Synthesis, Reactivity, and Properties of Benz[a]azulenes via the [8 + 2] Cycloaddition of 2H-Cyclohepta[b]furan-2-ones with an Enamine.

Starting with the reaction of 2H-cyclohepta[b]furan-2-ones with an enamine, which was prepared from 4-tert-butylcyclohexanone and pyrrolidine, benz[a]azulenes having both formyl and tert-butyl groups were obtained in the three-step sequence. Subsequently, both the formyl and tert-butyl groups were eliminated by heating the benz[a]azulene derivatives in 100% H3PO4 to give benz[a]azulenes without these substituents in high yields. In terms of product yield, this method is the best one ever reported for the synthesis of the parent benz[a]azulene so far. The conversion of the benz[a]azulene derivatives with a formyl group into cyclohept[a]acenaphthylen-3-one derivatives was also investigated via Knoevenagel condensation with dimethyl malonate, followed by Brønsted acid-mediated intramolecular cyclization. The structural features including the bond alternation in the benz[a]azulene derivatives were revealed by NMR studies, NICS calculations, and a single-crystal X-ray structural analysis. The optical and electrochemical properties of a series of benz[a]azulene derivatives were evaluated by UV/Vis, fluorescence spectroscopy, and voltammetry experiments. As a result, we found that some benz[a]azulene derivatives showed remarkable luminescence in acidic media. In addition, the benz[a]azulene derivatives with the electron-withdrawing group and cyclohept[a]acenaphthylen-3-one derivative displayed good reversibility in the spectral changes under the electrochemical redox conditions.

Biomechanical evaluation of internal fixation for the treatment of comminuted subtrochanteric femur fractures.

BACKGROUND: Several biomechanical studies on subtrochanteric femur fractures have reported that use of an intramedullary nail is superior to extramedullary implant. However, the optimal choice of intramedullary nail for the treatment of comminuted subtrochanteric femur fracture remains unclear. Here, we evaluated the biomechanical properties of comminuted subtrochanteric femur fracture treated with four different internal fixations. METHODS: A comminuted subtrochanteric femur fracture model was created with a 2-cm gap below the lessor trochanter in 20 synthetic femurs. The fractures were fixed with one of four implants - Antegrade Femoral Nail (AFN), Trochanteric Fixation Nail Advanced with a femoral neck blade (TFNA blade), TFNA with a femoral neck screw (TFNA screw), and the reversed distal femoral locking compression plate (DF-LCP) - all manufactured by DePuy Synthes. Axial compression tests and torsion tests were performed and the stiffness of each implant was compared. RESULTS: For compression, the TFNA blade, TFNA screw, and AFN provided significantly higher stiffness than DF-LCP (p < 0.001, p < 0.001, p = 0.001, respectively), and the TFNA blade provided significantly higher stiffness than AFN (p = 0.049). For torsion, there were no significant differences among the groups in internal rotation, while the TFNA screw had significantly lower torsional stiffness than the AFN, TFNA blade and DF-LCP in external rotation (p = 0.036, p = 0.034, p = 0.037, respectively). CONCLUSIONS: These findings could help to provide biomechanical evidence regarding choice of implant for the treatment of comminuted subtrochanteric femur fracture. The TFNA blade may be more suitable for the treatment of comminuted subtrochanteric femur fracture.

Discontinuation of sorafenib can lead to the emergence of FLT3-ITD-positive acute myeloid leukemia.

A 69-year-old woman who had been diagnosed with unresectable papillary thyroid cancer was referred to our hospital. We initially treated her with sorafenib, but she subsequently developed erythema multiforme, which was suspected to be a drug rush due to sorafenib; therefore, sorafenib was discontinued. At the time of discontinuation, immature blast cells were detected in her peripheral blood. Approximately two weeks later, her skin rash improved substantially, but the proportion of blasts in the peripheral blood increased. We performed a bone marrow examination, and she was diagnosed with FLT3-ITD-positive acute myeloid leukemia. FLT3-ITD expression is found in 20-25% of AML and is a known independent poor prognostic factor. To overcome the poor prognosis associated with FLT3-ITD, molecular drugs targeting FLT3-ITD are attracting much attention. Sorafenib, a multi-kinase inhibitor, also has an effect on FLT3-ITD. Although primary disease flares after tyrosine kinase inhibitor discontinuation have been reported, this is the first report to describe discontinuation of sorafenib treatment as a potential trigger of FLT3-ITD-positive acute myeloid leukemia in papillary thyroid cancer.

