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Although many studies investigating the mechanical behavior of loop mechanics have focused on loop designs to produce a higher moment-to-force ratio, few studies have clarified the effect of loop position on the force system and resultant tooth movements. This study aimed to simulate orthodontic tooth movements during space closure and to compare the effects of loop position in association with different degrees of gable bend on tooth movements using the finite element method.Two finite element models of the maxillary dentition were constructed, with the loop placed mesial or distal to the canine. Tooth movements during loop activation were simulated while varying the degree of gable bend.When the loop was placed distal to the canine, the incisor showed uncontrolled tipping even with the gable bend. Placement of the loop mesial to the canine produced controlled tipping or root movement of the incisor, depending on the degree of gable bend.Placement of the closing loop mesial to the canine in combination with the incorporation of a gable bend into the archwire distal to the canine could provide better control of incisor movements, such as controlled tipping or root movement, as compared with placement of a gable bend into the loop located distal to the canine.

Ionizing radiation can induce mutations in germ cells in various organisms, including fruit flies and mice. However, currently, there is no clear evidence for the transgenerational effects of radiation in humans. This review is an effort to identify possible reasons for the lack of such observations. Literature search and narrative review. 1) In both mice and humans, resting oocytes locate primarily in the cortical region of the ovary where the number of blood vessels is very low especially when young and extra-cellular material is rich, and this region is consequently hypoxic, which probably leads to immature oocytes being resistant to the cell killing and mutagenic effects of radiation. 2) In studies of spermatogonia, the mouse genes used for specific locus test (SLT) studies, which include coat color genes, were hypermutable when compared to many other genes. Recent studies which examined over 1000 segments of genomic DNA indicate that the induction rate of deletion mutation per segment was on the order of 10−6 per Gy, which is one order of magnitude lower than that obtained from the SLT data. Therefore, it appears possible that detecting any transgenerational effects of radiation following human male exposures will be difficult due to a lack of mutable marker genes. 3) Fetal malformations were examined in studies in humans, but the genetic component in such malformations is low, and abnormal fetuses are prone to undergo miscarriage which does not occur in mice, and which leads to difficulties in detecting transgenerational effects. The lack of clear evidence for radiation effects in humans probably does not result from any problem in the methodologies used but may be due largely to biological properties. Currently, whole genome sequencing studies of exposed parents and offspring are planned, but ethical guidelines need to be followed to avoid discrimination, which had once happened to the atomic bomb survivors.

This case report describes the orthodontic-orthognathic management of a 17-year-old male patient with extremely severe skeletal Class III malocclusion due to a marked mandibular protrusion with a small and narrowed upper jaw which increased the remarkable concave facial profile. Dental articulation was entirely lacking, resulting in great difficulty in masticating food. A two-jaw surgery combined with mandibular body ostectomy was performed to correct mandibular asymmetry and the severe sagittal skeletal discrepancy (Wits appraisal –36.5 mm and ANB angle –14.3°). Bi-maxillary surgery was performed in two-stages; the first surgery consisted of maxillary advancement with Le Fort I osteotomy followed by a second surgery where a combination of sagittal split ramus osteotomy (SSRO) and mandibular body ostectomy was performed to correct the severe mandibular prognathism. A partial glossectomy was also carried out to address macroglossia. After a total treatment time of 32 months, a Class I occlusion with a favorable facial profile and lip competence were obtained. The occlusion was made approximately ideal, and mastication improved remarkably. Three years after retention, the occlusion was stable and no relapse was observed. The patient’s complaints and orthodontic problems were completely resolved. Therefore, a combination of two-jaw surgeries with Le Fort I maxillary osteotomy, mandibular SSRO, mandibular ostectomy, and glossectomy may be a viable option in the correction of extremely severe anteroposterior skeletal discrepancy., APOS Trends in Orthodontics, 12 (3), pp. 221-229; 2022

