The 33rd International Conference on Arabidopsis Research (ICAR2023).

The 33rd International Conference on Arabidopsis Research (ICAR2023) was held at Makuhari Messe International Conference Hall in Chiba prefecture from June 5 to 9, 2023. This annual conference, which rotates among hosts in North America, Asia-Oceania, and Europe, covers the full range of plant biology research involving Arabidopsis and other plant species. The conference hosted more than 1200 participants, including approximately 800 international attendees from 42 countries (or regions), and featured about 900 oral and poster presentations. Reflecting the conference theme, "Arabidopsis for Sustainable Development Goals (SDGs)," there were numerous exemplary presentations regarding basic plant science using Arabidopsis and translational research conducted to achieve SDGs by exploiting the knowledge gained from Arabidopsis to improve crop production. The conference concluded on a high note, with more than 99% of survey respondents expressing their general satisfaction with ICAR2023. This report aims to summarize the organization, objectives, and outcomes of the conference.

Click-to-lead design of a picomolar ABA receptor antagonist with potent activity in vivo.

Abscisic acid (ABA) is a key plant hormone that mediates both plant biotic and abiotic stress responses and many other developmental processes. ABA receptor antagonists are useful for dissecting and manipulating ABA's physiological roles in vivo. We set out to design antagonists that block receptor-PP2C interactions by modifying the agonist opabactin (OP), a synthetically accessible, high-affinity scaffold. Click chemistry was used to create an ∼4,000-member library of C4-diversified opabactin derivatives that were screened for receptor antagonism in vitro. This revealed a peptidotriazole motif shared among hits, which we optimized to yield antabactin (ANT), a pan-receptor antagonist. An X-ray crystal structure of an ANT-PYL10 complex (1.86 Å) reveals that ANT's peptidotriazole headgroup is positioned to sterically block receptor-PP2C interactions in the 4' tunnel and stabilizes a noncanonical closed-gate receptor conformer that partially opens to accommodate ANT binding. To facilitate binding-affinity studies using fluorescence polarization, we synthesized TAMRA-ANT. Equilibrium dissociation constants for TAMRA-ANT binding to Arabidopsis receptors range from ∼400 to 1,700 pM. ANT displays improved activity in vivo and disrupts ABA-mediated processes in multiple species. ANT is able to accelerate seed germination in Arabidopsis, tomato, and barley, suggesting that it could be useful as a germination stimulant in species where endogenous ABA signaling limits seed germination. Thus, click-based diversification of a synthetic agonist scaffold allowed us to rapidly develop a high-affinity probe of ABA-receptor function for dissecting and manipulating ABA signaling.

Extension of the Antero-Posterior Necrotic Regions Associated With Collapse Cessation in Osteonecrosis of the Femoral Head.

BACKGROUND: Collapse cessation is of utmost importance following a long period of collapse due to osteonecrosis of the femoral head (ONFH). This study investigated the relationship between collapse cessation and the extent of the necrotic regions of ONFH. METHODS: Overall, 74 patients who had symptomatic ONFH (collapse < 3 mm) at the first visit with a minimum follow-up of 3 years were included in this study. Patients were categorized based on collapse progression or cessation into the progression and stable groups. The extent of the antero-posterior (AP) and medio-lateral necrotic regions between the groups was assessed using sagittal and coronal sections of T1-magnetic resonance imaging. Additionally, the most effective cutoff value was determined from the receiving operating characteristic curve where collapse cessation could be obtained, while the survival rates were determined with collapse progression as the endpoints were evaluated. RESULTS: Overall, 45 and 29 patients were in the progression and stable groups, respectively. The AP and medio-lateral necrotic regions were significantly different (P < .01 and P < .01, respectively) between the progression and stable groups. A cutoff value of 62.1% of the AP necrotic regions was determined from the receiving operating characteristic curve analysis. The 5-year survival rates with collapse progression as the endpoints were 5.4 and 77.8% in the AP necrotic regions of ≥62.1 and <62.1%, respectively (P < .01). CONCLUSIONS: Cases with AP necrotic regions of ≤62.1% can be expected to have collapse cessation, which could be a useful index for ONFH treatment strategies. LEVEL OF EVIDENCE: Level IV.

Risk factors for intraoperative femoral fractures in cementless bipolar hip arthroplasty for femoral neck fracture in multicenter: The TRON group study.

