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Abstract Hepatocytes play important roles in the liver, but in culture, they immediately lose function and dedifferentiate into progenitor-like cells. Although this unique feature is well-known, the dynamics and mechanisms of hepatocyte dedifferentiation and the differentiation potential of dedifferentiated hepatocytes (dediHeps) require further investigation. Here, we employ a culture system specifically established for hepatic progenitor cells to study hepatocyte dedifferentiation. We found that hepatocytes dedifferentiate with a hybrid epithelial/mesenchymal phenotype, which is required for the induction and maintenance of dediHeps, and exhibit Vimentin-dependent propagation, upon inhibition of the Hippo signaling pathway. The dediHeps re-differentiate into mature hepatocytes by forming aggregates, enabling reconstitution of hepatic tissues in vivo. Moreover, dediHeps have an unexpected differentiation potential into intestinal epithelial cells that can form organoids in three-dimensional culture and reconstitute colonic epithelia after transplantation. This remarkable plasticity will be useful in the study and treatment of intestinal metaplasia and related diseases in the liver.

Oral microbiota may be associated with serious local or systemic medical conditions resulting from chemotherapy. This study was conducted to evaluate the changes in the oral microbiota following the initiation of chemotherapy in patients with hematopoietic malignancies and to identify the characteristics of the oral microbiota associated with oral mucositis. Oral samples were collected from 57 patients with hematopoietic malignancies at 2 time points: before the start of chemotherapy and 8 to 20 days after the start of chemotherapy, when chemotherapy-induced oral mucositis often occurs, and 16S rRNA metagenomic analyses were performed. Comparative and linear discriminant analysis effect size (LEfSe) analyses were used to determine the characteristic bacterial groups before and after the initiation of chemotherapy and in those who developed oral mucositis. The alpha and beta diversities of oral microbiota before and after the initiation of chemotherapy differed significantly (operational taxonomic unit index, P

Abstract Background The acromioclavicular (AC) and coracoclavicular (CC) ligaments are important stabilizers of the AC joint. We hypothesized that AC and trapezoid ligament injuries induce AC joint instability and that the clavicle can override the acromion on cross-body adduction view even in the absence of conoid ligament injury. Accordingly, we investigated how sectioning the AC and CC ligaments contribute to AC joint instability in the cross-body adduction position. Methods Six fresh-frozen cadaveric shoulders were used in this study, comprising five male and one female specimen, with a mean age of 68.7 (range, 51–87) years. The left side of the trunk and upper limb, and the cervical and thoracic vertebrae and sternum were firmly fixed with an external fixator. The displacement of the distal end of the clavicle relative to the acromion was measured using an electromagnetic tracking device. We simulated AC joint dislocation by the sequential resection of the AC ligament, AC joint capsule, and CC ligaments in the following order of stages. Stage 0: Intact AC and CC ligaments and acromioclavicular joint capsule; stage 1: Completely sectioned AC ligament, capsule and joint disc; stage 2: Sectioned trapezoid ligament; and stage 3: Sectioned conoid ligament. The superior clavicle displacement related to the acromion was measured in the horizontal adduction position, and clavicle overriding on the acromion was assessed radiologically at each stage. Data were analyzed using a one-way analysis of variance and post-hoc tests. Results Superior displacement was 0.3 mm at stage 1, 6.5 mm at stage 2, and 10.7 mm at stage 3. On the cross-body adduction view, there was no distal clavicle overriding at stages 0 and 1, and distal clavicle overriding was observed in five cases (5/6: 83%) at stage 2 and in six cases (6/6: 100%) at stage 3. Conclusion We found that AC and trapezoid ligament sectioning induced AC joint instability and that the clavicle could override the acromion on cross-body adduction view regardless of conoid ligament sectioning. The traumatic sections of the AC and trapezoid ligament may lead to high grade AC joint instability, and the distal clavicle may subsequently override the acromion.