The objectives of this study were to simulate long-term orthodontic tooth movement in en-masse retraction using the finite element method and investigate the effects of power arms on tooth movements when using a lingual appliance in comparison with a labial appliance.A 3-dimensional finite element model of the maxillary dentition was constructed with 0.018-in brackets and 0.016 × 0.022-in stainless steel archwire. An en-masse retraction was performed by applying retraction force at various lengths of the power arm (4, 6, 8, and 10 mm) to the second molar tube, and long-term tooth movements with the lingual and labial appliances were analyzed using the finite element method.Although lingual crown tipping of the incisor was more marked with the lingual appliance than with the labial appliance in the early phase of space closure, only a slight difference was evident after space closure. Although the power arm was effective for achieving better-controlled tooth movement and reducing vertical and transverse bowing effects, bodily movement of the incisor could not be achieved, and bowing effects could not be eliminated.To provide better torque control of the incisor or prevent a vertical bowing effect, the incorporation of extra torque into brackets of incisors was recommended, and the use of power arms for the lingual appliance. To prevent a transverse bowing effect, incorporation of the antibowing bend or application of retraction force from both buccal and lingual sides or temporary skeletal anchorage devices was recommended.

The aim of this study was to clarify the effects of three different orthognathic surgical procedures on the temporomandibular joint after mandibular setback. Conventional sagittal split ramus osteotomy (SSRO) with segmental fixation (conv-SSRO), intraoral vertical ramus osteotomy (IVRO), or SSRO without fixation followed by the physiological positioning strategy (nonfix-SSRO) was performed for mandibular setback. Temporomandibular joint disorder (TMD) symptoms were clinically assessed, and the condylar head angle was measured. In total, 129 patients participated. Preoperative TMD and treatment procedure were related to postoperative TMD. A menton deviation of 3.43 mm was the cutoff for the risk of postoperative TMD. The incidence rate of postoperative TMD in the conv-SSRO group was higher than that in the IVRO (p = 0.0197) and nonfix-SSRO (p = 0.0001) groups in asymmetric cases. There was no significant postoperative change in the temporomandibular joint space in each group. In symmetric and asymmetric cases, the condylar head was rotated inwards by 5.82 ± 4.75° (p 0.0001) and 5.44 ± 3.10° (p 0.0001), respectively, in the conv-SSRO group, and outwards by -7.98 ± 5.05° (p 0.0001) and -8.32 ± 6.38° (p 0.0001), respectively, in the IVRO group, but it was almost stable in the nonfix-SSRO group. Within the limitations of the study it seems that nonfix-SSRO should be preferred over conv-SSRO and IVRO whenever appropriate.

Supplementary Data. 1. Supplementary Methods 2. Supplementary Data Supplementary Table 1, Patient information at sampling. Supplementary Figure 1, A: Genomic alterations of both tumor and normal samples in Cases A-16, A-20, and A-35. B: Analysis of TCR-γ gene rearrangement in a case. Supplementary Figure 2, Re-expression of INK4a or ARF into ATL cell lines. Supplementary Table 2, Status of CD58 and B2M in ATL samples. Supplementary Table 3, Genetic alterations related to acute transformation of chronic type ATL. 3. References

Epidemiological data have provided limited and inconsistent evidence on the relationship between radiation exposure and lymphoid neoplasms. We classified 553 lymphoid neoplasm cases diagnosed between 1950 and 1994 in the Life Span Study cohort of atomic bomb survivors into World Health Organization subtypes. Mature B-cell neoplasms represented 58%, mature T-cell and natural killer (NK)-cell neoplasms 20%, precursor cell neoplasms 5%, and Hodgkin lymphoma (HL) 3%, with the remaining 15% classified as non-Hodgkin lymphoid (NHL) neoplasms or lymphoid neoplasms not otherwise specified. We used Poisson regression methods to assess the relationship between radiation exposure and the more common subtypes. As in earlier reports, a significant dose response for NHL neoplasms as a group was seen for males but not females. However, subtype analyses showed that radiation dose was strongly associated with increased precursor cell neoplasms rates, with an estimated excess relative risk per Gy of 16 (95% Confidence interval: 7.0, >533) at age 50. The current data based primarily of tissue-based diagnoses suggest that the association between radiation dose and lymphoid neoplasms as a group is largely driven by the radiation effect on precursor cell neoplasms while presenting no evidence of a radiation dose response for major categories of mature cell neoplasms, either B- or T-/NK-cell, or more specific disease entities (diffuse large B-cell lymphoma, plasma cell myeloma, adult T-cell leukemia/lymphoma) or HL.

