Chemical and Chemoenzymatic Synthesis of Peptide and Protein Therapeutics Conjugated with Human N-Glycans.

Glycosylation is one of the most ubiquitous post-translational modifications. It affects the structure and function of peptides/proteins and consequently has a significant impact on various biological events. However, the structural complexity and heterogeneity of glycopeptides/proteins caused by the diversity of glycan structures and glycosylation sites complicates the detailed elucidation of glycan function and hampers their clinical applications. To address these challenges, chemical and/or enzyme-assisted synthesis methods have been developed to realize glycopeptides/proteins with well-defined glycan morphologies. In particular, N-glycans are expected to be useful for improving the solubility, in vivo half-life and aggregation of bioactive peptides/proteins that have had limited clinical applications so far due to their short duration of action in the blood and unsuitable physicochemical properties. Chemical glycosylation performed in a post-synthetic procedure can be used to facilitate the development of glycopeptide/protein analogues or mimetics that are superior to the original molecules in terms of physicochemical and pharmacokinetic properties. N-glycans are used to modify targets because they are highly biodegradable and biocompatible and have structures that already exist in the human body. On the practical side, from a quality control perspective, close attention should be paid to their structural homogeneity when they are to be applied to pharmaceuticals.

Phase 1, placebo-controlled, single ascending dose trial to evaluate the safety, pharmacokinetics and effect on altered states of consciousness of intranasal BPL-003 (5-methoxy-N,N-dimethyltryptamine benzoate) in healthy participants.

AIMS: To investigate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of BPL-003, a novel intranasal benzoate salt formulation of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), in healthy participants. METHODS: In all, 44 psychedelic-naïve participants enrolled in the double-blind, placebo-controlled single ascending dose study (1-12 mg BPL-003). Concentrations of 5-MeO-DMT and its pharmacologically active metabolite, bufotenine, were determined in plasma and urine. PD endpoints included subjective drug intensity (SDI) rating, the Mystical Experience Questionnaire (MEQ-30) and the Ego Dissolution Inventory (EDI). RESULTS: BPL-003 was well tolerated at doses up to 12 mg. There were no serious adverse events (AEs), and most AEs were mild; the most common being nasal discomfort, nausea, headache and vomiting. 5-MeO-DMT was rapidly absorbed and eliminated; the median time to peak plasma concentration was approximately 8-10 min and the mean terminal elimination half-life was <27 min. 5-MeO-DMT systemic exposure increased approximately dose-proportionally, while plasma bufotenine concentrations and urinary excretion of 5-MeO-DMT and bufotenine were negligible. The intensity of the SDI ratings was associated with plasma 5-MeO-DMT concentrations. MEQ-30 and EDI scores generally increased with the BPL-003 dose; 60% of participants had a 'complete mystical experience' at 10 and 12 mg doses. Profound and highly emotional consciousness-altering effects were observed with BPL-003, with a rapid onset and short-lasting duration. CONCLUSION: The novel intranasal formulation of BPL-003 was well tolerated with dose-proportional increases in PK and PD effects. The short duration of action and induction of mystical experiences suggest clinical potential, warranting further trials. CLINICAL TRIAL REGISTRATION: NCT05347849.

A preliminary study on benthic nutrient exchange across sediment-water interfaces in a shallow marine protected area of the Northwestern Arabian Gulf.

