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Chronic ankle instability (CAI) causes impairment in proprioception, such as ankle joint position sense and plantar cutaneous sensation. Although plantar vibration stimulation may be effective as a means of enhancing proprioception, its efficacy remains ambiguous. This study aimed to clarify the immediate effects of plantar vibration stimulation on healthy athletes and athletes with CAI. Eight healthy and eight CAI athletes participated in this study, and their joint position sense and cutaneous sensation were evaluated before and after the intervention of plantar vibration stimulation or non-intervention, designed as a cross-over study. There were no significant differences between the healthy group and the CAI group in both joint position and plantar cutaneous sensation. Also, there were no statistically significant changes in either group before or after the intervention. One possible explanation for the absence of differences between the healthy and CAI groups could be attributed to a high Foot and Ankle Ability Measure score. Neither group exhibited any changes in joint position or plantar cutaneous sensation following the vibration intervention. The frequency and amplitude of the vibration stimulation affecting proprioceptors may be different, and the joint position and plantar cutaneous sensation of CAI groups may be comparable with those of healthy participants. [ABSTRACT FROM AUTHOR]

Ankle brace is commonly used to treat and prevent ankle sprain. Its main aim is to restrict supination of the ankle. However, some braces restrict ankle dorsiflexion and plantar flexion. In addition, loosening and loss of restriction after exercise have also been reported. The purpose of this study was to reveal if thin-type ankle brace for ankle sprain restricts ankle dorsiflexion and plantar flexion and its effect of exercise. Five male adults (average age of 30.8 ± 5.2 years) were included in the study. Dorsiflexion and plantar flexion of subjects' right ankle was measured before and after wearing the brace, and before and after exercises. Exercises consisted of performing 20 times of calf raise, full squat, maximum vertical jump, and 5-minute running on a treadmill. Measurement was performed thrice, and their average was statistically analyzed between with and without the brace, and before and after each exercise. The results showed that there was no significant difference between all measured angles of with and without the brace and before and after each exercise. Thin-type ankle brace for ankle sprain have been reported to restrict supination. Considering our results, this brace does not restrict ankle dorsiflexion and plantar flexion. [ABSTRACT FROM AUTHOR]

Introduction: Fluorine 18-fluoro-glucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) is commonly used for the staging of head and neck cancer. This study aimed to evaluate the correlation between 18 F-FDG PET/CT, haematological parameters and prognosis in patients with advanced head and neck cancer., Methods: This was a single-institutional retrospective study of 83 patients with advanced head and neck squamous cell carcinoma (HNSCC) who underwent 18 F-FDG PET/CT imaging before initial treatment between 2014 and 2018. 18 F-FDG PET/CT after treatment was performed in 57 patients. The prognostic parameters of the pre- and post-treatment maximum standardised uptake value (SUV max ), metabolic tumour volume (MTV), total lesion glycolysis (TLG) of primary tumours and haematological parameters were analysed to evaluate the association between overall survival (OS) and progression-free survival (PFS)., Results: Pre-MTV, pre-TLG and post-SUV max were significantly associated with poor OS and PFS (p < 0.05). Haematological parameters, including pretreatment neutrophil/lymphocyte ratio and C-reactive protein/albumin ratio, were associated with 18 F-FDG PET/CT parameters. In multivariate analysis, post-SUV max was an independent prognostic factor for OS and PFS., Conclusion: A correlation between PET/CT metabolic and haematological parameters was observed. The volume and intensity of 18 F-FDG uptake region, in addition to haematological parameters, are feasible markers for predicting the progression of HNSCC in daily practice. Further, post-SUV max could be an independent parameter for predicting poor survival., (© 2024 John Wiley & Sons Ltd.)

Background: Dancesport is performed in high-heeled shoes. Dancesport athletes may have a higher prevalence and incidence of ankle sprains, which can affect their performance. However, the occurrence of ankle sprains among dancesport athletes remains unclear. This study aimed to determine the prevalence and incidence of ankle sprains among elite dancesport athletes and to investigate the related information., Method: We conducted a mixed descriptive epidemiological study (cross-sectional and longitudinal) involving 198 elite adolescent dancesport athletes, using past medical records and questionnaires administered to the participants. Data on the occurrence of ankle sprains among all participants were compiled using medical records and information on injury mechanisms, missed days, severity types, and countermeasures for ankle sprains were collected. The prevalence of chronic ankle instability (CAI) among the participants was assessed using a questionnaire. Following the initial survey, we conducted a one-year follow-up study to investigate the incidence of ankle sprains, incidence rate per 1000 exposure hours, and recurrence of ankle sprains., Result: The cross-sectional study and longitudinal study included 198 participants and 92 elite dancesport athletes, respectively. The prevalence of ankle sprains and CAI was 49.5% and 45.1%, respectively. Of all ankle sprains, 88% were medial injuries. The most common injury mechanisms were turning (46.9%) and jumping (46.9%). The average number of missed days due to ankle sprains was 11.2 days. Most injuries were managed with rest, and only one male athlete underwent surgery due to an ankle sprain sustained during dancing. During the one-year follow-up, the incidence of ankle sprains, incidence rate per 1000 exposure hours, and recurrence rate of ankle sprains were 46.6% (male, 41.2%; female, 48.8%), 0.65 ankle sprains/1000 h, and 35.3%, respectively. No sex-related differences were observed., Conclusion: It is crucial to focus on the occurrence of ankle sprains and CAI in dancesport athletes with high heels. Future research should clarify the impact of ankle sprains on dancesport performance and develop preventive measures to reduce the incidence and recurrence of these associated injuries.

Background: Dancers have a higher prevalence of hallux valgus (HV) than the general population. However, no reports specifically addressing treatment strategies for HV in dancers, or their effectiveness have been published. This study aimed to determine the effects of 4 weeks of foot exercises on subjective clinical outcomes, the HV angle, and change of foot plantar pressure during specific dance techniques., Methods: Thirteen female elite adolescent dancesport athletes (age: 16.4 ± 3.3 years) completed the program. The HV angle was measured based on foot photographs. Clinical assessments were performed using the visual analog scale for first metatarsophalangeal (1st MTP) joint pain, and the Foot and Ankle Outcome Score. The changes in plantar pressure during two dance techniques (demi-pointe and plié) were measured. The plantar pressure was measured in six areas of the foot. All of these parameters were compared before and after the intervention by using chi-square tests and Student's paired t-test (statistical significance: p < 0.05)., Results: The HV angle was significantly reduced from 20.1° to 15.4° after the intervention. Participants reported an average subjective completion rate of 70.3% ± 14.6% over 3 weeks, exhibiting no significant differences despite an apparent trend toward improvement. Significant changes were noted in 1st MTP joint pain and subjective outcomes, and toe function significantly improved in the "paper" movement. The foot-exercise program changed plantar pressure distribution during the demi-pointe and plié techniques, with increased hallux pressure and decreased 2nd-5th MTP joint pressure., Conclusions: In elite adolescent dancesport athletes, 4 weeks of foot-exercise rehabilitation reduced the HV angle and improved in subjective outcome and function during the two dance techniques. Coaches should consider utilizing foot-exercise training programs in a dancer training program for HV., (© 2024. The Author(s).)

