Immediate and late inflammatory and bone healing response post implantation of self-tapping and self-drilling osteosynthesis screws.

The aim of this study was to comparatively analyse osseointegration after the implantation of self-tapping screws (STS) and self-drilling screws (SDS). Thus, 24 four-month-old male Wistar rats, received SDS and STS screws in their left and right tibias, respectively. Sample collection was performed immediately at 0 hours (0h), two, seven, and 21 days after implantation (2d, 7d, 21d). Samples from immediately and 21 days after were analysed by micro computed tomography (MicroCT). All time points were evaluated by histology (Haematoxylin and Eoisin and Goldner's Trichrome) and immunohistochemistry for tartrate-acid resistant phosphatase positive (TRAP+) osteoclasts. MicroCT images revealed an intimate contact between bone and each type of screw at 0h. However, SDS group presented decreased bone volume (BV, mm3) at 21 days in comparison with STS. Both SDS and STS post implantation presented areas of suitable new bone formation surrounding screw threads from seven days, and inflammation decreased from two to 21 days. Also, TRAP+ osteoclasts were mainly identified at seven days in both STS and SDS groups, particularly surrounding areas of pressure, with significant differences between groups. In conclusion, differences in shape and insertion technique for SDS and STS screws did not affect immediate and late inflammatory and bone healing response post implantation in this animal model. Both osteosynthesis screws allowed satisfactory post-surgical outcomes.

Inhibition of Mertk Signaling Enhances Bone Healing after Tooth Extraction.

Regeneration of alveolar bone is an essential step in restoring healthy function following tooth extraction. Growth of new bone in the healing extraction socket can be variable and often unpredictable when systemic comorbidities are present, leading to the need for additional therapeutic targets to accelerate the regenerative process. One such target is the TAM family (Tyro3, Axl, Mertk) of receptor tyrosine kinases. These proteins have been shown to help resolve inflammation and maintain bone homeostasis and thus may have therapeutic benefits in bone regeneration following extraction. Treatment of mice with a pan-TAM inhibitor (RXDX-106) led to accelerated alveolar bone fill following first molar extraction in a mouse model without changing immune infiltrate. Treatment of human alveolar bone mesenchymal stem cells with RXDX-106 upregulated Wnt signaling and primed the cells for osteogenic differentiation. Differentiation of human alveolar bone mesenchymal stem cells with osteogenic media and TAM-targeted inhibitor RXDX-106 (pan-TAM), ASP-2215 (Axl specific), or MRX-2843 (Mertk specific) showed enhanced mineralization with pan-TAM or Mertk-specific inhibitors and no change with Axl-specific inhibitor. First molar extractions in Mertk-/- mice had increased alveolar bone regeneration in the extraction socket relative to wild type controls 7 d postextraction. Flow cytometry of 7-d extraction sockets showed no difference in immune cell numbers between Mertk-/- and wild type mice. RNAseq of day 7 extraction sockets showed increased innate immune-related pathways and genes associated with bone differentiation in Mertk-/- mice. Together, these results indicate that TAM receptor signaling, specifically through Mertk, can be targeted to enhance bone regeneration after injury.

Formation and evolution of carbonaceous asteroid Ryugu: Direct evidence from returned samples.

Samples of the carbonaceous asteroid Ryugu were brought to Earth by the Hayabusa2 spacecraft. We analyzed 17 Ryugu samples measuring 1 to 8 millimeters. Carbon dioxide-bearing water inclusions are present within a pyrrhotite crystal, indicating that Ryugu's parent asteroid formed in the outer Solar System. The samples contain low abundances of materials that formed at high temperatures, such as chondrules and calcium- and aluminum-rich inclusions. The samples are rich in phyllosilicates and carbonates, which formed through aqueous alteration reactions at low temperature, high pH, and water/rock ratios of <1 (by mass). Less altered fragments contain olivine, pyroxene, amorphous silicates, calcite, and phosphide. Numerical simulations, based on the mineralogical and physical properties of the samples, indicate that Ryugu's parent body formed ~2 million years after the beginning of Solar System formation.