Multiple myeloma (MM) predominantly occurs in older persons and its diagnosis depends on pathological and laboratory findings. Epidemiological studies have provided inconsistent results on relationship between radiation exposure and MM. The Life Span Study (LSS) of atomic bomb (A-bomb) survivors has not shown a statistically significant radiation risk for MM. We studied previously reported MM cases diagnosed between 1950 and 1994 in the LSS and assessed diagnostic certainty based on histological and clinical features. Among 122 incident MM cases, 67 were classified as definite, 23, probable and 32, undetermined. The incidence rate increased with attained age and was highest in the oldest age group of over 70 years. For definite MM, Poisson regression dose response analysis showed an elevated, though not statistically significant, radiation risk with an estimated excess relative risk (ERR) per Gy of 0.44 (95%CI

Background: Mastication is one of the most fundamental functions for the conservation of human life. To clarify the pathogenetic mechanism of various oral dysfunctions, the demand for devices for evaluating stomatognathic function has been increasing. The aim of the present study was to develop a system to reconstruct and visualize 3-dimensional (3D) mandibular movements relative to the maxilla, including dynamic transition of occlusal contacts between the upper and lower dentitions during mastication in mice. Methods: First, mandibular movements with six degrees of freedom were measured using a motion capture system comprising two high-speed cameras and four reflective markers. Second, 3D models of maxillofacial structure were reconstructed from micro-computed tomography images. Movement trajectories of anatomical landmark points on the mandible were then reproduced by integrating the kinematic data of mandibular movements with the anatomical data of maxillofacial structures. Lastly, 3D surface images of the upper dentition with the surrounding maxillofacial structures were transferred to each of the motion capture images to reproduce mandibular movements relative to the maxilla. We also performed electromyography (EMG) of masticatory muscles associated with mandibular movements. Results: The developed system could reproduce the 3D movement trajectories of arbitrary points on the mandible, such as incisor, molars and condylar points with high accuracy and could visualize dynamic transitions of occlusal contacts between upper and lower teeth associated with mandibular movements. Conclusions: The proposed system has potential to elucidate the mechanisms underlying motor coordination of masticatory muscles and to clarify their roles during mastication by taking advantage of the capability to record EMG data synchronously with mandibular movements. Such insights will enhance our understanding of the pathogenesis and diagnosis of oral motor disorders by allowing comparisons between normal mice and genetically modified mice with oral behavioral dysfunctions., BMC Oral Health, 21, art. no. 527; 2021