Background: Sports injuries often occur during landing, necessitating postural stability for injury prevention. Electrical stimulation of the plantar foot induces activities of the intrinsic foot muscles and improves somatosensory and postural stability during landing. However, this effect remains unclear. Therefore, the aim of this study was to investigate the immediate effects of electrical stimulation on the activities of the intrinsic foot muscles, plantar somatosensory system, and postural stability during landing., Methods: Twenty-two college athletes were divided into an electrical stimulation group and a control group. Electrical stimulation was applied to the plantar foot using a commercial device. The toe function and plantar tactile sensations were evaluated. The activities of the intrinsic muscles and the parameters of the ground reaction force were measured and calculated. We compared pre- and postintervention outcomes., Results: In the electrical stimulation group, two subjects showed improvement in toe function, and plantar tactile sensation improved significantly postintervention. The control group exhibited no significant change in plantar tactile sensation. A significant interaction was observed in anteroposterior postural stability during landing, notably improving in the electrical stimulation group., Conclusions: Electrical stimulation of the plantar foot immediately improved toe function, plantar tactile sensation, and postural stability during landing. Such stimulation would be beneficial in preventing sports injuries.

Background: The purpose of this study was to clarify the differences in the movement of the superficial microchambers and deep macrochambers of the heel fat pad during loading and unloading movements, and to clarify the influence of height and weight on this movement., Methods: The subjects were 21 healthy adults. The right foot was placed on an evaluation instrument stand made of polymethylpentene (PMP) resin plate, and the left foot was placed on a scale stand used to adjust the amount of load. When measuring, the heel fat pad is divided into the superficial microchamber layer and the deep macrochamber layer, and the thickness due to loading from 0% to 100% of the body weight and unloading from 100% to 0% is measured. Measurement was performed every 20% using an ultrasound imaging device. We also examined the rate of change in the thickness of the superficial and deep layers of the heel fat pad when applying 100% load (end load) from 0% load (unload)., Results: No changes were observed in the superficial layer of the heel fat pad during unloading, but significant changes were observed in the deeper layers. Additionally, the thickness of the microchamber and macrochamber layers tended to increase under each loading condition as the height and weight increased. On the other hand, the rate of change in the thickness of the macrochamber layer tended to decrease., Conclusion: The microchamber layer and the macrochamber layer of the heel fat pad may have different functions. As height and weight increase, the thickness of the microchamber and macrochamber layers may increase, and the rate of change in the thickness of the macrochamber layer appears to decrease. Although the thickness increases as the load increases, we found that the related elasticity decreases., Level of Evidence: Level Ⅳ, cross-sectional survey study., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Disclosure forms for all authors are available online., (© The Author(s) 2024.)

Toe flexor strength is generated primarily by the flexor hallucis longus (FHL) of the extrinsic foot muscles (EFMs) and the plantar intrinsic foot muscles (PIFMs) of the great toe. Toe flexion methods can be broadly classified into toe grip (TG) and toe push-down (TP). Additionally, TP's interphalangeal joint (IPJ) position may influence the FHL and PIFMs activity ratios. This study aimed to elucidate the differences in the muscle activity and muscle activity ratios of the FHL and AbdH during TG, TP with IPJ flexion (TPIF), and TP with IPJ extension (TPIE). Surface electromyography and a custom-made instrument were used to measure the FHL and AbdH muscle activity during TG, TPIF, and TPIE of the great toe in 28 healthy men. The muscle activity and AbdH/FHL muscle activity ratio in the three conditions were statistically compared. The FHL activity was significantly higher during TG and TPIF than during TPIE. The AbdH muscle activity was significantly higher during TPIF and TPIE than that during TG. The AbdH/FHL muscle activity ratio was significantly higher for TPIE, TPIF, and TG in that order. This study showed that the FHL and AbdH muscle activity differed depending on the TG and TP of the great toe, and that the AbdH/FHL muscle activity ratio was different in the IPJ position. These results suggest that selecting a toe flexion method according to the target muscle when measuring and training the great toe flexor strength is important., Competing Interests: Declaration of Competing Interest There are no conflicts of interest regarding this study., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Predictive biomarkers for nivolumab in recurrent or metastatic head and neck squamous cell carcinoma (RMHNSCC) have not yet been established., Methods: The tumor proportion score (TPS), combined positive score (CPS), and soluble forms of programmed cell death ligand-1 (PD-L1) and programmed cell death ligand-2 (PD-L2) were retrospectively analyzed in patients with RMHNSCC treated with nivolumab., Results: The positivity rates for TPS (PD-L1), CPS (PD-L1), TPS (PD-L2), and CPS (PD-L2) were 73.8%, 78.2%, 56.4%, and 78.2%, respectively. Patients with high TPS (PD-L1), CPS (PD-L1), or CPS (PD-L1 and PD-L2) showed significantly prolonged progression-free survival. Favorable overall survival was associated with high CPS (PD-L1 and PD-L2) and low soluble PD-L1 and PD-L2 levels. The expressions of tissue and soluble PD-L1/2 were not correlated., Conclusions: Our study revealed that compared to PD-L1 expression alone, dual expression of PD-L1 and PD-L2 in tissue or soluble form could be feasible biomarkers in patients with RMHNSCC who received nivolumab., (© 2024 Wiley Periodicals LLC.)

Background: This study aimed to determine the risk factors of hallux valgus angle among preprofessional adolescent dancesport athletes., Methods: A total of 275 athletes, (73 males and 202 females) aged between the ages of 11 and 18 years, participated in this study. A cross-sectional questionnaire was used to survey their demographic characteristics (sex and age), training information (starting age, weekly training time, and athletic career [number of years of training at this specific dancesport school]), and measured their height and weight. The hallux valgus angle was measured based on foot photographs. The chi-square test was used to compare the difference with prevalence of hallux valgus between male and female athletes. A normal distribution test was performed, and based on the test results, unpaired t-test and multiple logistic regression were conducted to identify training factors for the hallux valgus in this cohort., Results: Chi-square test showed higher prevalence of hallux valgus in female elite adolescent dancesport athletes than males. The t-test results did not show any significant differences between the hallux valgus group and non-hallux valgus groups with start age, athletic career, and weekly training time. Multiple logistic regression analysis with hallux valgus as the dependent variable revealed that the female sex was a strong predictor of a higher prevalence of hallux valgus (odds ratio [OR]: 3.954, 95% confidence interval 95% CI: 2.193-7.131, and p < 0.001). Weekly training time was also entered into the multiple logistic regression model (OR: 1.033, 95% CI: 1.001-1.067, and p = 0.041)., Conclusions: Our findings revealed that the prevalence of hallux valgus in adolescent dancesport athletes was higher in females than in males. Longer weekly training time was also a risk factor for hallux valgus. Training factors should be considered in preventive programs for elite adolescent dancesport athletes, and special attention should be paid to female athletes., (© 2024 The Author(s). Journal of Foot and Ankle Research published by John Wiley & Sons Australia, Ltd on behalf of Australian Podiatry Association and The Royal College of Podiatry.)