Comparison of Reconstruction Algorithms for Decreasing the Exposure Dose During Digital Tomosynthesis for Arthroplasty: a Phantom Study.

To explore the possibility of decreasing the radiation dose during digital tomosynthesis (DT) for arthroplasty, we compared the image qualities of several reconstruction algorithms, such as filtered back projection (FBP) and two iterative reconstruction (IR), methods maximum likelihood expectation maximization (MLEM) and the simultaneous iterative reconstruction technique (SIRT) under different radiation doses. The three algorithms were implemented using a DT system and experimentally evaluated by contrast-to-noise ratio (CNR), artifact spread function (ASF), and power spectrum measurements on a prosthesis phantom. The CNR and ASF data were statistically analyzed by a one-way analysis of variance. The effectiveness of each technique for enhancing the visibility of the prosthesis phantom was quantified by the CNR (reference dose vs. 20 % reduced dose in FBP, P = 0.62; reference vs. 37 % reduced dose in FBP, P = 0.16; reference vs. 55 % reduced dose in FBP, P < 0.05; reference vs. 20 % reduced dose in IR, P = 0.92; reference vs. 37 % reduced dose in IR, P = 0.40; reference vs. 55 % reduced dose in IR, P < 0.05) and ASF (reference dose vs. 20 % reduced dose in FBP, P = 0.25; reference vs. 37 and 55 % reduced dose in FBP, P < 0.05; reference vs. 20 % reduced dose in IR, P = 0.16; reference vs. 37 and 55 % reduced dose in IR, P < 0.05). The power spectra under the reference and reduced doses are equivalent. In this phantom study, the radiation dose of the reference dose could be decreased by 20 % with FBP and IR for consideration of common factors.

Comparison of internal fixations for distal clavicular fractures based on loading tests and finite element analyses.

It is difficult to apply strong and stable internal fixation to a fracture of the distal end of the clavicle because it is unstable, the distal clavicle fragment is small, and the fractured region is near the acromioclavicular joint. In this study, to identify a superior internal fixation method for unstable distal clavicular fracture, we compared three types of internal fixation (tension band wiring, scorpion, and LCP clavicle hook plate). Firstly, loading tests were performed, in which fixations were evaluated using bending stiffness and torsional stiffness as indices, followed by finite element analysis to evaluate fixability using the stress and strain as indices. The bending and torsional stiffness were significantly higher in the artificial clavicles fixed with the two types of plate than in that fixed by tension band wiring (P < 0.05). No marked stress concentration on the clavicle was noted in the scorpion because the arm plate did not interfere with the acromioclavicular joint, suggesting that favorable shoulder joint function can be achieved. The stability of fixation with the LCP clavicle hook plate and the scorpion was similar, and plate fixations were stronger than fixation by tension band wiring.

Correlation between the bone mineral density and stress on femur around a Duetto SI stem.

In cementless stem fixation, BMD reduction around the stem is of concern because it may cause loosening. This BMD reduction is assumed to be caused by stem implantation-induced alteration of the physiological feedback system, which may cause stress shielding and result in loosening, but the causal relationship has not been clarified. In this study, using a Duetto SI stem, we investigated the correlation between the postoperative BMD around the stem and stress. In patients who underwent their first THA at the orthopedic department of our university, the BMD was measured using DEXA, and FEA was performed with an equivalent time course. Time-course changes in the BMD, von Mises stress, and triaxial stress in Gruen zones 1 through 7 were calculated from those measured at 2 weeks and 5 months after surgery. The BMD and von Mises stress showed a bidirectional correlation when Gruen's classification was plotted on the horizontal axis. An increase in stress loaded on bone was assumed to be a factor increasing the BMD. The Duetto SI stem was fixed on the distal side, suggesting its stable fixation. BMD measurement and FEA were useful for quantification of the bone dynamics around the stem from an early phase.

Hydrogen supplementation of preservation solution improves viability of osteochondral grafts.