Increased levels of a pro-inflammatory IgG receptor in the midbrain of people with schizophrenia.

BACKGROUND: There is growing evidence that neuroinflammation may contribute to schizophrenia neuropathology. Elevated pro-inflammatory cytokines are evident in the midbrain from schizophrenia subjects, findings that are driven by a subgroup of patients, characterised as a "high inflammation" biotype. Cytokines trigger the release of antibodies, of which immunoglobulin G (IgG) is the most common. The level and function of IgG is regulated by its transporter (FcGRT) and by pro-inflammatory IgG receptors (including FcGR3A) in balance with the anti-inflammatory IgG receptor FcGR2B. Testing whether abnormalities in IgG activity contribute to the neuroinflammatory abnormalities schizophrenia patients, particularly those with elevated cytokines, may help identify novel treatment targets. METHODS: Post-mortem midbrain tissue from healthy controls and schizophrenia cases (n = 58 total) was used to determine the localisation and abundance of IgG and IgG transporters and receptors in the midbrain of healthy controls and schizophrenia patients. Protein levels of IgG and FcGRT were quantified using western blot, and gene transcript levels of FcGRT, FcGR3A and FcGR2B were assessed using qPCR. The distribution of IgG in the midbrain was assessed using immunohistochemistry and immunofluorescence. Results were compared between diagnostic (schizophrenia vs control) and inflammatory (high vs low inflammation) groups. RESULTS: We found that IgG and FcGRT protein abundance (relative to ß-actin) was unchanged in people with schizophrenia compared with controls irrespective of inflammatory subtype. In contrast, FcGRT and FcGR3A mRNA levels were elevated in the midbrain from "high inflammation" schizophrenia cases (FcGRT; p = 0.02, FcGR3A; p < 0.0001) in comparison to low-inflammation patients and healthy controls, while FcGR2B mRNA levels were unchanged. IgG immunoreactivity was evident in the midbrain, and approximately 24% of all individuals (control subjects and schizophrenia cases) showed diffusion of IgG from blood vessels into the brain. However, the intensity and distribution of IgG was comparable across schizophrenia cases and control subjects. CONCLUSION: These findings suggest that an increase in the pro-inflammatory Fcγ receptor FcGR3A, rather than an overall increase in IgG levels, contribute to midbrain neuroinflammation in schizophrenia patients. However, more precise information about IgG-Fcγ receptor interactions is needed to determine their potential role in schizophrenia neuropathology.

Radiology volunteers to support a breast cancer screening program in Peru: Description of the project, preliminary results, and impressions.

Breast cancer is the second most common cancer in Peruvian women. Due to limitations in national breast cancer screening programs, especially in rural areas, more than 50% of cases of breast cancer in Peru are diagnosed in advanced stages. In collaboration with a local clinic registered as a nongovernmental organization (CerviCusco), RAD-AID International aims to create a sustainable diagnostic structure to improve breast cancer screening in Cuzco. With the support of local, national, and international partners that have collaborated in analyzing radiological resources, raising awareness in the population, acquiring equipment, training clinical staff, and building referral networks, our teams of radiologists, included in the RAD-AID team, have participated in training CerviCusco staff in breast ultrasound, thus enabling additional training for radiology residents through a regulated international collaboration.

Voluntariado radiológico para apoyar un programa de detección precoz del cáncer de mama en Perú: descripción del proyecto, presentación de los primeros resultados e impresiones / Radiology volunteers to support a breast cancer screening program in Peru: description of the project, preliminary results, and impressions

El cáncer de mama es el segundo cáncer más frecuente en las mujeres peruanas. Las limitaciones de los programas nacionales de detección precoz, sobre todo en las regiones rurales, propician que más del 50% de los nuevos casos de cáncer de mama en Perú se diagnostiquen en estadios avanzados. RAD-AID Internacional, en colaboración con una clínica local registrada como organización no gubernamental (CerviCusco), pretende crear una estructura diagnóstica sostenible que mejore el cribado del cáncer de mama en Cuzco. Para ello se ha contado con socios locales, nacionales e internacionales que han colaborado en el análisis de recursos radiológicos, la concienciación de la población, la adquisición de equipamiento, el entrenamiento clínico y las redes de referencia. Nuestros equipos de radiólogos, incluidos en el equipo RAD-AID, han participado en la capacitación ecográfica del personal de CerviCusco, permitiendo una formación adicional a los residentes de radiología gracias a una colaboración internacional reglada.(AU)