Intratumoral hypoxia is associated with tumor progression, aggressiveness, and therapeutic resistance in several cancers. Hypoxia causes cancer cells to experience replication stress, thereby activating DNA damage and repair pathways. MutT homologue-1 (MTH1, also known as NUDT1), a member of the Nudix family, maintains the genomic integrity and viability of tumor cells in the hypoxic tumor microenvironment. Although hypoxia is associated with poor prognosis and can cause therapeutic resistance by regulating the microenvironment, it has not been considered a treatable target in cancer. This study aimed to investigate whether hypoxia-induced MTH1 is a useful target for immunotherapy and whether hypoxic conditions influence the antitumor activity of immune cells. Our results showed that MTH1 expression was elevated under hypoxic conditions in head and neck cancer cell lines. Furthermore, we identified a novel MTH1-targeting epitope peptide that can activate peptide-specific CD4+ helper T cells with cytotoxic activity. The proliferation and cytotoxic activity of T cells were maintained under hypoxic conditions, and PD-1 blockade further augmented the cytotoxicity. These results indicate that MTH1-targeted immunotherapy combined with checkpoint blockade can be an effective strategy for the treatment of hypoxic tumors.

Activities on sandy soil are known to contribute to improved leg strength and balance. Lifesavers (LSs) have shown that sandy soil activity promotes intrinsic foot muscle development and improves balance. LS improves leg strength and balance through activities on sandy soil. However, the effect of foot muscle development on the actual muscle activity of LS remains unclear. We aimed to evaluate the effect of foot muscle development on muscle activity in lifeguards on a sandy beach compared with the corresponding in healthy participants. Fifteen LSs and 15 healthy adults underwent a Y-balance test to assess dynamic balance and surface electromyography to measure muscle activity. The LSs exhibited a significantly higher percentage of maximum voluntary contraction values in the tibialis anterior muscle in all directions than the healthy adults. The LSs showed increased peroneus longus and abductor hallucis muscle activity in the posterolateral and posteromedial directions, suggesting their involvement in contralateral postural control during dynamic balance. These findings suggest that engaging in barefoot activities on sandy soil enhances foot muscle activity and improves dynamic balance in LSs., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Ethics Review Committee of Waseda University issued approval 2023-370. Written informed consent was obtained from the participants, who were informed in advance. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Suzuki et al.)

COVID-19 can lead to various complications, including severe respiratory symptoms. Both viral infections and total thyroidectomy are known to cause hypocalcemia, making a history of thyroidectomy a potential risk factor for hypocalcemia in COVID-19 patients. We present the case of a 34-year-old woman with Graves' disease who developed hypocalcemia due to COVID-19 following a total thyroidectomy. The patient underwent an uneventful total thyroidectomy, with preservation of at least three of the four parathyroid glands. Postoperatively, her parathyroid hormone (PTH) levels were normal, and she was discharged without tetany. However, on postoperative day 90, she experienced mild hypocalcemia during a COVID-19 infection, although it was asymptomatic. By postoperative day 127, she presented with severe tetany and general malaise. Testing confirmed a reinfection with SARS-CoV-2 and hypocalcemia, while PTH levels remained normal. Treatment with intravenous calcium gluconate, oral calcium lactate, and alfacalcidol effectively resolved the hypocalcemia and tetany. The patient was subsequently discharged without tetany and has since been monitored without the need for calcium or vitamin D supplementation. This case highlights that the COVID-19 infection following a total thyroidectomy can cause hypocalcemia. Postoperative hypocalcemia is a common issue in head and neck surgery, and viral infections like COVID-19 should be considered in the differential diagnosis of hypocalcemia., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Asahikawa Medical University Institutional Review Board issued approval 24077. The study was conducted ethically in accordance with the World Medical Association Declaration of Helsinki. Approval for data collection was obtained from the Asahikawa University Institutional Review Board (#24077). Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Inoue et al.)

Balance is important in lifesaving competitions. We aimed to investigate the relationship between dynamic balance and physical characteristics and functions in elite lifesavers by measuring the foot muscle cross-sectional area, ankle joint muscle strength, toe grasp strength, plantar superficial sensation, and dynamic balance (Y-balance test). In this observational study, we measured the foot muscle cross-sectional area, ankle dorsiflexion, plantar flexion, external flexion, isometric muscle strength, toe grasp strength, and superficial foot sensation of 15 adult lifesavers (12 males). The results show that toe grasp strength and ankle plantar flexion isometric muscle strength are particularly important for the dynamic balance of elite lifesavers working on sandy surfaces. Sand training improves intrinsic muscle strength and dynamic balance function. However, high training intensity may reduce plantar surface sensation; this needs to be verified through sand training interventions in the future.

Background: This study aimed to investigate age-related changes in the heel fat pad's microchamber and macrochamber layers, particularly focusing on load-induced alterations. Understanding these changes is crucial for elucidating age-related differences in foot mechanics and their potential implications for mobility and comfort., Methods: Fifty-five healthy individuals were divided into three age groups: young adults (≤29 years), middle-aged adults (30-44 years), and elderly individuals (≥45 years). Ultrasonic imaging was utilized to measure the thickness of the heel fat pad's microchamber and macrochamber layers under varying load conditions. Thickness, percentage changes, and ratios of load-induced thickness changes were calculated to assess age-related differences., Findings: Under no-load conditions, both microchamber and macrochamber layers of the heel fat pad were significantly thicker in middle-aged and elderly individuals than in young adults. When load was applied middle-aged and elderly participants exhibited smaller changes in the macrochamber layer and larger changes in the microchamber layer compared to young adults., Interpretation: Our findings suggest that age influences the structural characteristics and response of the heel fat pad to mechanical loading. Thicker heel fat pad layers in middle-aged and elderly individuals under no-load conditions may reflect age-related changes in fat distribution or composition. Moreover, differences in load-induced thickness changes indicate altered mechanical properties with age, potentially affecting shock absorption and overall foot function. Understanding these age-related variations can help develop interventions aimed at preserving foot health and mobility across the lifespan., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Ltd.)