BACKGROUND: Intraoperative femoral fractures are more common in cementless bipolar hip arthroplasty (BHA) for displaced femoral neck fractures than they are in cemented BHA and remain one of the major concerns. This study aimed to investigate the risk factors for intraoperative femoral fractures in cementless BHA. METHODS: The study included 1,392 patients who underwent cementless BHA for displaced femoral neck fractures from January 2015 to December 2019 in 14 hospitals of the Trauma Research Group. They were divided into two groups according to the presence or absence of intraoperative femoral fractures, and factors associated with intraoperative fractures were statistically examined. RESULTS: Forty (2.9 %) intraoperative and 28 (2.0 %) postoperative, totally 68 (4.9 %) femoral fractures occurred. The mean age of the patients, presence of opposite-side proximal femoral fracture, approach, and cementless stem design were significantly different between the two groups (P < 0.05). The logistic regression analysis model showed that a fully HA-coated stem (odds ratio, 4.12; 95 % confidence interval, 1.43-11.9) was an independent factor associated with intraoperative femoral fractures. CONCLUSION: This study investigated the risk factors associated with intraoperative fractures and showed that fully HA-coated stems were an independent factor associated with intraoperative femoral fractures. Surgeons should be cautious in the early stages of introducing fully HA-coated stems.

A large preoperative pelvic oblique angle affects perception of leg length discrepancy after total hip arthroplasty.

BACKGROUND: In some cases, patients feel a perceived leg length discrepancy (P-LLD) despite no radiographic leg length discrepancy (R-LLD) after total hip arthroplasty (THA). We aimed to investigate the rate of postoperative P-LLD and the factors that cause postoperative P-LLD. METHODS: A retrospective study was conducted on 100 patients with R-LLD ≤5 mm after THA. Patients were classified into two groups based on P-LLD post-THA: group P (with P-LLD) and group E (without P-LLD). Relevant data on the general characteristics and radiological findings between the two groups were compared. RESULTS: We observed that 25 & 75% of patients belonged to group P and group E, respectively, with no significant difference in patient background. Postoperative Japanese Orthopedic Association (JOA) classification of pain and activities of daily living scores were significantly lower in group P than in group E (37.2 ± 3.9 vs. 39.1 ± 2.2, respectively; P = 0.013, and 16.2 ± 4.2 vs. 18.2 ± 2.2, respectively; P = 0.011). The preoperative pelvic oblique angle (POA) was significantly larger in group P than in group E (3.3 ± 2.3° vs. -0.2 ± 2.1°; respectively; P < 0.01). The pelvis tilted toward the surgical side was significantly higher in group P than in group E(88% vs 57%; respectively; P = 0.013). The preoperative C7 coronal vertical axis (C7 CVA) was significantly larger in group P than in group E (6.7 ± 14.7 mm vs. -0.2 ± 10.3 mm; respectively; P = 0.028). Multivariate logistic analysis revealed that preoperative POA (OR, 3.71; 95% CI: 1.86-8.12; P < 0.01) and the pelvis tilted toward the surgical side (OR, 4.14; 95% CI: 2.07-9.71; P = 0.022) were independent risk factors for P-LLD after THA. CONCLUSION: Even though there was no postoperative R-LLD, 25% of patients had P-LLD. A large preoperative POA and the pelvis tilted toward the surgical side were independent risk factors for P-LLD after THA.

Fall risk in patient with dysplastic hip osteoarthritis.

PURPOSE: Patients with dysplastic hip osteo arthritis (DHOA) often have a spinopelvic imbalance, and they are more likely to experience falls. This study aimed to evaluate the risk factors for falls in patients with DHOA, including spinopelvic parameters. METHODS: In this cross-sectional study, a total of 103 patients with DHOA were included from 2019 to 2021. Fall risk was evaluated using the Fall Risk Index 5 items version (FRI-5). Demographics, functional outcomes, and spinopelvic parameters were compared between the high-risk group (FRI-5 ≥ 6) and the low-risk group (FRI-5 < 6). Multivariate analysis was performed using factors with significant differences in univariate analysis. RESULTS: High-risk and low-risk groups comprised 54 and 49 patients, respectively. Females were significantly more common in the high-risk group than in the low-risk group. The Harris Hip Score was significantly lower in the high-risk group than in the low-risk group (p = 0.02). Pelvic incidence, tilt, and obliquity were significantly higher in the high-risk group than in the low-risk group (p < 0.01). In multivariate analysis, female sex (odds ratio [OR]: 3.76, 95% confidence interval [CI]: 1.11-12.64, p = 0.03), pelvic obliquity (OR: 1.36, 95% CI: 1.09-1.71, p < 0.01), and Harris hip score (OR: 0.96, 95% CI: 0.93-0.99, p = 0.02) were identified as risk factors. CONCLUSION: Female sex, pelvic obliquity, and low Harris hip score were associated with an increased risk of falls among patients with DHOA.