Sedimentary processes are expected to play a crucial role in macronutrient cycling of the shallow Arabian Gulf. To investigate this aspect, sediment cores were collected from the shallow intertidal and subtidal expanses of the first Marine Protected Area (MPA) of Kuwait in the Northwestern Arabian Gulf (NAG). Porewater nutrient profiling and whole core incubation experiments were conducted to measure the nutrient fluxes, both with and without the addition of the nitrification inhibitor allylthiourea (ATU). The porewater data confirmed the potential of sediments to host multiple aerobic and anaerobic pathways of nutrient regeneration. The average (±SD) of net nutrient fluxes from several incubation experiments indicated that ammonium (NH4+) predominantly fluxed out of the sediment (3.81 ± 2.53 mmol m-2 d-1), followed by SiO44- (3.07 ± 1.21 mmol m-2 d-1). In contrast, the average PO43- flux was minimal, at only 0.06 ± 0.05 mmol m-2 d-1. Fluxes of NO3- (ranged from 0.07 ± 0.005 to 1.16 ± 0.35 mmol m-2 d-1) and NO2- (0.03 ± 0.003 to 0.71 ± 0.21 mmol m-2 d-1) were moderate, which either reduced or reversed in the presence of ATU (-0.001 ± 0.0001 to 0.01 ± 0.0001 mmol m-2 d-1 and -0.001 ± 0.0003 to 0.006 ± 0.001 mmol m-2 d-1 for NO3- and NO2- respectively). Thus, this study provides preliminary experimental evidence that nitrification can act as a source of NO3- and NO2- as well as contribute towards the relatively high concentrations of NO2- (>1 in the gulf waters.

Long-term outcomes of multidisciplinary treatment combining surgery and stereotactic radiotherapy with Novalis for craniopharyngioma.

Craniopharyngiomas are difficult to resect completely, recurrence is frequent, and hypothalamic/pituitary function may be affected after surgery. Therefore, the ideal treatment for craniopharyngiomas is local control with preservation of hypothalamic and pituitary functions. The purpose of this study is to retrospectively evaluate the long-term efficacy and adverse events of stereotactic radiotherapy (SRT) with Novalis for craniopharyngioma. This study included 23 patients with craniopharyngiomas who underwent surgery between 2006 and 2021 and underwent SRT as their first irradiation after surgery. The median post-irradiation observation period was 88 months, with the overall survival rates of 100 % at 10 years and 85.7 % at 20 years. One patient died of adrenal insufficiency 12 years after irradiation. The local control rate of the cystic component was 91.3 % at 5 years, 83.0 % at 15 years, with no increase in the solid component. No delayed impairment of visual or pituitary function due to irradiation was observed. No new hypothalamic dysfunction was observed after radiation therapy. No delayed adverse events such as brain necrosis, cerebral artery stenosis, cerebral infarction, or secondary brain tumors were also observed. SRT was safe and effective over the long term in patients irradiated in childhood as well as adults, with no local recurrence or adverse events. We believe that surgical planning for craniopharyngioma with stereotactic radiotherapy in mind is effective in maintaining a good prognosis and quality of life.

Left ventricular remodeling and long-term outcomes of aortic stenosis patients receiving 19 mm Mosaic.

Mosaic valve shows higher pressure gradient after aortic valve replacement compared to other same size labeled prostheses in postoperative echocardiogram. The purpose of this study was to evaluate the mid-term echocardiogram findings and long-term clinical outcomes of patients receiving a 19 mm Mosaic. Forty-six aortic stenosis patients receiving 19 mm Mosaic and 112 patients receiving either 19 mm Magna or Inspiris, who underwent mid-term follow-up echocardiogram were included in the study. Mid-term hemodynamic measurements evaluated by trans-thoracic echocardiogram and long-term outcomes were compared. Patients receiving Mosaic were significantly older (Mosaic: 76 ± 5.1 years vs. Magna/Inspiris: 74 ± 5.5 years, p = 0.046) and had smaller body surface area (Mosaic: 1.40 ± 0.114m2 vs. Magna/Inspiris: 1.48 ± 0.143m2, p < 0.001). There were no significant differences in comorbidities and medications. Post-operative echocardiogram performed at 1 week after the surgery showed higher maximum pressure gradient in patients receiving Mosaic (Mosaic: 38 ± 13.5 mmHg vs. Magna/Inspiris: 31 ± 10.7 mmHg, p = 0.002). Furthermore, mid-term echocardiogram follow-up performed at median duration of 53 ± 14.9 months after the surgery continuously showed higher maximum pressure gradient in patients receiving Mosaic (Mosaic: 45 ± 15.6 mmHg vs. Magna/Inspiris: 32 ± 13.0 mmHg, p < 0.001). However, there were no significant difference in changes in left ventricular mass from baseline in both groups. Kaplan-Meyer curve also showed no difference in long-term mortality and major adverse cardiac and cerebrovascular event between the two groups. Although the pressure gradient across the valve evaluated by echocardiogram was higher in 19 mm Mosaic compared to 19 mm Magna/Inspiris, there were no significant differences in left ventricular remodeling and long-term outcomes between the two groups.

