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We evaluated anti-spike protein antibody (anti-S) production in 130 hematopoietic stem cell transplant (HSCT) recipients who received the coronavirus disease-2019 vaccine. Sixty-five received allo-HSCT and 65 received auto-HSCT. Disease-specific treatments were being administered to 43.1% of allo-HSCT and 69.2% of auto-HSCT patients. Seropositivity was observed in 87.7% of allo-HSCT and 89.2% in auto-HSCT patients. Anti-S antibody production was significantly impaired in auto-HSCT patients compared with controls (178U/mL [0.4–4990.0] vs. 669 U/mL [40.3–4377.0], p < 0.001), but not in allo-HSCT patients (900 U/mL [0.4–12,893.0] vs. 860 U/mL [40.3–8988.0], P = 0.659). Clinically relevant anti-S antibody levels (> 264 U/mL) were achieved in 59.2% of patients (76.9% in allo-HSCT and 41.5% in auto-HSCT). The main factors influencing the protective level of the antibody response were the CD19 + cell count and serum immunoglobulin G levels, and these were significant in both allo-HSCT and auto-HSCT patients. Other factors included time since HSCT, complete remission status, use of immunosuppressive drugs, and levels of lymphocyte subsets including CD4, CD8 and CD56 positive cells, but these were only significant in allo-HSCT patients. Allo-HSCT patients had a relatively favorable antibody response, while auto-HSCT patients had poorer results.

A fusion protein comprising an antibody and a cationic peptide, such as arginine-9 (R9), is a candidate molecule for efficient and cell-specific delivery of siRNA into cells in order to reduce the side effects of nucleic acid drugs. However, their expression in bacterial hosts, required for their development, often fails, impeding research progress. In this study, we separately prepared anti-EGFR nanobodies with the K-tag sequence MRHKGS at the C-terminus and R9 with the Q-tag sequence LLQG at the N-terminus, and enzymatically ligated them in vitro by microbial transglutaminase to generate Nanobody-R9, which is not expressed as a fused protein in E. coli . Nanobody-R9 was synthesized at a maximum binding efficiency of 85.1%, without changing the binding affinity of the nanobody for the antigen. Nanobody-R9 successfully delivered siRNA into the cells, and the cellular influx of siRNA increased with increase in the ratio of Nanobody-R9 to siRNA. We further demonstrated that the Nanobody-R9–siRNA complex, at a 30:1 ratio, induced an approximately 58.6% reduction in the amount of target protein due to RNAi in mRNA compared to lipofectamine.

A comprehensive analysis to survey heme-binding proteins produced by the white-rot fungus Phanerochaete chrysosporium was achieved using a biotinylated heme–streptavidin beads system. Mitochondrial citrate synthase (PcCS), glyceraldehyde 3-phosphate dehydrogenase (PcGAPDH), and 2-Cys thioredoxin peroxidase (mammalian HBP23 homolog) were identified as putative heme-binding proteins. Among these, PcCS and PcGAPDH were further characterized using heterologously expressed recombinant proteins . Difference spectra of PcCS titrated with hemin exhibited an increase in the Soret absorbance at 414 nm, suggesting that the axial ligand of the heme is a His residue. The activity of PcCS was strongly inhibited by hemin with Ki oxaloacetate of 8.7 μM and Ki acetyl-CoA of 5.8 μM. Since the final step of heme biosynthesis occurred at the mitochondrial inner membrane, the inhibition of PcCS by heme is thought to be a physiological event. The inhibitory mode of the heme was similar to that of CoA analogues, suggesting that heme binds to PcCS at His 347 at the AcCoA–CoA binding site, which was supported by the homology model of PcCS. PcGAPDH was also inhibited by heme, with a lower concentration than that for PcCS. This might be caused by the different location of these enzymes. From the integration of these phenomena, it was concluded that metabolic regulations by heme in the central metabolic and heme synthetic pathways occurred in the mitochondria and cytosol. This novel pathway crosstalk between the central metabolic and heme biosynthetic pathways, via a heme molecule, is important in regulating the metabolic balance (heme synthesis, ATP synthesis, flux balance of the tricarboxylic acid (TCA) cycle and cellular redox balance (NADPH production) during fungal aromatic degradation. Key points • A comprehensive survey of heme-binding proteins in P. chrysosporium was achieved. • Several heme-binding proteins including CS and GAPDH were identified. • A novel metabolic regulation by heme in the central metabolic pathways was found.