Retrospective study comparing the accuracies of handheld infrared stereo camera and augmented reality-based navigation systems for total hip arthroplasty.

BACKGROUND: The use of portable navigation systems (PNS) in total hip arthroplasty (THA) has become increasingly prevalent, with second-generation PNS (sPNS) demonstrating superior accuracy in the lateral decubitus position compared to first-generation PNS. However, few studies have compared different types of sPNS. This study retrospectively compares the accuracy and clinical outcomes of two different types of sPNS instruments in patients undergoing THA. METHODS: A total of 158 eligible patients who underwent THA at a single institution between 2019 and 2022 were enrolled in the study, including 89 who used an accelerometer-based PNS with handheld infrared stereo cameras in the Naviswiss group (group N) and 69 who used an augmented reality (AR)-based PNS in the AR-Hip group (group A). Accuracy error, navigation error, clinical outcomes, and preparation time were compared between the two groups. RESULTS: Accuracy errors for Inclination were comparable between group N (3.5° ± 3.0°) and group A (3.5° ± 3.1°) (p = 0.92). Accuracy errors for anteversion were comparable between group N (4.1° ± 3.1°) and group A (4.5° ± 4.0°) (p = 0.57). The navigation errors for inclination (group N: 2.9° ± 2.7°, group A: 3.0° ± 3.2°) and anteversion (group N: 4.3° ± 3.5°, group A: 4.3° ± 4.1°) were comparable between the groups (p = 0.86 and 0.94, respectively). The preparation time was shorter in group A than in group N (p = 0.036). There were no significant differences in operative time (p = 0.255), intraoperative blood loss (p = 0.387), or complications (p = 0.248) between the two groups. CONCLUSION: An Accelerometer-based PNS using handheld infrared stereo cameras and AR-based PNS provide similar accuracy during THA in the lateral decubitus position, with a mean error of 3°-4° for both inclination and anteversion, though the AR-based PNS required a shorter preparation time.

Muscle strength and functional recovery for soft-tissue sarcoma of the thigh: a prospective study.

BACKGROUND: This study aimed to investigate changes in muscle strength and functional outcome before and after surgery for soft-tissue sarcoma of the thigh and to examine the timing of recovery. METHODS: From 2014 to 2019, 15 patients who underwent multiple resections of the thigh muscle for soft-tissue sarcoma of the thigh were included in this study. The muscle strength was measured with an isokinetic dynamometer for the knee joint and with a hand-held dynamometer for the hip joint. The functional outcome assessment was based on the Musculoskeletal Tumor Society (MSTS) score, Toronto Extremity Salvage Score (TESS), European Quality of Life-5 Dimensions (EQ-5D), and maximum walking speed (MWS). All measurements were conducted preoperatively and at 3, 6, 12, 18, and 24 months postoperatively, and the ratio of postoperative to preoperative value was used. A repeated-measures analysis of variance was performed to compare changes over time and to investigate the recovery plateau. Correlations between changes in muscle strength and functional outcomes were also examined. RESULTS: The muscle strength of the affected limb, MSTS score, TESS, EQ-5D, and MWS were significantly decreased at 3 months postoperatively. The recovery plateau was subsequently reached at 12 months postoperatively. The changes in muscle strength of the affected limb and functional outcome showed a significant correlation. CONCLUSIONS: The estimated postoperative recovery for soft-tissue sarcoma of the thigh is 12 months after surgery.

Risk factors for lateralization or superiorization of the center of the femoral head in eccentric rotational acetabular osteotomy.