Background: The identification of epitope peptides from tumor-associated antigens (TAAs) is informative for developing tumor-specific immunotherapy. However, only a few epitopes have been detected in mouse TAAs of head and neck cancer (HNSCC)., Methods: Novel mouse c-Met-derived T-cell epitopes were predicted by computer-based algorithms. Mouse HNSCC cell line-bearing mice were treated with a c-Met peptide vaccine. The effects of CD8 and/or CD4 T-cell depletion, and vaccine combination with immune checkpoint inhibitors (ICIs) were evaluated. Tumor re-inoculation was performed to assess T-cell memory., Results: We identified c-Met-derived short and long epitopes that elicited c-Met-reactive antitumor CD8 and/or CD4 T-cell responses. Vaccination using these peptides showed remarkable antitumor responses via T cells in which ICIs were not required. The c-Met peptide-vaccinated mice rejected the re-inoculated tumors., Conclusions: We demonstrated that novel c-Met peptide vaccines can induce antitumor T-cell response, and could be a potent immunotherapy in a syngeneic mouse HNSCC model., (© 2024 Wiley Periodicals LLC.)

We report three cases of young athletes with symptomatic ossicles of the medial malleolus who underwent arthroscopic resections of the ossicle combined with deltoid ligament repair. A differential diagnosis of the ossicles beneath the medial malleolus, accessory ossification center, avulsion fracture resulting in pseudoarthrosis, and accessory bone such as os subtibiale has been proposed. However, it is difficult to differentiate them clearly. Most of these ossicles are asymptomatic, although they can cause chronic medial ankle pain, especially in young athletes who require surgical treatment. All three patients had pain in the distal part of the medial malleolus, which restricted their sports activities. Plain radiographs of all three cases revealed a well-defined, round-shaped bony lesion beneath the medial malleolus. Ultrasonographic imaging, magnetic resonance imaging, and arthroscopic findings revealed that ligament attachment to the ossicle varies in volume and type according to the cases. In other words, the mechanisms through which the existence of the ossicles affects the stability of the ankle joint and foot alignment are different in each case, indicating that deltoid ligament repair is necessary according to the cases. In all three cases, we performed arthroscopic resections of ossicles combined with deltoid ligament repairs, achieving favorable short-term clinical outcomes., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Yabiku et al.)

Background: Tonsillectomy with steroid pulse therapy (TSP) and tonsillectomy monotherapy (T) have improved the prognosis of patients with immunoglobulin A nephropathy (IgAN). However, a consensus has not been reached on the best treatment for these patients. This study aimed to compare the efficacies of TSP and T., Methods: Data of patients with IgAN who received TSP or T were retrospectively analyzed. The exclusion criterion was a serum creatinine level > 1.5 mg/dL. The clinical remission and renal survival rates were compared., Results: Patients were divided into groups based on the treatment method: the TSP (n = 82) and T groups (n = 41). No significant differences were observed in patient characteristics, except for the observation period (TSP: 60 months, T: 113 months). The log-rank test revealed that the clinical remission rate was significantly higher in the TSP group than in the T group (p < 0.05). The superiority of TSP was also observed in the urinary protein excretion (> / = or < 1 g/day) of the two subgroups. According to the Cox proportional-hazards model, the treatment method and daily urinary protein extraction were independent factors affecting clinical remission. The 10-year renal survival rates in the TSP and T groups were 100% and 92.5%, respectively. The log-rank test revealed a tendency for a higher renal survival rate in the TSP group than in the T group (p = 0.09)., Conclusion: The clinical remission rate was significantly higher with TSP than with T, regardless of urinary protein levels. TSP tended to have a better renal survival rate than T., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Introduction: The menstrual cycle is an important indicator of health in female athletes. Female elite adolescent dancers are expected to control their weight while also training intensely, which can lead to menstrual disorders. This study aimed to investigate the relationship between body composition and menstrual status in female elite adolescent dancers. Methods : In total, 131 female elite adolescent dancers (age: 15.9 ± 1.5 years) were enrolled in this study. We measured the height, weight, and body fat percentage (BFP) for each participant and calculated their body mass index (BMI). We gathered information on individual menstruation patterns and the participants' menstrual cycles over the previous year using recall methods. We then compared the differences between dancers with menstrual cycle disorders and those without. Primary amenorrhea was defined as menarche occurring after the age of 15, while secondary amenorrhe was defined as experiencing fewer than 5 or no menstrual periods for at least 3 of the previous 12 months. We conducted a reliability test using the same questionnaire 2 weeks later. Statistical significance was defined as P  < .05, and we calculated the effect sizes (d) and 95% confidence intervals (95% CI). Results : The average BMI and BFP were 22.6 ± 3.0% and 19.4 ± 2.2 kg/m 2 , respectively. Low BFP and low BMI were observed in 51 (38.6%) and 47 (35.6%) participants, respectively. Primary amenorrhea in 3 participants (2.3%) and 29 (22.1%) reported experiencing secondary amenorrhea; they had lower BFP than the dancers who did not experience amenorrhea ( P  = .041, 95% CI, -2.51 to -0.05). Conclusion : Female elite adolescent dancers in China may have lower BFP and menstrual problems. Given that lower BFP may contribute to the occurrence of menstruation disorders, it is essential to pay an attention to both BFP and the menstruation status in female elite adolescent dancers., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Rationale: Osteochondral lesions on the lateral process of the talus involving the subtalar joint are rare; the optimal surgical treatment remains to be clarified as there are few reports. Additionally, bilateral cases are extremely rare. Therefore, the clinical outcomes of the surgical treatment for bilateral osteochondral lesions on the lateral process of the talus involving the subtalar joint have not been fully elucidated., Patient Concerns: A 16-year-old boy who played soccer presented to our hospital with bilateral hindfoot pain. The symptoms persisted even after 3 months of conservative treatment. The patient and family requested surgical treatment to relieve the symptoms., Diagnoses: The patient was diagnosed with bilateral osteochondral lesions on the lateral process of the talus, involving the subtalar joint based on computed tomography and magnetic resonance imaging findings., Interventions: Arthroscopic debridement and microfracture were performed bilaterally., Outcomes: Postoperative computed tomography and magnetic resonance imaging of both feet revealed remodeling of the subchondral bone. The patient returned to play at the pre-injury level with no pain., Lessons: This report describes a case of bilateral osteochondral lesions on the lateral process of the talus, involving the subtalar joint. Arthroscopic debridement and microfracture were effective in relieving symptoms and the subchondral bone remodeling. To the best of our knowledge, this is the first report of arthroscopic treatment of osteochondral lesions of the lateral process of the talus involving the subtalar joint., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: This study aimed to investigate the thickness changes of the heel fat pad and the plantar fascia associated with loading and unloading in healthy individuals and patients with heel pain and reveal the differences between them., Methods: The study included adult male participants with (n = 9) and without (n = 26) heel pain. The participants placed their right foot on an evaluation apparatus with a polymethylpentene resin board (PMP), while their left foot was positioned on a weighing scale used to adjust the loading weight. The heel fat pad was differentiated into superficial Microchamber and deep Macrochamber layers. These layers and plantar fascia thickness were measured using an ultrasonographic imaging device at loading phase ranging from 0% to 100% of their body weight and unloading phase from 100% to 0%. Additionally, the study examined the thickness change ratios of the superficial and deep heel fat pad layers when the load increased from 0% (unload) to 100% (full load)., Results: In healthy individuals and patients with heel pain, no significant thickness changes were observed in the Microchamber layer of the heel fat pad or the plantar fascia during loading and unloading evaluations. However, significant thickness changes were observed in the Macrochamber layer of the heel fat pad, and the pattern of change differed between the loading and unloading phases. Additionally, patients with heel pain showed differences in the thickness change and thickness change ratios of the microchamber and macrochamber layers of the heel fat pad during both loading and unloading phases. The thickness of the plantar fascia did not show significant differences between both groups., Conclusion: Compared with healthy individuals, in our relatively small study, patients with heel pain had greater deep fat pad compression in loading and less recovery after load removal. This finding suggests that these patients have different intrinsic fat pad function and related morphology than those without heel pain., Level of Evidence: Level III, retrospective cohort study., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Disclosure forms for all authors are available online., (© The Author(s) 2024.)