Primary renal neuroendocrine tumor: A case report with computed tomography findings.

We report a rare case of a primary renal neuroendocrine tumor. The patient was a 64-year-old woman. The patient's chief complaint was gross hematuria. Dynamic contrast-enhanced computed tomography (CT) revealed a hypovascular mass 13 cm in diameter in the right kidney. The border of the mass was clear. A grossly contrast-impaired area and internal granular calcification were observed. A right radical nephrectomy was performed. Macroscopically, the mass was hemorrhaged and necrotic. It was diagnosed as a neuroendocrine tumor (NET) (Grade 2) histologically. Findings, such as hypovascularity, calcification, and necrosis, in our case were similar to those in previous reports. These findings are considered relatively characteristic of primary renal NETs.

Aeolian dust and hydro-biological characteristics: Decoding dust storm impacts on phytoplankton in the northern Arabian Gulf.

Aeolian dust is an essential source of growth-limiting nutrients for marine phytoplankton. Despite being at the core of the Global Dust Belt, the response of the Arabian Gulf ecosystem to such atmospheric forcing is rarely documented. Here, the hydro-biological effect of mineral dust was studied in the northern Arabian Gulf (NAG) off Kuwait through monthly water sampling (December 2020 to December 2021), dust-storm follow-up sampling, and mineral dust and nutrient addition in-situ experiments. The multivariate analysis of oceanographic data revealed pronounced hydro-biological seasonality. The mineral dust deposition during two severe dust storm events in March and June 2021 showed a spatially varying effect of dust on coastal waters. The dust storms elevated the surface dissolved iron levels by several magnitudes, increased the dissolved inorganic nitrogen and phosphorous levels, changed their stoichiometry, and offset the hydrobiological seasonality. In the microcosms, dust input temporarily reduced phytoplankton phosphorous limitation in a dose-dependent manner when mesozooplankton (copepods) grazing was minimal. The microphytoplankton response to mineral dust inputs was comparable to that with nitrogen and phosphorous treatment. While Both treatments increased diatom size structure and biomass, the abundance of single-celled diatoms was comparatively higher in dust treatment. Multivariate analysis indicated that dust deposition alters the hydrographical properties of the surface ocean during dust storm events. The effects, though transient, were traceable for 3-16 days post-storm in coastal waters. The response of the summer phytoplankton to these changes, if delayed or muted, should be interpreted with caution given the summer water column stratification, the high nitrogen: phosphorous ratio and the low phosphorous solubility of aerosol dust, and the complex pelagic microbial food web interactions in the NAG. This study thus underlines the importance of a multivariate approach in documenting the ecological implications of Aeolian dust storms on marine environments closer to the dust source regions.

[Non-A Non-B Aortic Dissection Complicated with Right Aortic Arch Treated by Extended Thoracic Aortic Repair].

A 44-year old man with a history of Stanford type B acute aortic dissection was admitted for the treatment of acute aortic dissection. Computed tomography( CT) scan showed a descending entry-type non-A non-B aortic dissection with a maximum diameter of 65 mm occurring in a patient with Edwards typeⅢ right aortic arch whose left subclavian artery was obliterated. The patient was initially treated conservatively and underwent one-stage extended aortic repair from the ascending aorta to the descending thoracic aorta via median sternotomy 22 days after the symptom onset. Although the patient suffered from right empyema postoperatively, he was discharged from the hospital on postoperative day 64 after 4 weeks antibiotics therapy. The patient was also complicated by right recurrent nerve palsy, hoarseness improved over the 8 months after surgery.