Additive manufacturing techniques are being used in the medical field. Orthopedic hip prostheses and denture bases are designed and fabricated based on the patient’s computer-aided design (CAD) data. We attempted to incorporate this technique into dental implant bone augmentation. Surgical simulation was performed using patient data. Fourteen patients underwent bone augmentation using a selective laser melting (SLM) titanium mesh plate. The results showed no evidence of infection in any of the 14 patients. In 12 patients, only one fixation screw was used, and good results were obtained. The SLM titanium mesh plate was good adaptation in all cases, with bone occupancy greater than 90%. The average bone resorption of the marginal alveolar bone from the time of dental implant placement to the time of the superstructure placement was 0.69 ± 0.25 mm. Implant superstructures were placed in all cases, and bone augmentation with SLM titanium mesh plates was considered a useful technique.

Abstract Background Size of reference population is a crucial factor affecting the accuracy of prediction of the genomic estimated breeding value (GEBV). There are few studies in beef cattle that have compared accuracies achieved using real data to that achieved with simulated data and deterministic predictions. Thus, extent to which traits of interest affect accuracy of genomic prediction in Japanese Black cattle remains obscure. This study aimed to explore the size of reference population for expected accuracy of genomic prediction for simulated and carcass traits in Japanese Black cattle using a large amount of samples. Results A simulation analysis showed that heritability and size of reference population substantially impacted the accuracy of GEBV, whereas the number of quantitative trait loci did not. The estimated numbers of independent chromosome segments (M e ) and the related weighting factor (w) derived from simulation results and a maximum likelihood (ML) approach were 1900–3900 and 1, respectively. The expected accuracy for trait with heritability of 0.1–0.5 fitted well with empirical values when the reference population comprised > 5000 animals. The heritability for carcass traits was estimated to be 0.29–0.41 and the accuracy of GEBVs was relatively consistent with simulation results. When the reference population comprised 7000–11,000 animals, the accuracy of GEBV for carcass traits can range 0.73–0.79, which is comparable to estimated breeding value obtained in the progeny test. Conclusion Our simulation analysis demonstrated that the expected accuracy of GEBV for a polygenic trait with low-to-moderate heritability could be practical in Japanese Black cattle population. For carcass traits, a total of 7000–11,000 animals can be a sufficient size of reference population for genomic prediction.

Abstract Background The Problematic Online Gaming Questionnaire (POGQ) is an 18-item self-rated measure designed to assess the degree of problematic online gaming. This study translated the POGQ into Japanese (POGQ-J) and examined the POGQ-J’s factor structure, validity, and reliability for a Japanese population. Method A total of 285 undergraduate students (128 males, 157 females, M age = 19.66, SD = 1.36) participated in this study. Results A confirmatory factor analysis indicated the appropriateness of the POGQ-J’s six-factor structure, χ 2(129) = 106.027, p

Background: Humeral stem loosening has gained attention as it has been identified as a cause of revision surgery in reverse shoulder arthroplasty (RSA). In RSA, humeral stem revision is very difficult if there is humeral bone loss because of stress shielding. Some studies of humeral bone resorption after anatomic shoulder arthroplasty have been published, but there are few detailed reports of humeral bone resorption after RSA. This study aimed to investigate the prevalence of humeral bone resorption after RSA procedures and to evaluate the risk factors for bone resorption. Methods: This study included 48 shoulders that underwent RSA with an uncemented humeral stem from July 2014 to May 2017 and were followed up for more than 1 year. The prevalence of humeral bone resorption and risk factors were investigated. Logistic, multiple logistic, and multivariate logistic regression analyses were performed to evaluate the data. Results: Grade 0 bone resorption, the most advanced grade, occurred in 8 shoulders (16.7%); grade 1, in 0 (0%); grade 2, in 17 (35.4%); grade 3, in 14 (29.2%); and grade 4, in 9 (18.8%). A high occurrence of bone absorption was observed in zones 1, 2, and 7. Grade 4 bone resorption did not occur in zones 3, 5, and 6. Female sex and an onlay-type stem were significant independent risk factors for grade 4 bone resorption. Conclusions: Bone resorption was frequently observed in the greater tuberosity, lateral diaphysis, and calcar region. Significant risk factors included female sex and an onlay-type stem.