Recurrent chromosomal rearrangements are a hallmark of hematologic malignancies and play critical roles in pathogenesis. The TP53 analog TP63 is rearranged in 5-10% of diverse subtypes of both aggressive T- and B-cell lymphomas. Patients with TP63-rearranged lymphomas have dismal outcomes, with 5-year overall survival rates between 0-17%, depending on cohorts. The function and mechanisms of TP63 rearrangements and TP63 fusion proteins in tumorigenesis are poorly understood. As a result, attempts to treat these patients to date have been largely empiric. Thus, there is an urgent need to understand how TP63 fusions contribute to tumorigenesis and to translate the findings into novel therapeutic options for these patients. Here, we demonstrated that TP63 fusions are essential for the propagation of T-cell lymphomas (TCLs). Knockdown of TP63 fusions with specific shRNAs in TCL cell lines harboring TP63 fusions suppressed both cell growth in vitro and tumor growth in vivo. Retroviral expression of TBL1XR1-TP63, the most common TP63 fusion, conferred cytokine independence in Ba/F3 cells, consistent with its role as an oncogene. To investigate the role of TP63 fusions in T- and B-cell lymphomagenesis, we engineered a CAG-Loxp-Stop-Loxp-TBL1XR1-TP63 conditional knock-in mouse model and crossed with hCD2-Cre mice. This results in expression beginning during early lymphoid development. As observed in patients, transgenic mice developed multiple subtypes of both T- and B-cell lymphoma. To define the effects and mechanisms of TP63 fusions within T cells, we performed CRISPR scanning, transcriptomic, epigenomic, and proteomic analyses. Our data showed that domains within both the N-terminal TBL1XR1 and C-terminal TP63 portions contribute to the function of this fusion. We found that the N-terminal component of TP63 fusions interacts with components of the NCOR/SMRT complex. At the same time, the C-terminal portion of TP63 (which recapitulates the deltaN-p63 isoform expressed in some carcinomas) interacts with the enhancer modifier KMT2D and its complex members. TBL1XR1-TP63 binds to a novel distal enhancer to drive MYC expression, and thus upregulates the expression of the histone H3K27 methylase EZH2. Finally, we assessed whether EZH2 is a vulnerability of TP63-rearranged lymphomas. We found that knockdown of EZH2 in TP63-rearranged lines significantly impaired cell growth, as did treatment with the EZH2 and 1 dual inhibitor valemetostat. Valemetostat, which is now being tested in patients with lymphoma, counteracted the oncogenic effects of TP63 fusions in multiple preclinical models in vivo. Together, our results identify the TP63 fusion as a highly unique oncogenic driver in lymphomagenesis capable of recruiting multiple epigenetic modifier complexes and inducing a targetable dependence on EZH2. Citation Format: Gongwei Wu, Noriaki Yoshida, Jihe Liu, Xiaoyang Zhang, Yuan Xiong, Tayla Heavican-Foral, Huiyun Liu, Geoffrey Nelson, Lu Yang, Renee Chen, Katherine Donovan, Marcus Jones, Mikhail Roshal, Yanming Zhang, Ran Xu, Ajit Nirmal, Salvia Jain, Catharine Leahy, Kristen Jones, Kristen Stevenson, Natasha Galasso, Nivetha Ganesan, Tiffany Chang, Wen-Chao Wu, Abner Louissaint, Lydie Debaize, Hojong Yoon, Paola Dal Cin, Wing Chan Chan, Shannan Ho Sui Ho Sui, Samuel Ng, Andrew Feldman, Steven M. Horwitz, Mathew Meyerson, Karen Adelman, Eric Fischer, Chun-Wei Chen, David Weinstock, Myles Brown. TP63 fusions drive enhancer rewiring, lymphomagenesis, and dependence on EZH2. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5755.

Peripheral T‐cell lymphoma (PTCL) is a heterogeneous entity generally with a poor prognosis. Recent genomic analyses have characterized genomic alterations and described gene expression profiling and epigenetic mechanisms in PTCL, leading to reveal molecular pathophysiology in detail. One of several important findings is that heterogeneities exist in both the disease and in individuals. Among PTCL subtypes, adult T‐cell leukemia/lymphoma (ATLL) and peripheral T‐cell lymphoma, not otherwise specified (PTCL‐NOS) are common in Japan. ATLL is an incurable T‐cell malignancy induced by human T‐cell lymphotropic virus type 1 (HTLV‐1). The global genomics of ATLL can be summarized as alterations involving T‐cell receptor (TCR) signaling and immune escape mechanisms. This highlights the fact that ATLL is a viral‐mediated T‐cell malignancy. Interestingly, several previous studies have found that the genomics of ATLL differ according to geographical region and age at diagnosis, suggesting disease heterogeneity, though they share HTLV‐1 infection as initial disease hit. Clonal expansion of the cells acquired by somatic mutations in ATLL‐related genes is identified in a part of HTLV‐1 carriers who developed ATLL later. The risk for ATLL may be updated based on findings in detail. PTCL‐NOS is a heterogeneous disease type of T‐cell lymphoma that does not correspond to any other type of PTCL. Several studies have stratified PTCL‐NOS according to transcriptional, genomic, microenvironmental, and clinical aspects. These kinds of analysis from multiple aspects are useful to understand the heterogeneous group. These efforts will help guide suitable translational research to target PTCL., Coexistence of CD28 fusions is highly characteristic of young Japanese adult T‐cell leukemia/lymphoma (ATLL). This suggests the existence of heterogeneity of ATLL.