Allogenic osteochondral tissue (OCT) is used for the treatment of large cartilage defects. Typically, OCTs collected during the disease-screening period are preserved at 4°C; however, the gradual reduction in cell viability during cold preservation adversely affects transplantation outcomes. Therefore, improved storage methods that maintain the cell viability of OCTs are needed to increase the availability of high-quality OCTs and improve treatment outcomes. Here, we evaluated whether long-term hydrogen delivery to preservation solution improved the viability of rat OCTs during cold preservation. Hydrogen-supplemented Dulbecco's Modified Eagles Medium (DMEM) and University of Wisconsin (UW) solution both significantly improved the cell viability of OCTs during preservation at 4°C for 21 days compared to nonsupplemented media. However, the long-term cold preservation of OCTs in DMEM containing hydrogen was associated with the most optimal maintenance of chondrocytes with respect to viability and morphology. Our findings demonstrate that OCTs preserved in DMEM supplemented with hydrogen are a promising material for the repair of large cartilage defects in the clinical setting.

Combinatorial measurement of CDKN1A/p21 and KIF20A expression for discrimination of DNA damage-induced clastogenicity.

In vitro mammalian cytogenetic tests detect chromosomal aberrations and are used for testing the genotoxicity of compounds. This study aimed to identify a supportive genomic biomarker could minimize the risk of misjudgments and aid appropriate decision making in genotoxicity testing. Human lymphoblastoid TK6 cells were treated with each of six DNA damage-inducing genotoxins (clastogens) or two genotoxins that do not cause DNA damage. Cells were exposed to each compound for 4 h, and gene expression was comprehensively examined using Affymetrix U133A microarrays. Toxicogenomic analysis revealed characteristic alterations in the expression of genes included in cyclin-dependent kinase inhibitor 1A (CDKN1A/p21)-centered network. The majority of genes included in this network were upregulated on treatment with DNA damage-inducing clastogens. The network, however, also included kinesin family member 20A (KIF20A) downregulated by treatment with all the DNA damage-inducing clastogens. Downregulation of KIF20A expression was successfully confirmed using additional DNA damage-inducing clastogens. Our analysis also demonstrated that nucleic acid constituents falsely downregulated the expression of KIF20A, possibly via p16 activation, independently of the CDKN1A signaling pathway. Our results indicate the potential of KIF20A as a supportive biomarker for clastogenicity judgment and possible mechanisms involved in KIF20A downregulation in DNA damage and non-DNA damage signaling networks.

A novel primary stability test method for artificial acetabular shells considering vertical load during level walking and shell position.

Uncemented acetabular shell primary stability is essential for optimal clinical outcomes. Push-out testing, rotation testing, and lever-out testing are major evaluation methods of primary stability between the shell and bone. However, these test methods do not consider shell loads during daily activity and shell installation angle. This study proposes a novel evaluation method of acetabular shell primary stability considering load during level walking and acetabular installation angles such as inclination and anteversion. To achieve this, a novel primary stability test apparatus was designed with a shell position of 40° acetabular inclination and 20° anteversion. The vertical load, corresponding to walking load, was set to 3 kN according to ISO 14242-1, which is the wear test standard for artificial hip joints. The vertical load was applied by an air cylinder controlled by a pressure-type electro-pneumatic proportional valve, with the vertical load value monitored by a load cell. Torque was measured when angular displacement was applied in the direction of extension during the application of vertical load. For comparison, we also measured torque using the traditional lever-out test. The novel primary stability test yielded significantly higher primary stabilities; 5.4 times greater than the lever-out test results. The novel primary stability test failure mode was more similar to the clinical failure than the traditional lever-out test. It is suggested that this novel primary stability test method, applying physiological walking loads and extension motions to the acetabular shell, better reflects in vivo primary stability than the traditional lever-out test.

Irreversible Intrathecal Chemotherapy-induced Myelopathy in a Patient with Diffuse Large B-cell Lymphoma.

Intrathecal chemotherapy is often administered for prophylaxis and treatment of central nervous system involvement in hematological malignancies. However, it may rarely cause neurotoxicity as a side effect. We herein report a 74-year-old woman with diffuse large B-cell lymphoma including a spinal lesion. She received systemic and intrathecal chemotherapy. After five doses of intrathecal chemotherapy, she developed intrathecal chemotherapy-induced myelopathy. Intrathecal treatment was discontinued, and she was administered vitamin B12 and folic acid, along with steroid pulses. However, her symptoms did not improve. Intrathecal chemotherapy-induced myelopathy is rare, but may be irreversible; therefore, clinicians should be aware of this potential complication.

Utility of the refined EBMT diagnostic and severity criteria 2023 for sinusoidal obstruction syndrome/veno-occlusive disease.

Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a life-threatening complication of hematopoietic stem cell transplantation (HSCT). Early diagnosis of SOS/VOD is associated with improved clinical outcomes. In 2023, the refined European Society for Blood and Marrow Transplantation diagnostic and severity criteria (refined EBMT criteria 2023) have been advocated. The revision has introduced new diagnostic categories, namely; probable, clinical, and proven SOS/VOD. In addition, the Sequential Organ Failure Assessment (SOFA) score has been newly incorporated into the SOS/VOD severity grading. We performed a retrospective analysis to evaluate the utility of these criteria. We analyzed 161 cases who underwent allogeneic HSCT. We identified 53 probable, 23 clinical, and 4 proven SOS/VOD cases. Probable SOS/VOD was diagnosed a median of 5.0 days earlier (interquartile range: 2-13 days, P < 0.001) than that of clinical SOS/VOD. The development of probable SOS/VOD alone was associated with a significantly inferior survival proportion compared to non-SOS/VOD (100-day survival, 86.2% vs. 94.3%, P = 0.012). The SOFA score contributed to the prediction of prognosis. Consequently, the refined EBMT criteria 2023 demonstrated the utility of SOS/VOD diagnosis and severity grading. Further investigations and improvements in these criteria are warranted.

Two-stage revision total hip arthroplasty for periprosthetic infections using antibiotic-impregnated cement spacers of various types and materials.

Antibiotic-impregnated hip cement spacers of various types and materials have been used in the treatment of periprosthetic hip infections. We developed a handmade spacer by using polymethylmethacrylate (PMMA) and/or α -tricalcium phosphate ( α -TCP). In this study, we retrospectively reviewed the surgical outcomes in 36 consecutive patients treated with 2-stage revision total hip arthroplasty by using our antibiotic-impregnated hip cement spacers. We aimed to analyze the infection control and reinfection rates after revision surgery. Moreover, we analyzed the possible predictors of postoperative reinfection. After exclusion of 1 patient who died immediately after the first-stage surgery, infection was controlled in 33 of the 36 hips (success rate, 91.7%). Two of these 33 hips underwent resection arthroplasty. Of the 36 hips that had been treated with the antibiotic-cement spacer, 31 hips (86.1%) were eligible for the second-stage prosthesis re-implantation. The 31 protocol hip joints of patients followed up for >6 months (mean, 48.6 months). Ten of these 31 hips (32.3%) became reinfected. No possible predictor examined differed significantly between the reinfection-positive and reinfection-negative groups. However, spacers consisting of PMMA cement alone were associated with the highest risk of reinfection. Therefore, α -TCP-containing antibiotic-impregnated hip cement spacers might decrease the reinfection rate in patients undergoing re-implantation.

Unexpected appearance of KMT2A::MLLT10 fusion transcript in acute myeloid leukemia with t(5;11)(q31;q23.3).

As an uncommon but nonrandom translocation in acute myeloid leukemia (AML) t(5;11)(q31;q23) results in fusion between KMT2A at 11q23 and ARHGAP26 at 5q31. The 5q31 region has another KMT2A partner, AFF4, which was identified in acute lymphoblastic leukemia harboring ins(5;11)(q31;q13q23). We report here a 65-year-old woman with AML M5b. G-banding and spectral karyotyping demonstrated 46,XX,t(5;11)(q31;q23.3). Fluorescence in situ hybridization revealed not only separated 5' and 3' KMT2A signals but a faint 5' KMT2A signal. Reverse transcription polymerase chain reaction (RT-PCR), using a KMT2A sense primer and ARHGAP26 antisense primer, detected no band whereas RT-PCR with a AFF4 antisense primer revealed an amplified band. However, sequence analysis unexpectedly disclosed that KMT2A exon 6 was connected with MLLT10 exons 15 to 18. This may be due to cross-hybridization between MLLT10 exon 18 and AFF4 antisense primer derived from AFF4 exon 10 since both exons had eight identical bases (AAGCAGCT). The MLLT10 gene is located at 10p12.31; a faint 5' KMT2A signal was probably present at this locus. These findings indicate that in AML the 5' KMT2A fragment containing exons 1 to 6 may be cryptically inserted into MLLT10 intron 14 when a reciprocal translocation t(5;11)(q31;q23.3) involving KMT2A occurred.

Early diagnosis of sinusoidal obstruction syndrome after hematopoietic stem cell transplantation, with modified diagnostic criteria including refractory thrombocytopenia.