PURPOSE: This study aimed to clarify the factors that cause the lateralization and superiorization of the femoral head after eccentric rotational acetabular osteotomy (ERAO) by examining the three-dimensional morphology of the osteotomy site using computed tomography (CT). METHODS: This study included 52 patients who underwent ERAO for hip dysplasia. Postoperatively, the center of the femoral head was measured for lateralization and superiorization. We defined the iliac and sciatic osteotomy angles in the coronal and axial CT planes, respectively. The surgical factors for lateralization and superiorization were analysed using multiple logistic regression analysis. We also analysed the relationship between the femoral head relocation and clinical outcomes (as assessed using Japanese Orthopaedic Association (JOA) scores). RESULTS: Thirty-five patients had hips with lateralized femoral heads, and 25 patients' femoral heads were superiorized. Logistic regression analysis revealed that a higher osteotomy angle of the ilium in the coronal plane served as a significant predictor of superiorization of the femoral head. Similarly, a larger osteotomy angle of the ischium in the axial plane and the amount of change in the lateral centre edge angle were identified as predictors of lateralization. A weak negative correlation was observed between the amount of lateralization and the JOA score. CONCLUSION: Large osteotomy angles in the superior and posterior aspects of the acetabulum carry a risk of superiorization and lateralization of the center of the femoral head. Surgeons should be aware of the need to chisel through the internal plate to achieve the results described in the ERAO theory. STUDY DESIGN: A single-center, retrospective study.

Hip function in patients undergoing conservative treatment for osteonecrosis of the femoral head.

PURPOSE: Once collapsed, osteonecrosis of the femoral head (ONFH) generally obtains collapse cessation naturally and surgical intervention can be avoided in the long term. This study aimed to investigate the process of hip function and secondary osteoarthritis changes in ONFH patients undergoing conservative treatment. METHODS: We included 54 patients with symptomatic ONFH at the first visit with a minimum follow-up of three years with conservative treatment. Patients were divided into two groups based on collapse cessation < 3 mm (stable group) or progression to > 3 mm (progression group). Additionally, we investigated age, sex, body mass index (BMI), etiology, contralateral side hip joint, the Japanese Investigation Committee (JIC) type classification, Harris hip score (HHS), Japanese Orthopaedic Association Hip-Disease Evaluation Questionnaire (JHEQ), and survival rate with secondary osteoarthritis as the endpoint. RESULTS: The stable and progression groups had 31 and 23 patients, respectively. No significant differences in age, sex, BMI, and aetiology were observed between the two groups, except for the contralateral side hip joint and JIC type classification. The HHS and JHEQ were significantly improved at the final follow-up than at the first visit in the stable group. However, there were no significant differences in HHS and JHEQ at the final follow-up than at the first visit in the progression group. The five year survival rates with secondary osteoarthritis as the endpoint were significantly higher in the stable group (100%) than in the progression group (32.5%). CONCLUSION: Hip joint function improved by continuing conservative treatment in ONFH patients with collapse cessation < 3 mm.

Ligand-receptor interactions in plant hormone signaling.

Small-molecule plant hormones principally control plant growth, development, differentiation, and environmental responses. Nine types of plant hormones are ubiquitous in angiosperms, and the molecular mechanisms of their hormone actions have been elucidated during the last two decades by genomic decoding of model plants with genetic mutants. In particular, the discovery of hormone receptors has greatly contributed to the understanding of signal transduction systems. The three-dimensional structure of the ligand-receptor complex has been determined for eight of the nine hormones by X-ray crystal structure analysis, and ligand perception mechanisms have been revealed at the atomic level. Collective research has revealed the molecular function of plant hormones that act as either molecular glue or an allosteric regulator for activation of receptors. In this review, we present an overview of the respective hormone signal transduction and describe the structural bases of ligand-receptor interactions.

Influence of the adductor compartment resection on muscle strength and postoperative function in soft-tissue sarcoma of the thigh.

OBJECTIVE: To predict the muscle strength and postoperative function for soft-tissue sarcoma arising from the adductor compartment of the thigh. METHODS: Between 2003 and 2019, 17 cases that underwent resection of the adductor muscle group (adductor longus, adductor magnus, adductor brevis, gracilis and pectineus) for soft-tissue sarcoma in the adductor compartment of the thigh were included. The muscle strength was measured with an isokinetic dynamometer for the knee joint and with a hand-held dynamometer for the hip joint (ratio of affected to unaffected side). The Musculoskeletal Tumor Society score, Toronto Extremity Salvage Score, European Quality of Life-5 Dimensions and maximum walking speed were used to assess postoperative function and examine correlations with muscle strength. RESULTS: In 13 cases that underwent an isolated resection of the adductor compartment, reduced adduction strength correlated with increased number of resected muscles in the adductor muscle group (P < 0.001). Postoperative function was maintained, showing no correlations with adduction strength. In four cases that underwent combined resections of other compartments, a decrease was observed in adduction strength as well as the muscle strength of other resected muscles, in addition to a decline in postoperative function. In the 4 or 5 adductor muscle resection group, the comparison between isolated and combined resection revealed comparable results for adduction strength but a significant decrease in postoperative function for the combined resection group. CONCLUSIONS: Postoperative function can be preserved for isolated adductor compartment resection. Combined resections of multiple muscles in other compartments and most adductor muscles may result in decreased postoperative function.