Objective This study compared the tumor burden and prognostic impact of total diffusion volume (tDV) and total lesion glycolysis (TLG) in the same patients with newly diagnosed multiple myeloma (NDMM) simultaneously. We also examined the relationship between these imaging tumor volumes (TVs) and plasma cell (PC) TV in bone marrow (BM) specimens. Methods We retrospectively reviewed the data of 63 patients with newly diagnosed multiple myeloma (NDMM) from April 2016 to March 2018. tDV was calculated from whole-body diffusion-weighted imaging and TLG was calculated from the average standard uptake value and the metabolic tumor volume, respectively. Cellularity of BM hematopoietic tissue and the percentage of BM PCs were used as a reference of PC volume in the BM. Results The Spearman correlation coefficient between tDV and TLG was moderate (ɤs = 0.588, p < 0.001) when PET false-negative patients were excluded. There were positive correlations between the BM plasma cell volume (BMPCV) and the imaging TVs (ɤs = 0.505, vs. tDV; and 0.464, vs. TLG). Patients with high tDV and high TLG, as determined by the receiver operating characteristic curve, had worse survival; moreover, patients with both high tDV and high TLG showed the worst prognosis (median progression-free and overall survival: 13.2 and 28.9 months, respectively). Conclusions Although tDV and TLG each reflected the total TV, in several cases, tDV and TLG were discrepant due to the biological features of each MM. It is important to use both modalities for complementary assessment of total tumor burden and biological characteristics in MM. Key Points • Total diffusion volume (tDV) and total lesion glycolysis (TLG) reflect the total tumor volume and have prognostic value in patients with multiple myeloma (MM). • tDV and TLG could assess MM from different biological perspectives and should be considered for each patient individually.

Sarcopenia is associated with increased morbidity and mortality in chronic kidney disease (CKD). Pathogenic mechanism of skeletal muscle loss in CKD, which is defined as uremic sarcopenia, remains unclear. We found that causative pathological mechanism of uremic sarcopenia is metabolic alterations by uremic toxin indoxyl sulfate. Imaging mass spectrometry revealed indoxyl sulfate accumulated in muscle tissue of a mouse model of CKD. Comprehensive metabolomics revealed that indoxyl sulfate induces metabolic alterations such as upregulation of glycolysis, including pentose phosphate pathway acceleration as antioxidative stress response, via nuclear factor (erythroid-2-related factor)-2. The altered metabolic flow to excess antioxidative response resulted in downregulation of TCA cycle and its effected mitochondrial dysfunction and ATP shortage in muscle cells. In clinical research, a significant inverse association between plasma indoxyl sulfate and skeletal muscle mass in CKD patients was observed. Our results indicate that indoxyl sulfate is a pathogenic factor for sarcopenia in CKD.

A three-dimensional (3D) finite element (FE) model of the mandibular bone was created from 3D X-ray CT scan images of a live human subject. Simulating the clinical situation of implant therapy at the mandibular first molar, virtual extraction of the tooth was performed at the 3D FE mandibular model, and 12 different implant diameters and lengths were virtually inserted in order to carry out a mechanical analysis. (1) High stress concentration was found at the surfaces of the buccal and lingual peri-implant bone adjacent to the sides of the neck in all the implants. (2) The greatest stress value was approximately 6.0 MPa with implant diameter of 3.8 mm, approx. 4.5 MPa with implant diameter of 4.3 mm, and approx. 3.2 MPa with implant diameter of 6.0 mm. (3) The stress on the peri-implant bone was found to decrease with increasing length and mainly in diameter of the implant.

Rising prices are currently a problem in the world. In particular, the abnormal increases in the price of metals, which are often used in dental prosthetics, have increased the burden of dental costs on the public. There is therefore an urgent need to develop prosthetic devices made from materials that are not affected by the global situation and that have excellent biocompatibility and mechanical properties comparable to those of metals. Polyether ether ketone (PEEK) is a promising alternative to metal in dentistry. This study compared the effects of different molding orientations, highly accelerated aging, and water absorption on the flexural strength of PEEK fabricated by fused deposition modeling (FDM) and examined its potential for dental applications. The flexural strength of PEEK stacked at 0° to the molding stage (0° PF), with and without highly accelerated aging, was significantly greater than for the other molding orientations. As with PD, the maximum test load for 0° PF was measured without fracture. PEEK stacked at 45° (45° PF) and 90° (90° PF) to the molding stage easily fractured, as the applied load pulled the stacked layers. No statistically significant difference was found between the flexural strength of 45° PF and 90° PF. The flexural strength decreased under all conditions due to defects in the crystal structure of PEEK caused by highly accelerated aging.

