorganisms tested. Chromogenic LPS-neutralizing assays using Limulus amebocyte lysate showed that the 50% effective concentrations of these five peptides were between 0.11 and 3.09 μM. Tube-formation assays using human umbilical vein endothelial cells showed that all five peptides exhibited significant angiogenic activity at 1 μM and 10 μM, while none exhibited hemolytic activity toward mammalian red blood cells at concentrations up to 500 μM. Our results demonstrate that these five cationic peptides exhibit multiple biological functionalities with little or no hemolytic activity. Thus, fractions containing cationic peptides obtained from LPR by-products have the potential to be used as dietary supplements and functional ingredients in food products., (Copyright © 2019 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

Influenza A H3N2 has been linked to annual outbreaks within the human population attributable to continuous structural changes. H3N2 HA contains well identified antigenic sites and receptor-binding sites (RBS) that are possibly correlated to viral evolution and infection. However, the structural significance of amino acid residues associated with both viral evolution and infection were not fully demonstrated. Throughout this study, we generated and analyzed H3N2 HA models that represented the clade 3C.2 population (comprised of clades 3C.2, 3C.2a, and 3C.21 from the transitioning 2014-2018 H3N2 strains) and 3C.3a (from the 2016 H3N2 strain). Model quality estimation, structural analyses and superimposition, and network analytics of H3N2 HA1 evolution were performed. We found that the structural properties of residues 158-160 could influence the overall HA backbone. More specifically, amino acid substitutions at residues 159-160 affected the amino acid orientation at residue 158, thereby, causing the overall HA backbone structure to vary. Our results were consistent with 1968-2018 HA1 evolution. Taken together, we propose that our results would highlight the structural significance of residues 158-160 in HA1 for both antigenic drift and RBS., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective/hypothesis: Meniere's disease (MD) is a common inner ear disease characterized by repeated episodic vertigo, fluctuating sensorineural hearing loss, and tinnitus. Its pathology is defined as endolymphatic hydrops (EH) in the inner ear and EH has been hypothesized to correlate with the clinical symptoms of MD. We presented the dynamics of in vivo EH in MD patients during medical treatments., Study Design: Prospective, single-arm repeated measures., Methods: Eleven MD patients were enrolled. All subjects prospectively underwent gadolinium-enhanced inner ear magnetic resonance (MR) imaging and neuro-otological testing before and after medical treatment. The volume of EH was quantitatively evaluated by processing MR images. All MD patients were administered continuous medication and followed up for more than 12 months., Results: The frequency of vertigo episodes decreased in all patients and vestibular function decreased to 13-91% of the pre-treatment level. The volume ratio of post-treatment EH-to-pre-treatment EH ranged from 1.01-3.22. The total volume of pre-treatment EH was significantly correlated with cochlear symptom disease duration and the affected ear's hearing level., Conclusion: EH in MD patients developed longitudinally with deterioration of inner ear function during medical treatment. The natural course of MD may progress with development of EH at least for a certain period., Level of Evidence: 2b.

Due to habitual drinking and smoking and advanced age at diagnosis, patients with head and neck squamous cell carcinoma (HNSCC) frequently present with comorbidities. Several comorbidity indices have been developed and validated for HNSCC. However, none have become the standard method. In this study, we developed a new comorbidity index for Japanese patients with HNSCC, which was validated against an independent data set. A Cox proportional hazards analysis of 698 patients identified dementia, connective tissue diseases, and second primary malignancies in the oesophagus, head and neck, lungs, and stomach as prognostic comorbidities for overall survival. The Osaka head and neck comorbidity index (OHNCI) was generated from the weighted points of these comorbidities. In the independent data set, the 5-year overall survival rates for the low, moderate, and high scoring OHNCI groups were 62.1%, 64.3%, and 37.7%, respectively. In the multivariate analysis, the high scoring OHNCI group was an independent prognostic factor for overall survival (hazard ratio: 1.81, 95% confidence interval: 1.05-3.13; P = 0.031). The model including the OHNCI exhibited a higher prognostic capability compared to those including other commonly used comorbidity indices. The OHNCI could become the primary choice for comorbidity assessment in patients with HNSCC in Japan.

Background: Inflammatory markers are used to predict prognosis of nasopharyngeal carcinoma (NPC). Previous reports of neutrophil-to-lymphocyte ratio (NLR) and NPC mortality are inconsistent. This study aimed to quantify the prognostic impact of NLR on NPC., Methods: The primary outcome was overall survival (OS), and the secondary outcomes were disease-specific survival (DSS), progression-free survival (PFS) and distant metastasis-free survival (DMFS). We systematically searched electronic databases, identified articles reporting an association between NLR and NPC prognosis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted, and pooled HRs for each outcome were estimated using random effect models., Results: Nine studies enrolling 5397 patients were included in the analyses. NLR greater than the cutoff value was associated with poor overall survival (HR 1.51, 95% CI 1.27-1.78), disease-specific survival (HR 1.44, 95% CI 1.22-1.71), progression-free survival (HR 1.53, 95% CI 1.22-1.90), and distant metastasis-free survival (HR 1.83, 95% CI 1.14-2.95)., Conclusions: Elevated NLR predicts worse OS, DSS, PFS and DMFS in patients with NPC.