Evaluation of virtual monochromatic imaging with dual-energy computed tomography of small liver metastases from malignant abdominal tumours: Quantitative and qualitative analyses.

Background: The assessment of small metastatic liver tumours using dual-energy computed tomography (DECT) has not been fully established. Purpose: To assess the effect of low-keV virtual monochromatic imaging (VMI) with non-contrast and contrast-enhanced DECT on the qualitative and quantitative image parameters of small liver metastases. Material and methods: Two radiologists retrospectively evaluated 92 metastatic liver tumours (5-20 mm) in 32 patients. Non-contrast and contrast-enhanced VMI were reconstructed at seven energy levels (40-100 keV) with 10-keV intervals. Lesion boundary, lesion delineation, image noise, and overall image quality were evaluated using the visual analogue scale. A high subjective score indicates good overall image quality, clear nodal boundaries and delineation, and less noticeable image noise. Subjective scores were compared using the Kruskal-Wallis test. A quantitative analysis involving the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) was performed. Results: The lesion boundary was highest at 40 keV and significantly improved during the non-contrast portal venous phase compared to that at higher keV (p < .005). The lesion delineation score was significantly higher at 40 keV and tended to decrease at higher keV. Image noise and overall image quality were rated low at low keV; however, those at 80, 90, and 100 keV were rated the highest (p < .005). The CNR and SNR were highest for non-contrast CT at 100 keV. During the portal venous phase, no significant differences were observed in CNR and SNR at each keV. Conclusion: Low-keV imaging using non-contrast and contrast-enhanced DECT is useful for delineating small hepatic metastatic tumours.

In Vitro Characterization of Drug-Loaded Superabsorbent Polymer Microspheres: Absorption and Release Capacity of Contrast Material, Antibiotics and Analgesics.

PURPOSE: To examine the characteristics of drug-loaded superabsorbent polymer microspheres (SAP-MS) such as drug absorption, drug release, diameter, and visibility. MATERIALS AND METHODS: SAP-MS (HepaSphere150-200 µm; Merit Medical, South Jordan, UT, USA) were suspended in drug solutions: (a) cefazolin, (b) lidocaine, (c) iopamidol and cefazolin, (d) iopamidol and lidocaine, and (e) iopamidol, cefazolin, and lidocaine. The concentrations of drugs were measured, and the amount of each drug absorbed was calculated. Filtered drug-loaded SAP-MS were mixed with saline, and the drug release rates were calculated. The diameter changes of SAP-MS during absorption were observed. Radiography of drug-loaded SAP-MS was evaluated as radiopacity by contrast-to-noise ratio (CNR). RESULTS: The drug concentration did not change during absorption. The release rates increased for 10 min and then came to an equilibrium. The mean amounts of drug absorbed at 180 min and mean release rates at 24 h were (a) cefazolin: 265.4 mg, 64.2%; (b) lidocaine: 19.6 mg, 75.6%; (c) iopamidol: 830.2 mg, 22.5%; cefazolin: 137.6 mg, 21.2%; (d) iopamidol: 1620.6 mg, 78.5%; lidocaine: 13.5 mg, 81.4%; and (e) iopamidol: 643.7 mg, 52.9%; cefazolin: 194.0 mg, 51.6%; lidocaine: 5.3 mg, 58.4%. The diameter of SAP-MS increased for approximately 15 min. Finally, the diameters of SAP-MS were (a) 3.9 times, (b) 5.0 times, (c) 2.2 times, (d) 5.5 times, and (e) 3.6 times larger than the original size. Drug-loaded SAP-MS containing iopamidol were visible under X-ray imaging, with CNRs of (c) 3.0, (d) 9.0, and (e) 4.5. CONCLUSION: SAP-MS can absorb and release iopamidol, cefazolin, and lidocaine.