This study investigated the clinical significance of loss of spleen visualization (LSV) on whole-body diffusion-weighted imaging (WB-DWI) in patients with multiple myeloma (MM). The WB-DWI of 96 patients with newly diagnosed MM (NDMM) and 15 patients with smoldering MM (sMM) were retrospectively reviewed. LSV was observed in 56 patients with NDMM (58.3%) and 1 patient with sMM (6.7%). Patients with NDMM with LSV had a higher median infiltration of bone marrow plasma cells (80.0% vs. 50.0%, p  < 0.001) and median total diffusion volume (median; 540.2 vs. 137.0 mL, p  = 0.003) than patients without LSV. Patients with LSV had a lower spleen-to-spinal cord ratio (0.36 vs. 0.96, p  < 0.001) and worse 2-year overall survival (OS) (84.6% vs. 100%, p  = 0.032). Patients who did not recover spleen visualization during treatment had a worse prognosis, even when they obtained very good partial response (median progression-free survival: 13.2 months). Spleen histopathological findings revealed higher cellularity and diffuse myeloma cell infiltration in a patient with LSV and splenic amyloidosis without extramedullary hematopoiesis in a patient without LSV. Therefore, LSV indicates worse prognosis for patients with MM, even when the patient responds to treatment. Further studies are warranted to clarify the immunological role of spleen in MM.

Patients with lymphoma are at increased risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); therefore, evaluation of SARS-CoV-2 vaccination efficacy is essential. We conducted a prospective observational study to monitor the antibody response in 500 patients with lymphoma after SARS-CoV-2 vaccination. Antibody levels increased in a stepwise manner after the first and second dose of the vaccine. After completion of the two-dose series, anti-S antibody was negative in 109 patients (21.8%), and below clinically protective levels (anti-S ≥ 264 U/mL) in 236 patients (47.2%). The median anti-S titers at 0–6 months, 7–12 months, 13–24 months, and 24 months after treatment completion were 0.4 U/mL, 3.8 U/mL, 270 U/mL, and 650 U/mL, respectively. Multivariate analysis showed that receiving the vaccine < 6 months since completing treatment, white blood cell count < 5050/μL, percentage of CD19 + cells < 10%, CD4 + cells < 27%, immunoglobulin (Ig) A < 195 mg/dL, IgM < 50 mg/dL, serum soluble interleukin 2 receptor > 600 U/mL, and presence of lymphoma cells in the peripheral blood were significantly correlated with anti-S < 264 U/mL. Lymphoma patients had variably impaired antibody response to the SARS-CoV-2 vaccine. We identified various factors to predict COVID-19 vaccine effectiveness in lymphoma patients that may help tailoring possible vaccine boosters.

Orthognathic surgery has a high incidence of postoperative nausea (PON) and vomiting (POV), delaying mobility initiation and postoperative recovery. Bleeding is another risk associated with this surgical procedure. We aimed to compare total intravenous anesthesia (TIVA) and volatile anesthesia in patients undergoing orthognathic surgery in terms of postoperative nausea and vomiting (PONV) incidence and hemodynamic changes. This retrospective study included 82 patients who underwent bilateral sagittal split ramus osteotomies at Saga University Hospital between April 2016 and April 2021. We compared the effects of TIVA and volatile anesthesia on PONV onset after surgery, acute postoperative hemodynamic changes (blood pressure and heart rate), and factors contributing to PONV. PON was significantly lower in the TIVA group than in the volatile anesthesia group. The total dose of fentanyl contributed to the onset of POV, while the onset of PON was associated with low volumes of fluid infusion and urine in the TIVA and volatile anesthesia groups, respectively. Furthermore, post-extubation hemodynamic change was significantly smaller in the TIVA group than in the volatile anesthesia group. Therefore, TIVA could have a reduced risk of PONV and hemodynamic changes in patients undergoing orthognathic surgery. Employing TIVA could mitigate perioperative complications and enhance patient safety.