Effect of trochanter displacement on impingement and bone contact in total hip arthroplasty performed after curved intertrochanteric varus osteotomy for osteonecrosis of the femoral head: a simulation study.

BACKGROUND: Curved intertrochanteric varus osteotomy (CVO) is a useful treatment option for osteonecrosis of the femoral head (ONFH). However, the effect of proximal femoral deformity in cases of CVO converted to total hip arthroplasty (THA) remains unclear. The aim of this study was to evaluate the effect of trochanter displacement on impingement and the contact state of the implant and femur in THA. METHODS: Thirty-eight hips that had undergone CVO for ONFH were reviewed and compared with a control group of 30 contralateral hips that had not undergone surgery. The range of motion (ROM) and impingement patterns and the percentage of cortical bone in the stem placement within the femur were measured by simulation using CT-based three-dimensional template software. We also measured the ROM and the number of joints that achieved the ROM required for activities of daily living when the upward displaced apex of the greater trochanter with osteotomy was resected and compared the findings with those obtained when the apex was not resected. RESULTS: The CVO group showed a significantly greater bony impingement in external rotation (68.4% vs. 43.3%, p = 0.033) and abduction (78.9% vs. 33.3%, p < 0.001) than in the control group. The CVO group showed a significantly smaller range of external rotation (19.0° [interquartile range; 4.0-28.8] vs. 38.0° [interquartile range; 36.0-41.8], p < 0.001) and abduction (23.0° [interquartile range; 8.5-38.8] vs. 56.0° [interquartile range; 50.3-60.0], p < 0.001) than in the control group. Significantly more joints achieved the ROM necessary for activities of daily living when the apex was resected than when it was not (10.5% vs. 63.2%, p < 0.001). The percentage of cortical bone in the stem placement position was significantly higher in the CVO group than in the control group in the proximal portion of the stem (25.5% vs. 0.0%, p < 0.001). CONCLUSION: In cases requiring conversion to THA, we recommend resecting the upward displaced apex to achieve a sufficient ROM and carefully resecting the bone to avoid malignment of the stem.

Points of consideration when performing surgical procedures for proximal femoral bone metastasis.

BACKGROUND: To assess the points of consideration when performing surgical procedures for proximal femoral bone metastasis. METHODS: Fourty patients who underwent surgery for proximal femoral bone metastasis from 2009 to 2019 were included. Prognostic assessments were performed based on the Katagiri scoring system. The low-risk group underwent endoprosthetic replacement (EPR) following resection, while the high-risk group underwent internal fixation (IF). For the intermediate-risk group, one of the surgical procedures was chosen depending on general and local condition. Survival period, walking ability, and treatment failure were evaluated. RESULTS: Sixteen and 24 patients underwent EPR and IF, respectively. Although walking reacquisition rate was 94% (15 of 16 patients) for EPR and 75% (18 of 24 patients) for IF (p = 0.210), the median time to walking was shorter in IF compared to EPR (EPR, 29 days, interquartile range [IQR] 23-40; IF, 14 days, IQR 9-24; p = 0.014). Neither EPR nor IF resulted in treatment failure for those with survival periods of <1 year. The treatment failure rate for those with survival periods of ≥1 year was significantly different between EPR (9%, 1 of 11 patients) and IF (50%, 5 of 10 patients) (p = 0.038). All five patients of treatment failure for IF were renal cancer with no bone formation in the intermediate-risk group. Of the 13 patients who underwent IF for the intermediate-risk group, treatment failure did not occur in 5 patients with bone formation. CONCLUSIONS: Although EPR is a more reliable treatment than IF, patients with life expectancy of <1 year are sufficiently manageable with IF. For the intermediate-risk group, EPR should be selected for cases without expected bone formation, and IF can be considered for cases with expected bone formation due to the risk of treatment failure for IF at ≥ 1 year after surgery.