Background: To the best of our knowledge, no prior studies have identified any risk factors for subchondral insufficiency fractures of the medial tibial condyle. This study aimed to explain relationships between subchondral insufficiency fractures of the medial tibial condyle and the meniscus status, lower extremity alignment, or osteoporosis., Methods: This retrospective study included 325 consecutive patients whose chief complaint is knee joint pain and who had visited one institution between April 2016 and March 2021, of which 70 patients (8 men and 62 women) who had suspected subchondral insufficiency fractures of the medial tibial condyle had undergone magnetic resonance imaging and radiographic examination. These patients were divided into two groups based on the results of their magnetic resonance imaging: the insufficiency fracture group included 46 patients who had subchondral insufficiency fractures of the medial tibial condyle and the nonfracture group included 24 patients without fractures. The meniscus injury and medial meniscus extrusion (MME) were evaluated by using magnetic resonance imaging. The Kellgren-Lawrence grade, the femorotibial angle, and the percent mechanical axis (%MA) were evaluated with the use of knee radiographs. T-scores were also measured by using dual-energy X-ray absorptiometry with a bone densitometer., Results: MME were significantly larger and the %MA was significantly smaller in the insufficiency fracture group than that in the nonfracture group. The prevalence of medial meniscus injuries and pathological MME were higher in the insufficiency fracture group than those in the nonfracture group. The prevalence of varus knee and osteoporosis did not vary remarkably different between the two groups., Conclusion: The patients who had insufficiency fractures of the medial tibial condyle tended to have medial meniscus extrusion., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Prevalence of impaired foot function among baseball players with and without a disabled throwing shoulder/elbow was investigated. The study included 138 male players. Players who had previously complained of shoulder/elbow pain during throwing motion were defined as the players with a history, and those who experienced shoulder/elbow pain during the examination were defined as having the injury. Foot function was evaluated by foot "rock paper scissors" movements and floating toes. Their prevalence was assessed and the relationships between players with and without the injuries were statistically analyzed. The prevalence of players with a history and injury was 27% and 7%, respectively. The prevalence of impaired foot function on the non-throwing side among players with injury was significantly higher than those without (60% vs. 28%, P < 0.001) and higher tendency on the throwing side than those without (60% vs. 32%). Regarding floating toes, players with a relevant history showed a significantly higher prevalence on the throwing side than those without (49% vs 28%, P < 0.001) and higher tendency on the non-throwing side than those without (49% vs 32%). Players with disabled throwing shoulder/elbow have a significantly higher prevalence of impaired foot function and floating toes than players without it., (© 2024. The Author(s).)

Introduction: Patients with total knee arthroplasty occasionally develop postoperative abnormalities such as posttraumatic knee stiffness and arthrofibrosis, which may affect activities of daily living. However, there are no clear assessment methods or interventions for knee stiffness. Musculoskeletal ultrasound imaging enables real-time evaluation of mobility and flexibility of tissues. The purpose of this case report was to describe the use of musculoskeletal ultrasound imaging for evaluating the optimal location and methods of passive manipulation., Case Description: The patient was an 82-year-old woman who had undergone total knee arthroplasty. She was unable to climb stairs due to limited knee flexion. Based on the results of musculoskeletal ultrasound imaging assessment, we hypothesized that the knee flexion limitation was caused by decreased sliding movement of the suprapatellar pouch. Hence, we performed passive manipulation on the tissue with decreased sliding under musculoskeletal ultrasound guidance., Outcomes: The patient's knee flexion angle increased from 90° to 110° within 1 week of intervention, and her gait speed improved from 16.48 to 13.2 s per 10 m. Furthermore, after the intervention, she was able to climb 10 steps using a handrail., Discussion: Ultrasound imaging is important because it allows the examination of tissues with mobility changes such as in arthrofibrosis. Our work highlights the use of musculoskeletal ultrasound imaging for identifying the target region for therapy and for providing guidance during passive manipulation.

Head and neck squamous cell carcinoma (HNSCC) has a poor prognosis. Each year, approximately 880,000 patients are newly diagnosed with HNSCC worldwide, and 450,000 patients with HNSCC die. Risk factors for developing HNSCC have been identified, with cigarette smoking, alcohol consumption, and viral infections being the major factors. Owing to the prevalence of human papillomavirus infection, the number of HNSCC cases is increasing considerably. Surgery and chemoradiotherapy are the primary treatments for HNSCC. With advancements in tumor biology, patients are eligible for novel treatment modalities, namely targeted therapies, immunotherapy, and photoimmunotherapy. Because this area of research has rapidly progressed, clinicians should understand the basic biology of HNSCC to choose an appropriate therapy in the upcoming era of personalized medicine. This review summarized recent developments in tumor biology, focusing on epidemiology, genetic/epigenetic factors, the tumor microenvironment, microbiota, immunity, and photoimmunotherapy in HNSCC, as well as how these findings can be translated into clinical settings., Competing Interests: Declaration of Competing Interest No potential conflicts of interest were disclosed., (Copyright © 2023. Published by Elsevier B.V.)