Cell shape instability during cytokinesis in tetraploid HCT116 cells.

Tetraploidy is a hallmark of broad cancer types, but it remains largely unknown which aspects of cellular processes are influenced by tetraploidization in human cells. Here, we found that tetraploid HCT116 cells manifested severe cell shape instability during cytokinesis, unlike their diploid counterparts. The cell shape instability accompanied the formation of protrusive deformation at the cell poles, indicating ectopic contractile activity of the cell cortex. While cytokinesis regulators such as RhoA and anillin correctly accumulated at the equatorial cortex, myosin II was over-accumulated at the cell poles, specifically in tetraploid cells. Suppression of myosin II activity by Y27632 treatment restored smooth cell shape in tetraploids during cytokinesis, indicating dysregulation of myosin II as a primary cause of the cell shape instability in the tetraploid state. Our results demonstrate a new aspect of the dynamic cellular process profoundly affected by tetraploidization in human cells, which provides a clue to molecular mechanisms of tetraploidy-driven pathogenic processes.

Ultrastructure and fractal property of chromosomes in close-to-native yeast nuclei visualized using X-ray laser diffraction.

Genome compaction and activity in the nucleus depend on spatiotemporal changes in the organization of chromatins in chromosomes. However, the direct imaging of the chromosome structures in the nuclei has been difficult and challenging. Herein, we directly visualized the structure of chromosomes in frozen-hydrated nuclei of budding yeast in the interphase using X-ray laser diffraction. The reconstructed projection electron density maps revealed inhomogeneous distributions of chromosomes, such as a 300 nm assembly and fibrous substructures in the elliptic-circular shaped nuclei of approximately 800 nm. In addition, from the diffraction patterns, we confirmed the absence of regular arrangements of chromosomes and chromatins with 400-20 nm spacing, and demonstrated that chromosomes were composed of self-similarly assembled substructural domains with an average radius of gyration of 58 nm and smooth surfaces. Based on these analyses, we constructed putative models to discuss the organization of 16 chromosomes, carrying DNA of 4.1 mm in 800 nm ellipsoid of the nucleus at the interphase. We anticipate the structural parameters on the fractal property of chromosomes and the experimental images to be a starting point for constructing more sophisticated 3D structural models of the nucleus.

Low-dose nafamostat mesilate ameliorates tissue injury and inhibits 5-hydroxytryptamine synthesis in the rat intestine after methotrexate administration.

We aimed to clarify the effect of nafamostat mesilate (nafamostat) on intestinal mucositis as well as the potentiation of intestinal 5-hydroxytryptamine (5-HT) dynamics induced by methotrexate, an anti-cancer drug, in rats. Rats received intraperitoneal methotrexate at 12.5 mg/kg/day for 4 days. In addition, 1, 3, or 10 mg/kg/day of nafamostat was given subcutaneously for 4 days. Ninety-six hours after the first administration of methotrexate, jejunal tissues were collected for analysis. The results showed that 1 mg/kg, but not 3 or 10 mg/kg, of nafamostat significantly ameliorated the methotrexate-induced body weight loss. Moreover, 1 mg/kg of nafamostat significantly improved methotrexate-induced mucositis, including villus atrophy. Nafamostat (1 mg/kg) significantly inhibited the methotrexate-induced mRNA expression of pro-inflammatory cytokines and cyclooxygenase-2, as well as methotrexate-induced 5-HT content and tryptophan hydroxylase (TPH) activity. In addition, it tended to inhibit the number of anti-TPH antibody-positive cells and significantly inhibited the number of anti-substance P antibody-positive cells. These findings suggest that low-dose nafamostat ameliorates tissue injury and 5-HT and substance P synthesis in methotrexate-induced mucositis. Nafamostat may be a novel therapeutic strategy for the prevention and treatment of mucositis as well as 5-HT- and/or substance P-related adverse effects in cancer chemotherapy.