The formation of tropospheric ozone is influenced by emissions of volatile organic compounds (VOCs) and nitrogen oxides (NOx), and different regimes of sensitivity to the ozone formation have been identified depending on the concentrations of both groups of compounds. We studied the ozone formation sensitivity in the Mexico City Metropolitan Area (MCMA) using the formaldehyde to nitrogen dioxide ratio (FNR) as a proxy for the VOCs and NOx concentrations, with data retrieved from the Ozone Monitoring Instrument (OMI). To determine the different sensitivity regimes, we compared two previously established threshold values of FNR, which differ from each other in the range of ratios on which the regime transition occurs. The evaluation from 2006 to 2016 showed that the FNR gradually changed, causing variations in the ozone formation sensitivity. While in 2006, more regions were under NOx-limited/transitional regimes, in 2016, the VOC-limited conditions prevailed in most of the city. The analysis disclosed that this change is due to increasing NOx emissions in some regions of MCMA and decreasing VOC emissions in other areas. The observed trend is different from that in major cities in other parts of the world, such as the United States, where ozone formation sensitivity has moved towards NOx-limited conditions. Therefore, reducing VOC emissions would be a suitable approach for decreasing tropospheric ozone concentrations in the MCMA.

Abstract Background Treatment of anterior cruciate ligament injuries commonly involves the use of polyethylene terephthalate (PET) artificial ligaments for reconstruction. However, the currently available methods require long fixation periods, thereby necessitating the development of alternative methods to accelerate the healing process between tendons and bones. Thus, we developed and evaluated a novel technique that utilizes silicate-substituted strontium (SrSiP). Methods PET films, nano-coated with SrSiP, were prepared. Bone marrow mesenchymal cells (BMSCs) from femurs of male rats were cultured and seeded at a density of 1.0 × 104/cm2 onto the SrSiP-coated and non-coated PET film, and subsequently placed in an osteogenic medium. The osteocalcin concentration secreted into the medium was compared in each case. Next, PET artificial ligament, nano-coated with SrSiP, were prepared. BMSCs were seeded at a density of 4.5 × 105/cm2 onto the SrSiP-coated, and non-coated artificial ligament, and then placed in osteogenic medium. The osteocalcin and calcium concentrations in the culture medium were measured on the 8th, 10th, 12th, and 14th day of culture. Furthermore, mRNA expression of osteocalcin, alkaline phosphatase (ALP), bone morphogenetic protein-2 (BMP2), and runt-related transcription factor 2 (Runx2) was evaluated by qPCR. We transplanted the SrSiP-coated and non-coated artificial ligament to the tibiae of mature New Zealand white rabbits. Two months later, we sacrificed them and histologically evaluated them. Results The secretory osteocalcin concentration in the medium on the film was significantly higher for the SrSiP group than for the non-coated group. Secretory osteocalcin concentration in the medium on the artificial ligament was also significantly higher in the SrSiP group than in the non-coated group on the 14th day. Calcium concentration on the artificial ligament was significantly lower in the SrSiP group than in the non-coated group on the 8th, 10th, 12th, and 14th day. In qPCR as well, OC, ALP, BMP2, and Runx2 mRNA expression were significantly higher in the SrSiP group than in the non-coated group. Newly formed bone was histologically found around the artificial ligament in the SrSiP group. Conclusions Our findings demonstrate that artificial ligaments using SrSiP display high osteogenic potential and thus may be efficiently used in future clinical applications.

Ozone (O3) is a pollutant of concern in urban areas because of its effects on health, crops, ecosystems, and materials. Despite efforts to meet the Japanese air quality standard for O3 in the Kanto region, the attainment percentage is close to zero. Considering that O3 formation is sensitive to emissions of volatile organic compounds (VOC) and nitrogen oxides (NOx), this study evaluated a range of reductions in the emissions of both precursors using a regional air quality model (ADMER-PRO) and estimated their benefits measured as the economic change due to O3 concentration differences between scenarios. The simulation period was set during the 2016 O3 season. The results showed that O3 concentrations could be reduced using two approaches: significant reduction in VOC levels combined with minor NOx level changes or significant NOx emission reduction. Significant reduction in NOx levels was the most effective strategy for a generalized decrease in the O3 levels in the Kanto region, and the benefit analysis revealed that the most significant economic impacts could be achieved by adopting the latter approach.