Breast cancer is the second most common cancer in Peruvian women. Due to limitations in national breast cancer screening programs, especially in rural areas, more than 50% of cases of breast cancer in Peru are diagnosed in advanced stages. In collaboration with a local clinic registered as a nongovernmental organization (CerviCusco), RAD-AID International aims to create a sustainable diagnostic structure to improve breast cancer screening in Cuzco. With the support of local, national, and international partners that have collaborated in analyzing radiological resources, raising awareness in the population, acquiring equipment, training clinical staff, and building referral networks, our teams of radiologists, included in the RAD-AID team, have participated in training CerviCusco staff in breast ultrasound, thus enabling additional training for radiology residents through a regulated international collaboration.(AU)

Radiology volunteers to support a breast cancer screening program in Peru: description of the project, preliminary results, and impressions. / Voluntariado radiológico para apoyar un programa de detección precoz del cáncer de mama en Perú: descripción del proyecto, presentación de los primeros resultados e impresiones.

Breast cancer is the second most common cancer in Peruvian women. Due to limitations in national breast cancer screening programs, especially in rural areas, more than 50% of cases of breast cancer in Peru are diagnosed in advanced stages. In collaboration with a local clinic registered as a nongovernmental organization (CerviCusco), RAD-AID International aims to create a sustainable diagnostic structure to improve breast cancer screening in Cuzco. With the support of local, national, and international partners that have collaborated in analyzing radiological resources, raising awareness in the population, acquiring equipment, training clinical staff, and building referral networks, our teams of radiologists, included in the RAD-AID team, have participated in training CerviCusco staff in breast ultrasound, thus enabling additional training for radiology residents through a regulated international collaboration.

New methods for determination of the keyhole position in the lateral suboccipital approach to avoid transverse-sigmoid sinus injury: Proposition of the groove line as a new surgical landmark.

PURPOSE: The asterion is frequently used as an anatomical landmark to determine the location of a keyhole in the lateral suboccipital approach used in craniotomies. However, the asterion may not be ideal because of large individual differences among patients. We examined a simple and safe method for determining an optimal keyhole position (KP) using the digastric groove as a new landmark in the lateral suboccipital approach. METHODS: Thirty-three patients with trigeminal neuralgia who underwent surgery in our institute between April 2014 and December 2018 were included. The groove line (GL) was designed accurately, extending the digastric groove on the surface of the occipital bone, as the x-axis. The y-axis was depicted from the posterior edge of the digastric groove (the groove point: GP) vertical to the GL. The x-y coordinates represented the distances from GP on each axis. The x-y coordinates of median edge of the transverse-sigmoid sinus (TSJ point), asterion, and the intersection of the GL and transverse sinus (the transverse point: TP) were investigated, based on intraoperative findings and recorded videos. RESULTS: The x-y coordinated of the TSJ point were (23.9±3.9, 7.2±3.6). In all patients, the TSJ point was located superior to the GL. The x-y coordinates of the asterion were (27.3±6.0, 8.9±4.1), and in 28 of the 33 patients, their coordinates exceeded the TSJ points. The x-coordinate of the TP was 29.5±4.5, and was located behind the TSJ point on the GL in all patients. The shortest distance between the TSJ points and TP was approximately 3mm. According to these measurements, we decided that the optimal KP would be at 20mm from the GP, subjacent to the GL. CONCLUSIONS: Our methods of using the GL as a new surgical landmark for setting the optimal KP is simple, safe, and useful.

Transient ischemic attack without self-awareness of symptoms witnessed by bystanders: analysis of the PROMISE-TIA registry.