Lynch syndrome-associated chordoma with high tumor mutational burden and significant response to immune checkpoint inhibitors.

Chordoma is a rare malignant bone tumor arising from notochordal tissue. Conventional treatments, such as radical resection and high-dose irradiation, frequently fail to control the tumor, resulting in recurrence and re-growth. In this study, genetic analysis of the tumor in a 72-year-old male patient with refractory conventional chordoma of the skull base revealed a high tumor mutational burden (TMB) and mutations in the MSH6 and MLH1 genes, which are found in Lynch syndrome. The patient and his family had a dense cancer history, and subsequent germline genetic testing revealed Lynch syndrome. This is the first report of a chordoma that has been genetically proven to be Lynch syndrome. Chordomas usually have low TMB; however, this is an unusual case, because the TMB was high, and immune checkpoint inhibitors effectively controlled the tumor. This case provides a basis for determining the indications for immunotherapy of chordoma based on the genetic analysis. Therefore, further extensive genetic analysis in the future will help to stratify the treatment of chordoma.

Photo-and Heat-Induced Dismantlable Adhesion Interfaces Prepared by Layer-by-Layer Deposition.

The development of a dismantlable adhesion technology that allows switching between bonding and debonding states using external stimuli is important for realizing renewable and sustainable material cycles. Controlling the adhesion interface is an effective approach to manipulate the adhesion strength; however, research on dismantlable systems focusing on the interface has not been proceeded. Recently, we demonstrated a novel dismantlable system based on a stimuli-responsive molecular layer comprising cleavable anthracene dimers, which strengthen the initial adhesive force by forming chemical bonds between the substrate and adhesive and can be dismantled when required via stimulation-induced bond breaking. Here, we evaluate the use of the anthracene-based molecular layer with different components for verifying its versatility in the adhesive/dismantling system. The formation of the cleavable molecular layer by the stacking of relevant molecules enabled its usage with two types of adhesives, an epoxy adhesive and a silane-modified polymer adhesive. The initial adhesive strengths were improved in both types of molecular layers by creating chemical bonds at the adhesion interfaces. Light irradiation or heating stimuli for 1 min reduced the peel strength by up to 65%, and dismantling occurred in the cleavable photodimer layer. This study expands the versatile applicability of the molecular layer-based dismantling system.

CDKAL1 Drives the Maintenance of Cancer Stem-Like Cells by Assembling the eIF4F Translation Initiation Complex.

Cancer stem-like cells (CSCs) have a unique translation mode, but little is understood about the process of elongation, especially the contribution of tRNA modifications to the maintenance of CSCs properties. Here, it is reported that, contrary to the initial aim, a tRNA-modifying methylthiotransferase CDKAL1 promotes CSC-factor SALL2 synthesis by assembling the eIF4F translation initiation complex. CDKAL1 expression is upregulated in patients with worse prognoses and is essential for maintaining CSCs in rhabdomyosarcoma (RMS) and common cancers. Translatome analysis reveals that a group of mRNAs whose translation is CDKAL1-dependent contains cytosine-rich sequences in the 5' untranslated region (5'UTR). Mechanistically, CDKAL1 promotes the translation of such mRNAs by organizing the eIF4F translation initiation complex. This complex formation does not require the enzyme activity of CDKAL1 but requires only the NH2 -terminus domain of CDKAL1. Furthermore, sites in CDKAL1 essential for forming the eIF4F complex are identified and discovered candidate inhibitors of CDKAL1-dependent translation.

Granulomatosis with polyangiitis presenting as multiple renal masses: A case report with MRI findings.