Objectives and Design. Epiphyseal separation of the coracoid process (CP) rarely occurs in adolescents. In this retrospective case series, we reviewed the data of nine patients treated at our center and those of 28 patients reported in the literature. This injury can be classified into three types according to the injured area: Type I, base including the area above the glenoid; Type II, center including the coracoclavicular ligament (CCL); and Type III, tip with the short head of the biceps and coracobrachialis, as well as the pectoralis minor. Patients/Participants. A total of 37 patients were included in the analysis. Data on sex, age, cause and mechanism of injury, separation type, concomitant injury around the shoulder girdle, treatment, and functional outcomes were obtained. Main Outcome Measurements and Results. Type I is the most common type. The cause of injury and associated injury around the shoulder girdle were significantly different between Type I, II, and III fractures. The associated acromioclavicular (AC) dislocation and treatment were significantly different between Type I and III fractures. Our new classification system reflects the clinical features, imaging findings, and surgical management of epiphyseal separation of the CP. Type I and II fractures are mostly associated with AC dislocation and have an associated injury around the shoulder girdle. Type III fractures are typically caused by forceful resisted flexion of the arm and elbow. Although the latter are best managed surgically, whether conservative or surgical management is optimal for Type I and II fractures remains controversial. Conclusions. We noted some differences in the clinical characteristics depending on the location of injury; therefore, we aimed to examine these differences to develop a new system for classifying epiphyseal separation of the CP. This would increase the clinicians’ awareness regarding this injury and lead to the development of an appropriate treatment.

Study DesignCase–control study.PurposeThe aim of the present study was to identify physical findings useful for differentiating between cervical spondylotic amyotrophy (CSA) and rotator cuff tears to prevent the misdiagnosis of CSA as a rotator cuff tear.Overview of LiteratureCSA and rotator cuff tears are often confused among patients presenting with difficulty in shoulder elevation.MethodsTwenty-five patients with CSA and 27 with rotator cuff tears were enrolled. We included five physical findings specific to CSA that were observed in both CSA and rotator cuff tear patients. The findings were as follows: (1) weakness of the deltoid muscle, (2) weakness of the biceps muscle, (3) atrophy of the deltoid muscle, (4) atrophy of the biceps muscle, and (5) swallow-tail sign (assessment of the posterior fibers of the deltoid).ResultsAmong 25 CSA patients, 10 (40.0%) were misdiagnosed with a rotator cuff tear on initial diagnosis. The sensitivity and specificity of each physical finding were as follows: (1) deltoid weakness (sensitivity, 92.0%; specificity, 55.6%), (2) biceps weakness (sensitivity, 80.0%; specificity, 100%), (3) deltoid atrophy (sensitivity, 96.0%; specificity, 77.8%), (4) biceps atrophy (sensitivity, 88.8%; specificity, 92.6%), and (5) swallow-tail sign (sensitivity, 56.0%; specificity, 74.1%). There were statistically significant differences in each physical finding.ConclusionsCSA is likely to be misdiagnosed as a rotator cuff tear; however, weakness and atrophy of the biceps are useful findings for differentiating between CSA and rotator cuff tears to prevent misdiagnosis.

Jaw reconstruction using an additive-manufacturing titanium artificial bone (AMTAB) has recently attracted considerable attention. The synthesis of a titanium artificial bone is based on three-dimensional computed tomography images acquired before surgery. A histological evaluation of porous AMTAB (pAMTAB) embedded in rat calvarial bone defects was conducted. This study examined three groups: rats implanted with mixed-acid and heat-treated pAMTAB, rats implanted with untreated pAMTAB, and rats with no implant. In both pAMTAB groups, bone defects were created in rat calvarial bones using a 5-mm trephine bar, followed by pAMTAB implantation. The pAMTAB was fixed to the defect using the fitting force of the surrounding bones. The rats were sacrificed at 4, 8, and 16 weeks after implantation, and the skull was dissected. Undecalcified ground slides were prepared and stained with Villanueva Goldner. Compared with the no implant control group, both pAMTAB groups exhibited new bone formation inside the defect, with greater bone formation in the mixed-acid and heat-treated pAMTAB group than in the untreated pAMTAB group, but the difference was not significant. These data suggest that pAMTAB induces bone formation after implantation in bone defects. Bone formation appears to be enhanced by prior mixed-acid and heat-treated pAMTAB.