BACKGROUND AND PURPOSE: A transient ischemic attack (TIA) can occur without self-awareness of symptoms. We aimed to investigate characteristics of patients with a tissue-based diagnosis of TIA but having no self-awareness of their symptoms and whose symptoms were witnessed by bystanders. METHODS: We used data from the multicenter registry of 1414 patients with a clinical diagnosis of TIA. For patients without evidence of ischemic lesions on imaging, clinical characteristics were compared between patients with and without self-awareness of their TIA symptoms. RESULTS: Among 896 patients (559 men, median age of 70 years), 59 (6.6%) were unaware of their TIA symptoms, but had those symptoms witnessed by bystanders. Patients without self-awareness of symptoms were older and more frequently female, and more likely to have previous history of stroke, premorbid disability, and atrial fibrillation, but less likely to have dyslipidemia than those with self-awareness. Patients without self-awareness of symptoms arrive at hospitals earlier than those with self-awareness (P < 0.001). ABCD2 score was higher in patients without self-awareness of symptoms than those with self-awareness (median 5 vs. 4, P = 0.002). Having no self-awareness of symptoms was a significant predictor of ischemic stroke within 1 year after adjustment for sex, ABCD2 score, and onset to arrival time (hazard ratio = 2.44, 95% confidential interval: 1.10-4.83), but was not significant after further adjustment for arterial stenosis or occlusion. CONCLUSIONS: Patients with a TIA but having no self-awareness of their symptoms might have higher risk of subsequent ischemic stroke rather than those with self-awareness, suggesting urgent management is needed even if patients have no self-awareness of symptoms.

Influence of the trapeziometacarpal joint fusion on thumb muscles and thumb-tip movement: A cadaveric study.

BACKGROUND: Trapeziometacarpal (TMC) arthrodesis provides stability and strength of the thumb, whereas fixation of the TMC joint restricts motion of the thumb, which may consequently impair the activity of daily living. The objective of our study was to investigate how length and area of the thumb-tip trajectory were reduced after the TMC joint fusion. METHODS: Six fresh, frozen cadavers were used for this study. Tension was applied to the distal tendons of 4 extrinsic thumb muscles (extensor pollicis longus, flexor pollicis longus, abductor pollicis longus, and extensor pollicis brevis) by servomotor, whereas tension was applied to 4 intrinsic muscles (abductor pollicis brevis, opponens pollicis, flexor pollicis brevis, and adductor pollicis) using static weights. The thumb-tip trajectory was examined using a motion capture system without tension and with 5 different weights to induce intrinsic muscle tension before and after the TMC joint fusion. FINDINGS: When tension was applied to the intrinsic muscles, the length of the thumb-tip trajectory decreased in all conditions compared with that before the TMC joint fusion, whereas the trajectory decreased only when the abductor pollicis longus was pulled. The overall thumb-tip trajectory area was reduced to approximately 30% compared with that before the TMC joint fusion. INTERPRETATION: Thumb-tip trajectory was restricted by the TMC joint fusion to approximately 30%. However, the reduced area was found tolerable for performing daily activities. Thus, arthrodesis can be the first-line treatment in patients who wish to engage in activities of daily living without difficulties.

Thermoelectric properties of dispersant-free semiconducting single-walled carbon nanotubes sorted by a flavin extraction method.

Semiconducting single-walled carbon nanotubes (s-SWNTs) were extracted from SWNT mixtures using a flavin derivative (FC12). We evaluated the thermoelectric properties of the s-SWNT sheets. Electrical conductivity, power factor and figure of merit values of the sheets were increased by two orders of magnitude after removing FC12 simply by dipping in dichloromethane.

Does Shortened Application Time Affect Long-Term Bond Strength of Universal Adhesives to Dentin?