In CD70-expressing tumors, the interaction of CD70 on tumor cells with its lymphocyte receptor, CD27, is thought to play a role in immunosuppression in the tumor microenvironment and elevated serum levels of soluble CD27 (sCD27). Previous studies showed that CD70 is expressed in nasopharyngeal carcinoma (NPC), an Epstein-Barr virus (EBV)-related malignancy. However, the association between intratumoral CD70/CD27 expression and serum levels of sCD27 in NPC remains unclear. In the present study, we show that CD70 is primarily expressed by tumor cells in NPC and that CD27-positive lymphocytes infiltrate around tumor cells. NPC patients with CD27-positive lymphocytes had significantly better prognosis than patients lacking these cells. In addition, high CD70 expression by tumor cells tended to be correlated with shorter survival in NPC patients with CD27-positive lymphocytes. Serum sCD27 levels were significantly increased in patients with NPC and provided good diagnostic accuracy for discriminating patients from healthy individuals. The concentration of serum sCD27 in patients with CD70-positive NPC with CD27-positive lymphocytes was significantly higher than in patients with tumors negative for CD70 and/or CD27, indicating that the intratumoral CD70/CD27 interaction boosts the release of sCD27. Furthermore, positive expression of CD70 by NPC cells was significantly correlated with EBV infection. Our results suggest that CD70/CD27-targeted immunotherapies may be promising treatment options and that sCD27 may become an essential tool for evaluating the applicability of these therapies by predicting the intratumoral CD70/CD27 interaction in NPC., (© 2024 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: Local high-frequency percussive (HFP) massage has recently found widespread application in physical therapy. Although HFP massage reportedly improves range of motion (ROM), the mechanism underlying its action has not yet been proven. This study aimed to clarify whether a 5-minute percussive massage regimen affects muscular or connective tissues, such as the deep fascia and deep intermuscular fascia and the change in joint ROM., Method: The study sample was calculated using G*Power analysis program, and this study enrolled 15 healthy men who underwent 5-minute HFP massage to the medial gastrocnemius muscle. Shear-wave elastography was used to measure tissue stiffness in the deep fascia, muscle, and deep intermuscular fascia through shear-wave velocity as well as the ROM of the volunteers' ankle joint dorsiflexion before and after the HFP massage. A value of P < .05 was used to declare statistical significance, and post hoc was used to calculate the effect size using G*Power., Results: Shear-wave velocity revealed a significant change in the deep fascia (P = .003; shear-wave velocity: -0.7 m/s) and significant increase in ROM of ankle dorsiflexion (P = .002; increase in ROM: 3.0°) after 5 minutes of HFP massage. However, the muscle and deep intermuscular fascia did not exhibit any significant changes., Conclusions: HFP massage for 5 minutes modified the stiffness of the deep fascia and concurrently improved the ankle joint-dorsiflexion ROM. This method can be used as an intervention to decrease stiffness of the deep fascia and increase the ROM efficiently.

Salivary gland cancer (SGC) is rare and comprises over 20 histological subtypes. Recently, clinical experience regarding immunotherapies for SGCs has been accumulating, yet their efficacy remains controversial. Understanding the tumor microenvironment (TME), including the expression of immune checkpoint molecules in SGC, is crucial to optimizing immunotherapy. In this review, we demonstrate that high-grade mucoepidermoid carcinoma and salivary duct carcinoma generally exhibit immune-hot TME with high immune cell infiltration, frequent genetic mutations, and robust immune checkpoint molecule expression. In contrast, adenoid cystic carcinomas exhibit an immune-cold TME. While the reported efficacy of immune checkpoint inhibitors (ICIs) for SGCs is generally poor, several studies showed promising clinical efficacy of ICIs, with an objective response rate ranging from 20.0-33.3%, indicating that ICIs might be beneficial for a specific population of SGC. Molecule-targeted therapies including anti-human epidermal growth factor receptor 2 and anti-androgen receptor therapies have shown promising clinical efficacy against SGC. Recent evidence indicates that these molecules could be targets for antigen-specific immunotherapies including chimeric antigen receptor-T therapy and cancer vaccines. This review discusses the current understanding and future directions of immunotherapies for SGCs, including ongoing clinical trials.

Chronic rhinosinusitis (CRS) is a persistent inflammatory disease of the nasal cavity and paranasal sinuses. Traditional classification is denoted by the presence (CRSwNP) or absence of nasal polyps (CRSsNP). Particularly, CRSwNP is distinguished by the presence of infiltrating cells and inflammatory markers in the nasal mucosa. Patients with CRSwNP in Western countries predominantly display a type 2 endotype, whereas those in Asian regions display a mixed type 2 endotype. Nevertheless, recent transcriptome analyses have revealed two types of nasal polyps - type 2 and non-type 2 polyps, suggesting that geographical differences in endotypes likely resulted from the different proportions of each endotype. Moreover, various endotypes of CRSsNP have been identified, making phenotype a crucial factor for predicting treatment efficacy. Type 2 endotypes, designated as eosinophilic CRS (ECRS) in Japan, are characterized by severe eosinophilic infiltration into the paranasal sinus tissue and are particularly refractory. In this review, we discuss the latest developments in ECRS. We also provide recent findings on the involvement of nasal epithelial cells in pathogenesis., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023. Published by Elsevier B.V.)

Introduction: Immunoglobulin G4-related disease (IgG4-RD) is a systemic inflammatory disease characterized by elevated serum IgG4, tissue infiltration of IgG4-positive cells, and fibrosis. Although a number of IgG4-RD patients show sinonasal involvement, there is little known about sinonasal inflammation associated with IgG4-RD. This study aimed to describe the clinicopathological features of sinonasal inflammation associated with IgG4-RD and to compare with other inflammatory diseases, such as eosinophilic chronic rhinosinusitis (ECRS) and granulomatosis with polyangiitis (GPA)., Methods: A retrospective analysis of clinicopathological features of patients with sinonasal lesions and high serum IgG4 was performed. Patient data were reviewed to determine whether they fulfilled the diagnostic criteria for other inflammatory diseases., Results: Six of 7 patients were diagnosed with IgG4-RD, while 1 patient was diagnosed with GPA. In the 6 patients with IgG4-RD, intranasal findings showed nasal polyps in 3 patients (50%) and nasal crusting in the 3 patients (50%). Computed tomography showed ethmoid sinus involvement in 5 patients (83%). Five of the 6 patients (83%) were diagnosed with IgG4-RD based on nasal biopsy, whereas 1 patient (17%) was diagnosed based on lacrimal gland biopsy. Four patients fulfilled the Japanese epidemiological survey of refractory ECRS (JESREC) criteria. However, none of the patients showed eosinophil infiltration. Although the patient with GPA showed high levels of serum IgG4 and tissue infiltration of IgG4-positive cells in the nasal biopsy, the patient showed common clinical features of GPA., Conclusion: Patients with sinonasal inflammation associated with IgG4-RD had similar clinical characteristics with ECRS and GPA. Histopathological findings of the nasal biopsy from clinically diagnosed GPA was consistent with that of IgG4-RD. Sinonasal inflammation associated with IgG4-RD should be diagnosed based not only on tissue infiltration of IgG4-positive cells but in conjunction with clinical findings such as local nasal characteristics, involvement of other organs, and serum antineutrophil cytoplasmic antibody levels. IgG4-RD should be ruled out in patients with eosinophilia without histopathological eosinophil infiltration., (© 2024 S. Karger AG, Basel.)