Effects of body mass index and range of motion on intraoperative change in pelvic tilt during total hip arthroplasty using the direct anterior approach.

BACKGROUND: Intraoperative pelvic tilt changes that occurs during total hip arthroplasty (THA) in the supine position affects cup placement and sometimes causes malalignment. The relationship between body mass index (BMI) and pelvic movement has been reported for some procedures, but not the direct anterior approach (DAA). The purpose of this study was to investigate intraoperative pelvic tilt changes that occurs during DAA. METHODS: In this single-center, retrospective study, we reviewed 200 hips that underwent primary THA via DAA in the supine position using an accelerometer-based navigation system. Intraoperative changes in pelvic tilt and axial rotation from the start of surgery to cup placement were assessed using the navigation system. Preoperative clinical factors that increased pelvic tilt and axial rotation toward the surgical side by > 10° were analyzed via univariate and multiple logistic regression analyses. RESULTS: The mean pelvic tilt value increased by 7.6° ± 3.8° (95% confidence interval [CI], 7.1-8.2; range, - 5.0-19.0) intraoperatively, and the axial rotation increased by 3.2° ± 2.7° (95% CI, 2.7-3.7; range, - 13.0-12.0). Univariate analysis revealed that the group with increased pelvic tilt showed significantly greater range of abduction and internal rotation, and significantly lower BMI than the group with no increased tilt. Pre-incisional pelvic tilt was significantly greater in the group with increased axial rotation than in the group with no increased rotation. On logistic regression analysis, BMI (odds ratio [OR], 0.889; 95% CI, 0.809-0.977; p = 0.014) and the range of internal rotation (OR, 1.310; 95% CI, 1.002-1.061; p = 0.038) were predictors of large increases in pelvic tilt. No predictors of large increases in axial rotation were identified. CONCLUSION: Significant forward pelvic tilt was observed in patients with a low BMI values and high ranges of internal rotation via THA using the DAA. Findings indicated that surgeons should pay attention to intraoperative pelvic movements, which may help identify patients with significant pelvic tilt changes.

AtPep3 is a hormone-like peptide that plays a role in the salinity stress tolerance of plants.

Peptides encoded by small coding genes play an important role in plant development, acting in a similar manner as phytohormones. Few hormone-like peptides, however, have been shown to play a role in abiotic stress tolerance. In the current study, 17 Arabidopsis genes coding for small peptides were found to be up-regulated in response to salinity stress. To identify peptides leading salinity stress tolerance, we generated transgenic Arabidopsis plants overexpressing these small coding genes and assessed survivability and root growth under salinity stress conditions. Results indicated that 4 of the 17 overexpressed genes increased salinity stress tolerance. Further studies focused on AtPROPEP3, which was the most highly up-regulated gene under salinity stress. Treatment of plants with synthetic peptides encoded by AtPROPEP3 revealed that a C-terminal peptide fragment (AtPep3) inhibited the salt-induced bleaching of chlorophyll in seedlings. Conversely, knockdown AtPROPEP3 transgenic plants exhibited a hypersensitive phenotype under salinity stress, which was complemented by the AtPep3 peptide. This functional AtPep3 peptide region overlaps with an AtPep3 elicitor peptide that is related to the immune response of plants. Functional analyses with a receptor mutant of AtPep3 revealed that AtPep3 was recognized by the PEPR1 receptor and that it functions to increase salinity stress tolerance in plants. Collectively, these data indicate that AtPep3 plays a significant role in both salinity stress tolerance and immune response in Arabidopsis.

Anti-PD-1 antibody decreases tumour-infiltrating regulatory T cells.