Adult T-cell leukemia/lymphoma (ATLL) is caused by human T-cell leukemia virus type 1 (HTLV-1). HTLV-1-associated mRNA, including HBZ and tax, is deeply involved in the pathogenesis of ATLL. Using 88 ATLL tissue samples, we performed in situ mRNA analysis of HBZ and tax, and investigated its association with clinicopathological characteristics of ATLL. The median value of HBZ signals (/1000 ATLL cells) was 795.2 (range: 0.4–4013.1) and of tax signals (/1000 ATLL cells) was 5.1 (range: 0.1–891.2). The low-expression HBZ group displayed significant increase in the number of skin lesion (P = 0.0283). The high-expression tax group displayed significant increase in the number of PD-1-positive tumor-infiltrating lymphocytes (P

Adult T-cell leukemia/lymphoma (ATL) cells frequently exhibit chromosomal abnormalities, including numerical aberrations and structural defects. However, no studies have examined the correlation between these abnormalities and survival in patients with ATL after allogeneic HSCT (allo-HSCT). In this study, 300 patients with ATL (median age, 55 years; range, 24-74) who were registered in a Japanese nationwide registry database were analyzed. The majority (n = 183) had acute ATL. Specimens for chromosomal analysis were collected from bone marrow (n = 166), lymph nodes (n = 86), peripheral blood (n = 41), and other locations (n = 7). In survival analyses, breakpoints at 2q (hazard ratio [HR], 1.63; 95% confidence interval [CI], 1.12-2.38; P = .012) and 5q (HR, 2.18; 95% CI, 1.25-3.80; P = .006) were significantly poor prognostic factors for overall survival (OS). In terms of ATL-related death, loss of chromosome 14 and breakpoints at 3p, 1q, 5q, and 6q were extracted as significantly poor prognostic factors. Moreover, complex karyotypes were associated with ATL-related death. This study of the survival impact of chromosomal abnormalities in patients with ATL after allo-HSCT demonstrated that several structural breakpoints were independent risk factors for OS and ATL-related death.

INTRODUCTION Adult T-cell leukemia/lymphoma (ATLL) is a malignant peripheral T-cell neoplasm associated with human T-cell leukemia virus type-1 (HTLV-1). The acute and lymphoma subtypes are regarded as aggressive ATLLs, and the overall survival (OS) of patients remains poor. Transforming acidic coiled-coil-containing protein 3 (TACC3) regulates microtubules, which are associated with cancer-related proteins overexpressed in various cancers. Such a relationship has not been reported in hematopoietic tumors, including ATLL. METHODS We examined tissue microarrays of histological samples from 92 cases of aggressive ATLL and assessed clinical features, including TACC3 protein expression levels. RESULTS Compared with TACC3-low, TACC3-high ATLL patients were significantly older (P

This case report demonstrates two different uprighting mechanics separately applied to mesially tipped mandibular first and second molars. The biomechanical considerations for application of these mechanisms are also discussed. For repositioning of the first molar, which was severely tipped and deeply impacted, a novel cantilever mechanics was used. The molar tube was bonded in the buccolingual direction to facilitate insertion of a cantilever from the buccal side. By twisting the distal end of the cantilever, sufficient uprighting moment was generated. The mesial end of the cantilever was hooked over the miniscrew placed between the canine and first premolar, which could prevent exertion of an intrusive force to the anterior portion of the dentition as a side effect. For repositioning of the second molar, an uprighting mechanics using a compression force with two step bends incorporated into a nickel-titanium archwire was employed. This generated an uprighting moment as well as a distal force acting on the tipped second molar to regain the lost space for the first molar and bring it into its normal position. This epoch-making uprighting mechanics could also minimize the extrusion of the molar, thereby preventing occlusal interference by increasing interocclusal clearance between the inferiorly placed two step bends and the antagonist tooth. Consequently, the two step bends could help prevent occlusal interference. After 2 years and 11 months of active treatment, a desirable Class I occlusion was successfully achieved without permanent tooth extraction.