Selective laser melting (SLM) is a promising technology capable of producing individual characteristics with a high degree of surface roughness for implants. These surfaces can be modified so as to increase their osseointegration, bone generation and biocompatibility, features which are critical to their clinical success. In this study, we evaluated the effects on preosteoblast proliferation and differentiation of titanium metal (Ti) with a high degree of roughness (Ra = 5.4266 ± 1.282 µm) prepared by SLM (SLM-Ti) that was also subjected to surface bioactive treatment by mixed acid and heat (MAH). The results showed that the MAH treatment further increased the surface roughness, wettability and apatite formation capacity of SLM-Ti, features which are useful for cell attachment and bone bonding. Quantitative measurement of osteogenic-related gene expression by RT-PCR indicated that the MC3T3-E1 cells on the SLM-Ti MAH surface presented a stronger tendency towards osteogenic differentiation at the genetic level through significantly increased expression of Alp, Ocn, Runx2 and Opn. We conclude that bio-activated SLM-Ti enhanced preosteoblast differentiation. These findings suggest that the mixed acid and heat treatment on SLM-Ti is promising method for preparing the next generation of orthopedic and dental implants because of its apatite formation and cell differentiation capability.

The additive manufacturing (AM) technique has attracted attention as one of the fully customizable medical material technologies. In addition, the development of new surface treatments has been investigated to improve the osteogenic ability of the AM titanium (Ti) plate. The purpose of this study was to evaluate the osteogenic activity of the AM Ti with mixed-acid and heat (MAH) treatment. Fully customized AM Ti plates were created with a curvature suitable for rat calvarial bone, and they were examined in a group implanted with the MAH-treated Ti in comparison with the untreated (UN) group. The AM Ti plates were fixed to the surface of rat calvarial bone, followed by extraction of the calvarial bone 1, 4, 8, and 12 weeks after implantation. The bonding between the bone and Ti was evaluated mechanically. In addition, AM Ti plates removed from the bone were examined histologically by electron microscopy and Villanueva–Goldner stain. The mechanical evaluation showed significantly stronger bone-bonding in the MAH group than in the UN group. In addition, active bone formation was seen histologically in the MAH group. Therefore, these findings indicate that MAH resulted in rapid and strong bonding between cortical bone and Ti.

Self-immolative linker is a useful building block of molecular probes, with broad applications in the fields of enzyme activity analysis, stimuli-responsive material science, and drug delivery. This manuscript presents N-methyl dimethyl methyl (i.e., trimethyl) carbamate as a new class of self-immolative linker for the fluorescence detection of enzyme reactions. The trimethyl carbamate was shown to spontaneously undergo intramolecular cyclization upon formation of a carboxylate group, to liberate a fluorophore with the second time rapid reaction kinetics. Interestingly, the auto-cleavage reaction of trimethyl carbamate was also induced by the formation of hydroxyl and amino groups. Fluorescent probes with a trimethyl carbamate could be applicable for fluorescence monitoring of the enzyme reactions catalyzed by esterase, ketoreductase, and aminotransferase, and for fluorescence imaging of intracellular esterase activity in living cells, hence demonstrating the utility of this new class of self-immolative linker.

Repeatedly presented stimuli are affectively evaluated more positively than novel stimuli. This phenomenon, known as the mere exposure effect, is used in advertising. However, it is still unclear in which part of advertising images the mere exposure effect occurs. Given the recent suggestion that attention plays an important role in the mere exposure effect, it is possible that the mere exposure effect does not occur for commercial products when advertising images consist of a commercial product along with an attractive human model. To investigate this possibility, we manipulated the relationship between advertising images repeatedly presented in an exposure phase and images presented in a later rating phase. In the exposure phase, participants were repeatedly presented with advertising images consisting of a cosmetic product along with an attractive female model and were instructed to attend to a specified part of the image (Experiment 4) or were given no such an instruction (Experiments 1, 2, and 3). In the rating phase, participants were asked to evaluate their preference for complete advertising images (Experiment 1), the images of female models (Experiment 2), or images of products (Experiments 3 and 4) that were previously presented or not presented. The mere exposure effect was found for whole advertising images and images of female models. On the other hand, the mere exposure effect for the images of products was seen only when participants were explicitly encouraged to direct their attention to the product parts of the advertising image. That is, the results of this study suggest that the mere exposure effect does not always occur for every part of the repeated advertising images, and that attention would modulate the mere exposure effect for advertising images.