Introduction: Due to the rarity and various histological types, a standard chemotherapy regimen for recurrent or metastatic salivary gland carcinoma (SGC) has not been established. Molecular-targeted therapy is a novel cancer therapy based on the expression of target molecules. However, few molecular-targeted therapy types have shown satisfactory efficacy for patients with SGC. Our study described promising results of epidermal growth factor receptor (EGFR)-targeting therapy with paclitaxel in patients with SGC., Methods: The medical records of patients with recurrent SGC treated with weekly cetuximab combined with paclitaxel (Cmab-PTX) between December 2017 and December 2022 at our institutions were retrospectively analyzed., Results: Seven patients with SGC received Cmab-PTX therapy. The median age was 76 years. All patients were high-grade histological types, and EGFR expression was positive in all examined patients. Cmab-PTX was administered for a median period of 20 months (range of 2-36 months). The overall responses were three with complete response, two with partial response, one with stable disease (&gt;24 weeks), and one with progressive disease. The objective response and disease control rates were 71.4% and 85.7%, respectively. Progression-free survival ranged between 2 and 36 months (median 12 months), whereas overall survival ranged between 4 and 111 months (median 36 months). One patient experienced a grade 4 adverse event (neutropenia), which was conservatively manageable., Conclusion: Although the treatment sensitivity of SGC with high-grade histological types is usually poor, Cmab-PTX could be a promising treatment regimen for recurrent SGC. Due to the rarity and various histological types, a standard chemotherapy regimen for recurrent or metastatic salivary gland carcinoma (SGC) has not been established. Molecular-targeted therapy is a novel cancer therapy based on the expression of target molecules. However, few molecular-targeted therapy types have shown satisfactory efficacy in patients with SGC. Our study described promising results of cetuximab (Cmab), epidermal growth factor receptor (EGFR)-targeting therapy with paclitaxel (PTX) in patients with SGC. Seven patients with SGC received Cmab-PTX therapy. The median age was 76 years. All patients were high-grade histological types, and EGFR expression was positive in all examined patients. Cmab-PTX was administered for a median period of 20 months. The overall responses were three with complete response, two with partial response, one with stable disease (&gt;24 weeks), and one with progressive disease. The objective response rate was 71.4%. Progression-free survival ranged between 2 and 36 months (median 12 months), whereas overall survival ranged between 4 and 111 months (median 36 months). One patient experienced a grade 4 adverse event (neutropenia), which was conservatively manageable. Our study revealed a preferable objective response rate of Cmab-PTX for patients with high-grade SGC. Although the treatment sensitivity of SGC with high-grade histological types is usually poor, Cmab-PTX could be a promising treatment regimen for recurrent SGC., (© 2023 S. Karger AG, Basel.)

The incidence of thyroid cancer (TC) has increased over the past 30 years. Although differentiated thyroid cancer (DTC) has a good prognosis in most patients undergoing total thyroidectomy followed by radioiodine therapy (RAI), 5-10% of patients develop metastasis. Anaplastic thyroid cancer (ATC) has a low survival rate and few effective treatments have been available to date. Recently, tyrosine kinase inhibitors (TKIs) have been successfully applied to RAI-resistant or non-responsive TC to suppress the disease. However, TC eventually develops resistance to TKIs. Immunotherapy is a promising treatment for TC, the majority of which is considered an immune-hot malignancy. Immune suppression by TC cells and immune-suppressing cells, including tumor-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells, is complex and dynamic. Negative immune checkpoints, cytokines, vascular endothelial growth factors (VEGF), and indoleamine 2,3-dioxygenase 1 (IDO1) suppress antitumor T cells. Basic and translational advances in immune checkpoint inhibitors (ICIs), molecule-targeted therapy, tumor-specific immunotherapy, and their combinations have enabled us to overcome immune suppression and activate antitumor immune cells. This review summarizes current findings regarding the immune microenvironment, immunosuppression, immunological targets, and immunotherapy for TC and highlights the potential efficacy of immunotherapy.

BACKGROUND Malignant lymphomas can occur at various sites. Hypopharyngeal tumors are at risk for airway obstruction and require rapid diagnosis and treatment. Most hypopharyngeal malignancies are squamous cell carcinomas; other tumors are rare. To date, only a few cases of malignant hypopharyngeal lymphoma have been reported, and its specific characteristics are unknown. Herein, we report a case of right hypopharyngeal diffuse large B-cell lymphoma (DLBCL) in a 74-year-old man with dysphagia. CASE REPORT A 74-year-old man presented to our hospital with dysphagia. He had no relevant medical history. Endoscopic examination revealed a right hypopharyngeal tumor. The surface of the tumor was smooth, with no evidence of hemorrhage. Computed tomography revealed a 40-mm mass located in the hypopharynx. We performed a tracheotomy and biopsy of the tumor. Histopathological examination revealed a diffuse proliferation of large atypical B cells with negative staining for Epstein-Barr virus by in situ hybridization. Immunohistochemical staining was positive for CD20 but negative for CD3 and CD10. The patient was administered chemotherapy. The tumor reduced in size, and the patient recovered completely. During the two-year follow up, no recurrence of cancer was observed. CONCLUSIONS Although most hypopharyngeal tumors are squamous cell carcinomas (SCCs), the possibility of other types of tumors should also be considered. Malignant lymphoma of the hypopharynx is rare, and more cases need to be studied and reported in the future.

Background: Floating toes are a condition and deformity in which some of the toes are afloat. Many functional impairments in floating toes have been previously studied lately and several factors related to floating toes have also been reported. However, no reports have considered the relationship between lifestyle and floating toes among children. The purpose of this study was to reveal the prevalence of floating toes among school children and reveal its relationship with lifestyle., Methods: In total, 138 young male baseball players were recruited. Lifestyle was evaluated by using a questionnaire and chosen whether the main lifestyle was Japanese or Western, if the bedding was futons or beds, and if the toilet was Japanese style (a squat toilet) or Western style. Floating toes were defined as toes that were not in contact with the mat. Ankle dorsiflexion in the knee-flexed and knee-extended positions was measured in a weight-bearing position. The relationship between the floating toes and lifestyles, and the comparison of ankle dorsiflexion range of motion between the lifestyles were statistically analyzed., Results: Players living in a Western style showed a significantly higher prevalence of floating toes on both feet compared with the players living in a Japanese style (throwing side; 39% vs. 19%, p = 0.04, and non-throwing side; 43% vs. 19%, p = 0.01). Players living in a Western style with beds showed a significantly smaller range of motion on both sides of ankle dorsiflexion in the knee-flexed position compared with those who were not (throwing side; 37.2 ± 5.7° vs. 39.0 ± 6.6°, p = 0.04, and non-throwing side; 36.8 ± 5.8° vs. 38.6 ± 6.1°, p = 0.04)., Conclusion: Children mainly living in a Western lifestyle showed a significantly higher prevalence of floating toes on both feet compared to those mainly living in a Japanese lifestyle. The prevalence of floating toes may be related to lifestyles among children., Trial Registration: The study was approved by the institutional review board of the Waseda University Graduate School of Sport Sciences (IRB number 2021-185)., (© 2023. The Author(s).)