The interaction between CD47 and signal‐regulatory protein‐α (SIRPα) inhibits phagocytosis, thus affecting the clinical outcomes of neoplastic diseases. Although CD47 upregulation is associated with poor prognosis in several malignancies, the effect of SIRPα expression and its coexpression with CD47 remains unclear. This study aimed to investigate the clinicopathologic effect of CD47 and SIRPα expression in diffuse large B‐cell lymphoma (DLBCL). Immunostaining of 120 biopsy samples showed that CD47 is primarily expressed in tumor cells, whereas SIRPα is expressed in nonneoplastic stromal cells, mostly macrophages. CD47high cases showed higher MYC protein expression and lower MYC translocation. The SIRPαhigh cases presented significantly shorter overall survival (OS) and progression‐free survival (PFS) than SIRPαlow cases in the activated B‐cell (ABC) subtype of DLBCL (P = .04 and P = .02, respectively). Both CD47high and SIRPαhigh presented significantly shorter OS and PFS than other cases among all DLBCL patients (P = .01 and P = .004, respectively), and the ABC type (P = .04 and P = .008, respectively) but not the germinal center B‐cell type. Both CD47high and SIRPαhigh yielded a constant independent prognostic value for OS and PFS in multivariate analysis (hazard ratio [HR], 2.93; 95% confidence interval [CI], 1.20‐7.43; P = .02; and HR, 2.87; 95% CI, 1.42‐5.85; P = .003, respectively). To the best of our knowledge, this is the first study to report that combinatorial CD47 and SIRPα expression is a potential independent prognostic factor for DLBCL. Evaluation of CD47 and SIRPα expression could be useful before CD47 blockade therapy., This study investigated the clinicopathologic effect of CD47 and signal‐regulatory protein‐α (SIRPα) in diffuse large B‐cell lymphoma by immunohistochemical staining. CD47 and SIRPα coexpression is associated with a poor prognosis in the activated B‐cell type, but not in the germinal center B‐cell type.

Purpose: The aim of this study was to clarify the mechanical conditions of loop activation that produce the optimal force system allowing controlled movement of the anterior teeth. Materials and Me...

Adult T-cell leukemia/lymphoma (ATLL) in Japan presents at a median age of 70 years and only 5% of patients are

Objectives To examine whether lithium suppresses orthodontically induced root resorption (OIRR) via two mechanisms (prevention of hyalinization in periodontal tissue and suppression of odontoclasts) and to investigate the changes in the periodontal tissue and alveolar bone, focusing on the appearance of cell death, hyalinization, and odontoclasts. Materials and Methods The maxillary first molars of 10-week-old male Wistar rats were moved mesially by a closed-coil spring for 14 days. Lithium chloride (LiCl; 0.64 mM/kg) or saline (control) was administered intraperitoneally daily. Tooth movements were measured using micro–computed tomography. Appearances of cell death, hyalinization, and odontoclasts were evaluated by histological analysis. Results OIRR observed on day 14 in the control group was suppressed strongly by LiCl administration. Apoptotic cells observed on day 1 in the compression area were gradually diminished on days 2 and 3 and transformed to hyalinization tissue in the control group. LiCl administration remarkably suppressed this cell death and subsequent hyalinization. Also, the appearance of odontoclasts in the compression area observed on day 7 was significantly suppressed by LiCl administration. Accordingly, these degenerative processes to OIRR were suppressed substantially by LiCl treatment. Conclusions Lithium reduces OIRR through the suppression of periodontal ligament cell death, hyalinization, and odontoclast formation.