It is extremely rare for granulomatosis with polyangiitis to form masses in the kidneys. Magnetic resonance imaging findings of renal masses caused by this disease have been infrequently reported. In this study, we report a case of renal masses caused by granulomatosis with polyangiitis with different findings. While on steroid treatment for a recently diagnosed granulomatosis with polyangiitis, a man in his 60s underwent computed tomography for a hepatic dysfunction. Computed tomography showed incidental findings of a 40 mm × 35 mm mass in the left kidney and two 8 mm × 8 mm masses in the right kidney; all masses were hypovascular. On magnetic resonance imaging, the left renal mass showed a hyperintense signal with slightly hypointense signal rim on T2-weighted imaging. The left renal mass showed a strong hypointense signal where the mass abutted the renal capsule. On diffusion-weighted imaging, the left renal mass showed an isointense signal with a hyperintense signal rim. Both right renal masses showed an isointense signal with slightly hypointense signal rim on T2-weighted imaging and hyperintense signal on diffusion-weighted imaging. Suspecting renal masses caused by the disease, the patient was then treated with steroids and methotrexate. After 6 months of treatment, both right renal masses resolved; however, the left renal mass shrank but abnormal signal remained. Based on the treatment course, it is conceivable that the renal masses were caused by granulomatosis with polyangiitis.

Tetraploidy-linked sensitization to CENP-E inhibition in human cells.

Tetraploidy is a hallmark of cancer cells, and tetraploidy-selective cell growth suppression is a potential strategy for targeted cancer therapy. However, how tetraploid cells differ from normal diploids in their sensitivity to anti-proliferative treatments remains largely unknown. In this study, we found that tetraploid cells are significantly more susceptible to inhibitors of a mitotic kinesin (CENP-E) than are diploids. Treatment with a CENP-E inhibitor preferentially diminished the tetraploid cell population in a diploid-tetraploid co-culture at optimum conditions. Live imaging revealed that a tetraploidy-linked increase in unsolvable chromosome misalignment caused substantially longer mitotic delay in tetraploids than in diploids upon moderate CENP-E inhibition. This time gap of mitotic arrest resulted in cohesion fatigue and subsequent cell death, specifically in tetraploids, leading to tetraploidy-selective cell growth suppression. In contrast, the microtubule-stabilizing compound paclitaxel caused tetraploidy-selective suppression through the aggravation of spindle multipolarization. We also found that treatment with a CENP-E inhibitor had superior generality to paclitaxel in its tetraploidy selectivity across a broader spectrum of cell lines. Our results highlight the unique properties of CENP-E inhibitors in tetraploidy-selective suppression and their potential use in the development of tetraploidy-targeting interventions in cancer.

Out-of-Plane Needle Placements Using 3D Augmented Reality Protractor on Smartphone: An Experimental Phantom Study.

PURPOSE: To evaluate the accuracy of needle placement using a three-dimensional (3D) augmented reality (AR) protractor on smartphones (AR Puncture). MATERIALS AND METHODS: An AR protractor that can be rotated in three directions against the CT plane with angle guidance lines for smartphones was developed. The protractor center can be adjusted to an entry point by manually moving the smartphone with the protractor center fixed at the center of the screen (Fix-On-Screen) or by image tracking with a printed QR code placed at an entry point (QR-Tracking). Needle placement was performed by viewing a target line in the tangent direction with the Bull's eye method. The needle placement errors placed by four operators in six out-of-plane directions in a phantom using a smartphone (iPhone XR, Apple, Cupertino, CA, USA) were compared with two registration methods. RESULTS: No significant difference in the average needle placement error was observed between the Fix-On-Screen and QR-Tracking methods (5.6 ± 1.7 mm vs. 6.1 ± 2.9 mm, p = 0.475). The average procedural time of the Fix-On-Screen method was shorter than that of the QR-Tracking method (71.0 ± 23.9 s vs. 98.4 ± 59.5 s, p = 0.042). CONCLUSION: The accuracies of out-of-plane needle placements using the 3D AR protractor with the two registration methods were equally high, with short procedure times. In clinical use, the Fix-On-Screen registration method would be more convenient because no additional markers are required.