OBJECTIVE: This study evaluated the effect of shortened application time on long-term bond strength with universal adhesives. METHODS AND MATERIALS: Three universal adhesives were used: Clearfil Universal Bond (CU, Kuraray Noritake Dental Inc, Tokyo, Japan), Scotchbond Universal Adhesive (SB, 3M ESPE, St Paul, MN, USA) or G-Premio Bond (GP, GC Corp, Tokyo, Japan). Sixty molars were cut to expose midcoronal dentin and prepared with a regular diamond bur. Each adhesive was applied either according to the manufacturer's instruction or with shortened time. Specimens were stored in distilled water at 37°C for 24 hours and then cut into resin-dentin sticks. Microtensile bond strength (µTBS) was tested after either 24 hours or 1 year of water storage. Data were analyzed by the three-way ANOVA and Duncan tests ( α=0.05). Fracture modes were analyzed under a scanning electron microscope (SEM). One dentin stick per group was selected after fracture mode analysis and further observed using transmission electron microscopy (TEM). Six additional dentin discs were prepared and conditioned with each adhesive under the different application time to observe the adhesive-smear layer interaction by SEM. RESULTS: Shortened application time affected the µTBS ( p<0.001) while storage time did not affect bond strength ( p=0.187). A significant effect of shortened application time on µTBS was observed in the CU at 1 year and in the GP at both storage times. CONCLUSIONS: One-year storage time had no effect on the µTBS of universal adhesives to bur-cut dentin. The performance of universal adhesives can be compromised when applied using a shortened application time.

Changes in dermal structure and skin oxidative stress in overweight and obese Japanese males after weight loss: a longitudinal observation study.

BACKGROUND/PURPOSE: Previous studies have reported decreased dermal echogenicity and increased skin oxidative stress in overweight males. However, it is unknown whether these skin parameters of overweight and obese people are similar to those of individuals exhibiting a normal body weight following weight loss. The purpose of this study was to (1) compare the changes in the dermal structure parameters and levels of skin oxidative stress before and after weight loss in overweight and obese people in Japan and (2) to clarify how these aspects changed when body weight would be reduced to normal body weight. METHODS: Male volunteers with a body mass index of ≥25 kg/m2 were recruited. The dermal structure was visualized and dermal echogenicity and thickness were measured using ultrasound scanners. The mRNA expression level of heme oxygenase-1 in the hair follicles was quantitatively analyzed as a marker of skin oxidative stress. RESULTS: When overweight individuals in their 20s to 30s reduced their weight to normal, decreased dermal thickness in the abdominal region was observed in 50% of the subjects; however, no increase in dermal echogenicity was observed. A decrease in dermal thickness and an increase in dermal echogenicity in the thighs was observed in 83.3% of the subjects. No decrease in the level of dermal oxidative stress was observed. CONCLUSION: The dermal structure in the thighs of overweight young individuals can be improved to the level of the structure in those of normal body weight individuals following weight loss.

Effects of paraoxonase 1 on the cytodifferentiation and mineralization of periodontal ligament cells.

BACKGROUND AND OBJECTIVE: Single nucleotide polymorphisms (SNPs) of paraoxonase 1 (PON1) are known to be associated with the pathogenesis of osteoporosis and periodontitis. However, the effects of PON1 on the osteoblastic differentiation of periodontal ligament (PDL) cells are unclear. In this study, we examined the effects of PON1 on the osteoblastic differentiation of PDL cells, and analysed the role of PON1 SNPs on the pathogenesis of aggressive periodontitis (AgP) in the Japanese population. MATERIAL AND METHODS: Human PDL (HPDL) cells were exposed to the PON1 plasmid and PON1 inhibitor, 2-hydroxyquinoline, and cultured in mineralization medium. Expression of calcification-related genes and calcified nodule formation were assessed by real-time PCR, an alkaline phosphatase (ALPase) activity assay and Alizarin red staining. Sanger sequencing was performed to evaluate whether PON1 SNPs are associated with the pathogenesis of AgP in Japanese people. RESULTS: During osteoblastic differentiation of HPDL cells, expression of PON1 mRNA increased in a time-dependent manner. PON1 stimulated an increase in expression of mRNA for calcification-related genes, as well as ALPase activity. In contrast, 2-hydroxyquinoline clearly inhibited the expression of calcification-related genes, ALPase activity and calcified nodule formation in HPDL cells. Moreover, there was a statistically significant difference in the minor allele frequency of PON1 SNP rs854560 between the Japanese control database and patients with AgP in the Japanese population (P = .0190). CONCLUSION: PON1 induced cytodifferentiation and mineralization of HPDL cells, and PON1 SNP rs854560 may be associated with the pathogenesis of AgP in the Japanese population.