BACKGROUND Previous clinical observational studies have suggested that orthodontic tooth movement (OTM) is related, at least partly, to the mass and/or capabilities of the masticatory muscles. OBJECTIVES Our study aimed to examine the influence of masticatory muscle mass on the OTM in an animal experimental model in which the masseter muscle was modulated by botulinum neurotoxin type A (BTX) injection. METHODS Eighteen Wistar rats were equally divided into two groups: BTX injection and control. BTX was injected bilaterally into the masseter muscles. Three days after the injection, the maxillary left first molars were orthodontically moved for 14 days. At the end of the experiment, micro-computed tomography was performed to evaluate the rate of OTM and bone morphometry. The masseter muscles were weighed and prepared for histological analyses. RESULTS The masseter muscle mass in the BTX group was less than that in the control group, and histological findings showed atrophy of muscle fibers. The rate of OTM was significantly higher in the BTX group than in the control group. Furthermore, a negative correlation was detected between masseter muscle mass and OTM in the BTX group. Bone morphometry showed no difference between the control and BTX groups. CONCLUSION Decreased masseter muscle mass was found to be closely related to an increase in the rate of OTM in rats using BTX injection to modify the masseter muscle mass. Masseter muscle mass could be a predictive factor for OTM in rats injected with BTX.

Telomere length is maintained by the activation of telomerase, which causes continuous cell division and proliferation in many carcinomas. A catalytic reverse transcriptase protein (TERT) encoded by the TERT gene plays a critical role in the activation of telomerase. We performed a molecular and pathological analysis of the TERT against three different peripheral T‐cell lymphoma (PTCL) subtypes: PTCL, not otherwise specified (PTCL‐NOS), angioimmunoblastic T‐cell lymphoma (AITL), and adult T‐cell leukemia/lymphoma (ATLL). Immunohistochemical analysis demonstrated TERT expression in 31% of AITL, 11% of PTCL‐NOS, and 5% of ATLL. Among them, AITL frequently showed high TERT expression with statistical significance. TERT promoter mutation analysis and genomic copy number evaluation were performed. TERT promoter mutation was observed in two cases of PTCL‐NOS (2/40) and not in other PTCLs. Genome copy number amplification was detected in 33% of PTCL‐NOS, 33% of AITL, and 50% of ATLL cases. We evaluated the relationship between the analyzed TERT genomic abnormalities and protein expression; however, no apparent relationship was observed. Furthermore, immunostaining showed TERT expression in the PTCL cytoplasm, suggesting the existence of mechanisms other than the maintenance of telomere length. Statistical analysis of the effect of TERT expression on the prognosis in PTCL cases revealed that TERT expression tended to have a poor prognosis in PTCL‐NOS. Since TERT expression was not an independent factor in multivariate analysis, further research will be needed to clarify the poor prognosis of PTCL‐NOS in TERT expression., In this study, we performed TERT protein expression, mutation analysis of promoter region, and copy number analysis (chr.5) for PTCL (PTCL‐NOS, AITL, ATLL). In AITL, TERT expression was high, but there was no clear relationship between TERT protein expression and genomic abnormality. In the statistical analysis of TERT expression and PTCL prognosis, only PTCL‐NOS expressing TERT had a poor prognosis.

Objective To elucidate the clinical impact of humanized CCR4 antibody (mogamulizumab) on adult T-cell leukemia-lymphoma (ATL), we retrospectively analyzed the clinical and pathological features and treatment outcomes of aggressive ATL. Methods Twenty-two patients (median age: 65 years) with aggressive ATL [acute- (n=16) or lymphoma-type (n=6)] had their characteristics analyzed. All cases were treated with mogamulizumab at our institution from 2012 to 2018. In addition, we subjected 14 specimens of ATL to histological, immunological, and genetic analyses. Results Regarding the patient outcomes, the overall response rates were 68.1% and 31.8% after 4 and 8 courses (or after the final courses), respectively. The median overall survival (OS) was 95.5 days, while the OS rates at 6 and 12 months were 31.5% and 21.1%, respectively. Concerning patient pathological characteristics, 6 of the 14 patients examined (42.9%) had CCR4 mutations. Regarding the clinicopathological findings related to the mogamulizumab response, notably, the cases with somatic CCR4 mutation tended to have a poorer response (16.7%) than those with wild-type CCR4 (62.5%) after 4 cycles of mogamulizumab. Furthermore, the CCR4 global score tended to be higher in the responder cases than in the non-responder cases. Conclusion The present findings suggest that the CCR4 expression may be related to the mogamulizumab response, although no other significant predictive markers were identified in this study. Further studies will be needed in order to identify more markers related to the mogamulizumab response.