Sinusoidal obstruction syndrome (SOS) is a fatal complication of hematopoietic stem cell transplantation (HSCT). Early diagnosis for SOS can improve clinical outcomes significantly. Here, we performed a retrospective study to investigate the Cairo diagnostic criteria, in which SOS was defined as the development of two or more in seven events, including transfusion-refractory thrombocytopenia. Among 154 cases of allogeneic HSCT, 10 cases of SOS using the European Society for Blood and Marrow Transplantation criteria (EBMT16) as the reference standard were identified. The original Cairo criteria could diagnose SOS 5 days earlier than any other established criteria, with some false-positive results (sensitivity = 100.0%; specificity = 72.2%). When the cutoff was set to three events for the Cairo criteria, the diagnosis of SOS could be made 3 days earlier than that using the EBMT16 criteria, with comparable precision (specificity = 86.1%). The accuracy of the Cairo criteria improved further when the cutoff point was set to four (specificity = 93.8%). The fulfillment of the Cairo criteria was associated with high mortality. Based on our results, the Cairo criteria were also considered clinically useful, especially at three or four cutoff points. Further studies are required to validate and refine the criteria.

GSK3 inhibitor enhances gemtuzumab ozogamicin-induced apoptosis in primary human leukemia cells by overcoming multiple mechanisms of resistance.

In acute myeloid leukemia (AML), the heterogeneity of genetic and epigenetic characteristics makes treatment difficult. The prognosis for AML is therefore poor, and there is an urgent need for new treatments for this condition. Gemtuzumab ozogamicin (GO), the first antibody-drug conjugate (ADC), targets the CD33 antigen expressed in over 90% of AML cases. GO therefore has the potential to counter the heterogeneity of AML patients. However, a major clinical problem is that drug resistance to GO diminishes its effect over time. Here, we report that the inhibition of glycogen synthase kinase 3 (GSK3) alone overcomes several forms of GO resistance at concentrations without antileukemic effects. The GSK3 inhibitors tested significantly enhanced the cytotoxic effect of GO in AML cell lines. We elucidated four mechanisms of enhancement: (1) increased expression of CD33, the target antigen of GO; (2) activation of a lysosomal function essential for hydrolysis of the GO linker; (3) reduced expression of MDR1 that eliminates calicheamicin, the payload of GO; and (4) reduced expression of the anti-apoptotic factor Bcl-2. A similar combination effect was observed against patient-derived primary AML cells. Combining GO with GSK3 inhibitors may be efficacious in treating heterogeneous AML.

Safety and Accuracy of Professional Continuous Glucose Monitoring in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation.

Hyperglycemia in the early days following allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a well-known risk factor for acute graft-versus-host disease (GVHD) and non-relapse mortality. The FreeStyle Libre Pro, a factory calibrated continuous glucose monitoring (CGM) device, has been used for the retrospective analysis of glucose testing in patients with diabetes. We assessed the safety and accuracy of the device in patients undergoing allo-HSCT. We recruited eight patients who underwent allo-HSCT between August 2017 and March 2020. They wore the FreeStyle Libre Pro on the day before or on the day of transplantation until 28 days after transplantation. Adverse events, especially bleeding and infection, were monitored to assess safety, and blood glucose levels were measured and compared with the device values. None of the eight participants experienced bleeding that was difficult to stop from the sensor site or local infection that required antimicrobial administration. The device value was well correlated with blood glucose (correlation coefficient r=0.795, P<0.01); however, the overall mean absolute relative difference was 32.1%±16.0%. Our study demonstrated the safety of FreeStyle Libre Pro in allo-HSCT patients. However, the sensor results tended to be lower than the blood glucose levels.

Global longitudinal strain is superior to ejection fraction for long-term follow-up after allogeneic hematopoietic stem cell transplantation.

Global longitudinal strain (GLS), a new cardiac parameter measured by the speckle-tracking method, is reportedly more sensitive than ejection fraction (EF) in detecting slight cardiac dysfunction in heart failure patients. We validated the utility of GLS in allogeneic hematopoietic stem cell transplantation (HSCT) patients during a long-term follow-up. Medical records of patients who underwent allogeneic HSCT between 2013 and 2020 were reviewed retrospectively. We evaluated the last echocardiography performed before transplantation and those performed annually during the 5 years after transplantation. We also investigated newly diagnosed cardiac events, which developed after HSCT. Among 85 patients, 22 used cardioprotective drugs. The median follow-up duration in surviving patients was 54.1 months (range, 2.9-92.6 months). GLS significantly decreased year by year, and patients taking cardioprotective agents tended to have a better GLS at 5 years than at 3 years, while EF did not change. Fifteen patients developed newly diagnosed cardiac events. Multivariate analysis revealed that low GLS and high serum ferritin levels at baseline were independently associated with the development of cardiac events. Therefore, we need a continuous follow-up of cardiac function by GLS and prescription of cardioprotective drugs might be considered for HSCT patients with low GLS. Further research is warranted.