Toll-like receptor 3 in nasal CD103+ dendritic cells is involved in immunoglobulin A production.

Intranasal inoculation with influenza hemagglutinin subunit with polyinosine-polycytidylic (polyI:C), a synthetic analog for double-stranded RNA, enhances production of vaccine-specific immunoglobulin (Ig) A, which is superior to IgG in prophylactic immunity. The mechanism whereby polyI:C skews to IgA production in the nasal-associated lymph tissue (NALT) was investigated in mouse models. Nasally instilled polyI:C was endocytosed into CD103+ dendritic cells (DCs) and induced T-cell activation, including interferon (IFN)-γ production. According to knockout mouse studies, polyI:C activated the Toll-like receptor 3 signal via the adapter TICAM-1 (also called TRIF), that mainly caused T-cell-dependent IgA production. Nasal CD103+ DCs activated transforming growth factor-ß signaling and activation-induced cytidine deaminase upon polyI:C stimulation. IgA rather than IgG production was impaired in Batf3-/- mice, where CD103+ DCs are defective. Genomic recombination occurred in IgA-producing cells in association with polyI:C-stimulated DCs and nasal microenvironment. PolyI:C induced B-cell-activating factor expression and weakly triggered T-cell-independent IgA production. PolyI:C simultaneously activated mitochondrial antiviral signaling and then type I IFN receptor pathways, which only minimally participated in IgA production. Taken together, CD103+ DCs in NALT are indispensable for the adjuvant activity of polyI:C in enhancing vaccine-specific IgA induction and protective immunity against influenza viruses.

Response to Lefebvre et al.

Congenital scoliosis (CS) is a common vertebral malformation with incidence of up to 1 of 1000 births worldwide. Recently, TBX6 has been reported as the first disease gene for CS: about 10% of CS patients are compound heterozygotes of rare null mutations and a common haplotype composed by 3 SNPs in TBX6. Lefebvre et al in this journal reported that 2 patients with spondylocostal dysostosis (SCD), a rare skeletal dysplasia affecting spine and ribs also have TBX6 mutations: 1 carried the microdeletion and a rare missense variant, and another 2 rare missense variants. We investigated the pathogenicity of the 3 missense variants in SCD by a luciferase assay. The results were negative for the proposal of Lefebvre et al. We consider these 2 SCD patients are more probably compound heterozygotes of null mutations and a common risk haplotype just as CS patients with TBX6 mutations.

Prediction of hemorrhagic transformation after acute thrombolysis following major artery occlusion using relative ADC ratio: A retrospective study.

BACKGROUND: The relative apparent diffusion coefficient (ADC) ratio can be used to evaluate the extent of ischemia. We investigated the risk factors for, and correlation between, relative ADC ratio and hemorrhagic transformation (HT) after thrombolysis. METHODS: This single-center, retrospective study involved 105 patients with acute occlusion of the anterior circulation. Relative ADC ratio was calculated as the ratio of ADC pixel values, within the affected territory to ADC pixel values in the contralateral normal region. HT was determined by computed tomography and T2* weighted magnetic resonance imaging after endovascular revascularization. RESULTS: Data for 80 of the 105 patients were analyzed. Comparing the number of patients between the HT group (n=25) and the non-HT group (n=55), a significant difference was noted in tissue plasminogen activator (tPA) use (P=0.028), time from onset to reperfusion ≥380min (P<0.001), fluid-attenuated inversion recovery (FLAIR) hyperintensity (P=0.009), and relative ADC ratio<0.650 (P<0.001). Multivariable logistic regression analysis identified relative ADC ratio<0.650 as the only independent predictor of HT (odds ratio 7.79; 95% confidence interval 2.22-27.3; P=0.001). Twenty-nine patients (including 20 in the HT group) had a relative ADC ratio<0.650. Multivariable logistic regression analysis identified use of tPA as the only independent predictor of HT (odds ratio 13.8; 95% confidence interval 1.35-125.5; P=0.010). CONCLUSIONS: Relative ADC ratio<0.650 with use of tPA may be important for predicting HT.