In order to fabricate the TiO2 nano-structure coating on the Ti-free stainless steel with good adhesion, commercially obtained 316L stainless steel (316L SS) plates were chemically treated by KOH aqueous solution including TiH2 powder at 60oC for 3 days in an oil bath shaker, and subsequently heated up to 550-800oC under the air atmosphere. The crystal structure, color, adhesive strength and cytotoxic effects of coating were investigated. Fiber-like hydrogen titanate nano-structures were formed on the 316L SS surface and made a fine network. X-ray diffraction (XRD) patterns showed that hydrogen titanate phase converted to anatase and rutile after heat treatment above 550oC. The heat treated sample at 800oC for 1 h showed the highest adhesive strength and the lowest cytotoxicity. The alkali treatment method in this study is expected to be used on the other Ti-free metals with further research.

Al/graphite composites with small amounts of Al–Si alloy were consolidated by spark plasma sintering and hot-extrusion processes. The effect of Al–Si alloy addition on densification behavior, microstructure, thermal conductivity (TC), coefficient of thermal expansion (CTE), and compressive strength has been systematically investigated. The results showed that the addition of Al–Si alloy resulted in improvements in relative density of the composites, interfacial bonding between Al and graphite, and orientation degree of graphite. The composites with Al–Si alloy showed improved TC and reduced CTE values in comparison with those without Al–Si alloy. For example, the 450 °C-extruded Al/60 vol% graphite/9 vol% Al–Si composite showed a maximum TC of 297 W m−1 K−1 and a minimum CTE of 7.95 ppm K−1. Moreover, the hot-extruded Al/graphite composites containing Al–Si alloy exhibited higher compressive strength compared to conventional squeeze-cast composites and hot-extruded composites without Al–Si alloy.

Enhanced inflammatory responses have been suggested decades after radiation exposure in atomic-bomb survivors, but cellular and molecular alterations related to prolonged inflammation remain unclear. This study, utilizing longitudinal haematological data over 50 years for 14 000 persons, investigated whether radiation exposure promoted the relative increase in peripheral myeloid cells, known as an aging-associated indicator of low-grade inflammation. Statistical modelling was performed with a linear mixed-effects model for leucocyte subsets, together with a proportional hazards regression model for all-cause mortality. We found that age trends in lymphocyte, neutrophil and monocyte percentages or counts differed before versus after age 60 years. Radiation dose was associated with monocyte percentages and counts, but not with the lymphoid-myeloid cell ratio. Radiation effects on monocytes were stronger after versus before age 60 years. Increases in monocyte percentages and counts were associated with higher risk of all-cause mortality. Studies of chromosomal aberrations have shown a clonal expansion of haematopoietic stem cells among atomic-bomb survivors. Therefore, radiation exposure might accelerate aging-associated clonal haematopoiesis, which could result in a long-lasting elevation of circulating monocytes.

Intraoral vertical ramus osteotomy (IVRO) is used to treat mandibular prognathism and temporomandibular disorders. However, the improvement of temporomandibular disorders after IVRO is considered to be due to the anterior and downward movement of the mandibular condyle, which may lead to condylar sag, and in the worst case, condylar luxation. In this retrospective cohort study, we examined factors potentially associated with condylar sag. Univariate analysis indicated that condylar sag was significantly associated with the following factors: magnitude of setback (P = 0.001), less than 3 mm setback (P P = 0.002), Wilkes classification (P = 0.039), occlusal cant correction ≥ 2 mm (P = 0.018), and mandibular condyle deformation (P P = 0.032) and TMJ symptoms (P = 0.007) remained significant in the multivariate analysis. In the receiver operating characteristic curve, the setback magnitude cut-off value for condylar sag after IVRO was 3.25 mm. Thus, the incidence of condylar sag after IVRO is increased with a smaller setback magnitude (≤ 3.25 mm) and the presence of TMJ symptoms. These factors should be evaluated by surgeons during treatment planning for IVRO to estimate condylar sag, and it may be possible to predict the risk of condylar luxation.