Efficacy and Safety of Synbiotics in Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation: A Randomized, Double-blinded, Placebo-controlled Pilot Study.

Objective High-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HSCT) is an effective treatment option for relapsed and refractory aggressive malignant lymphoma. However, patients frequently experience treatment-induced gastrointestinal symptoms. Synbiotics, including live microorganisms and nondigestible food ingredients, reportedly ameliorate chemotherapy-induced mucosal damage. In this study, we assessed the efficacy and safety of synbiotics in patients undergoing auto-HSCT. Methods This randomized, double-blinded study included patients with malignant lymphoma eligible for auto-HSCT. The patients were randomly assigned to either a synbiotic group receiving Bifidobacterium longum (BB536) and guar gum or a placebo group receiving a placebo containing dextrin. The supplements were administered twice daily from the start of conditioning chemotherapy up to 28 days after auto-HSCT. The primary endpoint was the duration of total parenteral nutrition (TPN). Results In total, 12 patients were included and randomized. The median duration of TPN was 15 (range, 12-33) days in the synbiotic group and 17.5 (range, 0-32) days in the placebo group. The median duration of grade ≥3 diarrhea was shorter in the synbiotic group than in then placebo group (2.5 vs. 6.5 days), as was the duration of hospital stay (31.5 vs. 43 days). The oral intake and quality of life regarding diarrhea and anorexia improved in the synbiotic group after engraftment. Synbiotic infections, including bacteremia, were not observed. Conclusion Synbiotics may reduce gastrointestinal toxicity, thereby reducing nutritional problems and improving the quality of life of patients undergoing auto-HSCT, without severe adverse events.

Distinguishing heat-treated dead cells from viable cells using frequency dependence of electrical impedance.

BACKGROUND: There is currently no methodology for evaluating the accuracy of ablation in ablation therapy, and thus normal cells in the surrounding area can be damaged, possibly leading to complications. OBJECTIVE: The aim of this study was to distinguish heat-treated dead cells from viable cells using the electrical impedance-to-frequency ratio as an evaluation index. METHODS: Rat heart striated myocytes were cultured in a monolayer on collagen-coated microelectrodes placed in the center of an electrode-loaded chamber. The cells in the chamber were killed by heat treatment for 5 minutes at 50 °C, and the frequency response of the cell impedance was measured before and after heat treatment. The frequency of the input current was varied from 10 to 100 kHz. The measured electrical impedance at each frequency was divided by the value at 100 kHz, and we refer to the resulting values as the impedance ratio. RESULTS: The impedance ratio was high at low frequencies and low at high frequencies. Furthermore, the impedance ratio was lower at lower frequencies after heat treatment than before heat treatment. CONCLUSIONS: The electrical impedance ratio can be used to distinguish viable and dead cells after heat treatment.

Application of Methods for a Morphological Analysis of the Femoral Diaphysis Based on Clinical CT Images to Prehistoric Human Bone: Comparison of Modern Japanese and Jomon Populations from Hegi Cave, Oita, Japan.

A morphological analysis of ancient human bones is essential for understanding life history, medical history, and genetic characteristics. In addition to external measurements, a three-dimensional structural analysis using CT will provide more detailed information. The present study examined adult male human skeletons excavated from Hegi cave, Nakatsu city, Oita Prefecture. CT images were taken from the femurs of adult males (Initial/Early Jomon Period (n = 10) and Late Jomon Period (n = 5)). Cross-sectional images of the diaphysis from below the lesser trochanter to above the adductor tubercle were obtained using the method established by Imamura et al. (2019) and Imamura et al. (2021). Using Excel formulas and macros, the area of cortical bone, thickness, and degree of curvature were quantitatively analyzed. The results were compared with data on modern Japanese. The maximum thickness of cortical bone in the diaphysis and the degree of the anterior curvature were significantly greater in Late Jomon humans than in the other groups. In contrast to modern humans, the majority of Jomon femurs showed the S-shaped curvature with the medial side at the top position and the lateral side at the lower position. The present results demonstrate that Late Jomon humans had a wider range of activity than the other groups and also provide insights into diseases in the hip and knee joints of Jomon humans.