Brachyury is a transcription factor belonging to the T-box gene family and is involved in the posterior formation of the mesoderm and differentiation of chordates. As the overexpression of Brachyury is a poor prognostic factor in a variety of cancers, the establishment of Brachyury-targeted therapy would be beneficial for the treatment of aggressive tumors. Because transcription factors are difficult to treat with a therapeutic antibody, peptide vaccines are a feasible approach for targeting Brachyury. In this study, we identified Brachyury-derived epitopes that elicit antigen-specific and tumor-reactive CD4 + T cells that directly kill tumors. T cells recognizing Brachyury epitopes were present in patients with head and neck squamous cell carcinoma. Next, we focused on gemcitabine (GEM) as an immunoadjuvant to augment the efficacy of antitumor responses by T cells. Interestingly, GEM upregulated HLA class I and HLA-DR expression in tumor, followed by the upregulation of anti-tumor T cell responses. As tumoral PD-L1 expression was also augmented by GEM, PD-1/PD-L1 blockade and GEM synergistically enhanced the tumor-reactivity of Brachyury-reactive T cells. The synergy between the PD-1/PD-L1 blockade and GEM was also confirmed in a mouse model of head and neck squamous cell carcinoma. These results suggest that the combined treatment of Brachyury peptide with GEM and immune checkpoint blockade could be a promising immunotherapy against head and neck cancer., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The intrinsic and extrinsic muscles are considered to stabilize the foot and contribute to propulsion during walking. This study aimed to clarify the functional relationship between intrinsic and extrinsic muscles during walking. Thirteen healthy men participated in this study. The muscle activities of the intrinsic muscles (quadratus plantae and abductor hallucis), and the extrinsic muscles (flexor hallucis longus, flexor digitorum longus, and tibialis posterior) were measured using fine-wire and surface electromyography during walking. The muscle onset timing after foot contact was calculated and compared among muscles using the one-way ANOVA. The stance phase was divided into early and late braking, and early and late propulsion phases. Muscle activity among phases was compared using repeated-measures ANOVA. The onset time of the abductor hallucis was significantly earlier than those of the flexor digitorum longus and tibialis posterior. The quadratus plantae demonstrated significantly earlier onset than that of the tibialis posterior. In the late propulsion phase, the activity of extrinsic muscles decreased, whereas intrinsic muscles were continuously active. Early activation of the intrinsic muscles may stabilize the foot for efficient torque production by the extrinsic muscles. Furthermore, the intrinsic muscles may contribute to the final push-off after the deactivation of extrinsic muscles., 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 Elsevier Ltd. All rights reserved.)

[Purpose] To measure the sub-sesamoid soft tissue thickness change from non-loading to self-weight loading conditions. [Participants and Methods] The study included 17 female participants for the study. A questionnaire was used to collect the demographic data and participant anamnesis, such as the presence of foot injuries and diabetes. The measured height and weight were used to calculate the body mass index. Participants were required to stand on an evaluation device from non-loading to 100% loading conditions to measure the sub-sesamoid soft tissue thickness. [Results] Significant differences were observed between the tibial and fibular sub-sesamoid soft tissue thicknesses under non-loading and all loading conditions. Significant soft tissue thinning was observed with a change from non-loading to 25% loading condition. However, no significant differences in the rate of change were observed between the tibial and fibular sub-sesamoid soft tissue thicknesses at 100% loading. [Conclusion] The sub-fibular sesamoid soft tissue was thicker than the sub-tibial sesamoid soft tissue in all loading conditions. The sub-sesamoid soft tissue thickness change was larger during initial loading stage than during the late loading stage, which may be normal in healthy females in their 20s., Competing Interests: None., (2023©by the Society of Physical Therapy Science. Published by IPEC Inc.)

The prevalence of impaired foot function and floating toes of 91 baseball players with disabled throwing shoulder or elbow were retrospectively investigated. Foot function was evaluated by foot "rock paper scissors" and floating toes were confirmed if none of the toes made contact with the mat in standing posture. The prevalence of impaired foot function and floating toes and the relationship between between them were determined. Abnormal foot function was observed in 83 players (91%); of those, 73 players (88%) also had floating toes, and the prevalence was statistically significant compared to those without it (12%) ( P < 0.001). Floating toes were observed in 74 players (81%); of those, 73 players (99%) had impaired foot function, and the prevalence was also statistically significant compared to those without them (59%) ( P < 0.001). Baseball players with disabled throwing shoulder or elbow have high rates of impaired foot function and floating toes.

This study aimed to compare the foot muscle morphology and foot posture between healthy adults and lifesavers in sandy beach sports. The participants included 15 lifesaver athletes and 15 healthy adults. Using a non-contact three-dimensional foot measurement device, the foot length, width, and arch height of the right foot were measured while standing and sitting without back support, and the transverse arch length ratio and arch height index were subsequently calculated. Muscle cross-sectional area was measured using an ultrasound imaging device. Muscle cross-sectional areas, arch height, foot width, arch height index, and transverse arch length ratio were larger in the lifesaver than in the healthy adult group. Lifesavers had higher arches and more developed intrinsic and extrinsic muscles than healthy adults. Performing physical activity while barefoot on sandy beaches may effectively develop the foot intrinsic and extrinsic muscles and raise the arch.

The engagement of CD27 on lymphocytes with its ligand, CD70, on tumors is believed to mediate tumor immune evasion and the elevation of serum soluble CD27 (sCD27) levels in patients with CD70-positive malignancies. We previously showed that CD70 is expressed in extranodal natural killer/T-cell lymphoma, nasal type (ENKL), an Epstein-Barr virus (EBV)-related malignancy. However, little is known about serum sCD27 expression and its association with the clinical characteristics of, and the CD27/CD70 interaction in, ENKL. In the present study, we show that serum sCD27 is significantly elevated in the sera of patients with ENKL. The levels of serum sCD27 provided excellent diagnostic accuracy for discriminating patients with ENKL from healthy subjects, correlated positively with the levels of other diagnostic markers (lactate dehydrogenase, soluble interleukin-2 receptor, and EBV-DNA), and decreased significantly following treatment. Elevated serum sCD27 levels also correlated significantly with advanced clinical stage and tended to correspond with shorter survival, in patients with ENKL. Immunohistochemistry indicated that CD27-positive tumor-infiltrating immune cells exist adjacent to CD70-positive lymphoma cells. In addition, serum sCD27 levels in patients with CD70-positive ENKL were significantly higher than those in patients with CD70-negative ENKL, suggesting that the intra-tumoral CD27/CD70 interaction boosts the release of sCD27 in serum. Furthermore, the EBV-encoded oncoprotein latent membrane protein 1 upregulated CD70 expression in ENKL cells. Our results suggest that sCD27 may serve as a novel diagnostic biomarker and also may serve as a tool for evaluating the applicability of CD27/CD70-targeted therapies by predicting intra-tumoral CD70 expression and CD27/CD70 interaction in ENKL., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)