Background: Previous studies have tried to relieve deafferentation pain (DP) by using virtual reality rehabilitation systems. However, the effectiveness of multimodal sensory feedback was not validated. The objective of this study is to relieve DP by neurorehabilitation using a virtual reality system with multimodal sensory feedback and to validate the efficacy of tactile feedback on immediate pain reduction., Methods: We have developed a virtual reality rehabilitation system with multimodal sensory feedback and applied it to seven patients with DP caused by brachial plexus avulsion or arm amputation. The patients executed a reaching task using the virtual phantom limb manipulated by their real intact limb. The reaching task was conducted under two conditions: one with tactile feedback on the intact hand and one without. The pain intensity was evaluated through a questionnaire., Results: We found that the task with the tactile feedback reduced DP more (41.8 ± 19.8 %) than the task without the tactile feedback (28.2 ± 29.5 %), which was supported by a Wilcoxon signed-rank test result (p < 0.05)., Conclusions: Overall, our findings indicate that the tactile feedback improves the immediate pain intensity through rehabilitation using our virtual reality system.

To ensure reliable surgical margins, intraoperative frozen section histological analysis (FS) has been performed since October, 2005 as follows: i) the orientation at the anatomical position and extent of the tumor are shared between oral pathologists and oral surgeons using imaging evaluations and pathological pictures and the planned site of sampling for intraoperative FS is confirmed; ii) a tumor team is organized and the team marks the tumor area and sets the resection range to correct the setting errors of the resection range among operators; iii) vital Lugol staining is applied to the lesion prior to tumor resection, the surgical margin is set based on the non-stained region and the extent of the tumor is macroscopically confirmed in the maximum cross-sectional surface of the resected specimen; and iv) FS is performed using samples from resected specimens to confirm the mucoepithelium and safety margin of the deep stump. The aim of this study was to evaluate the usefulness of our FS method. The treatment outcomes of oral squamous cell carcinoma were retrospectively investigated in patients treated prior to (Group 1) and after (Group 2) the introduction of our FS method. The recurrence rate of the primary lesions was high (17.3%) in Group 1, but decreased significantly in Group 2 (6.9%). Regarding clinicopathological factors, the condition of the surgical margins was associated with recurrence of the primary lesion in Group 1, but not in Group 2. In conclusion, our FS method appears to be useful for resecting tumors with reliable safety margins.

Despite the efficient HIV-1 replication blockage achieved with current highly active antiretroviral therapy (HAART) therapies, HIV-1 persists in the body and survives in a latent state that can last for the entire life of the patient. A long-lived reservoir of latently infected CD4(+) memory T cells represents the most important sanctuary for the virus and the greatest obstacle for viral eradication. In this work, we present an initial step toward a gene therapy approach aimed at the activation of latent provirus to induce the death of latently infected T cells. Latent HIV-1 infection is characterized by the failure of viral gene expression as a consequence of uninitiated or aborted transcription. We have constructed an HIV-1-based lentiviral vector (p5p53RTAT3) that expresses the viral trans-activating protein Tat in a drug-regulated manner and p53 in a Rev-dependent manner. We have demonstrated that the Tat-expressed protein from p5p53RTAT3 vector reactivates latent HIV-1 proviruses in J1.1 and ACH-2 cell lines and promotes p53-induced apoptosis in the presence of Rev. Our system was able to trigger the trans-activation of the provirus 5' long terminal repeat (LTR), stimulate the expression of the Rev protein from a tat-defective provirus, and provoke apoptosis selectively in the cells transfected with a tat-defective HIV-1 provirus in contrast to those with no HIV-1 provirus. However, the Rev-dependent p53 killing of latently infected cells was not effective enough for complete elimination of the awakened HIV-1 viruses. In summary, we have developed a vector system that is efficient in activating latent HIV-1 proviruses but that needs further improvement to kill infected cells.

The inheritance of mitochondrial and chloroplast genomes does not follow Mendelian laws, but proceeds by vegetative segregation. Most organisms show organelle homoplasmy, which is probably produced and maintained during sexual reproduction. We have tested the effect of prolonged vegetative multiplication in the maintenance of mitochondrial homoplasmy and the generation of heteroplasmy in cultivated olive trees, Olea europaea L. Seven trees, each representing a different variety of olive, were analysed by the study of an intergenic spacer region of the mitochondrial genome. A very high level of heteroplasmy was detected in all cases. We found multiple genome variants of the sequence analysed. The frequency of genomes with no changes in the spacer region was 11.5%. This means that 88.5% of genomes contain at least one change. The same spacer mitochondrial region was sequenced in several clones from four olive trees of a second generation of sexually reproduced trees. In these trees, many clones were identical and had no changes, which represents a clear reduction of the heteroplasmy (p < 0.001). Therefore, this work supports the relevance of the role of sexual reproduction in the maintenance of mitochondrial homoplasmy and also shows that mutations accumulate in a non-coding sequence of the mitochondrial genome when vegetative propagation is maintained for a long period of time.