Prognostic value of sequencing-based minimal residual disease detection in patients with multiple myeloma who underwent autologous stem-cell transplantation.

BACKGROUND: Most patients with multiple myeloma (MM) are considered to be incurable, and relapse owing to minimal residual disease (MRD) is the main cause of death among these patients. Therefore, new technologies to assess deeper response are required. PATIENTS AND METHODS: We retrospectively analyzed 125 patients with MM who underwent high-dose melphalan plus autologous stem-cell transplantation (ASCT) to detect MRD in autograft/bone marrow (BM) cells using a next-generation sequencing (NGS)-based method and allele-specific oligonucleotide-polymerase chain reaction (ASO-PCR). RESULTS: NGS-based method was applicable to 90% and this method had at least one to two logs greater sensitivity compared to ASO-PCR. MRD negative by NGS [MRDNGS(-)] (defined as <10-6) in post-ASCT BM cases (n = 26) showed a significantly better progression-free survival (PFS) (96% at 4 years, P < 0.001) and overall survival (OS) (100% at 4 years, P =0.04) than MRDNGS(+) in post-ASCT BM cases (n = 25). When restricting the analysis to the 39 complete response cases, patients who were MRDNGS(-) (n = 24) showed a significantly better PFS than those that were MRDNGS(+) (n = 15) (P =0.02). Moreover, MRDNGS(-) in post-ASCT BM cases (n = 12) showed significantly a better PFS than MRDNGS(+) cases (n = 7) where MRD was not detected by ASO-PCR (P = 0.001). Patients whose autografts were negative by NGS-based MRD assessment (<10-7) (n = 19) had 92% PFS and 100% OS at 4 years post-ASCT. Conversely, the NGS-based MRD positive patients who received post-ASCT treatment using novel agents (n = 49) had a significantly better PFS (P = 0.001) and tended to have a better OS (P= 0.214) than those that were untreated (n = 33). CONCLUSIONS: Low level MRD detected by NGS-based platform but not ASO-PCR has significant prognostic value when assessing either the autograft product or BM cells post-ASCT.

Advanced Statistical Analyses to Reduce Inconsistency of Bond Strength Data.

This study was designed to clarify the interrelationship of factors that affect the value of microtensile bond strength (µTBS), focusing on nondestructive testing by which information of the specimens can be stored and quantified. µTBS test specimens were prepared from 10 noncarious human molars. Six factors of µTBS test specimens were evaluated: presence of voids at the interface, X-ray absorption coefficient of resin, X-ray absorption coefficient of dentin, length of dentin part, size of adhesion area, and individual differences of teeth. All specimens were observed nondestructively by optical coherence tomography and micro-computed tomography before µTBS testing. After µTBS testing, the effect of these factors on µTBS data was analyzed by the general linear model, linear mixed effects regression model, and nonlinear regression model with 95% confidence intervals. By the general linear model, a significant difference in individual differences of teeth was observed ( P < 0.001). A significantly positive correlation was shown between µTBS and length of dentin part ( P < 0.001); however, there was no significant nonlinearity ( P = 0.157). Moreover, a significantly negative correlation was observed between µTBS and size of adhesion area ( P = 0.001), with significant nonlinearity ( P = 0.014). No correlation was observed between µTBS and X-ray absorption coefficient of resin ( P = 0.147), and there was no significant nonlinearity ( P = 0.089). Additionally, a significantly positive correlation was observed between µTBS and X-ray absorption coefficient of dentin ( P = 0.022), with significant nonlinearity ( P = 0.036). A significant difference was also observed between the presence and absence of voids by linear mixed effects regression analysis. Our results showed correlations between various parameters of tooth specimens and µTBS data. To evaluate the performance of the adhesive more precisely, the effect of tooth variability and a method to reduce variation in bond strength values should also be considered.