BACKGROUND: There are many types of therapies for cancer. In these days, immunotherapies, especially immune checkpoint inhibitors, are focused on. Though many types of immune checkpoint inhibitors are there, the difference of effect and its mechanism are unclear. Some reports suggest the response rate of anti-PD-1 antibody is superior to that of anti-PD-L1 antibody and could potentially produce different mechanisms of action. On the other hand, Treg also express PD-1; however, their relationship remains unclear. METHODS: In this study, we used osteosarcoma cell lines in vitro and osteosarcoma mouse model in vivo. In vitro, we analyzed the effect of IFNγ for expression of PD-L1 on the surface of cell lines by flowcytometry. In vivo, murine osteosarcoma cell line LM8 was subcutaneously transplanted into the dorsum of mice. Mouse anti-PD-1 antibody was intraperitoneally administered. we analysed the effect for survival of anti-PD-1 antibody and proportion of T cells in the tumour by flowcytometry. RESULTS: We discovered that IFNγ increased PD-L1 expression on the surface of osteosarcoma cell lines. In assessing the relationship between anti-PD-1 antibody and Treg, we discovered the administration of anti-PD-1 antibody suppresses increases in tumour volume and prolongs overall survival time. In the tumour microenvironment, we found that the administration of anti-PD-1 antibody decreased Treg within the tumour and increased tumour-infiltrating lymphocytes. CONCLUSIONS: Here we clarify for the first time an additional mechanism of anti-tumour effect-as exerted by anti-PD-1 antibody decreasing Treg- we anticipate that our findings will lead to the development of new methods for cancer treatment.

A Review of T-Cell Related Therapy for Osteosarcoma.

Osteosarcoma is one of the most common primary malignant tumors of bone. The combination of chemotherapy and surgery makes the prognosis better than before, but therapy has not dramatically improved over the last three decades. This is partially because of the lack of a novel specialized drug for osteosarcoma, which is known as a tumor with heterogeneity. On the other hand, immunotherapy has been one of the most widely used strategies for many cancers over the last ten years. The therapies related to T-cell response, such as immune checkpoint inhibitor and chimeric antigen receptor T-cell therapy, are well-known options for some cancers. In this review, we offer the accumulated knowledge of T-cell-related immunotherapy for osteosarcoma, and discuss the future of the therapy.

Risk factor for wound complications following wide resection of soft tissue sarcoma in the adductor compartment of the thigh.

BACKGROUND: The purpose of this study was to investigate deep-seated soft tissue sarcoma (STS) occurring in the adductor compartment of the thigh that underwent wide resection and to clarify the high-risk group for wound complications. PATIENTS AND METHODS: From 2000 to 2017, we reviewed 104 cases of deep-seated STS occurring in the adductor compartment of the thigh that were treated at four specialized facilities with expertise in sarcoma treatment. RESULTS: Wound complications occurred in 40 cases (38.5%), of which 23 cases (22.1%) were cases with major wound complications (MWC). In univariate analysis, BMI (P < 0.01), maximum tumor diameter (P < 0.01), operation time (P < 0.01), amount of intraoperative bleeding (P < 0.01), and intraoperative intervention to the femoral artery and vein (P < 0.01) were significantly associated with wound complications. In multivariate analysis, the associated parameters were BMI (P < 0.01), maximum tumor diameter (P = 0.02), and intraoperative intervention to the femoral artery and vein (P = 0.01). When limited to cases with MWC, univariate analysis showed that maximum tumor diameter (P < 0.01), diabetes mellitus (P = 0.03), operation time (P < 0.01), amount of intraoperative bleeding (P < 0.01), and intraoperative intervention to the femoral artery and vein (P = 0.02) were significantly associated parameters. In multivariate analysis, maximum tumor diameter (P = 0.02) and amount of intraoperative bleeding (P = 0.04) were associated parameters. CONCLUSIONS: For patients with risk factors for wound complications, control of bleeding are crucial when resecting deep-seated STS in the adductor compartment of the thigh. In cases with large tumors, surgeons should be especially cautious of cases requiring interventions that surround the femoral artery and vein in order to attain an appropriate surgical margin.

The Regulation of Bone Metabolism and Disorders by Wnt Signaling.

Wnt, a secreted glycoprotein, has an approximate molecular weight of 40 kDa, and it is a cytokine involved in various biological phenomena including ontogeny, morphogenesis, carcinogenesis, and maintenance of stem cells. The Wnt signaling pathway can be classified into two main pathways: canonical and non-canonical. Of these, the canonical Wnt signaling pathway promotes osteogenesis. Sclerostin produced by osteocytes is an inhibitor of this pathway, thereby inhibiting osteogenesis. Recently, osteoporosis treatment using an anti-sclerostin therapy has been introduced. In this review, the basics of Wnt signaling, its role in bone metabolism and its involvement in skeletal disorders have been covered. Furthermore, the clinical significance and future scopes of Wnt signaling in osteoporosis, osteoarthritis, rheumatoid arthritis and neoplasia are discussed.